@article {pmid41781371, year = {2026}, author = {Zhang, L and Huang, Y and Huang, W and Huang, Q and Lin, Y and Gu, J}, title = {TDP-43 phosphorylation: Exploring kinases, phosphatases, and therapeutic potential in neurodegeneration.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {}, number = {}, pages = {13872877261424284}, doi = {10.1177/13872877261424284}, pmid = {41781371}, issn = {1875-8908}, abstract = {TAR DNA-binding protein 43 (TDP-43) is a multifunctional DNA/RNA-binding protein whose abnormal phosphorylation and aggregation are central to the pathogenesis of several neurodegenerative diseases. TDP-43 proteinopathy, characterized by hyperphosphorylation and cytoplasmic accumulation, is a defining pathological feature of amyotrophic lateral sclerosis and frontotemporal lobar degeneration, and is frequently observed in Alzheimer's disease. The phosphorylation state of TDP-43 is dynamically regulated by a network of protein kinases-including CK1, GSK3β, CDC7, and PKA-and counterbalanced by phosphatases such as PP2A and PP1; however, the precise molecular mechanisms governing this equilibrium in disease remain incompletely understood. Notably, phosphorylated TDP-43 acquires prion-like properties, enabling self-templated aggregation and cell-to-cell propagation, which amplifies pathology and drives disease progression. These insights have catalyzed the development of therapeutic strategies aimed at modulating TDP-43 phosphorylation, with kinase inhibitors and phosphatase enhancers emerging as promising candidates for targeting TDP-43 proteinopathies. This review integrates current knowledge on the regulatory networks controlling TDP-43 phosphorylation, examines its role in prion-like spread, and evaluates emerging therapeutic approaches aimed at mitigating TDP-43-mediated neurodegeneration.}, }
@article {pmid41777232, year = {2026}, author = {Yerraguntla, S and Bakshi, B and Chandran, K and Foucher, J and Benatar, M and Wicks, P and Bedlack, R and Shirilla, D and Sun, Y and Maragakis, N and Greenstein, E and Mascias Cadavid, J and Rao, A and Allen, O and Dyckman, K and Wang, O and Beauchamp, M and Chang, V and Brown, A and Carbunar, O and Paganoni, S and Bertorini, T and Pioro, E and Elsharif, B and Jiang, N and Pattee, G and Carter, G and Breevoort, S and Tito, E and Nathaniel, G and Jackson, C and Olby, N and McDermott, C and Ratner, D and Li, X}, title = {ALSUntangled #82: N-acetylcysteine.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-5}, doi = {10.1080/21678421.2026.2638590}, pmid = {41777232}, issn = {2167-9223}, abstract = {N-acetylcysteine is a thiol-containing compound and a precursor of glutathione, with mechanistic plausibility for ALS, including reducing oxidative stress, regulating neuroinflammation, and mitigating mitochondrial dysfunction. Preclinical studies have yielded conflicting results on whether N-acetylcysteine can delay the onset of motor impairment and prolong survival in ALS mouse models. Several case studies of oral or subcutaneous administration of N-acetylcysteine in patients with ALS did not demonstrate convincing benefits. Clinical trials to date have also failed to demonstrate efficacy in slowing ALS progression. While N-acetylcysteine shows theoretical promise, further research is needed to clarify its therapeutic role in ALS. At present, ALSUntangled does not support the use of N-acetylcysteine as a treatment to slow ALS progression.}, }
@article {pmid41653702, year = {2026}, author = {Sebastianelli, L and Versace, V and Ferrazzoli, D and Ortelli, P and Trinka, E and Sellner, J and Nardone, R}, title = {Neurophysiology in the mirror: A tri-layer model of mirror movements informed by TMS evidence.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {184}, number = {}, pages = {2111692}, doi = {10.1016/j.clinph.2026.2111692}, pmid = {41653702}, issn = {1872-8952}, mesh = {Humans ; *Transcranial Magnetic Stimulation/methods ; *Movement Disorders/physiopathology ; Evoked Potentials, Motor/physiology ; *Motor Cortex/physiopathology/physiology ; Movement/physiology ; Pyramidal Tracts/physiopathology/physiology ; }, abstract = {OBJECTIVE: Mirror movements are involuntary, task-coupled contractions in contralateral homologous muscles during unilateral movement. While often described as a developmental remnant or rare clinical sign, mirror movements offer insight into the physiological mechanisms that underlie motor lateralization and interhemispheric balance. This review aimed to synthesize the available neurophysiological evidence-primarily from transcranial magnetic stimulation (TMS)-and propose a structured, mechanism-based framework for interpreting mirror movements across neurological conditions.<br><br>METHODS: A structured narrative review was conducted of studies published between 1966 and November 2025 using TMS in individuals with congenital, developmental, or acquired mirror movements. Studies using neuroimaging or peripheral electrophysiology were included selectively to support anatomical or functional interpretation of TMS findings. Data were organized into three mechanistic layers based on prevailing neurophysiological signatures rather than etiology alone.<br><br>RESULTS: Three non-mutually exclusive mechanisms were identified: (I) persistent fast-conducting ipsilateral corticospinal projections, primarily in congenital mirror movement syndromes and early brain injury; (II) deficient transcallosal inhibition, observed in conditions affecting interhemispheric balance such as amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, and callosal agenesis; and (III) bilateral overactivation of premotor and supplementary motor areas, especially under conditions of impaired motor program selection or increased task demands.<br><br>CONCLUSIONS: Mirror movements can be interpreted within a tri-layer model reflecting distinct disruptions in corticospinal connectivity, interhemispheric inhibition, and supraspinal motor control.<br><br>SIGNIFICANCE: This framework provides an integrative model for interpreting neurophysiological findings in mirror movements, offering insight into hierarchical motor control without implying specific diagnostic or therapeutic applications.}, }
@article {pmid41502663, year = {2025}, author = {Ma, Y and Tian, H and Xiao, W and Ma, Y and Su, H and Zhu, L and Jiang, Y and Ge, L and Li, Y and Yuan, M and Liu, X}, title = {Machine Learning Approaches for Optimizing Drug Combinations in Neurodegenerative Diseases: A Brief Review.}, journal = {ACS omega}, volume = {10}, number = {48}, pages = {57950-57973}, pmid = {41502663}, issn = {2470-1343}, abstract = {As the global population ages, the prevalence of neurodegenerative diseases (NDDs)(?)including Alzheimer's disease, Parkinson's disease, Huntington's disease, Multisystem Atrophy (multiple system atrophy), and amyotrophic lateral sclerosis(?)continues to rise, largely driven by environmental, metabolic, and lifestyle risk factors. Advances in computational technologies, particularly machine learning (ML) and deep learning, are reshaping research in this field. This review summarizes the major features of these diseases and emphasizes the role of ML in drug discovery, virtual screening, drug repurposing, and drug combination optimization. Representative approaches include support vector machines for classification, convolutional neural networks|convolutional neural network for imaging analysis, recurrent neural networks for temporal biomedical data, and transformers for multimodal integration. These methods highlight the potential of computational strategies to improve therapeutic development. In addition, the review underscores the substantial incidence rates and socioeconomic burden of these conditions, which have made them focal points for algorithmic innovation. With research evolving rapidly, the development of AI-driven approaches is expected to enable more effective, targeted interventions and improve patient outcomes. This Perspective provides a concise overview of current progress and identifies promising future directions in the fight against NDDs.}, }
@article {pmid41775321, year = {2026}, author = {Lu, YH and Zhu, XP and Li, S and Zhang, FN and Cai, CB and Tian, M and Zhu, YH and Zeng, LH and Tan, J and Yu, CY and Chen, J}, title = {From scaffold to effector: reframing GFAP in neurodegeneration.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2026.02.051}, pmid = {41775321}, issn = {2090-1224}, abstract = {BACKGROUND: Neurodegenerative disorders impose a growing global burden, yet disease-modifying therapies remain limited. Glial fibrillary acidic protein (GFAP) has shifted from a passive astrocytic marker to an active effector that shapes neurodegenerative pathology.<br><br>AIM: of Review: This review synthesizes mechanistic and translational evidence that defines GFAP as a proteoform-governed hub and highlights its value for biomarker-guided precision intervention. Key Scientific Concepts of Review: An extensive literature search across major databases was conducted using predefined keywords and strict inclusion criteria, covering mechanistic, pathological, and clinical studies. Evidence supports a GFAP proteoform code in which alternative splicing generates functionally distinct isoforms, and PTMs encode context-dependent assembly dynamics and signaling outputs. We summarize how GFAP proteoforms integrate cytoskeletal remodeling with inflammatory transcriptional programs (notably STAT3 and NF-&#x3ba;B), proteostasis stress, and mitochondrial dysfunction, thereby coupling astrocyte state transitions to neuronal vulnerability and synaptic impairment. Disease trajectories are context-specific: GFAP dysfunction drives primary toxicity in Alexander disease (AxD); in Alzheimer's disease (AD), isoform-specific mechanisms intersect with amyloidogenic machinery and track early preclinical astrocyte activation; and in frontotemporal dementia (FTD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS), GFAP reflects inflammatory-metabolic coupling during progression. Translationally, ultrasensitive plasma assays reveal GFAP elevation years to decades before symptom onset, complementing NfL and amyloid/tau within AT(N)-oriented diagnostic frameworks. Therapeutically, we evaluate precision strategies beyond global suppression, including ASO-based modulation, targeting STAT3/NF-&#x3ba;B-driven reactive programs, and restoring proteostasis via chaperone/autophagy pathways. Future progress hinges on isoform-/PTM-specific probes, conformational sensors, and spatial proteomic atlases validated in prospective longitudinal cohorts. In conclusion, GFAP represents both a mechanistic driver and a scalable biomarker, offering a translationally actionable axis to advance precision medicine in neurodegeneration.}, }
@article {pmid41455589, year = {2026}, author = {Ruiz-Ortiz, M and Esteban-Pérez, J and Gómez-Grande, A and Martínez-Albero, E and Benito-León, J}, title = {Motor band sign in [18]F-FDG PET/CT studies: a biomarker of degenerative upper motor neuron disease? A study of three cases and literature review.}, journal = {Neurologia}, volume = {41}, number = {2}, pages = {501931}, doi = {10.1016/j.nrleng.2025.501931}, pmid = {41455589}, issn = {2173-5808}, mesh = {Humans ; *Positron Emission Tomography Computed Tomography ; Fluorodeoxyglucose F18 ; *Motor Neuron Disease/diagnostic imaging ; Male ; Middle Aged ; Female ; Aged ; Biomarkers ; Amyotrophic Lateral Sclerosis/diagnostic imaging ; Radiopharmaceuticals ; }, abstract = {INTRODUCTION: Motor neuron diseases (MND) encompass conditions like amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS), marked by progressive degeneration of upper and/or lower motor neurons. The identification of specific biomarkers is crucial to reduce diagnostic delays.<br><br>METHODS: This study presents three clinical cases evaluated at the Hospital Universitario 12 de Octubre, where the motor band sign on brain 18&#x202f;F-FDG PET/CT aided the diagnosis of MND. The studies were conducted using a SIEMENS Biograph True Point 6, with a review of relevant literature.<br><br>RESULTS: In all three patients, PET/CT revealed hypometabolism in the prerolandic region, indicative of the motor band sign, contributing to the diagnosis of PLS or ALS.<br><br>DISCUSSION: The motor band sign on 18F-FDG PET/CT emerges as a potential marker of upper motor neuron involvement, though the heterogeneity of MNDs and variability across studies call for further research to establish its specificity and sensitivity.<br><br>CONCLUSION: The motor band sign on 18F-FDG PET/CT is a promising biomarker for MNDs, although further studies are required to confirm its diagnostic validity.}, }
@article {pmid40708508, year = {2026}, author = {Rana, A and Malviya, R and Rajput, S and Sridhar, SB and Wadhwa, T}, title = {Trends in Nanoparticle-based Strategies for the Management of Neuroinflammation.}, journal = {CNS &amp; neurological disorders drug targets}, volume = {25}, number = {1}, pages = {39-55}, pmid = {40708508}, issn = {1996-3181}, mesh = {Humans ; *Neuroinflammatory Diseases/drug therapy ; Animals ; *Nanoparticles/therapeutic use ; *Drug Delivery Systems/methods ; *Neurodegenerative Diseases/drug therapy ; Blood-Brain Barrier/drug effects ; Microglia/drug effects ; }, abstract = {Neuroinflammation, characterised by an overactive immune system in the brain and spinal cord, has now been tied to several neurodegenerative diseases. Here, immune cells invade into the brain, activating astrocytes and microglia. Neuroinflammation is a common symptom of many neurodegenerative illnesses, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). This inflammatory reaction occurs within the central nervous system (CNS). Neurological dysfunction results from the inflammatory response, which arises in reaction to any kind of brain injury. Regulating neuroinflammation can be useful for controlling brain disorders associated with neuroinflammation. Several targeted drug delivery systems attempt to treat neuroinflammation caused by neurodegenerative illnesses or brain tumours by targeting the microglia and other immune cells in the central nervous system. Therefore, biodegradable and biocompatible NPs (nanoparticles) could be developed as a treatment for neurodegenerative diseases caused by neuroinflammation or as a less invasive means of transporting other drugs across the blood-brain barrier. Numerous applications of gold nanoparticles (AuNPs) in the treatment of neurological diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD), are studied in this article. To prevent neuroinflammation and microglia over-activation, some NPs have recently been found to be effective anti-inflammatory medication carriers that cross the blood-brain barrier.}, }
@article {pmid40103545, year = {2026}, author = {Sonaglioni, A and Torretta, P and Nicolosi, GL and Lombardo, M}, title = {Left ventricular mechanics assessment in amyloidosis patients: a systematic review and meta-analysis.}, journal = {Minerva cardiology and angiology}, volume = {74}, number = {1}, pages = {60-74}, doi = {10.23736/S2724-5683.24.06683-3}, pmid = {40103545}, issn = {2724-5772}, mesh = {Humans ; *Amyloidosis/physiopathology/diagnostic imaging/complications ; Echocardiography/methods ; *Ventricular Dysfunction, Left/diagnostic imaging/physiopathology/etiology ; Ventricular Function, Left ; Magnetic Resonance Imaging/methods ; Heart Ventricles/diagnostic imaging/physiopathology ; }, abstract = {BACKGROUND: Over the last decade, a small number of studies have used speckle tracking echocardiography (STE) or cardiac magnetic resonance (CMR) for measuring left ventricular (LV) mechanics in patients with amyloidosis. This systematic review and meta-analysis aimed at assessing the overall influence of amyloidosis on LV global longitudinal strain (GLS) and regional longitudinal strain at basal (BLS), mid (MLS) and apical (ALS) level, respectively.<br><br>METHODS: All imaging studies assessing LV-GLS, LV-BLS, LV-MLS and LV-ALS in amyloidosis patients versus healthy controls, selected from PubMed and EMBASE databases, were included. The risk of bias was assessed by using the National Institutes of Health (NIH) Quality Assessment of Case-Control Studies. Continuous data (LV-GLS, LV-BLS, LV-MLS and LV-ALS) were pooled as a standardized mean differences (SMDs) comparing amyloidosis group with healthy controls. The overall SMDs of LV-GLS, LV-BLS, LV-MLS and LV-ALS were calculated using the random-effect model.<br><br>RESULTS: The full-texts of 13 studies with 553 amyloidosis patients and 575 healthy controls were analyzed. STE (53.8%) and CMR (46.2%) studies were separately analyzed. Average LV-GLS magnitude was significantly impaired in amyloidosis patients vs. controls in both STE (13.8&#xb1;3.9 vs. 19.8&#xb1;2.7%) and CMR (12.3&#xb1;4 vs. 17.9&#xb1;3.5%) studies. The impairment of segmental strain detected in amyloidosis patients was prevalent at basal and mid level, with relative "apical sparing." SMDs obtained for LV-GLS (SMD -1.80, 95% CI: -2.35, -1.24, P <0.001), LV-BLS (-1.98; 95% CI: -2.51, -1.45, P <0.001) and LV-MLS (-1.84; 95% CI: -2.46, -1.23, P <0.001) assessment were significantly larger than that obtained for LV-ALS (-0.72; 95% CI: -1.31, -0.13, P=0.02) measurement. Substantial heterogeneity was found among the studies assessing LV-GLS (I[2]=92.5%), LV-BLS (I[2]=91.4%), LV-MLS (I[2]=94.3%) and LV-ALS (I[2]=94.6%). Egger's test yielded a P value of 0.10, 0.20, 0.09 and 0.55 for LV-GLS, LV-BLS, LV-MLS and LV-ALS assessment respectively, indicating no publication bias. On meta-regression analysis, none of the moderators was significantly associated with effect modification for LV-GLS, LV-BLS, LV-MLS and LV-ALS (all P<0.05).<br><br>CONCLUSIONS: Amyloidosis has a large negative effect on LV-GLS, primarily related to the deterioration of segmental longitudinal strain at the basal and mid level, with relative apical sparing.}, }
@article {pmid41772759, year = {2026}, author = {Donega, S and Gorospe, M and Harries, LW and Ferrucci, L}, title = {Loss of Splicing Homeostasis as a Hallmark of Aging.}, journal = {Molecular and cellular biology}, volume = {}, number = {}, pages = {1-19}, doi = {10.1080/10985549.2026.2627235}, pmid = {41772759}, issn = {1098-5549}, abstract = {Alternative splicing is a fundamental mechanism that ensures accurate gene expression, supports cellular adaptability, and expands protein diversity beyond the limits of a fixed gene pool. With aging, splicing fidelity weakens, contributing to decline in RNA homeostasis and disrupting essential cellular functions, including mitochondrial oxidative phosphorylation, genome stability, and immune regulation, and in turn accelerating tissue and organ dysfunction. Evidence from senescent cells, aged tissues, and model organisms shows that altered levels of splicing factors and increased RNA polymerase II elongation rates impair co-transcriptional splicing and promote mis-spliced isoforms that reinforce senescence and drive pathology. Dysfunction of RNA-binding proteins further contributes to aberrant splicing, linking splicing defects to age-related diseases such as atherosclerosis, osteoarthritis, sarcopenia, and neurodegenerative disorders like Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Therapeutic strategies to correct splicing defects, such as antisense oligonucleotides, RNA interference, CRISPR-Cas systems, ADAR-mediated editing, and RNA aptamers, can restore a homeostatic balance of mRNA isoforms. However, major challenges remain, including distinguishing adaptive physiological from pathological splicing 'noise' and achieving targeted delivery to tissues. Despite these obstacles, RNA splicing dysregulation represents a promising avenue to extend health span by reestablishing homeostatic RNA programs, and reinforces the idea that "transcriptomic instability" is a hallmark of aging.}, }
@article {pmid41772317, year = {2026}, author = {Weller, B and Lin, CW and Rothballer, S and Calderwood, MA and Falter-Braun, P and Falter, C}, title = {NeuroViOme: a viral orfeome collection for studies of neurodegenerative disease.}, journal = {Journal of neurovirology}, volume = {32}, number = {2}, pages = {}, pmid = {41772317}, issn = {1538-2443}, mesh = {Humans ; *Neurodegenerative Diseases/virology/genetics/pathology ; *Host-Pathogen Interactions/genetics ; *Viral Proteins/genetics/metabolism ; *Open Reading Frames/genetics ; Animals ; Virus Replication/genetics ; }, abstract = {Neurodegenerative diseases such as Alzheimer's and Parkinson's disease, Amyotrophic Lateral Sclerosis (ALS), and Multiple Sclerosis (MS) pose a global health challenge due to their progressive course and lack of curative therapies. These conditions lead to severe neurological decline, significantly impacting patient independence and quality of life, and ultimately result in lethal outcome. Emerging evidence suggests that viral infections contribute to the onset and progression of these neurological diseases, Leblanc and Vorberg (PLoS Pathog 18:e1010670, 2022), either by directly inducing neurological symptoms or by triggering immune responses resulting in neuropathology. Nevertheless, systematic studies of the direct interplay between viral and host proteins in neurodegeneration remain scarce. A key aspect of viral pathogenesis is direct interaction between viral and host proteins (protein-protein interactions, PPIs), which are essential for viral replication and can disrupt or redirect host cell function Kim et al. (Nat Biotechnol, 2022); Zhou et al. (Res Sq, 2022), potentially contributing to the development of diseases traditionally considered non-communicable. Understanding these molecular mechanisms is crucial for advancing diagnostic and therapeutic strategies in neurodegenerative conditions, particularly ALS and MS. To enable systematic studies of these interactions, we introduce NeuroViOme as ORFeome resource encompassing nearly all protein-coding sequences from nine viruses selected based on their prevalence, neurotropism, and mechanistic or epidemiological links to neurodegenerative processes. NeuroViOme includes ORFs from Enteroviruses (EV-A71, EV-D68, CVB3, Echovirus E30), Herpesviruses (HSV-1, EBV, HHV3/Varicella Zoster), the endogenous retrovirus HERV-K, and Polyomavirus JCPyV. To our knowledge, this represents the most comprehensive viral ORF set assembled for neurodegeneration research to date. The collection builds the foundation for interactome mapping and functional genomics analyses and provides a valuable basis for systematic studies of viral perturbations of host pathways.}, }
@article {pmid41765421, year = {2026}, author = {Niidome, T and Ishida, T}, title = {[Mechanism of action and clinical trial results of a new drug for amyotrophic lateral sclerosis (ALS), Mecobalamin (Rozebalamin[®]) for intramuscular injection, 25 mg].}, journal = {Nihon yakurigaku zasshi. Folia pharmacologica Japonica}, volume = {161}, number = {2}, pages = {115-122}, doi = {10.1254/fpj.25066}, pmid = {41765421}, issn = {0015-5691}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy ; Humans ; *Vitamin B 12/administration &amp; dosage/analogs &amp; derivatives/therapeutic use/pharmacology ; Injections, Intramuscular ; Animals ; Clinical Trials as Topic ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive, intractable neurodegenerative disease characterized by generalized muscle atrophy and weakness, dysarthria, dysphagia, and respiratory muscle paralysis. Respiratory dysfunction due to muscle weakness is the primary cause of death; without mechanical ventilation, death typically occurs within 2 to 5 years after onset. Mecobalamin, an active form of vitamin B12, is thought to suppress homocysteine-induced neuronal cell death in ALS by acting as a coenzyme for methionine synthase, which catalyzes the conversion of homocysteine to methionine. Since the 1990s, research on neurodegenerative diseases supported by Japan's Ministry of Health, Labour and Welfare has suggested that high-dose mecobalamin may confer clinical benefits in ALS. This led to the initiation of clinical development. A Phase II/III double-blind, placebo-controlled comparative trial was conducted, but did not meet its primary endpoint. Based on these trial findings, an investigator-initiated Phase III placebo-controlled, double-blind comparative trial was conducted primarily at Tokushima University Hospital, targeting patients who developed ALS within one year before starting the trial. The trial demonstrated the efficacy of high-dose mecobalamin in slowing the decline in the Revised ALS Functional Rating Scale total score, which was the primary endpoint. Safety was also confirmed. Based on these results, mecobalamin received regulatory approval in September 2024 for the indication "slowing the progression of functional impairment in ALS." It is expected to offer a new treatment option for patients with ALS.}, }
@article {pmid41764146, year = {2026}, author = {Ciuro, M and Sangiorgio, M and Leanza, G and Gulino, R}, title = {Neuroinflammation and Oxidative Stress in SOD1 Animal Models of ALS: A Meta-analysis Study of Their Effects on Disease Onset and Progression.}, journal = {Molecular neurobiology}, volume = {63}, number = {1}, pages = {}, pmid = {41764146}, issn = {1559-1182}, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/pathology/metabolism ; *Oxidative Stress/physiology ; Disease Models, Animal ; *Disease Progression ; *Superoxide Dismutase-1/metabolism ; *Neuroinflammatory Diseases/pathology ; Humans ; Mice ; *Inflammation/pathology ; Male ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a multifactorial neurodegenerative disorder characterized by progressive motor neuron degeneration. Among the key mechanisms implicated in ALS pathogenesis, neuroinflammation and oxidative stress have emerged as prominent contributors to disease progression. This systematic review with meta-analysis involved 344 preclinical studies conducted on SOD1 animal models of ALS, to quantitatively evaluate the effects of treatments targeting neuroinflammation and oxidative stress on functional outcomes such as disease onset, survival, motor neuron degeneration, and locomotion. Data extraction and validation were performed using a combination of a large language model and human review. Results show that while most interventions led to reduced astrogliosis, M1 microgliosis, and oxidative stress, and increased M2 microgliosis, these effects were more strongly associated with improved survival and motor outcomes than with delayed disease onset. The analysis also revealed that treatment timing significantly influences outcomes, with interventions initiated during the late pre-onset window showing the highest efficacy. Furthermore, sex differences were noted, with male mice displaying better outcomes in progression metrics but worse in the age at onset. Overall, this meta-analysis indicates that inflammation and oxidative stress are important contributors to ALS progression in SOD1 animal models, identifies potentially critical therapeutic windows, and supports the consideration of sex-balanced and stage-specific treatment strategies at the preclinical level.}, }
@article {pmid41565302, year = {2026}, author = {Warita, H and Urushitani, M and Atsuta, N and Izumi, Y and Kano, O and Shimizu, T and Nakayama, Y and Narita, Y and Nodera, H and Fujita, T and Mizoguchi, K and Morita, M and Aoki, M}, title = {Addendum to the 2023 clinical practice guidelines for amyotrophic lateral sclerosis in Japan: approval and integration of novel disease-modifying therapies.}, journal = {Rinsho shinkeigaku = Clinical neurology}, volume = {66}, number = {2}, pages = {67-73}, doi = {10.5692/clinicalneurol.cn-002198}, pmid = {41565302}, issn = {1882-0654}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics/therapy ; Japan ; *Practice Guidelines as Topic ; Edaravone/administration &amp; dosage ; Vitamin B 12/administration &amp; dosage/analogs &amp; derivatives ; Genetic Therapy ; Drug Approval ; Oligonucleotides/administration &amp; dosage ; Genetic Testing ; Oligonucleotides, Antisense/administration &amp; dosage ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is an intractable motor neuron disease characterized by progressive degeneration of motor neurons with varying degrees of frontotemporal lobe dysfunction. This English summary of the addendum to the Japanese clinical practice guidelines for ALS outlines major recent advances in pharmacological therapy in Japan. Following the development of the 2023 guidelines, three additional medications-oral edaravone, high-dose intramuscular mecobalamin, and tofersen-have been introduced. Oral edaravone, with its ease of administration, demonstrates pharmacokinetics comparable to the intravenous formulation. High-dose mecobalamin reduces functional decline when initiated early in the disease course. Tofersen, an antisense oligonucleotide, is the first gene-targeted therapy approved in Japan for patients with copper/zinc superoxide dismutase gene-related ALS, highlighting the importance of genetic testing and counseling in all ALS cases. This addendum provides updated expert consensus recommendations for the use, dosing, and monitoring of these therapies, while emphasizing the need for thorough communication about the ethical and psychological dimensions of genetic testing. It also addresses practical considerations for combination therapy, noting that up to three or four anti-ALS agents are now available in Japan. The long-term safety and efficacy of these therapies, as well as their potential synergistic or additive effects, remain to be clarified through real-world data and prospective registries. The objectives of this addendum are twofold: to present these advances and recommendations in English to foster international collaboration, and to inform the global ALS community about the latest therapeutic strategies in Japan. In addition, ongoing efforts to harmonize clinical evaluation standards and promote international clinical trials are highlighted, with the goal of improving patient outcomes and advancing ALS research worldwide.}, }
@article {pmid41334667, year = {2026}, author = {Kalita, M and Jędrzejowska, M and Potulska-Chromik, A and Aragon-Gawińska, K and Franaszczyk, M and Stokłosa, T and Lipowska, M and Kostera-Pruszczyk, A}, title = {SIGMAR1 gene-related neuromuscular disorders - what do we know?.}, journal = {Neurologia i neurochirurgia polska}, volume = {60}, number = {1}, pages = {92-99}, doi = {10.5603/pjnns.106304}, pmid = {41334667}, issn = {0028-3843}, mesh = {Humans ; Sigma-1 Receptor ; *Receptors, sigma/genetics ; Child ; Male ; *Hereditary Sensory and Motor Neuropathy/genetics/diagnosis ; Mutation ; }, abstract = {INTRODUCTION: Distal hereditary motor neuropathies (dHMNs) are a clinically and genetically diverse group of rare neuromuscular disorders characterized by progressive distal muscle weakness and atrophy, often with early onset and sparing of sensory function. One subtype, Jerash-type dHMN (dHMNJ), is caused by biallelic mutations in the SIGMAR1 gene and presents with pyramidal signs in addition to distal weakness.<br><br>MATERIAL AND METHODS: A literature review was conducted by searches of the MEDLINE and PubMed databases using selected terms. Relevant original articles, case reports, case series, and reviews were selected as data sources.<br><br>DISCUSSION: SIGMAR1-related disorders (SIGMAR1-RD) encompass a broad clinical spectrum including dHMN and juvenile amyotrophic lateral sclerosis (ALS) phenotypes. The Sigma-1 receptor plays a key role in cellular stress responses, ER-mitochondria interaction, and neuronal survival. Clinical presentation often includes distal muscle weakness and atrophy with pyramidal signs.<br><br>We present a 12-year-old boy with distal muscle weakness, foot drop, and pyramidal signs. Genetic testing identified a homozygous c.247T > C (p.Phe83Leu) SIGMAR1 variant, previously classified as a variant of uncertain significance (VUS).<br><br>CONCLUSION: This article supports the pathogenicity of the c.247T > C (p.Phe83Leu) SIGMAR1 variant and underlines the need for broader genetic testing in hereditary motor neuropathies.}, }
@article {pmid41312566, year = {2026}, author = {Kwinta, R and Morawiec, N and Bączyk, J and Kubicka-Bączyk, K and Adamczyk-Sowa, M}, title = {Aging immunity - the role of T and B cells in neurological disorders among older adults.}, journal = {Neurologia i neurochirurgia polska}, volume = {60}, number = {1}, pages = {15-25}, doi = {10.5603/pjnns.106498}, pmid = {41312566}, issn = {0028-3843}, mesh = {Humans ; *Aging/immunology ; *B-Lymphocytes/immunology ; Aged ; *T-Lymphocytes/immunology ; *Immunosenescence/immunology ; *Nervous System Diseases/immunology ; Alzheimer Disease/immunology ; Adaptive Immunity ; Parkinson Disease/immunology ; }, abstract = {INTRODUCTION: Immunosenescence is a natural process of immune system aging, which leads to significant changes in the functioning of both innate and adaptive immunity. Alterations in T and B lymphocytes can significantly impact the progression of neurological diseases including multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS).<br><br>STATE OF THE ART: Immunosenescence affects T and B cell subsets, reducing their proliferative capacity and altering cytokine profiles. In MS, these changes promote disease progression and diminish responses to immunomodulatory therapies. In AD and PD, dysfunctional T and B cells contribute to sustained neuroinflammation, exacerbating neurodegeneration. ALS is similarly associated with altered adaptive immunity.<br><br>CLINICAL IMPLICATIONS: Recognizing how immunosenescent T and B cells contribute to disease in older adults is crucial for refining treatment strategies. These age-related immune changes may explain varied responses to therapies and highlight the need for novel approaches targeting the aged immune system in neurodegenerative diseases.<br><br>FUTURE DIRECTIONS: Future research should focus on identifying the mechanisms by which immunosenescent lymphocytes modulate neuroinflammation and neurodegeneration in aging populations. Novel biomarkers and immunomodulatory therapies tailored to older adults could significantly improve outcomes in patients with neurological diseases.}, }
@article {pmid41222474, year = {2026}, author = {Bagheri, S and Saboury, AA and Ahmad, O and Khan, RH and Ryszkiel, I and Stanek, A}, title = {Association of mercury exposure with neurodegenerative diseases - a reality or a misconception?.}, journal = {Neurologia i neurochirurgia polska}, volume = {60}, number = {1}, pages = {26-36}, doi = {10.5603/pjnns.108158}, pmid = {41222474}, issn = {0028-3843}, mesh = {Humans ; *Neurodegenerative Diseases/chemically induced/epidemiology ; *Mercury/toxicity ; *Environmental Exposure/adverse effects ; Risk Factors ; Animals ; }, abstract = {INTRODUCTION: Exposure to heavy metals has long been considered a potential risk factor for neurodegenerative diseases.<br><br>STATE OF THE ART: Most existing studies include in vitro and animal models, and research involving human subjects has yielded conflicting results, obscuring the overall understanding of this topic.<br><br>AIMS OF THE STUDY: In this article, the aim is to clarify the situation by carefully reviewing and categorizing the available body of knowledge in this field. Specifically, the focus is on research that explores the relationship between mercury exposure and common neurodegenerative diseases.<br><br>CONCLUSIONS: Despite its neurotoxic properties, results show that mercury is not associated with frequent neurodegenerative disorders.}, }
@article {pmid40600544, year = {2026}, author = {El Elhaj, A and Onger, ME}, title = {Exploring Neurodegenerative Diseases: Bridging the Gap between in vitro and in vivo Models.}, journal = {Current pharmaceutical design}, volume = {32}, number = {6}, pages = {407-414}, pmid = {40600544}, issn = {1873-4286}, mesh = {*Neurodegenerative Diseases/drug therapy/physiopathology/pathology ; Humans ; Animals ; *Disease Models, Animal ; }, abstract = {Neurological disorders are brain conditions characterized by the loss of nerve cells, leading to a decline in function. Standard examples include dementia, tremors, involuntary movements, muscle weakness, and autoimmune attacks. The most common form of dementia is Alzheimer's, affecting over 5 million elderly individuals, while tremors, stiffness, and slow movement are caused by Parkinson's. Involuntary movements and emotional problems are caused by Huntington's, while muscle weakness and eventual demise are caused by Amyotrophic lateral sclerosis. Vision problems, fatigue, and difficulty walking are caused by Multiple sclerosis (MS), an autoimmune disease that attacks the myelin sheath. In vitro models provide cost and complexity reduction, environmental control, and high-throughput. Researchers employ both cell-based (in vitro) and animal- based (in vivo) models to investigate neurodegenerative illnesses and endeavor to formulate novel treatments for diverse conditions. In vitro models provide cost and complexity reduction, environment control, and high-throughput screening of potential therapeutic agents compared to in vivo models. Nevertheless, they possess constraints, including the absence of intricate interactions that transpire in the entire organism and the inability to reproduce the disease progression completely.}, }
@article {pmid41772347, year = {2026}, author = {Ahuja, V and Sahu, B and Khurana, S and Kumari, K and Ganguly, NK and Gourie-Devi, M and Verma, S and Dastidar, SG and Taneja, V}, title = {Granules Gone Rogue: Nuclear and Cytoplasmic Ribonucleoprotein Structures in Amyotrophic Lateral Sclerosis-Fused in Sarcoma (ALS-FUS) Pathology.}, journal = {Molecular neurobiology}, volume = {63}, number = {1}, pages = {}, pmid = {41772347}, issn = {1559-1182}, support = {211610027970//University Grants Commission/ ; EMDR/IG/9/2024-01739//Indian Council of Medical Research/ ; 3/1/2/151/Neuro/2021-NCD-I//Indian Council of Medical Research/ ; IIRPIG-2023-0001508//Indian Council of Medical Research,India/ ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the selective loss of motor neurons. Among its genetic subtypes, mutations in the fused in sarcoma (FUS) gene represent an aggressive form, often associated with early onset and rapid progression. FUS is a ubiquitously expressed DNA/RNA-binding nuclear protein involved in maintaining DNA damage repair and RNA metabolism. It also plays a crucial role in the formation of ribonucleoprotein (RNP) granules such as cytoplasmic stress granules and nuclear paraspeckles under stress. In ALS, pathogenic FUS mutations frequently disrupt the subcellular distribution of FUS, leading to cytoplasmic mislocalization and aggregation. Mutant FUS further disrupts granular dynamics by its aberrant incorporation into stress granules and altering their biophysical properties. The loss of nuclear FUS function leads to elevated levels of the long non-coding RNA NEAT1 and enhanced paraspeckle assembly with disrupted structural integrity. The impaired nucleocytoplasmic granular dynamics compromise the cellular resilience, thereby increasing motor neuron vulnerability. The interaction of FUS with other ALS-associated proteins causes pathological alterations in the cellular milieu, suggesting a common underlying disease mechanism. This comprehensive review emphasizes the FUS-mediated RNP granule regulation under physiological and pathological conditions. Further, clinically approved and emerging therapeutic strategies aimed at attenuating FUS pathology and RNP granule dynamics have been described.}, }
@article {pmid41768173, year = {2026}, author = {Capitani, G and Lozzi, D and Curcio, G and Migliore, S}, title = {Moral decision-making in patients with neurodegenerative diseases: a systematic review.}, journal = {Frontiers in psychology}, volume = {17}, number = {}, pages = {1745923}, pmid = {41768173}, issn = {1664-1078}, abstract = {INTRODUCTION: Moral decision-making, a core component of social cognition, relies on integrating affective and cognitive processes supported by distributed neural networks. Neurodegenerative diseases disrupt these systems to varying degrees, offering unique models to investigate the neural bases of moral cognition. This review aimed to systematically examine moral decision-making deficits across neurodegenerative diseases, delineate disease-specific patterns of moral cognition impairment, and highlight conceptual and methodological gaps to inform future research and clinical assessment.<br><br>METHODS: A systematic search of PubMed, Web of Science, and Scopus was conducted for studies published up to January 2025, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines.<br><br>RESULTS: Seventeen studies met inclusion criteria. Convergent evidence indicates that behavioral variant frontotemporal dementia (bvFTD) produces a distinctive utilitarian bias characterized by diminished empathy, emotional blunting, and impaired integration of intention and outcome, reflecting degeneration of the ventromedial prefrontal cortex, anterior insula, and amygdala within the salience and default mode networks. In contrast, Alzheimer's disease (AD) patients typically preserve affective aversion to harm, suggesting relative sparing of limbic-ventromedial circuits despite conceptual and executive decline. Moral reasoning in Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS) remains largely intact unless frontotemporal involvement occurs, while dementia with Lewy bodies (DLB) manifests intermediate profiles marked by reduced cognitive theory of mind and aberrant moral affect.<br><br>DISCUSSION: These findings delineate disease-specific patterns of moral dysfunction linked to network-level degeneration rather than global cognitive decline. Understanding these mechanisms holds translational relevance for early diagnosis, ethical capacity assessment, and the development of ecologically valid tools to monitor socio-emotional deterioration in neurodegenerative disorders.}, }
@article {pmid41767843, year = {2026}, author = {Ben Khalaf, N}, title = {Heat shock proteins (Hsp70 and Hsp90) in neurodegeneration: pathogenic roles and therapeutic potential.}, journal = {Frontiers in aging neuroscience}, volume = {18}, number = {}, pages = {1711422}, pmid = {41767843}, issn = {1663-4365}, abstract = {The maintenance of protein homeostasis is essential for neuronal survival and function; however, it progressively declines with age, predisposing the brain to neurodegenerative diseases. Molecular chaperones Hsp70 and Hsp90 are key guardians of proteostasis, pivotally regulating protein folding, refolding, and degradation under both physiological and stress conditions. This review integrates an overview of the structural features, isoforms, and mechanistic interactions of Hsp70 and Hsp90. It highlights how their dysfunction contributes to the pathogenesis of major neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease. We first examine the architecture and ATP-driven chaperone cycles of Hsp70 and Hsp90, their co-chaperone networks, and the feedback regulation by the Heat Shock Factor-1 pathway. We then discuss evidence linking age-related declines in chaperone expression and HSF-1 activity to proteostasis collapse and neuronal vulnerability. The review particularly examines how Hsp70 and Hsp90 differentially influence pathogenic protein aggregation (e.g., tau, α-synuclein, TDP-43, and mutant huntingtin) and how this balance is altered in the aging brain. Regarding therapeutic approaches, we summarize current strategies targeting these chaperones, including small-molecule modulators of Hsp70 and Hsp90, co-chaperone inhibitors, and recombinant chaperone therapy, which has shown to restore proteostasis and cognitive function in experimental models. These emerging interventions underscore the dual nature of Hsp70/Hsp90 systems, acting as both protectors and potential contributors to neurodegeneration, depending on their regulation and interaction context. By linking molecular chaperone biology to aging and translational therapeutics, this review establishes a framework for developing precision approaches that enhance proteostasis capacity, delay age-associated neurodegeneration, and promote healthy brain aging.}, }
@article {pmid41765206, year = {2026}, author = {Kotapati, C and Van Tran, LT and Cardoso, FC}, title = {Voltage-gating and neuronal signalling in neurodegeneration: From neuropathology to therapeutic opportunities in motor neuron disease.}, journal = {Neurobiology of disease}, volume = {}, number = {}, pages = {107336}, doi = {10.1016/j.nbd.2026.107336}, pmid = {41765206}, issn = {1095-953X}, abstract = {Voltage-gated ion channels (VGICs) are central to motor neuron excitability, governing the initiation and propagation of action potentials and synaptic transmission. Disruption of their finely tuned gating properties contributes to pathology-associated hyperexcitability, a hallmark of several neurodegenerative conditions, including motor neuron disease (MND). In this review, we examine the physiological roles of voltage-gated sodium, calcium and potassium channels in motor neurons, and evaluate how mutations, altered expression, aberrant biophysics, and maladaptive signalling impair the voltage signalling processes that drive and underlie neuronal dysfunction and degeneration. We synthesise evidence linking ion channel dysfunction to altered excitability, excitotoxicity, impaired neurotransmission, motor system instability and progressive motor neuron loss in MND. We discuss current therapies that offer modest benefit and may act directly or indirectly on neuronal excitability but with limited target specificity. Motivated by the the urgent need for effective treatments for MND, we discuss emerging strategies that leverage highly selective VGIC modulators, particularly gating-modifier peptides inhibitors, to counteract hyperexcitability in MND. We further highlight that understanding how voltage-sensing and channel gating are altered in MND offers new avenues for selective targeted intervention. Together, the evidence supports VGICs as critical yet poorly explored therapeutic targets for halting motor neurodegeneration.}, }
@article {pmid41763443, year = {2026}, author = {Zafarjonovna, AZ and Aysulu, E and Matlyuba, S and Rashid, H and Azamatovich, JB and Ahmadjon, A and Barno, A and Kurbanovna, AM and Ugli, MRM and Shaxodat, I and Rustam, T and Jumaniyazovna, MG and Ishankulov, A}, title = {Small extracellular vesicles as emerging biomarkers and therapeutic targets in neurodegenerative diseases.}, journal = {Clinica chimica acta; international journal of clinical chemistry}, volume = {}, number = {}, pages = {120932}, doi = {10.1016/j.cca.2026.120932}, pmid = {41763443}, issn = {1873-3492}, abstract = {Small extracellular vesicles (sEVs) have rapidly emerged as versatile mediators of intercellular communication with significant potential to transform the diagnosis and treatment of neurodegenerative diseases (NDDs). Increasing evidence shows that sEVs not only participate in the propagation of pathogenic proteins but also serve as accessible, CNS-informative carriers of molecular signatures that reflect neuronal, glial, and systemic disease processes. This dual role positions sEVs at the intersection of biomarker discovery and therapeutic innovation. In the diagnostic domain, advances in immunoaffinity capture, single-vesicle analysis, and multi-omics profiling have enabled increasingly precise characterization of neuron-, astrocyte-, and microglia-derived sEVs, revealing candidate markers for Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and related disorders. However, translation remains limited by methodological heterogeneity, a lack of large-scale validation, and the need for standardized pre-analytical and analytical pipelines aligned with the ISEV/MISEV guidelines. On the therapeutic front, native and engineered sEVs, particularly those derived from mesenchymal and neural stem cells, demonstrate promising neuroprotective effects, including the modulation of neuroinflammation; the enhancement of synaptic resilience; and the delivery of antioxidant, anti-amyloid, or gene-modifying cargo across the blood-brain barrier. Scalable GMP manufacturing, cargo-loading strategies, targeting specificity, and long-term safety remain key challenges for clinical translation. This narrative review synthesizes current advances in sEV-based biomarkers and therapeutics, outlines technological and regulatory barriers, and proposes a translational roadmap spanning mechanistic discovery, platform standardization, and integration into precision-medicine frameworks. Collectively, emerging data position sEVs as powerful tools capable of reshaping the diagnostic and therapeutic landscape of NDDs, provided that coordinated multidisciplinary efforts address the remaining gaps in validation, scalability, and regulatory readiness.}, }
@article {pmid41762823, year = {2026}, author = {Nissinen, P and Silén-Lipponen, M and Kähkönen, O and Saaranen, T}, title = {Nursing students' learning experiences, outcomes, and methods in distance education: An integrative literature review.}, journal = {Nurse education today}, volume = {162}, number = {}, pages = {107051}, doi = {10.1016/j.nedt.2026.107051}, pmid = {41762823}, issn = {1532-2793}, abstract = {BACKGROUND: The transformation of nursing education has emphasized the role of distance education as a permanent component. Nursing students' learning experiences and outcomes in this format show considerable variation and raise questions about the most effective distance learning methods.<br><br>AIMS: The aim of this integrative review was to explore nursing students' experiences with distance learning, identify the learning outcomes it produces, and examine the distance learning methods used in nursing education.<br><br>DESIGN: Integrative literature review.<br><br>METHODS: A systematic literature search was conducted in the CINAHL (EBSCO, PubMed/Medline, Education database (ProQuest), Scopus and ERIC (EBSCO) databases, including peer-reviewed studies published in English between 2018 and 2024. The review followed the PRISMA 2020 guidelines. Quality appraisal was performed using Hawker et al.'s evaluation tool. Data was analyzed using inductive content analysis.<br><br>RESULTS: A total of 43 studies were included in the review. Five main themes were identified describing students' experiences: the accessibility of digital learning platforms, the quality and structure of learning materials, the acquisition of practical and clinical skills, social interaction and peer support, motivation, self-regulation, and emotional well-being. Learning outcomes were categorized into cognitive, psychomotor, and affective domains. The most common learning methods included synchronous, asynchronous, and blended approaches, with blended learning showing particularly positive results.<br><br>CONCLUSION: Distance education can support nursing students' learning when it is well-structured and combines pedagogical planning with interactive and practical elements. Not all competencies, particularly clinical skills, can be taught remotely. The learning experience is shaped by individual abilities, guidance, and technical conditions, and distance education may not suit all students equally well. Effective methods, especially blended learning, support engagement and learning when aligned with student needs and pedagogical goals.}, }
@article {pmid41746390, year = {2026}, author = {Kural, I and M Mombeek, LM and Wilson, DM}, title = {Role of mitochondria in neuronal function and survival in the enteric and central nervous systems.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {83}, number = {1}, pages = {}, pmid = {41746390}, issn = {1420-9071}, support = {11P4G24N//Fonds Wetenschappelijk Onderzoek/ ; G0A9625FWO//Fonds Wetenschappelijk Onderzoek/ ; }, abstract = {UNLABELLED: Mitochondria are indispensable organelles that not only generate cellular energy through oxidative phosphorylation but also regulate calcium homeostasis, redox balance, and apoptotic signaling. Given the high metabolic demands of neurons, mitochondrial function and resilience mechanisms are essential for neuronal development, maturation, and survival; when these systems fail, pathological outcomes can arise. This review highlights the critical role of mitochondria in maintaining neuronal function, with discussion related to both the central (CNS) and enteric (ENS) nervous systems. We present how mitochondrial dysfunction, through impaired bioenergetics, oxidative stress, defective quality control, and altered dynamics, can drive neuronal cell loss. Furthermore, we highlight the link between mitochondrial defects and nervous system pathological outcomes in both primary mitochondrial disorders, such as mitochondrial neurogastrointestinal encephalomyopathy, and secondary mitochondrial disorders, such as Alzheimer, Parkinson, and Huntington disease, as well as amyotrophic lateral sclerosis. By integrating evidence from the CNS and ENS, this review highlights the central role of mitochondria in supporting and preserving neuronal health, as well as the potential of mitochondria as therapeutic targets in neurodegenerative disease.<br><br>GRAPHICAL ABSTRACT: [Image: see text]}, }
@article {pmid41762049, year = {2026}, author = {Zhang, Y and Chen, B and Lin, Y and Kang, D and Zhao, T}, title = {Advances and Challenges in the Use of Spinal Cord Organoids in ALS.}, journal = {Journal of integrative neuroscience}, volume = {25}, number = {2}, pages = {44709}, doi = {10.31083/JIN44709}, pmid = {41762049}, issn = {0219-6352}, support = {82301543//National Natural Science Foundation of China/ ; 2021QNA025//Youth Scientific Research Project of Fujian Provincial Health Commission/ ; 2021Y2001//Technology Platform Construction Project of Fujian Province/ ; 2020Y2003//Technology Platform Construction Project of Fujian Province/ ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease. No effective treatments have yet been found for ALS, primarily because the molecular mechanisms that underlie its pathogenesis are unknown. Although animal models are suitable for ALS research, species differences between these models and human spinal cord organs make it difficult to accurately predict the progression of disease in humans. Therefore, the development of more suitable models is urgently needed. Human stem cells have unlimited development potential and can be used to make three-dimensional organoid structures that mimic the architecture and function of actual organs. Organoid models can be used to overcome some of the species differences and accelerate experimental research, leading to the development of practical applications for the treatment of ALS. This article discusses the pathological mechanisms and cell types involved in ALS, as well as the genes associated with this disease. We also discuss the possible applications of spinal cord organoids (SCOs) in ALS research, such as the modeling of disease characteristics, study of pathological mechanisms, and drug screening. Finally, the prospects for SCOs in ALS treatment are highlighted, while acknowledging the need for further development of relevant technologies.}, }
@article {pmid41759446, year = {2026}, author = {Salmon, PM and King, B and Hall, D and McLean, S and Thompson, J and Cooke, N and Salas, E and Loft, S and Read, GJM}, title = {The big five model of teamwork and human autonomy teams: a scoping review.}, journal = {Applied ergonomics}, volume = {135}, number = {}, pages = {104761}, doi = {10.1016/j.apergo.2026.104761}, pmid = {41759446}, issn = {1872-9126}, abstract = {Teams play a critical role in society and represent a key area for Human Factors and Ergonomics. Salas et al.'s Big Five model is widely cited; however, the increasing use of Human-Autonomy Teams (HATs) has fuelled debate over its continued relevance. It is important to reflect on how the Big five model has been applied, in what contexts, and whether applications to contemporary teams are emerging. This article presents the findings from a scoping review undertaken to identify and synthesise the peer reviewed literature describing applications of the Big Five model. Articles were deemed eligible for inclusion if they were published in the peer reviewed literature and described an application of the Big Five model to study teamwork. 38 articles were included in the review and no applications of the Big Five model to study HATs were identified. Over half of the studies were undertaken in healthcare and a range of assessment methods have been used (e.g., questionnaires, surveys, interviews, observer-rating scales, communication transcript analysis). Just under a third of included studies evaluated all model components (i.e., the five processes and three coordinating mechanisms) and few considered the relationships between model components or between model components and team effectiveness. Research is required to explore the validity of the Big Five model for HATs, to gather evidence for the relationship between model components and team effectiveness, and to develop more precise Big five-based measures.}, }
@article {pmid41752118, year = {2026}, author = {Kurdi, MA and Alotaibi, H and Alkhuraymi, AT and Aldahery, LN and Alhawaj, AF and Aldali, HJ}, title = {Amyotrophic Lateral Sclerosis (ALS) Genetics and Microbiota: A Comprehensive Review.}, journal = {International journal of molecular sciences}, volume = {27}, number = {4}, pages = {}, pmid = {41752118}, issn = {1422-0067}, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a severe, progressive neurodegenerative disorder characterized by the loss of upper and lower motor neurons, affecting 0.5 to 2.6 per 100,000 people, with a median survival of 2 to 5 years. It is increasingly seen as a multisystem disorder, sharing essential clinicopathological features with Frontotemporal Dementia (FTD). This convergence arises from overlapping molecular processes, including severe oxidative stress, glutamate-mediated excitotoxicity, mitochondrial dysfunction, and widespread aggregated TDP-43 proteinopathy in both sporadic and familial cases. Several key genetic factors have been identified, particularly mutations in C9orf72, SOD1, TARDBP, and FUS, which serve as important targets for novel treatments, such as Tofersen, a recently approved SOD1-specific antisense oligonucleotide (ASO) gene therapy. Additionally, there is increasing evidence of the gut-brain connection. Dysbiosis, involving species such as Akkermansia muciniphila, and lower levels of neuroprotective metabolites, such as nicotinamide, may affect the course of the disease. As a result, treatment strategies are shifting toward a personalized approach. This includes using gene therapy, ranging from ASOs and RNA interference (RNAi) to new CRISPR-based genome editing. It also involves exploring microbiome-modulating treatments, such as specific probiotics and Fecal Microbiota Transplantation (FMT). While microbiome and gene therapies remain largely experimental, their potential is promising, as highlighted by the recent approval of Tofersen. These novel approaches could be further enhanced and guided by more robust diagnostic criteria and by investigating early multimodal treatment strategies to slow the progression of this complex disease.}, }
@article {pmid41751793, year = {2026}, author = {Ptáček, O and Musil, Z and Guarnieri, G and Vrbacká, A and Moudrá, P and Zlámalová, A and Röszlerová, P and Tonhajzer, M and Musil, V and Morelli, A and Zach, P}, title = {Amyotrophic Lateral Sclerosis: The State of the Art on Treatments and the Therapeutic Role of the Intestinal Microbiome in Human Studies.}, journal = {International journal of molecular sciences}, volume = {27}, number = {4}, pages = {}, pmid = {41751793}, issn = {1422-0067}, support = {Cooperatio 39 - Oncology and Haematology//Charles University/ ; Cooperatio 33-Intensive Care Medicine//Charles University/ ; Cooperatio 36-Medical Diagnostics and Basic Medical Sciences//Charles University/ ; #NEXTGENERATIONEU//European Commission/ ; MNESYS (PE0000006) - A Multiscale integrated approach to the study of the nervous system in health and disease (DR. 1553 11.10.2022)//Ministry of University and Research (MUR), National Recovery and Resilience Plan (NRRP)/ ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a common neurodegenerative disorder; to date, there is no long-term effective treatment. Recently, a relationship has been discovered between the human intestinal microbiome and the pathogenesis of ALS, on which basis faecal microbiota transplantation (FMT) has been proposed as a potential treatment for ALS. In this review, we compare three existing case studies examining the effect of FMT on the course of ALS, highlighting differences in methodology and results. In two of the studies, a halt in the progression of ALS symptoms was observed following FMT, accompanied by improvement in patient health. However, in the third and largest study, no significant effect of FMT was observed. The possible explanation for this discrepancy may be the intentional depletion of intestinal microorganisms using antibiotics prior to FMT in the third study. Future studies and/or completion of the ongoing clinical studies will help clarify the therapeutic effectiveness of FMT in ALS patients.}, }
@article {pmid41751374, year = {2026}, author = {Trabulo, A and Sousa, P and Alvites, R and Maurício, AC}, title = {Mesenchymal Stem Cell-Based Therapies Applied in Neurological Diseases: A Systematic Review.}, journal = {Biomedicines}, volume = {14}, number = {2}, pages = {}, pmid = {41751374}, issn = {2227-9059}, abstract = {Background/Objectives: Neurodegenerative diseases (NDs) have a severe impact on patients' quality of life, and effective treatments remain limited. As the focus is on treating the symptoms, the root cause of the problem is commonly not addressed. Mesenchymal stem cells show an emerging potential due to the ability for self-renewal combined with their capability for differentiation into various cell lines, which makes them a strong candidate for regenerative therapies in general, and for application in neurological issues in particular. This article provides an overview of the safety, efficacy, and challenges associated with the use of mesenchymal stem cells (MSCs) and their derived secretome in clinical and preclinical models of Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS). Methods: A systematic search was conducted on PubMed to identify published studies providing clinical and preclinical evidence on the use of MSCs in neurodegenerative disorders. Results: Overall, the literature consistently indicates that MSCs and their derivatives exert disease-modifying effects across multiple NDs. Across AD, PD, HD and ALS, preclinical studies uniformly report improvements in behavioural outcomes, attenuation of neuroinflammation, and neuroprotective effects, largely mediated by MSCs' paracrine signalling rather than direct cell replacement. Clinical studies to date consistently support the safety and feasibility of MSC-based therapies, while efficacy signals remain modest, heterogeneous and predominantly short-term, highlighting the need for larger, well-controlled trials. Conclusions: Integration of genetic engineering, preconditioning, and EV technology may represent an emerging therapeutic approach that may complement existing neuroregeneration treatments, offering a scalable and minimally invasive frontier to improve long-term clinical outcomes in patients with AD, PD, HD, and ALS.}, }
@article {pmid41750236, year = {2026}, author = {Eisen, A}, title = {Exploring the ALS Multistep Model.}, journal = {Brain sciences}, volume = {16}, number = {2}, pages = {}, pmid = {41750236}, issn = {2076-3425}, abstract = {ALS is a multistep disease, in which (epi)genetic, environmental, and age-related processes, including senescence, converge over decades to reduce resilience resulting in self-sustaining symptomatic disease. The multistep model visualizes five to six impactful events in sporadic ALS, but fewer in those carrying high-penetrance mutations, such as SOD1, FUS, or C9orf72 expansions. The timing, duration, and cumulative effects of specific steps are presumed to have individual variability but, the steps themselves are inferred since they have not been observed and remain agnostic as to biological identity. Nevertheless, the model gives an opportunity to integrate genetics, aging, environmental exposures, and systems-level vulnerability into a single framework. Acting as step modifiers, environmental exposures including trauma lower the threshold for step acquisition, accelerate the accumulation of steps, influence the anatomical site of disease onset, and unmask preclinical disease. Because ALS emerges from the gradual collapse of multiple layers of biological robustness, tackling a single pathway will be insufficient and the multistep model forces a reconsideration of therapeutic timing and strategies. Protection against early-life insults, anti-aging, and anti-senescent therapies may curtail step accumulation preventing ALS from exceeding threshold and disease manifestation.}, }
@article {pmid41746412, year = {2026}, author = {Tarazona-Santabalbina, FJ and Belenguer-Varea, A and Borrás-Blasco, J and García-Tercero, E and Martin, ML and Prior, NP and Mariscal, G and Valcuende-Rosique, A}, title = {Safety profile of tofersen in amyotrophic lateral sclerosis: a systematic review and meta-analysis.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {47}, number = {3}, pages = {}, pmid = {41746412}, issn = {1590-3478}, }
@article {pmid41745965, year = {2026}, author = {Haroun, M and Tratrat, C and Mathew, RT and Munir, M and Sattar, MN and Shawky, M and Kochkar, H and Aldakhilallah, ON and Ghafoor, A and Turk, KGB and Geronikaki, A and Ghazzawy, HS}, title = {Avian Candidiasis: A Comprehensive Review of Pathogenesis, Diagnosis, and Control.}, journal = {Veterinary sciences}, volume = {13}, number = {2}, pages = {}, pmid = {41745965}, issn = {2306-7381}, support = {Grant number: KFU260519//Deanship of Scientific Research, Vice Presidency for Graduate Studies and Scientific Research, King Faisal University, Saudi Arabia/ ; }, abstract = {This review is a comprehensive investigation of avian candidiasis, mainly caused by Candida albicans, although the prevalence of non-albicans Candida species has increased in domestic and wild birds. Avian candidiasis causes significant economic losses in poultry production through increased mortality, cost of treatments, and reduced growth rates, particularly in young birds and intensive farming operations. The pathogenesis section provides a description of the molecular virulence factors such as adhesin-mediated attachment (ALS, Agglutinin-Like Sequence family; HWP1, Hyphal Wall Protein 1), yeast-to-hypha morphogenesis, tissue damage by Candidalysin, biofilm formation on mucosal and abiotic surfaces, and secreted hydrolytic enzymes including secreted aspartyl proteinases (SAPs) and phospholipases. The identified predisposing factors include immunosuppression, malnutrition, abuse of antibiotics, bad husbandry, and crop stasis. The diagnostic methods discussed encompass cytological analysis and fungal culture on selective media to more sophisticated methods of molecular analysis (PCR, MALDI-TOF MS, and NGS). Antifungal susceptibility investigations indicate that nystatin and amphotericin B are still very effective against most avian isolates and that resistance to the azoles is on the rise, especially with respect to the non-albicans Candida species. Nystatin is still the first-line treatment of localized infections; azoles are still used for resistant or systemic infections despite their hepatotoxicity. Sanitation, proper nutrition, and proper use of antimicrobials are essential to prevent diseases. The knowledge gaps comprise the absence of avian-specific pharmacokinetic information, poor knowledge of species-species virulence phenotypes, and the lack of point-of-care diagnostics. The need to have integrated One Health surveillance systems is emphasized by the zoonotic potential of the avian Candida reservoirs.}, }
@article {pmid41744765, year = {2026}, author = {Dellazizzo Toth, T and Bond, S and Saxena, S}, title = {The Calcium Connection: Explaining Motor Neuron Vulnerability in ALS.}, journal = {Cells}, volume = {15}, number = {4}, pages = {}, pmid = {41744765}, issn = {2073-4409}, abstract = {ALS is a severe neuromuscular disease classically characterized by the progressive loss of motor neurons, leading to incremental muscle weakness and eventually death. Current treatment options for ALS have proven to have limited effect, merely delaying the progression of symptoms and prolonging patient survival. This motor neuron subtype-related differential vulnerability has been linked to neuron excitability, metabolism, and protein aggregation. Calcium dysregulation, which serves as an important second messenger in neural signaling pathways, has been implicated in each of these mechanisms and represents a potential target for therapeutic intervention. Armed with cutting-edge tools for visualizing and recording calcium transients in vivo, ALS researchers have delved deeper into the role of calcium dysregulation in disease in recent years. Vulnerable motor neuron populations display an excess of calcium-permeable ion channels together with reduced expression of calcium-binding proteins, generating a cellular environment primed for excitotoxic stress. Loss of inhibitory synaptic input further heightens susceptibility to calcium overload. Paradoxically, some evidence suggests that elevated neuronal activity can exert neuroprotective effects, highlighting the complexity of activity-dependent calcium signaling in ALS. Additionally, ALS-related toxic protein accumulation disrupts calcium homeostasis, contributing to endoplasmic reticulum stress and mitochondrial dysfunction. Emerging data indicate that calcium dysregulation impairs neuron-glia communication, amplifying neuroinflammation and accelerating disease progression. This review aims to synthesize current evidence on how calcium imbalance contributes to motor neuron vulnerability and degeneration in ALS. By exploring the cellular, synaptic, and network-level mechanisms of calcium dysregulation in ALS, the review examines its interplay with mitochondrial and ER stress and explores its impact on neuron-glia interactions with the aim of synthesizing key mechanistic insights into the disease pathogenesis and therapeutic targets.}, }
@article {pmid41743427, year = {2026}, author = {Luo, Y and Liu, X and Yang, M}, title = {Current status and future prospects of brain-computer interfaces in the field of neurological disease rehabilitation.}, journal = {Frontiers in rehabilitation sciences}, volume = {7}, number = {}, pages = {1666530}, pmid = {41743427}, issn = {2673-6861}, abstract = {Neurological disorders represent a significant category of diseases that profoundly affect human health, accounting for the second leading cause of global mortality. This group of conditions includes stroke, multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), spinal cord injury, Parkinson's disease, and cerebral palsy, among others. These disorders are highly susceptible to sequelae and profoundly impact individuals' daily lives. In this context, Brain-Computer Interface (BCI) technology has demonstrated considerable potential in the domain of neurorehabilitation, although numerous challenges remain. The manuscript provides a comprehensive review of recent advancements in research and clinical applications, highlighting current limitations and outlining future directions. It elucidates the applicability and constraints of Brain-Computer Interface (BCI) technology across various diseases and patient populations. To facilitate insights across different conditions, comparative tables are presented, aligning BCI strategies with therapeutic targets, outcomes, advantages, limitations, and existing evidence gaps. The scope extends beyond motor restoration to include under-explored domains, such as neuropathic pain, with a focus on real-world translation, including home and community feasibility and the distinction between assistive and rehabilitative applications. The review distills overarching limitations within the field, such as small sample sizes, protocol heterogeneity, and limited longitudinal evidence, while synthesizing the most recent studies. An actionable research and development roadmap is proposed to guide next-generation BCI rehabilitation, incorporating individualized cortical-network simulators, self-architecting decoders, adaptive therapy approaches akin to game seasons, and proprioceptive "write-back" mechanisms via peripheral interfaces. Moreover, the review reveals significant research focal points and critical issues that warrant further investigation in the context of neurological rehabilitation utilizing BCI technology.}, }
@article {pmid41741312, year = {2026}, author = {Herrero Babiloni, A and Dal Fabbro, C and Samin, F and Schmittbuhl, M and Blanchet, PJ and Lavigne, GJ and Rouleau, G}, title = {The role of dentists in the recognition of neurodegenerative and systemic conditions with neurological involvement.}, journal = {Oral surgery, oral medicine, oral pathology and oral radiology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.oooo.2026.01.010}, pmid = {41741312}, issn = {2212-4411}, abstract = {Dentists are often the first healthcare providers to observe subtle orofacial and behavioral changes that may reflect underlying neurological diseases, including altered salivary flow, dysphagia, oral burning sensations, unusual orofacial movements, or tremors and pain, among others. These are symptoms of conditions such as Parkinson's disease, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, and other systemic disorders with neurological involvement, which are frequently misattributed to local or functional causes, thereby delaying diagnosis and care. As the frequency of neurodegenerative and neuromuscular conditions rises with aging, the dental setting offers a critical opportunity for early recognition and referral. This clinical review summarizes orofacial manifestations, dental care challenges, and referral strategies across different neurological and systemic diseases. Organized by disease stage and functional impairment, the review provides practical tools for decision-making. Guidance on screening, behavioral adaptation, and care coordination is also provided, including multiple practical tables, figures, and chairside screening tools to support early recognition and referral. Finally, the review advocates for improved training, interdisciplinary collaboration, and progressive integration of artificial intelligence, machine learning, and other emerging technologies (e.g., biosensors, salivary biomarker platforms, or high-density electrophysiologic tools) to support clinicians in recognizing neurological diseases.}, }
@article {pmid41737317, year = {2026}, author = {Luo, R}, title = {Next questions of autophagy in neurodegenerative diseases: From mechanisms to therapeutics.}, journal = {Innovation (Cambridge (Mass.))}, volume = {7}, number = {1}, pages = {100989}, pmid = {41737317}, issn = {2666-6758}, abstract = {Autophagy, a key cellular degradation pathway, is central to the pathogenesis of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Despite progress in understanding its role, critical questions remain. This perspective highlights pressing issues, including cell-type-specific autophagy regulation, interactions with other cellular pathways, and challenges in translating autophagy-modulating therapies to clinical practice. Addressing these questions will advance our understanding of neurodegenerative diseases and pave the way for novel therapeutics.}, }
@article {pmid41734662, year = {2026}, author = {Alam, P and Hasan, GM and Mohammad, T and Hassan, MI}, title = {Next-generation computational strategies for neurodegenerative biomarkers: Multi-omics integration, AI, and molecular modeling.}, journal = {Computational biology and chemistry}, volume = {123}, number = {}, pages = {108973}, doi = {10.1016/j.compbiolchem.2026.108973}, pmid = {41734662}, issn = {1476-928X}, abstract = {Neurodegenerative diseases (NDs) are progressively debilitating conditions driven by complex molecular perturbations and selective neuronal loss. Conventional approaches to discovering biomarkers, using single-omics or empirical screening, often fail to capture the multi-factorial nature of these disorders. It is now possible to integrate large-scale omics data with structural and molecular modeling methods to reveal mechanistically relevant biomarkers using integrative computational biology. Here, we review recent advances in integrative computational strategies that combine multi-omics, encompassing genomics, transcriptomics, proteomics, and metabolomics, with structural bioinformatics and molecular modeling to identify mechanistically informative biomarkers. We cover systems-level and network-based integration methods, machine learning (ML) and artificial intelligence (AI) frameworks, and structure-guided validation approaches, including homology/AI-based modeling, molecular docking, and molecular dynamics. We also discuss case studies illustrating how omics-based predictions are validated through protein structure modeling to identify key biomarkers and therapeutic targets. Finally, we discuss major challenges, such as data heterogeneity, reproducibility, and limitations of structural modeling, and emerging trends, such as AI-powered multi-omics, single-cell spatial profiling, and digital twin simulations. Together, the integrative computational strategies are likely to accelerate the discovery of reliable, mechanistically informative, and clinically translatable biomarkers for precision medicine in NDs.}, }
@article {pmid41731547, year = {2026}, author = {Jammal, JK and Gomez, EA and Al-Chalabi, A and Iacoangeli, A}, title = {Classification of ALS molecular subtypes: a literature review on machine learning applications and their clinical value.}, journal = {BMC medicine}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12916-026-04725-y}, pmid = {41731547}, issn = {1741-7015}, support = {772376-EScORIAL/ERC_/European Research Council/International ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterised by considerable heterogeneity in both its underlying biological mechanisms and clinical presentation. High-dimensional transcriptomic datasets offer an opportunity to characterise this variation at the molecular level; however, traditional statistical methods struggle with their scale and complexity.<br><br>MAIN BODY: Machine learning approaches can reduce dimensionality and uncover latent patterns, enabling the identification of molecular subtypes that may refine prognosis and support patient stratification. Recent transcriptomic studies employing unsupervised machine learning have identified ALS subtypes with distinct molecular and clinical characteristics. Redefining ALS into more homogeneous molecular and clinical subtypes could transform all areas of ALS research by supporting novel experimental designs and precision medicine approaches.<br><br>CONCLUSIONS: In this review, we summarise and critically assess these studies, discussing their findings, strengths, and limitations, and highlighting research gaps and challenges that must be addressed to enable their translation into biomedical and clinical practice.}, }
@article {pmid41729684, year = {2026}, author = {Paulo-Ramos, A and Rhymes, ER and Villarroel-Campos, D and Sleigh, JN}, title = {Disruption of BDNF signalling in neuropathologies.}, journal = {Biochemical Society transactions}, volume = {54}, number = {2}, pages = {}, doi = {10.1042/BST20253079}, pmid = {41729684}, issn = {1470-8752}, support = {MR/Y010949/1/MRC_/Medical Research Council/United Kingdom ; 23GRO-PG36-0675-1//Muscular Dystrophy UK/ ; }, mesh = {*Brain-Derived Neurotrophic Factor/metabolism/genetics ; Humans ; *Signal Transduction ; Animals ; Receptor, trkB/metabolism ; Neuronal Plasticity ; Neurons/metabolism ; }, abstract = {The vital role of brain-derived neurotrophic factor (BDNF) in neuronal development, synaptic plasticity, and neuroprotection has been explored for decades. Therefore, the expression, processing, and signalling activities of this neurotrophin, which is reliant upon TrkB and p75NTR receptors, have been well characterised in both health and disease. This review summarises the latest findings on BDNF dysregulation in neuropathologies. Indeed, across diseases of both the central and peripheral nervous systems, BDNF signalling is frequently disrupted, contributing to neuronal dysfunction and degeneration. Consequently, through direct or indirect enhancement of its expression and/or function, BDNF has proved to be a promising therapeutic target across many neurological conditions. However, the complexity of its regulation and interaction with several different receptors underpins the need for further research to deepen our understanding of BDNF disruption in neuropathologies and to achieve its therapeutic potential.}, }
@article {pmid41724277, year = {2026}, author = {Zhao, X and Pu, L and Zeng, X and Nie, J}, title = {Role of nuclear import proteins in maintaining proteostasis and disease pathogenesis.}, journal = {Biochemical pharmacology}, volume = {248}, number = {}, pages = {117831}, doi = {10.1016/j.bcp.2026.117831}, pmid = {41724277}, issn = {1873-2968}, abstract = {Nuclear import receptors (NIRs), particularly the importin α/β heterodimer system, function as essential gatekeepers of nucleocytoplasmic trafficking by decoding diverse nuclear localization signals (NLSs) to orchestrate cellular proteostasis. This review delineates the structural basis of NLS recognition and the coordinated mechanisms that facilitate the nuclear import of critical cargoes, including transcription factors, RNA-binding proteins, and DNA repair factors. Beyond their canonical transport role, we emphasize the emerging functions of NIRs as molecular chaperones that suppress aberrant phase separation and their co-translational regulatory roles in ensuring proper protein biogenesis and folding. The collapse of these regulatory functions underpins the pathogenesis of major human diseases. We examine in detail the pathological consequences of nuclear import dysfunction, highlighting its central role in specific neurodegenerative disorders such as Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD), oncogenic transformation, and viral pathogenesis. The discussion provides a critical appraisal of emerging therapeutic strategies that target the nuclear import machinery, including small-molecule inhibitors (e.g., importazole, ivermectin), peptide competitors, and advanced delivery platforms. We conclude by providing the associated challenges such as achieving tissue specificity, avoiding off-target effects and the significant opportunities that lie in pharmacologically modulating this fundamental pathway to restore proteostasis and develop disease modifying therapies.}, }
@article {pmid41720758, year = {2026}, author = {Falahati, M and Orangi, K and Shaabanpoor Haghighi, A and Pouroushaninia, N and Niknam, N and Soltani, S and Radnia, P and Arab Bafrani, M and Shirdel, S and Aarabi, MH}, title = {Microstructural alterations of the amygdala in neurodegenerative and neuroinflammatory disorders: insights from diffusion tensor imaging.}, journal = {Reviews in the neurosciences}, volume = {}, number = {}, pages = {}, pmid = {41720758}, issn = {2191-0200}, abstract = {Diffusion tensor imaging (DTI) is a valuable method for evaluating microstructural changes in the amygdala associated with neurodegenerative and neuroinflammatory disorders. This systematic review examines amygdala microstructural alterations in Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), dementia with Lewy bodies (DLB), and multiple sclerosis (MS) using DTI metrics. Following PRISMA 2020 guidelines, we searched PubMed, Scopus, and Web of Science databases through August 2025, identifying 4,442 records. After screening and eligibility assessment, 13 studies were included, comprising 1,412 patients and 1,146 healthy controls. Due to sample heterogeneity and lack of standardized effect size measures, meta-analysis was not performed. Across disorders, elevated mean diffusivity (MD) emerged as the most consistent finding, present in 100 % of AD patients and observed in all examined conditions. Reduced fractional anisotropy (FA) was the second most frequent alteration, with 36.6 % of AD patients showing decreased FA. In MS, increased radial diffusivity (RD) was prominent, while longitudinal DLB studies revealed progressive free water (FW) increases. These DTI-based microstructural changes often preceded volumetric atrophy and correlated with clinical severity. Our findings demonstrate that DTI metrics, particularly MD and FA, serve as sensitive markers of amygdala pathology across neurodegenerative diseases and may facilitate early diagnosis, disease monitoring, and differential diagnosis of these conditions.}, }
@article {pmid41718986, year = {2026}, author = {Shadfar, S and Assar Kashani, S and Gautam, S and Takalloo, Z and Farzana, F and Parakh, S and Atkin, JD}, title = {The Role of the Golgi Apparatus in Neurodegeneration.}, journal = {Sub-cellular biochemistry}, volume = {111}, number = {}, pages = {413-440}, pmid = {41718986}, issn = {0306-0225}, mesh = {*Golgi Apparatus/metabolism/pathology ; Humans ; *Neurodegenerative Diseases/metabolism/pathology ; Animals ; *Neurons/metabolism/pathology ; }, abstract = {The Golgi apparatus has important, well characterised functions in the trafficking, processing, and post-translational modification of proteins and lipids. However, roles in other cellular processes are increasingly reported, including autophagy, apoptosis, DNA repair, and cytoskeletal (microtubules and actin) function. The Golgi therefore serves as a regulatory hub for multiple signalling pathways that maintain essential cellular activities. The Golgi normally consists of flattened stacks of membrane (cisternae), but during normal physiology and pathological conditions it 'fragments', resulting in altered morphology and distribution. This is well described as an early pathological feature of many neurodegenerative diseases, including Alzheimer's (AD), Parkinson's (PD), Huntington's (HD) and prion diseases, and amyotrophic lateral sclerosis (ALS). These age-related conditions are characterised by the death of neurons: highly specialised, unique cells that form the foundation of the nervous system. Interestingly, many Golgi-related functions are also dysregulated in these diseases. However, this has received relatively little attention compared to other pathogenic mechanisms. The Golgi apparatus in neurons shares features common to other eukaryotic cells but it also has unique properties, such as the presence of distinctive assemblies: Golgi outposts and satellites, which remain poorly characterised. Here we discuss the increasing evidence describing dysfunction and fragmentation of the Golgi apparatus and its possible role in the pathogenesis of neurodegenerative diseases.}, }
@article {pmid41718496, year = {2026}, author = {Judge, S and Ballesteros, K and McDermott, CJ and Bloch, S}, title = {Timing of communication and technology control support in ALS - a systematic review.}, journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration}, volume = {}, number = {}, pages = {1-9}, doi = {10.1080/21678421.2026.2627899}, pmid = {41718496}, issn = {2167-9223}, abstract = {Objective: To review evidence on the optimal timing of interventions that support communication and technology control for people living with Amyotrophic Lateral sclerosis (ALS). Methods: A systematic review was conducted following a pre-registered protocol. Databases were searched for studies involving people living with ALS that addressed timing of assistive technology interventions for communication or technology control. Screening and data extraction were completed in duplicate, findings were synthesized using a thematic analysis, and relevant findings presented as a descriptive summary. Results: Twenty-eight studies met the inclusion criteria. Evidence focused overwhelmingly on communication support rather than wider assistive technology interventions. Need for a communication aid typically occurs between one and five years from diagnosis and the timing of this varies significantly according to the site of onset of ALS. There are significant variations in the timing of changes for individuals within these groupings and there are likely a larger number of groupings that would be clinically useful. A significant correlation between changes in speaking rate and intelligibility has been shown. Once changes to speech do start to occur then the time to the loss of functional speech appears relatively consistent across the types of ALS. Conclusion: Current best practice guidelines are not reflective of the findings of this review and do not support professionals in identifying how to provide timely support. Monitoring speech changes systematically may support timely intervention. There is potential for individual level predictive modeling to help support people living with ALS to be proactive and prepared for changes.}, }
@article {pmid41714394, year = {2026}, author = {Warmann, S}, title = {[Motor neuron diseases from a radiological perspective : Focus on amyotrophic lateral sclerosis].}, journal = {Radiologie (Heidelberg, Germany)}, volume = {}, number = {}, pages = {}, pmid = {41714394}, issn = {2731-7056}, abstract = {BACKGROUND: Motor neuron diseases (MND) affect the upper and/or lower motor neurons. Radiological diagnostics primarily serve to systematically exclude treatable mimics and support the clinical and electrophysiological diagnosis. The focus is on amyotrophic lateral sclerosis (ALS); supplementary progressive muscular atrophy (PMA, purely lower motor neuron, LMN disease) and spinal muscular atrophy (SMA).<br><br>OBJECTIVE: Which imaging signs support the diagnosis of ALS, how do electromyography/magnetic resonance imaging (EMG/MRI) fit into the Gold Coast criteria and which other motor neuron diseases are relevant?<br><br>MATERIAL AND METHODS: Overview of clinical criteria (Gold Coast), genetics and typical MRI findings of the brain, spinal cord and musculature.<br><br>RESULTS: Gold Coast core: progressive motor deterioration, upper motor neuron (UMN) and LMN signs in &#x2265;&#x202f;1 region or LMN in &#x2265;&#x202f;2&#xa0;regions and exclusion of alternative causes.<br><br>IMAGING: susceptibility-weighted imaging (SWI) motor band sign as UMN marker; T2/fluid-attenuated inversion recovery (FLAIR) hyperintensities along the corticospinal tract with low sensitivity, moderate specificity; T1 bright tongue as an indication of chronic denervation in bulbar involvement. EMG: detection of subclinical LMN involvement, sometimes limited in UMN-dominant/bulbar courses. PMA: Pure purely LMN symptoms, often continuum to ALS. SMA: Autosomal autosomal recessive (SMN1 deletion).<br><br>DISCUSSION: The diagnosis remains primarily clinical; EMG and MRI are supportive. The radiological priority is the exclusion of mimics. The UMN markers increase diagnostic certainty in the context of clinical/EMG findings but do not replace them. Clear findings facilitate classification according to Gold Coast. The PMA and SMA require careful differential diagnostics; characteristic MRI patterns support progression and treatment planning.}, }
@article {pmid41673645, year = {2026}, author = {Sterr, K and Bachner, J and Scheller, DA and Mess, F and Blaschke, S and Mühlberg, T and Butscher, F and Schmid-Ellinger, J}, title = {No healthy schools without healthy teachers: a scoping review on implementation determinants, strategies and outcomes of mental health-promoting interventions for school teachers.}, journal = {BMC public health}, volume = {26}, number = {}, pages = {}, pmid = {41673645}, issn = {1471-2458}, abstract = {BACKGROUND: The mental health and well-being of school teachers is critical not only for their individual health but also for the quality and stability of educational systems. Numerous interventions have been developed to address teachers’ mental health challenges, yet their implementation in everyday school settings remains limited. Understanding implementation determinants, strategies, and outcomes is essential for improving sustainable implementation, intervention effectiveness and broader public health impact. This scoping review explored how implementation is addressed in studies evaluating mental health-promoting interventions for teachers.<br><br>METHODS: Following Arksey and O&#x2019;Malley&#x2019;s (2005) and Levac et al.&#x2019;s (2010) frameworks and PRISMA-ScR guidelines, we systematically searched Scopus and EBSCOhost up to April 2025. Studies were included if they evaluated an intervention targeting teachers&#x2019; mental health and reported at least one implementation aspect. Data extraction was guided by leading implementation science frameworks.<br><br>RESULTS: Of 4,062 identified records, 16 met the inclusion criteria. Most studies were primarily effectiveness-focused and assessed early-stage implementation rather than long-term implementation or sustainment. Implementation outcomes such as acceptability and feasibility were frequently reported but rarely grounded in implementation frameworks. Implementation determinants appeared in most studies, predominantly as post hoc barriers, with few studies assessing them a priori to guide implementation planning. Implementation strategies were commonly described but seldom explicitly labeled as such. Most studies examined implementation and intervention outcomes separately, limiting insights into how implementation processes influenced effectiveness. Nevertheless, several insights emerged, including the relevance of training and educating stakeholders, tailoring interventions to context, and strengthening relational dynamics, all examples of implementation strategies, as well as the importance of considering intervention content and implementation jointly.<br><br>CONCLUSION: Although implementation determinants, strategies, and outcomes were reported in studies on teachers&#x2019; mental health interventions, reporting was often fragmented, unsystematic and rarely guided by established frameworks or terminology. Future research should adopt comprehensive, theory-informed approaches that link implementation and intervention content. From a public health perspective, aligning evidence-based interventions, addressing both organizational and individual levels, with context-sensitive implementation strategies is key to sustainably improving teachers&#x2019; mental health and strengthening schools as healthy, supportive environments.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12889-026-26589-w.}, }
@article {pmid41710159, year = {2026}, author = {Pang, Y and Yang, J and Liu, J and Xie, Z and Wang, J}, title = {Metabolic interactions in the brain: the crucial roles of neurons, astrocytes, and microglia in health and disease.}, journal = {Frontiers in neuroscience}, volume = {20}, number = {}, pages = {1731771}, pmid = {41710159}, issn = {1662-4548}, abstract = {This review provides an in-depth exploration of the intricate energy metabolism pathways within the brain, with a particular focus on the dynamic interplay between neurons, astrocytes, and microglia. Neurons, with their high energy demands, primarily rely on oxidative phosphorylation and the tricarboxylic acid (TCA) cycle to sustain synaptic activity and neurotransmitter synthesis. In contrast, astrocytes predominantly engage in glycolysis, producing lactate and glutathione, which are essential for supporting neuronal function and protecting against oxidative stress. Additionally, microglia, the brain's resident immune cells, exhibit a metabolic flexibility that allows them to shift between oxidative phosphorylation and glycolysis, depending on their activation state, which significantly influences neuroinflammation and synaptic plasticity. The review highlights the critical role of astrocyte-neuron metabolic coupling, particularly through the lactate shuttle and glutathione metabolism, in maintaining neuronal homeostasis and facilitating synaptic function. It also delves into the metabolic underpinnings of neurodegenerative diseases such as Alzheimer's, Parkinson's, and Amyotrophic Lateral Sclerosis, illustrating how disruptions in brain energy metabolism contribute to disease progression. By synthesizing recent findings, this review not only underscores the centrality of brain energy metabolism in both normal and pathological conditions but also identifies potential therapeutic targets aimed at modulating these metabolic pathways to mitigate the effects of neurodegenerative disorders. This comprehensive analysis offers valuable insights that could propel further research and innovation in the field of neurology, making it essential reading for experts interested in the molecular mechanisms underlying brain function and disease.}, }
@article {pmid41709060, year = {2026}, author = {Yadav, AK and Verma, P and Srivastava, A and Srivastava, P and Rai, R and Rathour, S}, title = {Molecular insights into glial neuroimmune cross reactivity with CNS antigens and its role in neuroinflammation.}, journal = {Inflammopharmacology}, volume = {}, number = {}, pages = {}, pmid = {41709060}, issn = {1568-5608}, abstract = {Neuroinflammation has been increasingly considered a key player of neurodegenerative as well as psychiatric disorders. This review integrates existing knowledge on glial-neuroimmune interactions, emphasizing the roles of cytokine signaling, glial activation, and BBB modulation in neuro-pathogenesis. A systematic review was performed studying peer-reviewed literature on molecular pathways of microglia, astrocytes, endothelial cells, and peripheral immune mediators. A possible explanation of this finding could be that the model is based on the underlying pathophysiology, and this is shared across disease contexts, including multiple sclerosis, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and traumatic brain injury. Novel in vitro platforms, including the organ-on-a-chip and brain organoids, were also discussed for their translational potential. Microglia M1/M2 polarization and astrocyte reactivity appeared to be a common feature in neurotoxicity as well as excitotoxicity and chronic inflammation. Cytokine cascade of TNF-α, IL-1β, and IL-6 led to the disrupted BBB, allowing for peripheral immune cells to infiltrate. Both the NLRP3 inflammasome and mitochondrial dysfunction were identified as enhancers of neuroimmune signaling. Comparing across disease models, shared relationships emerged between glia-cytokines-BBB. Advanced in vitro systems proved to be useful to model these interactions and screen prescription drugs. This review highlights existing insights into glia-neuroimmune cross-reactivity and its critical role in CNS disease. The molecular interactions between these molecules could represent promising targets for novel therapeutic options. We suggests integrative systems platforms and AI-driven strategies to expedite clinical translation in neuroinflammation.}, }
@article {pmid41699331, year = {2026}, author = {Ercin, N and Besli, N and Beker, M and Celik, U}, title = {Non-canonical cell death in neurodegeneration: emerging mechanisms and therapeutic Frontiers.}, journal = {Apoptosis : an international journal on programmed cell death}, volume = {31}, number = {3}, pages = {72}, pmid = {41699331}, issn = {1573-675X}, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/pathology/metabolism/genetics ; *Cell Death/drug effects ; Animals ; Necroptosis/drug effects ; Ferroptosis/drug effects ; Neuroprotective Agents/therapeutic use/pharmacology ; Pyroptosis/drug effects ; Oxidative Stress ; }, abstract = {Neurodegenerative diseases, specifically Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic Lateral Sclerosis (ALS) are defined by progressively increased neuronal loss that lacks curative therapies. Increasing evidence supports that non-canonical regulated cell death pathways including ferroptosis, necroptosis, pyroptosis, and parthanatos, are implicated in pathological mechanisms of neuroinflammation, and oxidative stress, and mitochondrial dysfunction, likely impacting neurodegenerative pathologies. In this review, we summarize the existing literature on the molecular pathways and potential pathogenic implications of these cell death pathways in neurodegenerative diseases, highlighting their upstream triggers, regulatory proteins, and downstream effectors. We also briefly describe representative pharmacological agents, including ferrostatin-1, necrostatin-1, MCC950 and PARP-inhibitors, that have shown neuroprotective effects in experimental studies. Experimental studies provide valuable information, but translation to clinical treatments presents barriers including overlapping regulated cell death mechanisms, constraints of bloodbrain barrier penetrance and concern for safety. Future development may come through concepts such as biomarker-based patient stratification strategies, multivalent interventions, and improved translational models. Identifying these new regulated cell death pathways may eventually provide new avenues to slow the progression of neurodegeneration and develop more targeted therapies.}, }
@article {pmid41698629, year = {2026}, author = {Patwekar, F and Patwekar, M and Wei, LS and Rather, GA and Mohammed, A and Hussain, MS and Gupta, G and Fuloria, S and Fuloria, NK}, title = {Marine-Derived bioactive compounds from Aquaculture: Receptor-Mediated neuroprotection in neurodegenerative disorders.}, journal = {Brain research}, volume = {1879}, number = {}, pages = {150208}, doi = {10.1016/j.brainres.2026.150208}, pmid = {41698629}, issn = {1872-6240}, abstract = {Neurodegenerative diseases, like Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and ischemic stroke (IS), are a major global health challenge because of their complex, multifactorial pathology, and the lack of effective disease-modifying therapies. In recent years, aquaculture-derived marine bioactive molecules like fucoidan, phlorotannins, fucoxanthin, laminarin, alginate oligosaccharides, and C-phycocyanin have developed as promising agents for neuroprotection with their structural diversity and multi-target biological activity. This review showcase predominantly preclinical evidence, including in silico molecular docking analyses, in vitro functional assays, and in vivo animal models, to critically understand the receptor-mediated mechanisms with the neuroprotective actions of marine bioactives originated from aquaculture systems. Available studies shows these compounds can modulate large neuro-receptor systems, like cholinergic, dopaminergic, GABAergic, glutamatergic, toll-like, and nuclear receptors, leading in attenuation of oxidative stress, lowering of neuro-inflammation, regulation of neurotransmission, and conservation of mitochondrial and synaptic function. However, the positive approach of mechanistic evidence varies across compounds and receptor classes, with large interactions assisted by functional outcomes instead of direct receptor-binding validation. The review even discusses emerging and enabling technologies like brain organoids, multi-electrode array platforms, omics-based profiling, and artificial intelligence assisted drug discovery, which are increasingly utilized to refine mechanistic understanding and optimize marine-derived products. Importantly, current evidence stay largely preclinical, with little human studies and a lack of validated receptor-specific biomarkers. Overall, this review provides a well-balanced, evidence-based assessment of aquaculture-derived marine bioactive as potential neurotherapeutic agents.}, }
@article {pmid41521074, year = {2026}, author = {Ham, HJ and Lee, JA}, title = {Stress granules as a central hub linking organelle stress, aging, and neurodegeneration.}, journal = {BMB reports}, volume = {59}, number = {2}, pages = {85-100}, pmid = {41521074}, issn = {1976-670X}, mesh = {Humans ; *Aging/metabolism/physiology ; *Neurodegenerative Diseases/metabolism/pathology ; *Stress Granules/metabolism/physiology ; Animals ; *Organelles/metabolism ; Mitochondria/metabolism ; Neurons/metabolism ; Cytoplasmic Granules/metabolism ; Autophagy ; Stress, Physiological ; }, abstract = {Stress granules (SGs) are dynamic cytoplasmic assemblies composed of RNAs and proteins that form in response to cellular stress, serving to halt translation and protect cellular integrity. In neurons, SGs mediate adaptive, pro-survival responses to acute stress; however, their dysregulation has been increasingly associated with both aging and neurodegenerative diseases. Aging neurons frequently exhibit changes in SG dynamics-with an increased propensity to form SGs while displaying reduced efficiency in their clearance-resulting in persistent granules that can facilitate the accumulation of pathological protein aggregates (e.g., TDP-43 or tau). Aberrant SG formation and defective clearance mechanisms are implicated in the pathogenesis of key neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alzheimer's disease (AD), and Parkinson's disease (PD). Recent findings have shown that SGs interface with organelles such as lysosomes, mitochondria, and the endoplasmic reticulum, utilizing autophagic and other protein quality-control mechanisms for clearance. As these clearance pathways progressively decline with age, SGs can transition from promoting cellular adaptation to contributing to cellular dysfunction. In this mini-review, we examine how aging influences SG biology, detail the role of SGs in neurodegenerative diseases, and discuss emerging mechanistic insights and therapeutic strategies aimed at modulating SG dynamics in the context of brain aging. [BMB Reports 2026; 59(2): 85-100].}, }
@article {pmid41693708, year = {2025}, author = {Mudda, NS and Zhang, L and Sampelli, P}, title = {Targeting gut-brain-immune axis in amyotrophic lateral sclerosis.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1637976}, pmid = {41693708}, issn = {1664-3224}, mesh = {*Amyotrophic Lateral Sclerosis/immunology/microbiology/therapy/metabolism ; Humans ; *Gastrointestinal Microbiome/immunology ; Animals ; *Brain/immunology/metabolism ; Dysbiosis/immunology ; *Brain-Gut Axis/immunology ; Cytokines/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron neurodegenerative disorder with a median survival of only 3-5 years. The heterogeneity of the disease and lack of effective therapies highlight the importance of identifying novel pathogenic mechanisms. We hypothesize that dysbiosis of gut microbiota enhances ALS by disrupting intestinal barrier function and altering metabolite profiles to drive systemic inflammation and neuronal stress. Precisely, the decrease in health-promoting bacteria (e.g., Akkermansia muciniphila, Bifidobacterium and Lactobacillus spp.) in ALS can reduce neuroprotective metabolite production (short-chain fatty acids, nicotinamide, GABA, precursors of serotonin) and increase gut permeability, enabling lipopolysaccharide (LPS) and pro-inflammatory cytokines into the circulation. Such changes would activate microglia and impair motor neuron homeostasis by glutamate excitotoxicity and mitochondrial dysfunction. The gut-brain axis operates through immune-mediated mechanisms, where ALS-associated microbiota changes compromise mucosal immunity and trigger peripheral Th1/Th17-biased responses with impaired Treg regulation. Elevated endotoxin levels correlate with TLR4-driven inflammation, promoting pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) that cross into the CNS and prime microglia toward a neurotoxic M1 phenotype, creating a milieu where IL-17A and other mediators directly injure motor neurons. Our hypothesis relies on establishing human and animal evidence of microbiome derangements, barrier dysfunction, and immune deregulation with ALS. We hypothesize that restoration of an "ALS-protective" microbiota consortium or its metabolic by-products can potentially slow disease progression. Testable hypotheses include improvement of ALS model motor deficits by probiotic or fecal-microbiota therapies, and normalization of inflammatory biomarkers. This paradigm recontextualizes ALS as a gut-brain disease and suggests new directions for translational research into this unmet medical indication.}, }
@article {pmid41690071, year = {2026}, author = {El-Moaty, HIA and Sameh, A and Saber, S and Hamad, RS and Elmorsy, EA and Alsoqih, NS and Farrag, AA and Eissa, H and El-Kott, AF and Negm, S and AlShehri, MA and Ali, MAM and Hasan, WA and Gaafar, A and Khalifa, HS and Ibrahim, EH and Morsy, K and Elnaghy, F}, title = {Adenosine A2A receptor as a dual-acting molecular switch: Glial morphological changes and neurovascular tissue remodeling in neuroinflammation and neurodegeneration.}, journal = {Tissue &amp; cell}, volume = {100}, number = {}, pages = {103389}, doi = {10.1016/j.tice.2026.103389}, pmid = {41690071}, issn = {1532-3072}, abstract = {Neuroinflammation appears in a variety of neurological disorders, including multiple sclerosis (MS), Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis. The adenosine A2A receptor (A2AR), a Gs protein-coupled receptor that affects cAMP signaling and downstream kinases like PKA, CREB, and NF-κB, is one of the primary regulators of this process. Context-dependent effects of A2AR activation include lowering acute inflammation and promoting neuronal survival when stimulated moderately, but increasing glial activation and cytokine production when overexpressed over an extended period of time. In microglia and astrocytes, A2AR signaling regulates inflammatory pathways mediated by NF-κB and MAPK, affecting oxidative stress, blood-brain barrier (BBB) stability, and excitotoxicity. Acute or transient (short-term) A2AR activation, on the other hand, increases the production of anti-inflammatory cytokines like IL-10 and enhances neurotrophic support through BDNF. A2AR antagonists, including istradefylline and SCH58261, may reduce microglial triggering and have neuroprotective benefits, according to clinical and experimental data. The context-dependent activity of the receptor is shown by the fact that total receptor blockage interferes with adaptive immune control. Therefore, the therapeutic challenge is to carefully modify A2AR signaling in particular cell populations, specifically targeting astrocytic or microglial receptors while maintaining the peripheral immunoregulatory activities. The dual regulatory role of A2AR in neuroinflammation is summarized in this review along with its molecular mechanisms, disease-specific actions, and therapeutic significance. Developing next-generation neuroprotective strategies that reduce A2AR signaling's pro-inflammatory and neurotoxic effects while preserving its beneficial homeostatic effects will require an understanding of the temporal and cell-specific dynamics of this signaling.}, }
@article {pmid41689968, year = {2026}, author = {Qaisar, R and Deepa, SS}, title = {A Narrative Review of Necroptosis in Neuromuscular Junction Disorders: Pathogenesis and Therapeutic Strategies.}, journal = {Archives of medical research}, volume = {57}, number = {5}, pages = {103401}, doi = {10.1016/j.arcmed.2026.103401}, pmid = {41689968}, issn = {1873-5487}, abstract = {Necroptosis is a regulated and inflammatory form of cell death that has emerged as a key contributor to neuromuscular junction (NMJ) dysfunction. This narrative review aims to synthesize current evidence on the role of necroptosis in NMJ pathology and its potential therapeutic implications. First, we present the conceptual framework linking necroptosis to NMJ degradation, focusing on core mediators such as receptor-interacting protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like pseudokinase (MLKL). Second, we summarize the available evidence across NMJ compartments, including motor neurons, Schwann cells, and skeletal muscle. We also describe how necroptosis activation correlates with structural and functional deficits in conditions such as spinal muscular atrophy, amyotrophic lateral sclerosis, and Duchenne muscular dystrophy. Third, we examine the translational potential of targeting necroptosis, highlighting preclinical studies on RIPK1, RIPK3, and MLKL inhibitors. Although these findings suggest therapeutic value, current evidence is predominantly derived from animal models, and clinical applicability remains uncertain. Rigorous trials are needed to confirm the safety and efficacy of these treatments. Understanding necroptosis as a shared mechanism across NMJ components may inform future strategies to preserve neuromuscular function.}, }
@article {pmid41686369, year = {2026}, author = {Qaisar, R}, title = {Extracellular vesicles at the neuromuscular junction: messengers of synaptic health and disease.}, journal = {Cell and tissue research}, volume = {403}, number = {2}, pages = {20}, pmid = {41686369}, issn = {1432-0878}, mesh = {Humans ; *Extracellular Vesicles/metabolism ; *Neuromuscular Junction/metabolism/pathology ; Animals ; *Synapses/metabolism ; }, abstract = {Extracellular vesicles (EVs) have emerged as pivotal modulators of neuromuscular junction (NMJ) biology, reshaping our understanding of synaptic communication, maintenance, and degeneration. This review consolidates current insights into the roles of EVs derived from motor neurons, muscle fibers, and Schwann cells in regulating NMJ integrity. In healthy states, EVs deliver trophic factors, structural proteins, and regulatory RNAs that promote the clustering of acetylcholine receptors, presynaptic stability, and axonal growth. Motor neuron EVs carry Wnt7a, synaptophysin, and PGC-1α, while muscle-derived EVs deliver miR-206, agrin, and caveolin-3. Schwann cell EVs contribute neurotrophic support via NRG1 and GDNF. In contrast, diseased or aged NMJs exhibit EV cargo dysregulation, marked by the presence of misfolded proteins (e.g., SOD1, TDP-43), pro-inflammatory cytokines, and reduced regenerative miRNAs. These changes contribute to synaptic dismantling, neuroinflammation, and impaired repair in conditions such as ALS, SMA, MG, and sarcopenia. The review highlights the bidirectional nature of EV signalling and its dynamic regulation by neuronal activity and stress. Emerging therapeutic strategies include engineering EVs to deliver protective cargo, targeting them to NMJ components, and designing biomaterial-based depots for sustained release. Furthermore, EV signatures in blood and muscle hold promise as non-invasive biomarkers for early detection of NMJ decline in ALS, SMA, MG, and sarcopenia. Despite promising preclinical data, challenges remain in EV characterization, targeting specificity, and clinical translation. This review underscores a paradigm shift: EVs are not passive byproducts but active messengers of neuromuscular health and disease, with realistic applications in diagnostics, regenerative therapy, and personalized medicine.}, }
@article {pmid41684011, year = {2026}, author = {Chico, L and Schirinzi, E and Balestrini, L and Polzella, M and Siciliano, G}, title = {Nrf2-Activating Natural Compounds in Neurodegenerative Diseases: Targeting Oxidative Stress and Protein Aggregation.}, journal = {International journal of molecular sciences}, volume = {27}, number = {3}, pages = {}, pmid = {41684011}, issn = {1422-0067}, mesh = {Humans ; *NF-E2-Related Factor 2/metabolism ; *Oxidative Stress/drug effects ; *Neurodegenerative Diseases/metabolism/drug therapy ; *Biological Products/pharmacology/therapeutic use ; Animals ; *Protein Aggregates/drug effects ; *Protein Aggregation, Pathological/drug therapy/metabolism ; Neuroprotective Agents/pharmacology/therapeutic use ; Antioxidants/pharmacology/therapeutic use ; Signal Transduction/drug effects ; }, abstract = {Neurodegenerative diseases (NDs) are among the leading causes of disability and mortality worldwide and are characterized by multifactorial pathogenesis involving interconnected mechanisms, such as oxidative stress, protein misfolding and aggregation, neuroinflammation, and mitochondrial dysfunction. Dysregulation of transcription factors, governing cellular defense responses, particularly nuclear factor erythroid 2-related factor 2 (Nrf2), a key regulator of antioxidant and proteostatic pathways, plays a critical role in neurodegenerative processes. Currently, available pharmacological treatments for NDs are largely symptomatic, as no disease-modifying therapies exist. Natural bioactive compounds have emerged as promising multi-target agents, demonstrating antioxidant, anti-aggregative, and anti-apoptotic properties, frequently mediated through activation of the Nrf2 signaling pathways. These compounds may represent valuable supportive strategies alongside conventional drug treatments, potentially contributing to the modulation of multiple pathogenic mechanisms. This review summarizes key oxidative stress- and protein aggregation-driven mechanisms underlying Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease. It further examines the neuroprotective potential of plant-, fungi-, and marine-derived natural compounds, with particular emphasis on Nrf2 activation. Beyond redox regulation, the broader role of Nrf2 in maintaining proteostasis is discussed. Overall, the review highlights Nrf2-inducing nutraceuticals as promising complementary, multi-target approaches for neuroprotection in NDs.}, }
@article {pmid41683920, year = {2026}, author = {Auburger, GWJ and Key, J and Gispert, S and Lastres-Becker, I and Almaguer-Mederos, LE and Bassa, C and Auburger, A and Auburger, G and Arsovic, A and Deller, T and Sen, NE}, title = {Bioinformatic Analyses of the Ataxin-2 Family Since Algae Emphasize Its Small Isoforms, Large Chimerisms, and the Importance of Human Exon 1B as Target of Therapies to Prevent Neurodegeneration.}, journal = {International journal of molecular sciences}, volume = {27}, number = {3}, pages = {}, pmid = {41683920}, issn = {1422-0067}, support = {AU96/21-1//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Humans ; *Ataxin-2/genetics/metabolism/chemistry ; *Computational Biology/methods ; *Exons ; Protein Isoforms/genetics/metabolism ; Peptides/genetics/metabolism ; Animals ; *Neurodegenerative Diseases/genetics/prevention &amp; control ; Phylogeny ; }, abstract = {Polyglutamine expansion in Ataxin-2 (ATXN2) is responsible for rare, dominantly inherited Spinocerebellar Ataxia type 2 (SCA2). Together with its paralog Ataxin-2-like (ATXN2L), both proteins have received much interest, since the deletion of their yeast and fly orthologs alleviates TDP-43-triggered neurotoxicity in Amyotrophic Lateral Sclerosis models. Their typical structure across evolution combines LSm with LSm-Associated Domains and a PAM2 motif. To understand the physiological regulation and functions of Ataxin-2 homologs, the phylogenesis of sequences was analyzed. Human ATXN2 harbors multiple alternative start codons, e.g., from an intrinsically disordered sequence (IDR) present since armadillo, or from the polyQ sequence that arose since amphibians, or from the LSm domain since primitive eukaryotes. Multiple smaller isoforms also exist across the C-terminus. Therapeutic knockdown of polyQ expansions in human ATXN2 should selectively target exon 1B. PolyQ repeats developed repeatedly, usually framed and often interrupted by (poly)Pro, originally near PAM2. The LSmAD sequence appeared in algae as the characteristic Ataxin-2 feature with strong conservation. Frequently, Ataxin-2 has added domains, likely due to transcriptional readthrough of neighbor genes during cell stress. These chimerisms show enrichment of rRNA processing; nutrient store mobilization; membrane strengthening via lipid, protein, and glycosylated components; and cell protrusions. Thus, any mutation of Ataxin-2 has complex effects, also affecting membrane resilience.}, }
@article {pmid41683564, year = {2026}, author = {Jamerlan, A and Hulme, J}, title = {From Evasion to Collapse: The Kinetic Cascade of TDP-43 and the Failure of Proteostasis.}, journal = {International journal of molecular sciences}, volume = {27}, number = {3}, pages = {}, pmid = {41683564}, issn = {1422-0067}, support = {RS-2025-02292973//Ministry of Oceans and Fisheries/ ; RS-2021-NR060117//Ministry of Education/ ; }, mesh = {Humans ; *DNA-Binding Proteins/metabolism/genetics/chemistry ; *Proteostasis ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; Autophagy ; Animals ; *Frontotemporal Dementia/metabolism/genetics/pathology ; Protein Folding ; Kinetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are devastating neurodegenerative diseases that, despite the availability of symptomatic and modestly beneficial treatments, still lack therapies capable of halting disease progression. A histopathological hallmark of both diseases is the cytoplasmic deposition of TDP-43 in neurons, which is attributed to both intrinsic (e.g., mutations, aberrant cleavage) and extrinsic factors (e.g., prolonged oxidative stress, impaired clearance pathways). Mutations and certain PTMs (e.g., cysteine oxidation) destabilize RNA binding, promoting monomer misfolding and increasing its half-life. Disruptions to core ubiquitin-proteasome system (UPS) subunits impede efficient processing, contributing to the clearance failure of misfolded TDP-43 monomers. The accumulation of monomers drives phase separation within stress granules, creating nucleation hotspots that eventually bypass the thermodynamic barrier, resulting in exponential growth. This rapid growth then culminates in the failure of the autophagy-lysosome pathway (ALP) to contain the aggregation, resulting in a self-sustaining feed-forward loop. Here, we organize these factors into a conceptual kinetic cascade that links TDP-43 misfolding, phase separation, and clearance failure. Therapeutic strategies must therefore move beyond simple clearance and focus on targeting these kinetic inflection points (e.g., oligomer seeding, PTM modulation).}, }
@article {pmid41683467, year = {2026}, author = {Czaj, PV and Szewczyk-Golec, K and Nuszkiewicz, J and Woźniak, A}, title = {Gut Dysbiosis and Microbiota-Derived Metabolites in Neurodegenerative Diseases: Molecular and Biochemical Mechanisms Along the Gut-Brain Axis.}, journal = {Molecules (Basel, Switzerland)}, volume = {31}, number = {3}, pages = {}, pmid = {41683467}, issn = {1420-3049}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Dysbiosis/metabolism/microbiology ; *Neurodegenerative Diseases/metabolism/microbiology ; Animals ; *Brain/metabolism ; Oxidative Stress ; Signal Transduction ; Parkinson Disease/metabolism/microbiology ; }, abstract = {Neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) share key molecular features, including neuroinflammation, oxidative stress, mitochondrial dysfunction, and progressive neuronal loss. Increasing evidence indicates that gut dysbiosis and alterations in microbiota-derived metabolites are involved in these processes through multiple pathways along the gut-brain axis. However, while broad compositional changes are well-documented, a critical knowledge gap remains regarding the specific biochemical signal transduction pathways translating dysbiosis into pathology. This narrative review addresses this gap by synthesizing current human and experimental studies addressing gut microbiota alterations in AD, PD, and ALS, with particular emphasis on the biochemical and molecular mechanisms mediated by gut-derived metabolites. Dysbiosis in neurodegenerative diseases is frequently associated with reduced abundance of short-chain fatty acid (SCFA)-producing bacteria and altered metabolism of SCFAs, bile acids, tryptophan-derived indoles, trimethylamine-N-oxide (TMAO), and lipopolysaccharides (LPS). These microbial metabolites have been shown to modulate intestinal and blood-brain barrier integrity, influence Toll-like receptor- and G protein-coupled receptor-dependent signaling, regulate microglial activation, and affect molecular pathways related to protein aggregation in experimental models. In addition, emerging evidence highlights the involvement of oxidative and nitrosative stress, immune-metabolic crosstalk, and altered xenobiotic metabolism in microbiota-host interactions during neurodegeneration. By integrating microbiological, metabolic, and molecular perspectives, this review underscores the important and emerging role of microbiota-derived molecules in neurodegenerative disorders and outlines key chemical and metabolic pathways that may represent targets for future mechanistic studies and therapeutic strategies.}, }
@article {pmid40960388, year = {2026}, author = {Jhilal, S and Marchesotti, S and Thirion, B and Soudrie, B and Giraud, AL and Mandonnet, E}, title = {Implantable Neural Speech Decoders: Recent Advances, Future Challenges.}, journal = {Neurorehabilitation and neural repair}, volume = {40}, number = {2}, pages = {157-172}, doi = {10.1177/15459683251369468}, pmid = {40960388}, issn = {1552-6844}, mesh = {Humans ; *Speech/physiology ; *Locked-In Syndrome/rehabilitation/physiopathology ; *Brain-Computer Interfaces ; }, abstract = {The social life of locked-in syndrome (LIS) patients is significantly impacted by their difficulties to communicate. Consequently, researchers have started to explore how to decode intended speech from neural signals directly recorded from the cortex. The first studies in the late 2000s reported modest decoding accuracies. However, thanks to fast advances in machine learning, the most recent studies have reached decoding accuracies high enough to be optimistic about the clinical benefit of neural speech decoders in the near future. We first discuss the selection criteria for implanting a neural speech decoder in LIS patients, emphasizing the advantages and disadvantages associated with conditions such as brainstem stroke and amyotrophic lateral sclerosis. We examine the key design considerations for neural speech decoders, demonstrating how successful implantation requires careful optimization of multiple interrelated factors including language representation, cortical recording areas, neural features, training paradigms, and decoding algorithms. We then discuss current approaches and provide arguments for potential improvements in decoder design and implementation. Finally, we explore the crucial question of who should learn to use the neural speech decoder-the patient, the machine, or both. In conclusion, while neural speech decoders present promising avenues for improving communication for LIS patients, interdisciplinary efforts spanning neurorehabilitation, neuroscience, neuroengineering, and ethics are imperative to design future clinical trials.}, }
@article {pmid40735987, year = {2025}, author = {Ergin, AD}, title = {Nanotechnological Approaches for Mitochondrial Targeting in Neurodegenerative Diseases.}, journal = {Current topics in medicinal chemistry}, volume = {25}, number = {28}, pages = {3251-3266}, pmid = {40735987}, issn = {1873-4294}, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/metabolism/pathology ; *Mitochondria/drug effects/metabolism ; *Nanotechnology ; *Drug Delivery Systems ; Animals ; Nanoparticles/chemistry ; *Neuroprotective Agents/chemistry/pharmacology ; }, abstract = {OBJECTIVES: Mitochondria are dynamic organelles essential for energy metabolism and cellular homeostasis, playing critical roles in ATP production, calcium regulation, redox balance, and apoptosis. However, mitochondrial dysfunction is a central factor in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, and Parkinson's disease. Given the essential role of mitochondria in neuronal survival, targeted therapeutic strategies that restore mitochondrial function have gained significant attention. This review explores the latest advances in mitochondrial-targeted therapies and their potential applications in neurodegenerative diseases.<br><br>METHODS: A comprehensive literature review was conducted on mitochondrial-targeted therapeutic strategies, with a focus on nanotechnology-based drug delivery systems. The analysis includes various nanoparticle-based approaches, such as liposomes, DQAsomes, and polymeric nanoparticles, which have demonstrated high biocompatibility, controlled drug release, and enhanced mitochondrial targeting efficiency. Additionally, mitochondria-penetrating peptides and delocalized lipophilic cations (DLCs) are discussed for their role in improving drug localization within mitochondria and overcoming biological barriers, including the blood-brain barrier (BBB).<br><br>RESULTS: Recent research shows the potential of mitochondrial-targeted antioxidants, peptides, and biocompatible nanocarriers in arranging mitochondrial dysfunction and protecting neurons from oxidative damage. Various nanoparticle-based drug delivery systems have demonstrated the ability to selectively target mitochondria, improving drug bioavailability, therapeutic efficacy, and neuroprotective outcomes in neurodegenerative diseases.<br><br>CONCLUSION: Mitochondria-targeted therapies provide promising avenues for disease-modifying treatments aimed at preserving neuronal integrity and delaying disease progression. The unique properties of nanoparticles, such as their ability to enhance drug stability, facilitate controlled release, and achieve precise mitochondrial localization, make them valuable tools for neurodegenerative disease therapy. Future research should focus on optimizing delivery systems, validating clinical applicability, and exploring interdisciplinary approaches to accelerate translation into effective treatments.}, }
@article {pmid41678537, year = {2026}, author = {Helal, MM and Almosilhy, NA and Abo-Elnour, DE and Jaffal, RSY and Allam, EG and Almosilhy, MA and Batarseh, SF and Meshref, M}, title = {Targeting metabolic dysfunction in amyotrophic lateral sclerosis: therapeutic potential of GLP-1 receptor agonists.}, journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration}, volume = {}, number = {}, pages = {1-27}, doi = {10.1080/21678421.2026.2627901}, pmid = {41678537}, issn = {2167-9223}, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive motor neuron loss and profound systemic metabolic dysfunction, including hypermetabolism, weight loss, insulin resistance, and altered glucose and lipid homeostasis. Increasing recognition of these metabolic abnormalities has driven interest in repurposing antidiabetic therapies, particularly glucagon-like peptide-1 (GLP-1) and GLP-1 receptor agonists (GLP-1RAs), for ALS. Beyond their established metabolic actions, GLP-1RAs exert pleiotropic effects relevant to neurodegeneration, including modulation of neuroinflammation, mitochondrial function, oxidative stress, excitotoxicity, and cell-survival signaling, with selected agents demonstrating central nervous system penetration. This narrative review summarizes current knowledge on metabolic impairment in ALS and critically evaluates the mechanistic rationale, preclinical evidence, and emerging clinical data supporting or opposing the use of GLP-1-based therapies in this disease. Preclinical studies suggest that GLP-1 signaling can provide neuroprotective and neurotrophic effects in ALS models, although findings are heterogeneous and highly dependent on compound selection, delivery strategy, and experimental design. In contrast, available clinical evidence is limited and does not demonstrate therapeutic benefit in ALS, while raising important safety concerns, particularly related to weight loss, lean mass reduction, and altered glucose regulation, factors associated with a worse prognosis in ALS. Collectively, current data indicate that although GLP-1-based therapies may have compelling biological plausibility and beneficial effects in other neurodegenerative disorders (NDGs), their role in ALS remains uncertain and potentially harmful. Well-designed, ALS-specific clinical studies are required to clarify safety, efficacy, and patient selection before GLP-1RAs can be considered for therapeutic use in this vulnerable population.}, }
@article {pmid41678108, year = {2026}, author = {Umesh, SB and Sadanandan, B and Marabanahalli Yogendraiah, K and Vijayalakshmi, V}, title = {The Impact of Zinc on Cellular Dynamics, Brain Function, and its Therapeutic Potential in Neuronal Regeneration.}, journal = {Molecular neurobiology}, volume = {63}, number = {1}, pages = {436}, pmid = {41678108}, issn = {1559-1182}, mesh = {Humans ; *Zinc/pharmacology/metabolism/therapeutic use ; Animals ; *Nerve Regeneration/drug effects/physiology ; *Brain/physiology/drug effects ; *Neurons/drug effects/metabolism ; Neurogenesis/drug effects ; }, abstract = {Zinc is a vital trace element that plays a central role in maintaining brain function, regulating cellular dynamics, and promoting neuronal repair. As the second most abundant transition metal in the central nervous system, zinc is essential for neurotransmission, synaptic plasticity, and neurogenesis, processes that underlie higher cognitive functions such as learning and memory. Its homeostasis is tightly controlled, as dysregulation contributes to the onset and progression of neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. At the cellular level, zinc serves as a critical regulator of proliferation, differentiation, and survival, influencing the behavior of neural and mesenchymal stem cells. Through modulation of signaling pathways such as PI3K/Akt and MAPK, zinc governs cell growth, maturation, and neuroprotection. Physiological levels support axonal sprouting, neurite extension, and synaptic connectivity, whereas excessive release under pathological conditions exacerbates oxidative stress and excitotoxicity. Emerging evidence highlights zinc's therapeutic role in neuronal regeneration. Controlled supplementation enhances neurogenesis, reduces apoptosis, restores synaptic activity, and improves memory outcomes in experimental models of neural injury. Zinc-enriched biomaterials and scaffolds are also being developed for neural tissue engineering, where the incorporation of zinc enhances neurite outgrowth, cell adhesion, and network repair. Beyond neuroregeneration, zinc-based nanomaterials are gaining biomedical significance. Zinc oxide nanoparticles (ZnO NPs) exhibit potent anticancer activity against human cancer cell lines by inducing reactive oxygen species generation, DNA damage, and apoptosis. Additionally, other zinc nanoparticles, including zinc sulfide and zinc-doped biomaterials, show potential in tissue repair, wound healing, and drug delivery applications. Collectively, these findings underscore zinc's multifaceted role in neural function, regenerative biology, and nanomedicine. Advancing our understanding of zinc-mediated mechanisms may enable the development of novel zinc-targeted therapeutic strategies for treating neurodegenerative diseases and promoting functional recovery after brain injury.}, }
@article {pmid41677614, year = {2026}, author = {Salamotas, I and Stavropoulou De Lorenzo, S and Stachtiari, A and Taxiarchis, A and Tsolaki, M and Michailidou, I and Preza, E}, title = {From Dish to Trial: Building Translational Models of ALS.}, journal = {Cells}, volume = {15}, number = {3}, pages = {}, pmid = {41677614}, issn = {2073-4409}, mesh = {*Amyotrophic Lateral Sclerosis/pathology/therapy ; Humans ; Induced Pluripotent Stem Cells/metabolism/cytology ; *Translational Research, Biomedical ; Clinical Trials as Topic ; Animals ; *Models, Biological ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease, marked by progressive degeneration of upper and lower motor neurons. Clinically, genetically, and pathologically heterogeneous, ALS poses a major challenge for disease modeling and therapeutic translation. Over the past two decades, induced pluripotent stem cells (iPSCs) have reshaped our understanding of ALS pathogenesis and emerged as a promising translational platform for therapy development. ALS modeling has further expanded with the advent of three-dimensional systems, including ALS-on-chip platforms and organoid models, which better capture cell-cell interactions and tissue-level phenotypes. Despite these advances, effective disease-modifying therapies remain elusive. Recent clinical trial setbacks highlight the need for improved trial design alongside robust, translational iPSC models that can better predict therapeutic response. Nonetheless, the outlook is promising as large iPSC patient cohorts, quantitative phenotyping combined with genetically informed patient stratification, and reverse translational research are beginning to close the gap between in vitro discovery and clinical testing. In this review, we summarize the major advances in iPSC technology and highlight key iPSC-based studies of sporadic ALS. We further discuss emerging examples of iPSC-informed therapeutic strategies and outline the challenges associated with translating iPSC-derived mechanistic insights and pharmacological findings into successful clinical therapies.}, }
@article {pmid41675725, year = {2026}, author = {Patel, T and Henna, F and Sharif, I and Javed, I and Mustafa, F and Sharif, H and Nasir, F and Javaid, M and Usman, SF and Hanani, C and Anand, N}, title = {A narrative review on the therapeutic potential of stem cells in neurodegenerative diseases: advances, insights, and challenges.}, journal = {Annals of medicine and surgery (2012)}, volume = {88}, number = {2}, pages = {1441-1453}, pmid = {41675725}, issn = {2049-0801}, abstract = {BACKGROUND: Neurodegenerative diseases (NDs) such as Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD) are set apart by progressive neuronal loss and concomitant functional decline. Traditional therapies are equipped with only symptomatic relief, devoid of neurorestorative properties. Stem-cell-based therapies have the potential to revolutionize neurological care by replenishing lost cells, mitigating inflammation, and fostering a neuroprotective environment.<br><br>OBJECTIVES: This narrative review aims to appraise the treatment potential of various stem cell types in managing NDs, highlighting their functional pathways, delivery methods, and current experimental validation.<br><br>METHODS: A comprehensive literature search was carried out based on data retrieved from PubMed, The Cochrane Library, and ClinicalTrials.gov. Thirty-one studies that fulfill PICO criteria and only English-language publications are incorporated in this review. No part of the study design, data collection, analysis, or interpretation was conducted using artificial intelligence.<br><br>RESULTS: Stem cells, including embryonic stem cells, mesenchymal stem cells (MSCs), induced pluripotent stem cells, and neural stem cells, possess distinctive regenerative properties. MSC-derived exosomes can traverse the blood-brain barrier and improve nerve cell longevity. Administration routes such as intravenous, intranasal, and direct brain transplantation are being studied. Neurodegenerative conditions such as PD, AD, HD, and ALS have been widely studied for therapeutic benefits.<br><br>CONCLUSION: Regardless of their potential, stem cell therapies raise health risks, including neoplastic growth and immunological incompatibility, alongside bioethical issues. Developments in genetic modification, nanotechnology, and preconditioning strategies are being analyzed to optimize outcomes. Long-term research, harmonization of protocols, and extended patient follow-up are essential for the safe and effective development of medical applications.}, }
@article {pmid41674784, year = {2025}, author = {Yashooa, RK and Nabi, AQ and Smail, SW and Azeez, SS and Nooh, WA and Mustafa, SA and Al-Farha, AA and Capitanio, N and Shekha, MS}, title = {CRISPR-Cas technologies in neurodegenerative disorders: mechanistic insights, therapeutic potential, and translational challenges.}, journal = {Frontiers in neurology}, volume = {16}, number = {}, pages = {1737468}, pmid = {41674784}, issn = {1664-2295}, abstract = {CRISPR-Cas genome-editing technologies have emerged as powerful tools for precise DNA and RNA modulation, offering promising therapeutic strategies for neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). This review critically evaluates current CRISPR/Cas applications in neurodegeneration, with emphasis on mechanistic insights, therapeutic outcomes, and translational feasibility. Preclinical and early translational studies demonstrate that CRISPR-Cas platforms can correct pathogenic mutations, suppress toxic gene expression, and restore neuronal function. Advanced modalities, including base and prime editing, CRISPRi/a, and RNA-targeting Cas systems, improve precision and reduce genomic damage, which is particularly advantageous in post-mitotic neurons. Emerging CRISPR-based diagnostics (e.g., SHERLOCK and DETECTR), AI-assisted sgRNA design, and machine-learning approaches for predicting off-target effects further enhance the safety, stratification, and monitoring of CRISPR therapeutics. In parallel, patient-derived brain organoids and assembloids provide scalable human-relevant platforms for mechanistic studies and preclinical validation. Despite this progress, major challenges remain, including efficient delivery across the blood-brain barrier, immune responses, long-term safety, and ethical and regulatory considerations. Overall, CRISPR-Cas technologies hold strong potential as disease-modifying interventions for neurodegenerative disorders, provided that advances in delivery systems, artificial intelligence integration, and regulatory oversight continue to evolve toward clinical translation.}, }
@article {pmid41673769, year = {2026}, author = {Sharma, S and Vandenakker, A and Cortés-Pérez, C and Milne, S and Douville, RN}, title = {Implications of virus-induced stress granules in tauopathies.}, journal = {Translational neurodegeneration}, volume = {15}, number = {1}, pages = {4}, pmid = {41673769}, issn = {2047-9158}, support = {#2401-3152//St. Boniface Hospital Foundation/ ; RGPIN-2016-05761//Natural Sciences and Engineering Research Council of Canada/ ; }, mesh = {Humans ; *Tauopathies/metabolism/virology/pathology ; *Stress Granules/metabolism/virology ; Animals ; *tau Proteins/metabolism ; *Virus Diseases/metabolism/complications ; }, abstract = {Tauopathies are characterized by aberrant tau structure and function, which is associated with neurodegenerative dementias, such as Alzheimer's disease, Pick's disease, and frontotemporal dementia, as well as the motor neuron disease amyotrophic lateral sclerosis. Consistent association of these neurodegenerative conditions with viruses suggests an interplay between viral activity and the development of tauopathy. In this review, we explore how tau dysregulation may facilitate viral activity, and conversely, how viruses may drive tauopathy. We further discuss how stress granules (SGs) are a likely hub for the interactions between tau and viral components, leading to tau deregulation. Within the network of SG proteins analyzed, 15 proteins were identified to be both tau interactors and implicated in viral processes, having dual functionality. These SG proteins are further discussed in terms of their relationship with tauopathy, viral replication, and neurodegeneration. Concrete examples of synergistic and competing effects between tau and viruses are highlighted, revealing both pathological and protective mechanisms. This dichotomy underscores a complexity that is both disease- and virus-specific, within the context of SG biology and tau pathology. While the viral involvement in tauopathies could be considered detrimental, it may provide insights into antiviral therapeutics to target the accumulation and misfolding of tau in these neurodegenerative diseases.}, }
@article {pmid41672134, year = {2026}, author = {Maneu, V and García, AG}, title = {P2X7 receptors as targets for neuroprotection.}, journal = {Neuropharmacology}, volume = {289}, number = {}, pages = {110877}, doi = {10.1016/j.neuropharm.2026.110877}, pmid = {41672134}, issn = {1873-7064}, abstract = {In this review we explore the potential of P2X7 receptor blockers to elicit neuroprotection. This conjecture is based on a reasonably well-established role of this receptor in activating glial cells to maintain a chronic low-level neuroinflammatory state in the brain of patients suffering some neurodegenerative diseases (NDDs). In this context we briefly discuss evidence supporting the role of P2X7 receptors (P2X7) in the pathogenesis of Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, multiple sclerosis, and retinal degeneration. From a pathogenic point of view these diseases have specific features but all share a low level neuroinflammatory state with microglia activation and enhanced P2X7 expression. Next, we comment on available P2X7 blockers with central nervous system (CNS) target engagement. Then, we deal with the proof-of-concept concerning the potential of some blockers to mitigate the neuroinflammatory state in preclinical models of the target diseases above mentioned. We follow with a discussion of the scarce number of clinical trials done with some P2X7 blockers in inflammatory diseases. Finally, we discuss the current discrepancy between promising preclinical data and the limited number of clinical trials exploring P2X7 antagonists in NDDs. We provide some clues that may boost clinical trials with single P2X7 blockers but particularly, with their association with other medicines currently being used or that are intended to be prescribed in the treatment of NDDs.}, }
@article {pmid41564770, year = {2026}, author = {Lee, H and Jo, Y and Jung, M and Lee, JH and Kim, TH and Lee, J and Kim, DJ and Rahmati, M and Smith, L and Pizzol, D and Son, Y and Park, J and Ahn, SH and Yon, DK and Choi, DW and Kang, J}, title = {Heavy metal exposure and all health outcomes: An umbrella review of meta-analyses.}, journal = {Journal of hazardous materials}, volume = {503}, number = {}, pages = {141141}, doi = {10.1016/j.jhazmat.2026.141141}, pmid = {41564770}, issn = {1873-3336}, mesh = {Humans ; *Metals, Heavy/toxicity ; *Environmental Exposure/adverse effects ; Meta-Analysis as Topic ; *Environmental Pollutants/toxicity ; Female ; Arsenic ; }, abstract = {We aimed to systematically evaluate the strength and credibility of evidence linking exposure to five major heavy metals, including arsenic, cadmium, lead, mercury, and chromium, with health outcomes (PROSPERO, CRD420251169899). Literature searches of PubMed/Embase, CINAHL, and Google Scholar up to April 20, 2025, identified meta-analyses of observational studies assessing these associations. Effect sizes were recalculated using random-effects models and expressed as equivalent odds ratios (eOR) with 95 % confidence intervals (CIs). The methodological quality of the included reviews was assessed using the AMSTAR2, and the credibility of associations was graded according to predefined criteria: Class I (convincing), Class II (highly suggestive), Class III (suggestive), Class IV (weak), and non-significant (NS). A total of 35 meta-analyses encompassing 103 health outcomes were included. Arsenic exposure was associated with melanoma (eOR 1.50 [95 % CI, 1.0-2.24], CE=IV), digestive cancers (1.23 [1.07-1.41], CE=III), gestational diabetes mellitus (1.47 [1.11-1.95], CE=III), hypertension (1.15 [1.06-1.24], CE=III), and preterm birth (1.12 [1.04-1.21], CE=III). Lead exposure showed significant associations with autistic disorder in children (12.70 [3.93-41.10], CE=IV), hearing loss (7.55 [6.69-8.53], CE=III), age-related eye disease (9.80 [1.72-55.85], CE=IV), and amyotrophic lateral sclerosis (1.46 [1.16-1.83], CE=III). Mercury exposure was linked to increased risk in membranous nephropathy (5.75 [1.54-21.44], CE=IV) and thyroid cancer (1.90 [1.55-2.33], CE=IV). Cadmium exposure was associated with renal cancer (1.47 [1.26-1.71], CE=II), cardiovascular disease (1.33 [1.05-1.69], CE=IV), stroke (1.36 [1.10-1.68], CE=III), diabetes mellitus (1.27 [1.07-1.52], CE=III), fracture risk (1.30 [1.13-1.49], CE=III), and age-related eye disease (113.26 [16.86-760.68], CE=III). Chromium exposure was associated with stomach cancer (1.28 [1.16-1.41], CE=I), supporting convincing evidence. Overall, exposures to these metals were consistently associated with diverse diseases across organ systems and life stages, suggesting proactive implications against heavy metal exposures.}, }
@article {pmid41666800, year = {2026}, author = {Maidi, AZM and Suram, RP and Deniz, Y and An, SL and Hong, Y}, title = {Heart rate variability as a non-invasive biomarker of autonomic dysfunction in amyotrophic lateral sclerosis: A systematic review and meta-analysis.}, journal = {Autonomic neuroscience : basic &amp; clinical}, volume = {264}, number = {}, pages = {103393}, doi = {10.1016/j.autneu.2026.103393}, pmid = {41666800}, issn = {1872-7484}, abstract = {OBJECTIVE: This study assessed heart rate variability (HRV) alterations in amyotrophic lateral sclerosis (ALS) patients compared to healthy control groups using both frequency-domain and time-domain HRV parameters.<br><br>METHODS: A systematic review and meta-analysis were conducted using studies retrieved from PubMed, Embase, Web of Science, and Cochrane Library databases up to November 13, 2024. Fourteen studies were included in the qualitative synthesis and eight in the quantitative analysis.<br><br>RESULTS: ALS patients exhibited significantly reduced Low Frequency (LF) and High Frequency (HF) HRV parameters compared to healthy controls (p&#xa0;<&#xa0;0.001 and p&#xa0;=&#xa0;0.02, respectively). Time-domain parameters also showed significant reductions: RMSSD (p&#xa0;<&#xa0;0.001), SDNN (p&#xa0;<&#xa0;0.001), and pNN50% (p&#xa0;=&#xa0;0.01). Despite an overall decrease in HRV, the LF/HF ratio did not show a statistically significant difference (p&#xa0;=&#xa0;0.12).<br><br>CONCLUSION: Patients with ALS demonstrate autonomic dysfunction, evidenced by significant reductions in key time-domain (RMSSD, SDNN, pNN50%) and frequency-domain (LF, HF) parameters, suggesting impaired parasympathetic modulation. HRV may serve as a valuable, non-invasive biomarker for the early detection and management of cardiorespiratory complications in ALS.}, }
@article {pmid41665706, year = {2026}, author = {Giacomini, PS and Voss, P and Devonshire, V and Schneider, R and Macaron, G and Hussein, S and Blanchette, F and de Villers-Sidani, &#xc9;}, title = {Eye tracking as a digital biomarker in neurodegenerative diseases.}, journal = {Journal of neurology}, volume = {273}, number = {2}, pages = {133}, pmid = {41665706}, issn = {1432-1459}, mesh = {Humans ; *Neurodegenerative Diseases/diagnosis/physiopathology/complications ; Biomarkers ; *Eye-Tracking Technology ; *Eye Movements/physiology ; }, abstract = {Oculomotor abnormalities are a common finding in neurodegenerative diseases due to degeneration of neural pathways and brain regions involved in controlling eye movements. Pathological changes to the dorsolateral prefrontal cortex, basal ganglia, superior colliculus and cerebellum produce subtle changes in eye-movement metrics that may not be detected by clinical examination. The present review addresses the potential use of eye-movement biomarkers in neurodegenerative conditions such as multiple sclerosis, Parkinson's disease, Alzheimer's disease and other dementias, and amyotrophic lateral sclerosis. Eye-movement metrics such as saccades, anti-saccades, fixation and smooth pursuit are prognostic of disease progression, can differentiate pathologic subtypes as an aid to diagnosis, and enable clinicians to evaluate early worsening of motor and cognitive function. The cost of medical technologies limits their optimal use and accessibility in clinical practice. The shortage of subspecialist neurologists further limits access to care. New eye-tracking technologies incorporated into widely-accessible digital devices such as smart phones and tablets now permit detailed assessments with minimal equipment requirements, providing an important non-invasive and potentially cost-effective method for patient evaluation in routine clinical practice and as an aid to treatment decision-making. Digital biomarkers can be readily employed by healthcare professionals such as family physicians, nurses and pharmacists to bridge the care gaps, potentially providing them with powerful tools that can be broadly adopted to improve the delivery of care to patients with neurodegenerative conditions.}, }
@article {pmid41663779, year = {2026}, author = {Roy, KK and Kumari, R and Upadhyay, AK and Mohanty, S}, title = {Tailoring treatments: pharmacogenomics in the management of neurodegenerative diseases.}, journal = {Acta neurologica Belgica}, volume = {}, number = {}, pages = {}, pmid = {41663779}, issn = {2240-2993}, abstract = {Neurodegenerative diseases like Alzheimer's, Parkinson's, Huntington's, and amyotrophic lateral sclerosis are growing more common worldwide, yet treatment is still poor. Conventional therapies can have unforeseen side effects, produce poor medication reactions, and take longer to work. This persistent treatment gap highlights the need for novel approaches to these disorders' complex distinctions. Pharmacogenomics, which examines how genetic differences affect drug response, is a promising new subject and an urgent solution. Pharmacogenomics tailors medicine selection and administration to each patient's genetic profile, addressing the main causes of poor treatment response and preventable side effects. This research has enabled precision medicine that can improve neurodegenerative disease therapy and reduce harm. In this in-depth research, we examine neurodegenerative disease management issues, pharmacogenomics breakthroughs, and how incorporating genetics to clinical practice can improve outcomes. We examine the latest evidence that genetics affect drug breakdown, efficacy, and toxicity. We also discuss the challenges and opportunities of applying this knowledge. Pharmacogenomic approaches must be widely applied to make medicines for these awful disorders safer, more effective, and really suited to patient needs, according to our compilation.}, }
@article {pmid41657419, year = {2026}, author = {Wang, Z and Huang, J and Yun, D}, title = {Current and emerging therapeutic strategies for amyotrophic lateral sclerosis: from pharmacological approaches to gene and stem cell therapies.}, journal = {Frontiers in neurology}, volume = {17}, number = {}, pages = {1729302}, pmid = {41657419}, issn = {1664-2295}, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that involves upper and lower motor neurons, severely impairing patients' quality of life. The complex interaction of genetic and environmental factors in ALS pathophysiology complicates therapeutic development. Currently available disease-modifying pharmacological therapies for ALS offer limited efficacy, only slowing disease progression to a modest degree. The recent market withdrawal of a previously approved therapy (AMX0035) further underscores the challenges in this field. Biological targets for ALS and related neurodegenerative diseases offer a unique avenue for therapeutic intervention. With the advancement of genetic engineering technology, innovative therapies such as Stem cell therapy and gene therapy are also discussed, offering a promising horizon for ALS treatment. In addition, the management of ALS symptoms plays a key role in improving the daily lives of people with the disease. In this review, we summarize various strategies for treating ALS, providing an overview of the disease.}, }
@article {pmid41653014, year = {2026}, author = {Abrahao, A and Ciepielewska, M and Zinman, L}, title = {Value of Clinical Evidence and Health Economics and Outcomes Research (HEOR) Studies.}, journal = {Muscle &amp; nerve}, volume = {73 Suppl 1}, number = {Suppl 1}, pages = {S7-S12}, pmid = {41653014}, issn = {1097-4598}, support = {//Mitsubishi Tanabe Pharma America, Inc./ ; }, mesh = {Humans ; *Outcome Assessment, Health Care/economics ; *Economics, Medical ; Randomized Controlled Trials as Topic ; Amyotrophic Lateral Sclerosis/therapy/economics ; *Evidence-Based Medicine/economics ; Cost-Benefit Analysis ; }, abstract = {Randomized controlled trials (RCTs) remain the gold standard for establishing the efficacy and safety of new treatments. However, clinical evidence derived from the systematic analysis of real-world data generated through routine clinical practice can complement RCT data by offering insights into treatment performance in broader, more heterogeneous patient populations and clinical care settings. The integration of high-quality clinical evidence into health economics and outcomes research (HEOR) is increasingly important, as it supports healthcare decision-making across multiple stakeholders, including regulatory agencies, payers, clinicians, and patients. Multiple study designs, such as pragmatic trials, hybrid RCTs, external control arms, and observational studies, can provide valuable clinical evidence beyond the controlled trial setting. These data can enhance understanding of comparative effectiveness, patient-reported outcomes, treatment safety, and healthcare utilization and costs. The field of amyotrophic lateral sclerosis offers a compelling example of how clinical evidence derived from global registries and clinical studies has advanced understanding of disease epidemiology, treatment patterns, and the effectiveness of therapies, including riluzole and edaravone. Consequently, this review and the associated supplementary articles are meant to serve as a primer to inform clinicians of the potential contribution of clinical evidence to HEOR studies.}, }
@article {pmid41653010, year = {2026}, author = {Abrahao, A and Zinman, L and Apple, S}, title = {Current and Ongoing Clinical Studies.}, journal = {Muscle &amp; nerve}, volume = {73 Suppl 1}, number = {Suppl 1}, pages = {S26-S28}, pmid = {41653010}, issn = {1097-4598}, support = {//Mitsubishi Tanabe Pharma America, Inc./ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Edaravone/therapeutic use ; *Clinical Trials as Topic ; *Free Radical Scavengers/therapeutic use/administration &amp; dosage ; }, abstract = {This article provides a comprehensive overview of current and ongoing studies evaluating intravenous (IV) edaravone and edaravone oral suspension in the treatment of amyotrophic lateral sclerosis (ALS). In addition to data from clinical practice and post hoc analyses, multiple observational and interventional studies are underway to better understand the efficacy, safety, and biological impact of edaravone in clinical settings. Key studies include SUNRISE Japan, a long-term postmarketing surveillance study of IV edaravone in Japanese patients with ALS; the ALS/Motor Neuron Disease Natural History Study, a longitudinal registry designed to inform clinical trial design and track ALS progression; and the REFINE-ALS study, which is actively collecting biomarker data to elucidate the pathophysiologic mechanisms influenced by edaravone. For edaravone oral suspension, United States Food and Drug Administration approval was supported by Study MT-1186-A01, a phase 3 trial assessing safety and tolerability over 48 weeks, with extension Study MT-1186-A03. Study MT-1186-A02, conducted as an FDA postmarketing commitment, and its extension, Study MT-1186-A04, evaluated whether investigational once daily dosing showed superior efficacy vs. the approved on/off dosing regimen. Collectively, these studies contribute to a growing body of evidence supporting the use of edaravone as a therapeutic option for ALS. They also underscore the importance of continued data collection from both clinical trials and clinical settings to inform optimal treatment strategies and combination therapy approaches as more agents become available in an evolving ALS treatment landscape.}, }
@article {pmid41646005, year = {2026}, author = {Peng, J and Fan, T and Wang, J and Deng, Y and Xu, R}, title = {Current potential biomarkers for Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis: review of literature.}, journal = {Dialogues in clinical neuroscience}, volume = {28}, number = {1}, pages = {17-39}, pmid = {41646005}, issn = {1958-5969}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/blood/metabolism ; *Biomarkers/cerebrospinal fluid/blood ; *Alzheimer Disease/diagnosis/blood/metabolism/cerebrospinal fluid ; *Parkinson Disease/diagnosis/blood/metabolism/cerebrospinal fluid ; }, abstract = {INTRODUCTION: Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS) are several common neurodegenerative diseases (NDs). At present, is the lack of effective diagnosis, progression, prognosis and therapeutic biomarkers. it is a urgent demand to search the relevant confident biomarkers.<br><br>AREA COVERED: This review systematically analysed the potential biomarkers of blood, cerebrospinal fluid, neuroimaing and emerging non-invasive indicators, and synthesises current evidences on the biomarkers of AD, PD and ALS about diagnosis, progression, prognosis and therapeutic, especially diagnosis biomarkers.<br><br>EXPERT COMMENTARY: In this review, we focus on discussing relevant diagnosis, progression, prognosis and therapeutic biomarkers for AD, PD and ALS in recent years, and prospecting the possible future directions of relevant biomarkers.}, }
@article {pmid41645941, year = {2026}, author = {Iammeechai, W and Srikulmontri, T and White, BAA}, title = {Emotional intelligence development in medical education: A scoping review of educational interventions.}, journal = {Medical teacher}, volume = {}, number = {}, pages = {1-14}, doi = {10.1080/0142159X.2026.2621214}, pmid = {41645941}, issn = {1466-187X}, abstract = {Background and aims: Emotional intelligence (EI) is an essential competency for physicians. Medical educators seek educational interventions to cultivate EI in their learners. This scoping review aimed to conceptualize current knowledge about educational interventions for developing EI in medical education. Methods: This study adopted the first five stages of Levac et al.'s scoping review framework, which builds on Arksey and O'Malley's scoping review methodology. The authors accessed three databases-PubMed, CINAHL, and PsycINFO-to review the literature from 2014 to February 2025. Two authors (WI and TS) independently screened the literature for eligibility. A third author (BAAW) resolved any discrepancies. Two authors (WI and BAAW) charted the eligible articles. Results: Of the 638 studies, 64 were eligible. Approximately one-third of eligible studies focused on interventions for medical students. Stress management, leadership, communication, and professionalism were key topics integrated into EI development interventions. Various methods were employed, such as small-group discussions, case-based discussions, and simulations. Most studies used self-rating questionnaires as assessment tools. Half of the studies (56.25%) reported positive impacts from their interventions. Conclusions: The findings could serve as a guide for educators and researchers seeking to implement or study such interventions.}, }
@article {pmid41642483, year = {2026}, author = {Alhajeri, MM and Abukhaled, Y and Alkhanjari, RR and Bassiouni, W and Al-Ali, H and Baig, A and Sembaij, SH and Al Muhairi, FA and Dimassi, Z and Hamdan, H and Abd-Elrahman, KS}, title = {Neuroglial Function and Hormonal Modulation in Neurodegenerative Diseases: The Influence of Sex Hormones.}, journal = {Cellular and molecular neurobiology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10571-026-01674-1}, pmid = {41642483}, issn = {1573-6830}, abstract = {Astrocytes, microglia, and oligodendrocytes, key neuroglial cell types, are essential for central nervous system (CNS) homeostasis, immune regulation, and neuronal support. In neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), glial dysfunction contributes to pathogenesis via chronic inflammation, synaptic disruption, oxidative stress, and impaired myelination. Growing evidence highlights the regulatory influence of sex hormones on glial function. These hormones modulate inflammatory tone, synaptic remodeling, and remyelination, potentially contributing to sex-based differences in disease incidence, progression, and treatment response. This review synthesizes current understanding of glial involvement in neurodegeneration and examines how gonadal hormones interact with astrocytes, microglia, and oligodendrocytes. By integrating glial biology with neuroendocrinology, we propose that hormone-glia interactions represent promising, personalized targets for sex-informed therapies in CNS disorders.}, }
@article {pmid41640615, year = {2026}, author = {Wang, G and Pan, SJ}, title = {Integrative acupoint stimulation within enhanced recovery after endoscopic procedures: Harnessing the neuroimmune axis for enhanced gastrointestinal recovery.}, journal = {World journal of gastroenterology}, volume = {32}, number = {3}, pages = {114048}, pmid = {41640615}, issn = {2219-2840}, mesh = {Humans ; *Acupuncture Points ; Recovery of Function ; *Enhanced Recovery After Surgery ; *Gastrointestinal Tract/innervation/surgery/immunology ; Neuroimmunomodulation ; Randomized Controlled Trials as Topic ; *Perioperative Care/methods ; Hypothalamo-Hypophyseal System/immunology ; *Transcutaneous Electric Nerve Stimulation/methods ; Pituitary-Adrenal System ; *Endoscopy, Gastrointestinal/adverse effects ; Treatment Outcome ; }, abstract = {Enhanced recovery after surgery (ERAS) programs have transformed perioperative care, yet delayed gastrointestinal function and excessive neuroendocrine stress remain major obstacles to optimal recovery. Hong et al's randomized controlled trial embedded acupoint-based neuromodulation - meridian-timed acupoint application combined with transcutaneous electrical acupoint stimulation - within an ERAS framework and demonstrated accelerated gastrointestinal recovery accompanied by endocrine attenuation. This article offers a structured critical appraisal of the trial, emphasizing methodological rigor, mechanistic plausibility, and alignment with ERAS core principles of stress mitigation, functional restoration, and patient experience. The observed reductions in norepinephrine, cortisol, and aldosterone suggest modulation of the hypothalamic-pituitary-adrenal axis as a key mediator of benefit. Future research priorities include multicenter, sham-controlled validation; integration of autonomic and inflammatory biomarkers (heart rate variability, interleukin-6, tumor necrosis factor-α, C-reactive protein); and pragmatic evaluation of cost-effectiveness and acceptability. Positioning acupoint stimulation within precision-integrative perioperative care could advance ERAS from a recovery protocol to a system of host-response modulation. Integrative acupoint neuromodulation thus represents a biologically coherent, low-risk, and scalable strategy for enhancing resilience, accelerating gastrointestinal recovery, and improving surgical outcomes worldwide.}, }
@article {pmid41640104, year = {2026}, author = {Karros, M and DiFulco, M and Nogid, A}, title = {Tofersen: A Novel Option for the Treatment of Amyotrophic Lateral Sclerosis.}, journal = {The Annals of pharmacotherapy}, volume = {}, number = {}, pages = {10600280251408862}, doi = {10.1177/10600280251408862}, pmid = {41640104}, issn = {1542-6270}, abstract = {OBJECTIVE: This review summarizes current evidence on the efficacy and safety of tofersen (Qalsody) in treating amyotrophic lateral sclerosis (ALS).<br><br>DATA SOURCES: PubMed, MEDLINE, Google Scholar, and ClinicalTrials.gov were searched using the keywords: Qalsody, BIIB067, antisense oligonucleotides, SOD1, and amyotrophic lateral sclerosis. Articles published from inception to November 2025 were included.<br><br>English-language studies assessing the pharmacokinetics, pharmacology, efficacy, and safety of tofersen were included. Prescribing information and real-world evidence were also reviewed.<br><br>DATA SYNTHESIS: Tofersen is an intrathecally administered antisense oligonucleotide targeting superoxide dismutase 1 (SOD1) mRNA. Early trials demonstrate dose-dependent reductions in cerebrospinal fluid (CSF) SOD1 protein levels of -33% and slower ALS Functional Rating Scale (ALSFRS-R) decline compared to placebo (-1.19 vs -5.63 points). In Phase 3 trials, tofersen reduced CSF SOD1 by 29% and plasma neurofilament light chain (NfL) by 60%, while biomarkers increased in the placebo group. There was no significant difference in ALSFRS-R decline between tofersen and placebo (-6.98 vs -8.14; P = 0.97). Real-world data show favorable patient-related outcomes and improvement in ALSFRS-R. Adverse effects are primarily lumbar puncture related with serious neurologic events documented in 7% of tofersen recipients.Relevance to Patient Care and Clinical Practice in Comparison to Existing Drugs:As the first Food and Drug Administration (FDA)-approved gene-directed therapy for SOD1 ALS, tofersen directly targets the underlying genetic cause. Barriers include the need for genetic confirmation and intrathecal administration.<br><br>CONCLUSION: Tofersen provides a promising targeted treatment option for pathogenic SOD1 ALS. Ongoing studies will clarify its long-term clinical impact.}, }
@article {pmid41639687, year = {2026}, author = {Zhang, N and Su, WM and Chen, T and Zhang, Q and Cao, B and Wang, Y and Chen, YP}, title = {From pathogenesis to therapy: the emerging role of regulatory T cells in amyotrophic lateral sclerosis.}, journal = {Journal of neuroinflammation}, volume = {23}, number = {1}, pages = {50}, pmid = {41639687}, issn = {1742-2094}, support = {82371422//National Natural Science Fund of China/ ; 2022YFC2703101//National Key Research and Development Program of China/ ; 2023HXFH032//1&#xb7;3&#xb7;5 project for disciplines of excellence Clinical Research Fund, West China Hospital, Sichuan University/ ; }, abstract = {UNLABELLED: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive loss of motor neurons in the brain and spinal cord, with a pathogenesis that remains incompletely understood. Increasing evidence in recent years has highlighted the pivotal role of neuroinflammation in ALS, in which regulatory T cells (Tregs) emerge as key modulators of the neuroimmune response. This review systematically summarizes recent advances in understanding Treg biology in ALS, including their dynamic alterations across different disease stages and their potential immunoregulatory mechanisms, while also highlighting ongoing clinical trials and emerging cellular therapeutic strategies targeting Tregs. Current evidence suggests that Tregs not only participate in the immunopathology of ALS but also represent a promising target for therapeutic intervention. Nevertheless, there are still significant challenges, including incomplete mechanistic insights, limited clinical validation and obstacles to the implementation of Treg-based therapies. Overall, Treg research in ALS provides valuable directions for elucidating disease mechanisms and developing novel immune-based interventions.<br><br>GRAPHICAL ABSTRACT: [Image: see text]}, }
@article {pmid41635116, year = {2026}, author = {Wang, Y and Lipton, SA}, title = {Aberrant Protein S-Nitrosylation Mimics the Effect of Rare Genetic Mutations in Neurodegenerative Diseases.}, journal = {Journal of neurochemistry}, volume = {170}, number = {2}, pages = {e70365}, doi = {10.1111/jnc.70365}, pmid = {41635116}, issn = {1471-4159}, support = {DP1 DA041722/DA/NIDA NIH HHS/United States ; R01 DA048882/DA/NIDA NIH HHS/United States ; ReMIND-L DISC4 16292//California Institute for Regenerative Medicine/ ; R01 AG056259/AG/NIA NIH HHS/United States ; R01 AG078756/AG/NIA NIH HHS/United States ; R35 AG071734/AG/NIA NIH HHS/United States ; R56 AG065372/AG/NIA NIH HHS/United States ; RF1 AG057409/AG/NIA NIH HHS/United States ; U01 AG088679/AG/NIA NIH HHS/United States ; /NH/NIH HHS/United States ; /NH/NIH HHS/United States ; }, mesh = {Humans ; *Neurodegenerative Diseases/genetics/metabolism ; Animals ; *Mutation/genetics ; *Protein Processing, Post-Translational/genetics ; }, abstract = {Neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease/Lewy body dementia (PD/LBD), and amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) are driven by complex interactions of genetic and environmental factors. While genome wide association studies (GWAS) have uncovered a number of risk gene variants (e.g., APOE, SNCA [encoding α-synuclein], and protein disulfide isomerase [PDI]), these genetic factors alone cannot fully explain disease onset or progression. Emerging evidence suggests that post-translational modifications of proteins, particularly S-nitrosylation (SNO), act as a critical link between environmental stress and neurodegenerative pathology. Here, we review data showing that while physiological protein SNO regulates diverse neuronal processes, aberrant SNO, occurring very commonly in the diseased brain, can disrupt protein function in ways that mimic the deleterious effects of rare genetic mutations. We advance the concept of "mutational mimicry," whereby aberrant SNO of key neuronal or glial proteins reproduces the functional consequences of known specific genetic mutations, ultimately converging on common pathways of synaptic dysfunction emanating from mitochondrial and metabolic impairment, proteostasis, neuroinflammation, and so on. Supporting this framework, proteomic analyses show significant overlap between abnormally S-nitrosylated proteins in diseased brains and known genetic risk factors in AD and PD/LBD as well as in ALS. By linking redox biology to human genetics, this review highlights how environmental factors can phenocopy or enhance genetic susceptibilities. Understanding this convergence not only provides novel insight into disease mechanisms but also suggests new therapeutic targets to intervene in these convergent pathways with the goal of halting neurodegenerative processes.}, }
@article {pmid41633676, year = {2025}, author = {Šoša, I and Sergi, CM}, title = {Genomics for Sudden Cardiac Death: A Review of the Topic and Call for Increased Professionalism in Clinico-Molecular Autopsy and Forensic Laboratory Sciences.}, journal = {Annals of clinical and laboratory science}, volume = {55}, number = {6}, pages = {859-868}, pmid = {41633676}, issn = {1550-8080}, mesh = {Humans ; *Death, Sudden, Cardiac/pathology ; *Genomics/methods ; Autopsy ; *Professionalism ; Gene Frequency ; *Forensic Genetics ; Genome, Human/genetics ; }, abstract = {In 2001, the first draft sequence of the human genome was released, the culmination of a decade-long, multibillion-dollar effort. Since then, an OMICs platform has been proposed to further evaluate and edit the human genome for diagnostic and therapeutic purposes. The Human Genome Project opened a Pandora's box, expanding the forensic laboratory physicians' toolbox. Kinship analysis has been used extensively for parentage testing and identifying cases of human remains and missing persons. The Combined DNA Index System has played a significant role in forensic DNA databases. Nanopore sequencing and improved genomic tools aid enormously in identifying amplicons from degraded samples. The application of genomics in determining the potential channelopathies of sudden cardiac death (SCD) has been an enormous step forward in recent years in forensic histopathology. We reviewed the literature. Kong et al.'s meta-analysis of the mean allele frequencies of SCN5A, NOS1AP, KCNH2, KCNE1, and KCNQ1 genes across Black, Caucasian, Asian, and Hispanic ethnicities has been pivotal to forensic science in the last decade. The authors used sequenced genomic data from the Exome Aggregation Consortium to compare allele frequencies between different ethnicities. They found that Asians had the highest overall mean allele frequencies for NOS1AP and SCN5A, Caucasians had the highest KCNH2 frequency, and Hispanics had the highest KCNQ1 frequency. In 2026, the call for increased professionalism in clinico-molecular autopsy and forensic laboratory sciences is driven by rapid technological advancements (e.g., forensic molecular genomic autopsies), critical workforce shortages in some geographical areas, and the increasing complexity of death investigations. This professionalization focuses on standardizing molecular protocols, enhancing ethical frameworks, and addressing the need for specialized interdisciplinary expertise.}, }
@article {pmid41629214, year = {2026}, author = {Malard, F}, title = {Transcript-Level Modulation of O-GlcNAc Transferase for Aging-Related Neurodegenerative Diseases.}, journal = {Chembiochem : a European journal of chemical biology}, volume = {27}, number = {2}, pages = {e202500774}, pmid = {41629214}, issn = {1439-7633}, mesh = {Humans ; *N-Acetylglucosaminyltransferases/genetics/metabolism ; *Neurodegenerative Diseases/metabolism/genetics/drug therapy ; *Aging/metabolism/genetics ; RNA, Messenger/metabolism/genetics ; RNA Splicing ; Animals ; }, abstract = {The O-GlcNAc Transferase (OGT) is responsible for the addition of β-O-linked N-acetyl-D-glucosamine (O-GlcNAc) to serine and threonine residues, thereby regulating more than 8000 human proteins through O-GlcNAcylation. In the brain, reduced O-GlcNAc levels, which can arise from insufficient OGT activity, have been increasingly linked to aging-related neurodegenerative diseases such as Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis. While current strategies focus on restoring O-GlcNAc levels via O-GlcNAcase (OGA) inhibition, recent discoveries highlight transcript-level regulation of OGT as a direct and promising therapeutic target. This concept article explores the role of intron detention and decoy exon-mediated splicing repression in limiting OGT pre-mRNA maturation and proposes the use of antisense oligonucleotides or selective splicing factor degraders to promote productive splicing and nuclear export of OGT mRNA. By enhancing OGT expression independently of O-GlcNAc feedback, these approaches aim to restore proteostasis and improve resilience to neurodegeneration, offering a novel therapeutic approach for aging-related neurodegenerative diseases.}, }
@article {pmid41569095, year = {2026}, author = {Charbonnel, T and Richard, E and Dupuis, A and Palla, M and Vourc'h, P and Corcia, P and Al Ojaimi, Y and Blasco, H}, title = {The preclinical discovery and development of edaravone for the treatment of amyotrophic lateral sclerosis: what lessons have we learnt?.}, journal = {Expert opinion on drug discovery}, volume = {21}, number = {2}, pages = {147-160}, doi = {10.1080/17460441.2026.2619067}, pmid = {41569095}, issn = {1746-045X}, mesh = {*Edaravone/pharmacology/administration &amp; dosage ; *Amyotrophic Lateral Sclerosis/drug therapy/physiopathology ; Humans ; Animals ; *Neuroprotective Agents/pharmacology/administration &amp; dosage ; Disease Models, Animal ; Free Radical Scavengers/pharmacology/administration &amp; dosage/pharmacokinetics ; Drug Development/methods ; Drug Discovery/methods ; Oxidative Stress/drug effects ; Mice, Transgenic ; Mice ; Drug Evaluation, Preclinical ; Blood-Brain Barrier/metabolism ; }, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron loss, with limited therapeutic options. Among the few approved drugs, edaravone, a free radical scavenger developed originally for ischemic stroke, has attracted particular attention for its ability to counteract oxidative stress, a key driver of neurodegeneration. Its amphipathic structure and ability to cross the blood-brain barrier support its potential neuroprotective action.<br><br>AREAS COVERED: The authors discuss preclinical studies demonstrating edaravone's ability to reduce oxidative damage, preserve mitochondrial function, and modulate neuroinflammatory responses in ALS cellular and animal models. They discuss variations in dosage, timing, and disease models that produced heterogeneous results. In transgenic mice, edaravone may delay symptom onset and modestly extend survival, but these effects are inconsistent and often limited to early disease stages.<br><br>EXPERT OPINION: Clinically, edaravone provides modest benefits in a subset of patients, reflecting the translational gap between preclinical efficacy and clinical relevance. This case highlights broader challenges in ALS drug discovery, including limited model predictivity, methodological variability, and lack of patient stratification. The edaravone experience highlights key lessons for future neuroprotective approaches: the importance of standardized preclinical design, integration of human-based models, early pharmacokinetic validation, and biomarker-driven trials to advance precision neuroprotection in ALS.}, }
@article {pmid41622338, year = {2026}, author = {Salehcheh, M and Nikravesh, M and Aghebat-Bekheir, S and Matin, M}, title = {Manganese concentrations in biological matrices and amyotrophic lateral sclerosis (ALS): a systematic review and meta-analysis.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {47}, number = {2}, pages = {216}, pmid = {41622338}, issn = {1590-3478}, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/blood ; Humans ; *Manganese/blood/metabolism/analysis ; }, abstract = {BACKGROUND: Manganese (Mn) is an essential but neurotoxic trace element implicated in neurodegenerative disorders. Its association with amyotrophic lateral sclerosis (ALS) remains uncertain. We conducted a systematic review and meta-analysis to evaluate whether Mn concentrations differ between ALS patients and healthy controls.<br><br>METHODS: We systematically searched PubMed, EMBASE, Web of Science, and Scopus for observational studies comparing Mn concentrations between ALS patients and healthy controls. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were pooled using a random-effects model. Heterogeneity was assessed with the I&#xb2; statistic, and publication bias was evaluated by Egger's test.<br><br>RESULTS: Twelve studies (446 ALS cases, 652 controls) measuring Mn in blood, serum, cerebrospinal fluid (CSF), hair, urine, toenail, plasma, or tissue were included. The pooled SMD was 0.05 (95% CI: -&#x2009;0.20 to 0.30; p&#x2009;=&#x2009;0.68; I&#xb2; = 71.7%), indicating no significant difference in Mn concentrations. Subgroup analyses by biological matrix and analytical method showed no consistent pattern; meta-regression identified analytical method as a significant source of heterogeneity.<br><br>CONCLUSION: No publication bias was detected (Egger's p&#x2009;=&#x2009;0.53). Peripheral Mn concentrations do not differ significantly between ALS patients and controls. Future research should employ longitudinal and CNS-targeted approaches, incorporating occupational exposure assessment and standardized analytical protocols.}, }
@article {pmid41621017, year = {2026}, author = {Aynaashe, A and Kursula, P}, title = {Genetic commonalities between rare subtypes of ALS and CMT: insights into molecular mechanisms of neurodegeneration.}, journal = {Amino acids}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00726-026-03500-w}, pmid = {41621017}, issn = {1438-2199}, abstract = {Amyotrophic lateral sclerosis (ALS) and Charcot-Marie-Tooth disease (CMT) are two distinct neurodegenerative disorders. While ALS is characterised by rapidly progressive motor neuron degeneration, leading to severe complications and death, CMT as a peripheral neuropathy is less severe, and patients have a longer life span, although with a compromised quality of life. Despite their clinical differences, current knowledge suggests that familial ALS (fALS) and CMT may share common genetic and molecular mechanisms. We aimed to identify shared genes mutations and molecular pathways between fALS and CMT through a literature and database search. Thirteen genes were identified, involved in distinct cellular processes: axonal transport (DYNC1H1, KIF5A, SPG11, DCTN1), protein homeostasis (NEFH, VCP, SOD1), RNA metabolism (GARS, SETX), cellular stress response (HSPB1, FIG4), and mitochondrial function (MFN2, CHCHD10). While these linkages to the two diseases are rare for each gene, understanding possible mechanistic commonalities at the molecular level can initiate new research directions, help in identifying additional common genes between neurodegenerative disorders, and improve diagnostics.}, }
@article {pmid41619791, year = {2026}, author = {Yazdani, S and Seitz, C and Andersson, J and Ingre, C and Fang, F and Lovik, A}, title = {Methodological considerations in the analysis of survival data in amyotrophic lateral sclerosis.}, journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration}, volume = {}, number = {}, pages = {1-12}, doi = {10.1080/21678421.2026.2615111}, pmid = {41619791}, issn = {2167-9223}, abstract = {Survival outcomes are commonly analyzed in studies with data from patients with progressive, neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS). Given the fast progression of ALS, survival analyses are, however, often difficult to perform and interpret. In this methodological article we demonstrate on real-world data how the choices we make in the study design, data collection, and analysis could influence the results. The factors we consider in this study are length of follow-up, sample size, timing of sample collection, and choice of covariables adjusted for in the models. We further discuss the importance of each of these contributing factors and about how to avoid mistakes in interpreting and reporting survival data in ALS and other rare, progressive diseases.}, }
@article {pmid41558230, year = {2026}, author = {Ye, J}, title = {Beyond binary diagnosis: Key questions on AI accuracy, real-world applicability, and safety in clinical decision support.}, journal = {International journal of medical informatics}, volume = {209}, number = {}, pages = {106292}, doi = {10.1016/j.ijmedinf.2026.106292}, pmid = {41558230}, issn = {1872-8243}, mesh = {*Artificial Intelligence ; *Decision Support Systems, Clinical ; Humans ; *Patient Safety ; }, abstract = {This comment relates to Kücking et al.'s (2026) study on the bidirectional effects of artificial intelligence recommendations and healthcare provider related factors on the accuracy of wound impregnation diagnosis. While acknowledging the valuable contributions of this research, including distinguishing between correct/incorrect artificial intelligence outputs, rigorous simulation design, and emphasis on clinical safety, we have raised key questions to enhance the interpretation of results and real-world translation. The main focuses include the moderating role of artificial intelligence system accuracy in automation bias, external effectiveness in real clinical environments, potential mechanisms for gender differences in diagnostic performance, the impact of visual cue design on decision-making, and the potential of explainable artificial intelligence (XAI) in risk mitigation. This review aims to promote further research and facilitate the safe and effective integration of artificial intelligence based clinical decision support systems (CDSS) into clinical practice.}, }
@article {pmid40740123, year = {2026}, author = {Giacomelli, E and Scirocco, E and Higgins, M and Pilja, A and Paganoni, S and Ho, D}, title = {Research access barriers in amyotrophic lateral sclerosis.}, journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration}, volume = {27}, number = {1-2}, pages = {207-214}, doi = {10.1080/21678421.2025.2539900}, pmid = {40740123}, issn = {2167-9223}, mesh = {*Amyotrophic Lateral Sclerosis/therapy/epidemiology ; Humans ; *Biomedical Research ; *Health Services Accessibility ; }, abstract = {As the general population ages, amyotrophic lateral sclerosis (ALS) incidence and prevalence are expected to rise, and the barriers that limit participation in ALS clinical research studies may increase. In this report, we highlight key challenges and available resources for accessing clinical research. We emphasize the importance of education and engagement among individuals with ALS and their families, clinicians, and researchers. Addressing accessibility and fostering trust in ALS research participation is essential to advance treatments for this devastating disease. We propose practical strategies to overcome participation barriers, including decentralized trial models, remote participation options, and expanded outreach through patient navigators, advisory committees, and digital tools. Strengthening partnerships among individuals with ALS, caregivers, researchers, ALS organizations, regulators, and industry, will help align research efforts with community needs and accelerate therapeutic development.}, }
@article {pmid40517187, year = {2026}, author = {Haro-Martínez, E and Muscolino, E and Moral, N and Duran, J and Fornaguera, C}, title = {Crossing the blood-brain barrier: nanoparticle-based strategies for neurodegenerative disease therapy.}, journal = {Drug delivery and translational research}, volume = {16}, number = {3}, pages = {797-824}, pmid = {40517187}, issn = {2190-3948}, support = {2021 SGR 00537//Ag&#xe8;ncia de Gesti&#xf3; d'Ajuts Universitaris i de Recerca/ ; 2024-LLAV-00042//Ag&#xe8;ncia de Gesti&#xf3; d'Ajuts Universitaris i de Recerca/ ; ICREA Acad&#xe8;mia 2024//Ag&#xe8;ncia de Gesti&#xf3; d'Ajuts Universitaris i de Recerca/ ; 202207-31//Fundaci&#xf3; la Marat&#xf3; de TV3/ ; PID2020-118699GB-100//Agencia Estatal de Investigaci&#xf3;n/ ; Not specified//Fundaci&#xf3;n Ram&#xf3;n Areces/ ; FISDUR-2024//Departament d'Universitats, Recerca i Societat de la Informaci&#xf3;/ ; }, mesh = {Humans ; *Blood-Brain Barrier/metabolism ; *Neurodegenerative Diseases/drug therapy/metabolism ; Animals ; *Nanoparticles/administration &amp; dosage/chemistry ; Drug Delivery Systems ; Drug Carriers/chemistry ; }, abstract = {Neurodegenerative conditions, including Alzheimer's, Parkinson's, amyotrophic lateral sclerosis, and Huntington's disease, represent a critical medical challenge due to their increasing prevalence, severe consequences, and absence of curative treatments. Beyond the need for a deeper understanding of the fundamental mechanisms underlying neurodegeneration, the development of effective treatments is hindered by the blood-brain barrier, which poses a major obstacle to delivering therapeutic agents to the central nervous system. This review provides a comprehensive analysis of the current landscape of nanoparticle-based strategies to overcome the blood-brain barrier and enhance drug delivery for the treatment of neurodegenerative diseases. The nanocarriers reviewed in this work encompass a diverse array of nanoparticles, including polymeric nanoparticles (e.g. micelles and dendrimers), inorganic nanoparticles (e.g. superparamagentic iron oxide nanoparticles, mesoporous silica nanoparticles, gold nanoparticles, selenium and cerium oxide nanoparticles), lipid nanoparticles (e.g. liposomes, solid lipid nanoparticles, nanoemulsions), as well as quantum dots, protein nanoparticles, and hybrid nanocarriers. By examining recent advancements and highlighting future research directions, we aim to shed light on the promising role of nanomedicine in addressing the unmet therapeutic needs of these diseases.}, }
@article {pmid41619021, year = {2026}, author = {Dressler, D and Frevert, J and Johnson, EA and Fink, K and Pellett, S and Pandey, S and Walter, U and Tacik, P and Kanovsky, P and Shahidi, GA and Brüggemann, N and Rosales, RL and Relja, M and Jin, L and Rodriguez, JAS and Pan, L and Francisco, GE and Shang, H and Bai, X and Adib Saberi, F}, title = {Iatrogenic botulism: a risk for botulinum toxin's medical use?.}, journal = {Journal of neural transmission (Vienna, Austria : 1996)}, volume = {}, number = {}, pages = {}, pmid = {41619021}, issn = {1435-1463}, abstract = {Botulinum toxin (BT) is infamous for its extreme toxicity. If it enters the bloodstream, it can cause botulism presenting with a typical pattern of motor and autonomic dysfunction. An international expert panel organised by IAB-Interdisciplinary Working Group for Movement Disorders explored iatrogenic botulism after BT's medical use (IB), reached conclusions and formulated recommendations. When injected into its target tissue, BT binds to gangliosides on cholinergic nerve terminals before it is internalised permanently. Small amounts of BT, however, are circulating within the bloodstream. When BT type B is applied, IB-B occurs frequently, typically affecting the autonomic nervous system. When BT type A is applied, IB-A only occurs in special circumstances, even when high doses are used. We identified 236 patients with IB-A in the literature. All IB-A was mild or moderate and fully reversible. In 212 patients, it occurred with unapproved BT use. In 116 of them, unapproved BT preparations were used, in 81, unapproved indications were treated and in 15, underlying neuromuscular impairment including myasthenia gravis, Lambert-Eaton myasthenic syndrome, amyotrophic lateral sclerosis and spinal muscle atrophy were contraindications for BT use. In 24 patients, IB-A occurred in approved BT use. Their evaluation was frequently incomplete, so that causes for IB-A often remain unclear. They may include presence of differential diagnosis, subclinical neuromuscular impairment and interference with additional diseases. When IB is suspected, proper evaluation is necessary to verify it and to identify its causes. Off-label use is common in BT therapy. However, it should be performed with caution, especially in children and when high doses are applied. High BT doses should not be applied to low volumes of target tissues, in order not to exceed the BT binding capacity.}, }
@article {pmid41618645, year = {2026}, author = {Verhoeff, MC and van Selms, MKA and Lobbezoo, F}, title = {A Personal Exploration of Oral Health in Amyotrophic Lateral Sclerosis (ALS) Through the Eyes of a Multifaceted Authority.}, journal = {Journal of oral rehabilitation}, volume = {}, number = {}, pages = {}, doi = {10.1111/joor.70157}, pmid = {41618645}, issn = {1365-2842}, abstract = {BACKGROUND AND OBJECTIVE: Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease that impairs motor function, including oral musculature, complicating oral hygiene and care. Despite its impact, oral health in ALS patients remains under-addressed. This personal scoping review explores oral health in ALS through the dual lens of Dr. Maurits K.A. van Selms-a dental researcher and ALS patient-highlighting care, research, and education priorities.<br><br>METHODS: Semi-structured interviews were conducted via email with Dr. van Selms, using a topic guide adapted from a prior personal scoping review. The interview covered personal experiences and professional insights into oral health care, research, and education in ALS. Responses were analysed and synthesised into thematic agendas.<br><br>RESULTS: Dr. van Selms emphasised the neglect of oral hygiene in ALS care. He advocated for patient-informed, tailored guidelines based on functional capacity, interdisciplinary collaboration, and improved accessibility to dental services. In research, he called for ethically sensitive, patient-centered studies that reduce the burden of oral care. Educationally, he stressed the need for inclusive training across disciplines and stakeholder levels, promoting self-advocacy and awareness. Instructional materials, such as videos, were recommended to support caregivers and patients.<br><br>CONCLUSION: This personal scoping review underscores the importance of integrating oral health into ALS management. Dr. van Selms' unique perspective reveals gaps in care delivery, research ethics, and education, advocating for interdisciplinary collaboration and proactive guideline development. His insights offer a roadmap for improving oral health outcomes and quality of life in ALS and similar neurodegenerative conditions.}, }
@article {pmid41613186, year = {2025}, author = {An, W and Jin, Z and Li, Y}, title = {Dual role of exosomes in neurodegenerative diseases: a molecular bridge between neuroinflammation and transmission of pathological proteins.}, journal = {Frontiers in neurology}, volume = {16}, number = {}, pages = {1708655}, pmid = {41613186}, issn = {1664-2295}, abstract = {Neurodegenerative diseases (NDDs) are complex disorders characterized by the progressive loss of neuronal function. Their pathological mechanisms involve multiple levels, including neuroinflammation, abnormal protein aggregation, and disrupted cell signaling. Diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS), multiple sclerosis (MS), and prion diseases not only severely impact patients' quality of life but also pose significant challenges for medical research due to their complex pathogenesis and the lack of effective treatments. In recent years, extracellular vesicles (EVs), particularly exosomes, have garnered increasing attention for their critical role in cell-to-cell communication. Exosomes are membrane-enclosed nanovesicles approximately 30-150 nm in diameter that can carry proteins, lipids, nucleic acids, and other bioactive molecules, influencing recipient cells through paracrine or distant signaling. This review aims to summarize the roles of exosomes as mediators of neuroinflammation and as vehicles for intercellular transmission of pathogenic proteins in neurodegenerative diseases.}, }
@article {pmid41612406, year = {2026}, author = {Bigi, A and Chiti, F}, title = {Understanding liquid-liquid phase separation through TDP-43: fundamental principles, subcellular compartmentalisation, and role of solid inclusion formation.}, journal = {Genome biology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s13059-026-03956-9}, pmid = {41612406}, issn = {1474-760X}, support = {#NEXTGENERATIONEU (NGEU) - National Recovery and Resilience Plan (NRRP), Investment PE8&#x2500;Project Age-It: "Ageing Well in an Ageing Society" (D.R. 1557 11.10.2022).//Ministero dell'Universit&#xe0; e della Ricerca/ ; Fondi di Ateneo RICATEN 2024 and RICATEN 2025//Universit&#xe0; degli Studi di Firenze/ ; Fondi di Ateneo RICATEN 2023, RICATEN 2024 and RICATEN 2025//Universit&#xe0; degli Studi di Firenze/ ; }, abstract = {Phase separation is an important process in biology associated with formation of membraneless organelles but possibly related to the emergence of solid inclusions. TDP-43 is a largely studied paradigmatic case, as it forms neuronal cytoplasmic inclusions in neurodegenerative diseases and is an essential component of many membraneless organelles. Here, we review the physicochemical fundamentals of liquid-liquid phase separation (LLPS) of TDP-43 and its fragments in vitro, showing that full-length TDP-43 requires RNA or chaperones to form stable liquid droplets. We describe TDP-43-containing membraneless organelles and the debate on whether these assemblies represent reservoirs for pathological solid inclusion formation.}, }
@article {pmid41605610, year = {2026}, author = {Oreskovic, E and Petzold, A and Petropoulos, IN and Hau, S}, title = {Corneal confocal microscopy as a paraclinical test in neurodegenerative disease: a scoping review.}, journal = {The British journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1136/bjo-2025-328181}, pmid = {41605610}, issn = {1468-2079}, abstract = {Corneal confocal microscopy (CCM) is a non-invasive imaging technique that enables quantification of the corneal sub-basal nerve plexus and has emerged as a potential surrogate biomarker for peripheral neurodegeneration. This scoping review evaluated current evidence on the use of CCM in assessing corneal nerve fibre changes across neurodegenerative diseases (NDDs) and explored its potential as a paraclinical diagnostic and monitoring tool. A comprehensive search of PubMed and Scopus was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines to identify studies reporting quantitative CCM metrics, including corneal nerve fibre density (CNFD), corneal nerve branch density (CNBD) and corneal nerve fibre length (CNFL). Both cross-sectional and longitudinal studies of patients with NDDs were included, and findings were narratively synthesised. 50 studies were included: Parkinson's disease (n=13), multiple sclerosis (n=11), cerebrovascular accidents (n=7), post-COVID-19 neuropathy (n=5), amyotrophic lateral sclerosis (n=4), chronic inflammatory demyelinating polyneuropathy (n=4), Alzheimer's disease (n=3), Fabry disease (n=2) and neurofibromatosis type 1 (n=1). CNFL and CNFD were consistently reduced in Parkinson's disease, multiple sclerosis, cerebrovascular accidents, amyotrophic lateral sclerosis, chronic inflammatory demyelinating polyneuropathy and post-COVID-19 neuropathy, whereas CNBD results were inconsistent. The strongest evidence supported the role of CCM in Parkinson's disease and multiple sclerosis. CNFL and CNFD emerged as the most reliable CCM-derived metrics across NDDs, supporting their potential as objective biomarkers for neurodegeneration. While findings support the potential of CCM as a paraclinical diagnostic tool, methodological heterogeneity in image acquisition, analysis software and study design limited comparability. Standardised imaging and analysis protocols are needed to enable broader clinical application and validation across NDDs.}, }
@article {pmid41604971, year = {2026}, author = {Ahamad, S and Akshinthala, P and Fazal, F and Sah, GK and Khan, MH and Upadhyay, A and Bhat, SA and Hussain, MK}, title = {Small-molecule-based activation of Wnt/β-catenin signaling: An underexplored yet promising strategy for neuroprotection.}, journal = {Bioorganic chemistry}, volume = {170}, number = {}, pages = {109540}, doi = {10.1016/j.bioorg.2026.109540}, pmid = {41604971}, issn = {1090-2120}, abstract = {The Wnt/β-catenin pathway regulates key processes such as neurogenesis, synaptic plasticity, and neuroinflammation, each disrupted in neurodegenerative disorders like AD, PD, ALS, and stroke. Small molecules have shown potential to restore this signaling axis and confer neuroprotection. While these molecules modulate Wnt activity, none has achieved FDA approval, primarily due to poor brain permeability, off-target effects, and insufficient biomarker-based validation. Moreover, current strategies remain disproportionately focused on GSK-3β, with other viable targets, such as DKK1, NOTUM, SFRP-1, sclerostin, and Dvl-CXXC5 or Axin-β-catenin interactions, largely underexplored. Natural products, particularly flavonoids and diterpenoids, offer valuable scaffolds; however, their SAR remain poorly characterized, and promising synthetic leads often lack further development. This review highlights recent pharmacological advances, emerging molecular targets, and key translational barriers. Future success will depend on optimizing pharmacokinetics, improving brain-targeted delivery, and integrating biomarker-driven strategies into clinical trial design.}, }
@article {pmid41604235, year = {2026}, author = {Al-Ameer, HJ and Basheer, NM and H, M and Shankhyan, A and Panigrahi, R and Arora, V and Azizjanov, K and Eshchanov, E and Ataullaev, Z}, title = {Neuroimmune Cross-Talk and Multilevel Cascades in Fentanyl Toxicity: Interplay of Hypoxic Stress, Glial Activation, and Synaptic Dysregulation in Systems-Level Neurodegeneration.}, journal = {Journal of applied toxicology : JAT}, volume = {}, number = {}, pages = {}, doi = {10.1002/jat.70069}, pmid = {41604235}, issn = {1099-1263}, abstract = {Fentanyl, an ultra-potent synthetic opioid, has traditionally been characterized by its acute toxic effects, particularly respiratory depression. However, accumulating research indicates that its neurobiological influence extends far beyond its short pharmacological window, intersecting with several core mechanisms implicated in major neurodegenerative disorders. This review integrates multiscale evidence to propose a unified conceptual framework in which fentanyl may function not only as an acute neurotoxin but also as a putative accelerator of long-term neurodegenerative vulnerability. Drawing from molecular signaling, cellular stress pathways, glial-neuronal cross-talk, neurovascular regulation, synaptic architecture, and large-scale neural networks, we highlight fentanyl's capacity to trigger a convergent cascade encompassing hypoxic-metabolic reprogramming, mitochondrial fragmentation, TLR4-NF-κB-driven inflammation, NLRP3 inflammasome activation, complement-mediated synaptic pruning, astrocytic EAAT2 downregulation, and blood-brain barrier compromise. These alterations propagate through recursive cross-talk loops that progressively diminish neuronal resilience, destabilize oscillatory coherence, and weaken circuit-level adaptability. Importantly, mechanistic overlaps with Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis suggest that fentanyl exposure may be mechanistically associated with processes capable of accelerating disease onset, exacerbating progression, or unmasking latent vulnerabilities, particularly in genetically or metabolically predisposed individuals. By reframing fentanyl as a systems-level destabilizer capable of imprinting persistent neurobiological changes, this model underscores the need for comprehensive biomarker development, longitudinal risk assessment, and targeted neuroprotective interventions. The integrative framework presented herein offers a foundation for predicting the long-term neurological consequences of fentanyl exposure and calls for urgent reconsideration of its role in population-level neurodegenerative risk.}, }
@article {pmid41601803, year = {2025}, author = {An, X and Hou, D and Miao, MY and Zhou, YM and Qi, S and Zhang, L and Li, H and Zhou, JX}, title = {Noninvasive monitoring of inspiratory effort in mechanical ventilation: a dual-database bibliometric analysis from 1990 to 2025.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1747437}, pmid = {41601803}, issn = {2296-858X}, abstract = {INTRODUCTION: This study conducts a bibliometric analysis to map the intellectual structure, evolution, and emerging trends in research on airway pressure-based indexes for monitoring inspiratory effort.<br><br>METHODS: Systematic searches of the Web of Science Core Collection (WOSCC) and Pubmed were performed for publications dated between 1990 and 2025. Bibliometric parameters, including publication trends, country and affiliation contributions, author influence, journal distribution, keyword co-occurrence, and reference co-citation networks, were analyzed using Bibliometrix and CiteSpace.<br><br>RESULTS: The analysis included 291 publications from WOSCC. The annual publication output showed a near U-shaped trend, with an initial decline after the 1990s, followed by a strong resurgence after 2011. Italy was the most productive country, followed by the USA and France. The Institut National de la Sante et de la Recherche Medicale emerged as the leading institution. The journal Chest published the most articles, while the American Journal of Respiratory and Critical Care Medicine had the highest total citations. Laurent Brochard was identified as the most prolific and influential author. Keyword analysis highlighted "occlusion pressure" and "mechanical ventilation" as core themes. Reference co-citation clustering revealed major research domains, including "acute respiratory distress syndrome," "self-inflicted lung injury," and "nasal high flow." Burst detection analysis indicated that "respiratory drive," "lung injury," and "critically ill patients" are emerging research frontiers. Complementary analysis of 242 PubMed clinical studies confirmed these trends and highlighted growing clinical focus on "fluid responsiveness" and "amyotrophic lateral sclerosis."<br><br>CONCLUSION: Research on airway pressure-based indices has evolved from physiological studies into a crucial clinical tool for respiratory monitoring. The field exhibits strong international collaboration and emphasizes core areas, including acute respiratory failure and lung-protective ventilation. Analysis of clinical study data confirms these trends and highlights emerging applications in the assessment of fluid responsiveness and neuromuscular disorders. These findings support the ongoing development of personalized ventilation strategies based on monitoring respiratory effort.}, }
@article {pmid41601624, year = {2025}, author = {Yang, J and Song, X and Yan, S and Li, Q and Yang, W}, title = {The gut microbiota influences neurodegenerative diseases through the gut-brain axis: molecular mechanisms and effects on immune function.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1739329}, pmid = {41601624}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Neurodegenerative Diseases/immunology/microbiology/therapy/metabolism/etiology ; Animals ; *Brain/immunology/metabolism ; *Brain-Gut Axis/immunology ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Prebiotics ; }, abstract = {The pathogenesis of neurodegenerative diseases (NDDs), including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), is complex and multifactorial. Recent studies indicate that the microbiota-gut-brain axis (MGBA) plays a crucial role in the development and progression of NDDs. The MGBA concept reveals a complex bidirectional regulatory network between the gut microbiota and the central nervous system (CNS), linking them through immune, neural, endocrine, and metabolic pathways. This review summarizes the components of the MGBA, communication pathways between gut microbiota and the brain, and mechanisms by which gut microbiota influence the onset and progression of NDDs. Finally, preclinical therapeutic approaches for NDDs are discussed, evaluating preclinical trial data for probiotics, prebiotics, and fecal microbiota transplantation.}, }
@article {pmid41599691, year = {2026}, author = {Zhao, X and Zheng, Y and Cai, X and Yao, Y and Qin, D}, title = {The Expanding Role of Non-Coding RNAs in Neurodegenerative Diseases: From Biomarkers to Therapeutic Targets.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {19}, number = {1}, pages = {}, pmid = {41599691}, issn = {1424-8247}, support = {Y202248634//Zhejiang Provincial Department of Education Project/ ; Y202454271//Zhejiang Provincial Department of Education Project/ ; }, abstract = {Non-coding RNAs have emerged as central regulators of gene expression in neurodegenerative diseases, offering new opportunities for diagnosis and therapy. This review synthesizes current knowledge on microRNAs, long non-coding RNAs, and circular RNAs in Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, emphasizing their roles in synaptic function, proteostasis, mitochondrial biology, and neuroinflammation. We evaluate evidence supporting non-coding RNAs as circulating and tissue-based biomarkers for early detection, disease monitoring, and patient stratification, and we compare analytical platforms and biofluid sources. Mechanistic insights reveal how non-coding RNAs modulate pathogenic protein aggregation, neuronal excitability, immune cell crosstalk, and blood-brain barrier integrity. Translational efforts toward RNA-targeted interventions are reviewed, including antisense oligonucleotides, small interfering RNAs, miRNA mimics and inhibitors, circular RNA decoys, and extracellular vesicle-mediated delivery systems. We discuss pharmacological modulation, delivery challenges, safety concerns, and strategies to enhance specificity and CNS penetration. Finally, we outline emerging computational and multi-omics approaches to prioritize therapeutic targets and propose a roadmap for advancing non-coding RNA research from preclinical models to clinical trials. Addressing biological heterogeneity and delivery barriers will be pivotal to realizing the diagnostic and therapeutic promise of the non-coding transcriptome in neurodegenerative disease. Collaboration across disciplines and rigorous clinical validation are urgently needed.}, }
@article {pmid41599368, year = {2026}, author = {Niziński, P and Szalast, K and Makuch-Kocka, A and Paruch-Nosek, K and Ciechanowska, M and Plech, T}, title = {Experimental Models and Translational Strategies in Neuroprotective Drug Development with Emphasis on Alzheimer's Disease.}, journal = {Molecules (Basel, Switzerland)}, volume = {31}, number = {2}, pages = {}, pmid = {41599368}, issn = {1420-3049}, support = {2022/47/O/NZ7/00155//National Science Centre/ ; }, mesh = {Humans ; *Alzheimer Disease/drug therapy/metabolism/pathology ; *Neuroprotective Agents/pharmacology/therapeutic use ; *Drug Development ; Animals ; *Translational Research, Biomedical ; Disease Models, Animal ; Induced Pluripotent Stem Cells ; }, abstract = {Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), are becoming more prevalent and still lack effective disease-modifying therapies (DMTs). However, translational efficiency remains critically low. For example, a ClinicalTrials.gov analysis of AD programs (2002-2012) estimated ~99.6% attrition, while PD programs (1999-2019) achieved an overall success rate of ~14.9%. In vitro platforms are assessed, ranging from immortalized neuronal lines and primary cultures to human-induced pluripotent stem cell (iPSC)-derived neurons/glia, neuron-glia co-cultures (including neuroinflammation paradigms), 3D spheroids, organoids, and blood-brain barrier (BBB)-on-chip systems. Complementary in vivo toxin, pharmacological, and genetic models are discussed for systems-level validation and central nervous system (CNS) exposure realism. The therapeutic synthesis focuses on AD, covering symptomatic drugs, anti-amyloid immunotherapies, tau-directed approaches, and repurposed drug classes that target metabolism, neuroinflammation, and network dysfunction. This review links experimental models to translational decision-making, focusing primarily on AD and providing a brief comparative context from other NDDs. It also covers emerging targeted protein degradation (PROTACs). Key priorities include neuroimmune/neurovascular human models, biomarker-anchored adaptive trials, mechanism-guided combination DMTs, and CNS PK/PD-driven development for brain-directed degraders.}, }
@article {pmid41599225, year = {2026}, author = {Bernatoniene, J and Kopustinskiene, DM and Casale, R and Medoro, A and Davinelli, S and Saso, L and Petrikonis, K}, title = {Nrf2 Modulation by Natural Compounds in Aging, Neurodegeneration, and Neuropathic Pain.}, journal = {Pharmaceutics}, volume = {18}, number = {1}, pages = {}, pmid = {41599225}, issn = {1999-4923}, support = {S-A-UEI-23-7//Research Council of Lithuania (LMTLT)/ ; }, abstract = {This review summarizes the role of nuclear factor erythroid 2-related factor 2 (Nrf2) as a common link between aging, neurodegeneration, and neuropathic pain. Aging is characterized by oxidative stress and constant inflammation, which coincides with reduced Nrf2 activity and weaker antioxidant responses, increasing vulnerability to diseases. In neurodegenerative disorders-including Alzheimer's, Parkinson's, Huntington's disease, and amyotrophic lateral sclerosis-evidence indicates that impaired Nrf2 signaling contributes to oxidative damage, neuroinflammation, and mitochondrial dysfunction. Furthermore, in neuropathic pain, similar mechanisms are involved, and Nrf2 could play a role as a potential analgesic target because of its role in regulating cellular defense pathways. We also review natural Nrf2 modulators (e.g., flavonoids, other polyphenols, terpenoids, alkaloids), discussing their benefits alongside common translational limitations such as poor solubility, low oral bioavailability, rapid metabolism, and potential safety issues, including possible pro-oxidant effects and chemoresistance. We also outline future directions that should prioritize improving delivery systems, addressing NRF2/KEAP1 gene variations, evaluating combinations with standard therapies, exploring preventive applications, and defining dosing, treatment duration, and long-term safety. Overall, current evidence indicates that Nrf2 modulation is a practical, cross-cutting approach relevant to healthy aging and disease management.}, }
@article {pmid41599185, year = {2026}, author = {Benech, H and Flament, V and Lhotellier, C and Roucairol, C and Joudinaud, T}, title = {New Insights into Drug Development via the Nose-to-Brain Pathway: Exemplification Through Dodecyl Creatine Ester for Neuronal Disorders.}, journal = {Pharmaceutics}, volume = {18}, number = {1}, pages = {}, pmid = {41599185}, issn = {1999-4923}, abstract = {Brain disorders remain a major global health challenge, highlighting the urgent need for innovative therapeutic strategies and efficient drug-delivery approaches. Among alternative routes, intranasal administration has garnered significant interest over recent decades, not only for its systemic delivery but also for its unique ability to bypass the bloodstream and the blood-brain barrier via the Nose-to-Brain (NtB) pathway. While numerous reviews have explored the opportunities and challenges of this route, industrial considerations-critical for successful clinical implementation and commercial development-remain insufficiently addressed. This review provides a comprehensive and critical assessment of the NtB pathway from a drug development and chemistry, manufacturing, and controls perspective, addressing key constraints in pre-clinical-clinical extrapolation, formulation design, device selection, dose feasibility, chronic safety, and regulatory requirements. We also discuss recent advances in neuronal targeting mechanisms, also with a focus on the role of trigeminal nerves. Dodecyl creatine ester (DCE), a highly unstable in plasma creatine prodrug developed by Ceres Brain Therapeutics, is presented as an illustrative case study. Delivered as a nasal spray, DCE enables direct neuronal delivery, exemplifying the potential of the NtB pathway for disorders characterized by neuronal energy deficiency, including creatine transporter deficiency and mitochondrial dysfunction. Overall, the NtB pathway-or, more precisely, the "Nose-to-Neurons" pathway-offers distinct advantages for unstable molecules and metabolic supplementation, particularly in neuron-centric diseases. Its successful implementation will depend on rational molecule design, optimized nasal formulations, appropriate devices, and early integration of industrial constraints to ensure feasibility, scalability, and safety for long-term treatment.}, }
@article {pmid41596533, year = {2026}, author = {Bogus, K and Marchesi, N and Campagnoli, LIM and Pascale, A and Pałasz, A}, title = {Glial Cells as Key Mediators in the Pathophysiology of Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {27}, number = {2}, pages = {}, pmid = {41596533}, issn = {1422-0067}, mesh = {Humans ; *Neurodegenerative Diseases/pathology/metabolism/physiopathology ; *Neuroglia/metabolism/pathology ; Animals ; Microglia/metabolism/pathology ; Astrocytes/metabolism/pathology ; }, abstract = {Neurodegenerative disorders are characterized by progressive neuronal loss and dysfunction, yet increasing evidence indicates that glial cells are central mediators of both disease initiation and progression. Astrocytes, microglia, and oligodendrocyte lineage cells modulate neuronal survival by regulating neuroinflammation, metabolic support, synaptic maintenance, and proteostasis. However, dysregulated glial responses, including chronic microglial activation, impaired phagocytosis, altered cytokine production, and mitochondrial dysfunction, contribute to persistent inflammation and structural degeneration observed across Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease and multiple sclerosis. Recent advances in single-cell and spatial omics have revealed extensive glial heterogeneity and dynamic shifts between neuroprotective and neurotoxic phenotypes, emphasizing the context-dependent nature of glial activity. This review summarizes current knowledge regarding the multifaceted involvement of glial cells in neurodegenerative disorders.}, }
@article {pmid41596063, year = {2025}, author = {Herbert, A}, title = {G-Quadruplexes Abet Neuronal Burnout in ALS and FTD.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {15}, number = {1}, pages = {}, pmid = {41596063}, issn = {2076-3921}, abstract = {Expansion of d(GGGGC)n repeat in the C9ORF72 gene is causal for Amyotrophic Lateral Sclerosis (ALS) and Frontal Temporal Dementia (FTD). Proposed mechanisms include Repeat-Associated Non-AUG translation or the formation of G-quadruplexes (GQ) that disrupt translation, induce protein aggregation, sequester RNA processing factors, or alter RNA editing. Here, I show, using AlphaFold V3 (AF3) modeling, that the TAR DNA-binding protein (TDP-43) docks to a complex of GQ and hemin. TDP-43 methionines lie over hemin and likely squelch the generation of superoxide by the porphyrin-bound Fe. These TDP-43 methionines are frequently altered in ALS patients. Tau protein, a variant of which causes ALS, also binds to GQ and heme and positions methionines to detoxify peroxides. Full-length Tau, which is often considered prone to aggregation and a prion-like disease agent, can bind to an array composed of multiple GQs as a fully folded protein. In ALS and FTD, loss-of-function variants cause an uncompensated surplus of superoxide, which sparks neuronal cell death. In Alzheimer's Disease (AD) patients, GQ and heme complexes bound by β-amyloid 42 (Aβ4) are also likely to generate superoxides. Collectively, these neuropathologies have proven difficult to treat. The current synthesis provides a framework for designing future therapeutics.}, }
@article {pmid41595662, year = {2026}, author = {Stoian, II and Nistor, D and Levai, MC and Popa, DI and Popescu, R}, title = {Directional Modulation of the Integrated Stress Response in Neurodegeneration: A Systematic Review of eIF2B Activators, PERK-Pathway Agents, and ISR Prolongers.}, journal = {Biomedicines}, volume = {14}, number = {1}, pages = {}, pmid = {41595662}, issn = {2227-9059}, abstract = {Background and Objectives: The integrated stress response (ISR) is a convergent node in neurodegeneration. We systematically mapped open-access mammalian in vivo evidence for synthetic ISR modulators, comparing efficacy signals, biomarker engagement, and safety across mechanisms and disease classes. Methods: Following PRISMA 2020, we searched PubMed (MEDLINE), Embase, and Scopus from inception to 22 September 2025. Inclusion required mammalian neurodegeneration models; synthetic ISR modulators (eIF2B activators, PERK inhibitors or activators, GADD34-PP1 ISR prolongers); prespecified outcomes; and full open access. Extracted data included model, dose and route, outcomes, translational biomarkers (ATF4, phosphorylated eIF2α), and safety. Results: Twelve studies met the criteria across tauopathies and Alzheimer's disease (n = 5), prion disease (n = 1), amyotrophic lateral sclerosis and Huntington's disease (n = 3), hereditary neuropathies (n = 2), demyelination (n = 1), and aging (n = 1). Among interpretable in vivo entries, 10 of 11 reported benefit in at least one domain. By class, eIF2B activation with ISRIB was positive in three of four studies, with one null Alzheimer's hAPP-J20 study; PERK inhibition was positive in all three studies; ISR prolongation with Sephin1 or IFB-088 was positive in both studies; and PERK activation was positive in both studies. Typical regimens included ISRIB 0.1-2.5 mg per kg given intraperitoneally (often two to three doses) with reduced ATF4 and phosphorylated eIF2α; oral GSK2606414 50 mg per kg twice daily for six to seven weeks, achieving brain-level exposures; continuous MK-28 delivery at approximately 1 mg per kg; and oral IFB-088 or Sephin1 given over several weeks. Safety was mechanism-linked: systemic PERK inhibition produced pancreatic and other exocrine toxicities at higher exposures, whereas ISRIB and ISR-prolonging agents were generally well-tolerated in the included reports. Conclusions: Directional ISR control yields consistent, context-dependent improvements in behavior, structure, or survival, with biomarker evidence of target engagement. Mechanism matching (down-tuning versus prolonging the ISR) and exposure-driven safety management are central for translation.}, }
@article {pmid41594924, year = {2026}, author = {Bao, Y and Miao, G and He, N and Bao, X and Shi, Z and Hu, C and Liu, X and Wang, B and Sun, C}, title = {Melatonin as a Guardian of Mitochondria: Mechanisms and Therapeutic Potential in Neurodegenerative Diseases.}, journal = {Biology}, volume = {15}, number = {2}, pages = {}, pmid = {41594924}, issn = {2079-7737}, abstract = {Mitochondrial dysfunction is a key early pathological process in neurodegenerative diseases (NDs), leading to oxidative stress, impaired energy metabolism, and neuronal apoptosis prior to the onset of clinical symptoms. Although mitochondria represent important therapeutic targets, effective interventions targeting mitochondrial function remain limited. This review summarizes current evidence regarding the mechanisms by which melatonin protects mitochondria and evaluates its therapeutic relevance, with a primary focus on Alzheimer's disease, Parkinson's disease, and Huntington's disease-the major protagonists of NDs-while briefly covering other NDs such as amyotrophic lateral sclerosis, multiple sclerosis, and prion diseases. Melatonin selectively accumulates in neuronal mitochondria and exerts neuroprotection through multiple pathways: (1) direct scavenging of reactive oxygen species (ROS); (2) transcriptional activation of antioxidant defenses via the SIRT3 and Nrf2 pathways; (3) regulation of mitochondrial dynamics through DRP1 and OPA1; and (4) promotion of PINK1- and Parkin-mediated mitophagy. Additionally, melatonin exhibits context-dependent pleiotropy: under conditions of mild mitochondrial stress, it restores mitochondrial homeostasis; under conditions of severe mitochondrial damage, it promotes pro-survival autophagy by inhibiting the PI3K/AKT/mTOR pathway, thereby conferring stage-specific therapeutic advantages. Overall, melatonin offers a sophisticated mitochondria-targeting strategy for the treatment of NDs. However, successful clinical translation requires clarification of receptor-dependent signaling pathways, development of standardized dosing strategies, and validation in large-scale randomized controlled trials.}, }
@article {pmid41594611, year = {2026}, author = {Dong, C and Lv, D and Dong, Y and Zhang, Z and Li, Q and Chen, Z}, title = {Advances in Cardiolipin Analysis: Applications in Central Nervous System Disorders and Nutrition Interventions.}, journal = {Biomolecules}, volume = {16}, number = {1}, pages = {}, pmid = {41594611}, issn = {2218-273X}, support = {2022CXPT037//the Key R&amp;D Program of Shandong Province, China/ ; 5501290015//the Advanced Researcher Fund of Jiangsu University/ ; 202510299087//National Training Program of Innovation and Entrepreneurship for Undergraduates/ ; }, mesh = {*Cardiolipins/metabolism/analysis ; Humans ; *Central Nervous System Diseases/metabolism/diet therapy ; Animals ; Mitochondria/metabolism ; }, abstract = {Cardiolipin (CL), a unique dimeric phospholipid predominantly enriched in the inner mitochondrial membrane, is a crucial determinant of mitochondrial structure and function. Its content, fatty acyl composition, and oxidation state are associated with mitochondrial bioenergetics, dynamics, and cellular signaling. Disruptions in CL metabolism are increasingly implicated in the pathogenesis of various central nervous system (CNS) disorders, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, epilepsy, and traumatic brain injury. This narrative review summarizes recent advances in the analytical techniques employed for CL analysis. The principles and applications of mass spectrometry-based platforms, nuclear magnetic resonance, Fourier-transform infrared spectroscopy, atomic force microscopy-infrared spectroscopy, and fluorescent probes were discussed, with an emphasis on their strengths in revealing the structure, composition, dynamics, and spatial distribution of CL. Furthermore, the evidence of CL abnormalities in various CNS disorders was assessed, often showing decreased CL levels, loss of polyunsaturated species, and increased oxidation associated with mitochondrial dysfunction and neuronal apoptosis. Furthermore, the nutritional interventions for CL modulation were discussed, such as polyunsaturated fatty acids, polyphenols, carotenoids, retinoids, alkaloids, and triterpenoids, which summarize their potential health-beneficial effects in remodeling the CL acyl chain, preventing oxidation, and regulating mitochondrial homeostasis. Overall, this review provided insight into integrating CL analysis and dietary modulation in understanding CL-related pathologies in CNS disorders.}, }
@article {pmid41593859, year = {2026}, author = {Pathak, K and Kumari, T and Aggarwal, L and Singh, V}, title = {Preventive dietary and lifestyle strategies for neurodegenerative diseases: a comprehensive review.}, journal = {Nutritional neuroscience}, volume = {}, number = {}, pages = {1-26}, doi = {10.1080/1028415X.2026.2615456}, pmid = {41593859}, issn = {1476-8305}, abstract = {Neurodegenerative diseases (NDDs), including Alzheimer's, Parkinson's, Huntington's disease, and amyotrophic lateral sclerosis, are rising sharply across the globe. These incurable and progressive conditions lead to severe cognitive and motor impairments, diminish the quality of life, and place a substantial burden on healthcare systems. In response to this growing challenge, the present review offers an integrative and forward-thinking perspective focused on modifiable daily habits that have the potential to preserve brain health and reduce the risk of neurodegeneration. Mounting evidence reveals that everyday lifestyle choices, including food habits, physical activity, sleep, and stress, profoundly shape long-term cognitive outcomes. Neuroprotective diets such as the Mediterranean and ketogenic diets reduce oxidative stress, enhance mitochondrial efficiency, and promote neurogenesis, whereas the Western diet accelerates cognitive decline. Intermittent fasting and caloric restriction trigger autophagy and ketone production, offering metabolic resilience. Functional foods such as berries, walnuts, and leafy greens combat inflammation and oxidative damage. Physical activity and resistance training boost synaptic plasticity and neurotransmitter balance. In addition, high-quality sleep and effective stress control help preserve neuronal integrity and lower neuroinflammatory markers. By integrating insights from neuroscience, nutrition, and behavioral medicine, this review highlights how multiple modifiable factors, when adopted consistently, can work in synergy to preserve cognitive health, delay disease onset, and reduce progression.}, }
@article {pmid41592170, year = {2026}, author = {Allen, MD and Diab, V and Lezaic, N and Binet, M and Gentil, BJ and Blanchard, O and Genge, A and Massie, R}, title = {The genetics of autosomal recessive ALS: a review of the common forms and their phenotypes.}, journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration}, volume = {}, number = {}, pages = {1-10}, doi = {10.1080/21678421.2026.2615110}, pmid = {41592170}, issn = {2167-9223}, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease marked by progressive degeneration of upper and lower motor neurons. Most forms of ALS associated with a suspected causal variant are inherited in an autosomal dominant manner. However, there is an important subset of autosomal recessive (AR) variants, often associated with early-onset or atypical clinical features. Advances in genetic sequencing have led to increased recognition of AR ALS. In this review, we focus on four key confirmed AR ALS-associated genes, which appear to be most common-ALS2, SPG11, OPTN, and the D90A variant of SOD1-reviewing their pathophysiology and unique clinical manifestations. We also highlight very rare AR mutations implicated in ALS, including SYNE1, ATP13A2, and FUS, and some associated with overlap syndromes or debated pathogenicity including SIGMAR1, ERLIN1, and ERLIN2. These genes are involved in an array of processes including axonal transport, endosomal trafficking, oxidative stress response, and autophagy, suggesting distinct mechanisms of motor neuron degeneration. Some forms of AR ALS more frequently present with juvenile onset and slower progression, but other genes are associated with broader phenotypic spectra. This includes overlap with hereditary spastic paraplegia (HSP) and hereditary ataxias. Understanding these AR forms of ALS may enhance diagnostic precision, improve prognostication, and may pave the way for targeted gene therapies. This review underscores the emerging significance of AR inheritance in ALS and calls for deeper investigation into its molecular and clinical dimensions.}, }
@article {pmid41585268, year = {2025}, author = {Srivastav, J and Sharma, S}, title = {Viral and non-viral cellular therapies for neurodegeneration.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1718669}, pmid = {41585268}, issn = {2296-858X}, abstract = {Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) are characterized by progressive loss of neurons and still lack curative treatment options. In this review, we describe current and developing therapeutic strategies that include viral vector-based gene delivery, antisense oligonucleotide (ASO) and RNA interference methods, stem cell transplantation, and genome editing technologies. Adeno-associated viruses (AAVs) and lentiviruses have been used for gene delivery in preclinical and clinical studies, while ASOs are under development to reduce expression of pathogenic proteins such as tau, α-synuclein, and mutant huntingtin. Cellular therapies, including mesenchymal stem cell (MSC)-based paracrine support and transplantation of neurons derived from induced pluripotent stem cells (iPSCs), are being evaluated, particularly in PD and AD. We also discuss important gene targets such as APOE4, GBA1, SCNA, and MAPT, and how treatment strategies may differ between monogenic and polygenic forms of these disorders. Lastly, we highlight recent efforts focused on genes like TREM2, PINK1, and progranulin, and examine their role in the future development of gene- and cell-based interventions.}, }
@article {pmid41581940, year = {2026}, author = {Behera, P and Rangappa, N and Chandrashekar, M and Mishra, A and Chinnathambi, S and Mishra, M}, title = {The multifaceted role of antimicrobial peptides in neurodegeneration: Insights from Drosophila and beyond.}, journal = {Advances in protein chemistry and structural biology}, volume = {149}, number = {}, pages = {419-444}, doi = {10.1016/bs.apcsb.2025.08.003}, pmid = {41581940}, issn = {1876-1631}, mesh = {Animals ; Humans ; *Neurodegenerative Diseases/immunology/metabolism/pathology ; *Antimicrobial Peptides/metabolism/immunology ; *Drosophila ; Disease Models, Animal ; Immunity, Innate ; }, abstract = {Antimicrobial peptides (AMPs) are tiny proteins essential for innate immunity in various taxa, including mammals and insects. They provide defence against a wide range of pathogens, including bacteria, viruses, fungi, and parasites. Apart from their antimicrobial properties, new studies have revealed the roles of AMPs in brain ageing, neurodegeneration, and neuroinflammation. With an emphasis on their dysregulation in glial and neuronal tissues and their role in neuroinflammation, mitochondrial dysfunction, and neuronal loss, we reviewed the new function of AMPs beyond their antimicrobial activity. Findings from Drosophila models of Huntington's disease, Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis, and Ataxia-telangiectasia show that immune pathways, like Toll and immune deficiency, drive persistent or ectopic AMP expression, which is similar to the inflammatory processes seen in human neurodegenerative diseases. Furthermore, the dual function of AMPs as mediators of sterile inflammation and protective immunological agents reveals a universal paradox. The translational relevance of these findings is further supported by comparisons with human AMPs, such as LL-37 and β-defensins. LL-37 and β-defensins levels were found to be increased in the cerebrospinal fluid of patients suffering from meningitis. LL-37 is released from neurons and activates glial cells, boosting the production of inflammatory cytokines and decreasing neuronal survival. This chapter redefines AMPs as not only sentinels of microbial defence but also as important participants in preserving or disturbing brain homeostasis by establishing them as a link between immunity and neurobiology.}, }
@article {pmid41575675, year = {2026}, author = {Kopalli, SR and Wankhede, N and Rahangdale, SR and Sammeta, S and Aglawe, M and Koppula, S and Taksande, B and Upaganlawar, A and Umekar, M and Kale, M}, title = {Age-driven dysbiosis: gut microbiota in the pathogenesis and treatment of aging disorders.}, journal = {Biogerontology}, volume = {27}, number = {1}, pages = {42}, pmid = {41575675}, issn = {1573-6768}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis/therapy/microbiology ; *Aging/physiology ; Animals ; Probiotics/therapeutic use ; }, abstract = {Aging, a complex physiological and molecular process, has undergone significant changes, of which gut microbiome composition has surfaced as an important key in the maintenance of neurological health. Recent studies have revealed the significant impact of age-related gut dysbiosis in the induction of neuroinflammation, metabolic syndrome, disruptions in gut-brain axis, and age-related neurological decline. Although significant studies have revealed the impact of the microbiome-gut-brain axis in individual neurological diseases, an aging-focused holistic synthesis has not yet been adequately developed. This review provides a critical assessment of the involvement of age-related dysbiosis of gut microbiota in the development and progression of neurological disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, and cognitive aging of the elderly, and to focus on age-related microbial patterns and mechanisms of dysbiosis related to neurological aging, including inflammation and immune system dysregulation, metabolic changes, oxidative stress, barrier dysfunction, and gut-brain communication through enteroendocrine, enteric neural, and vagal mechanisms, and to emphasize disease-specific and common microbial patterns of dysbiosis and beneficial and harmful microbial roles in aging diseases. This review assesses some of the latest promising therapies aimed at the microbiota, such as probiotics, prebiotics, dietary therapies, fecal microbiota transplantation, as well as pharmacological therapies, and critically discusses their limitations in terms of interindividual variability and their generalisation and applicability. Focusing on mechanistic, comparative, and translation aspects, this review offers a comprehensive approach to neurological aging due to gut microbiota and identifies gaps for future precision microbiome-based interventions.}, }
@article {pmid41572495, year = {2026}, author = {Zaman, A and Drake, SS and Fournier, AE}, title = {Extracellular Vesicle-Derived microRNAs as Fluid Biomarkers in Neurodegenerative Diseases: A Systematic Review.}, journal = {Journal of neurochemistry}, volume = {170}, number = {1}, pages = {e70323}, pmid = {41572495}, issn = {1471-4159}, support = {//MS Canada/ ; /CAPMC/CIHR/Canada ; //Fonds de Recherche du Qu&#xe9;bec - Sant&#xe9;/ ; //Myelin Repair Foundation/ ; //Fonds de recherche du Qu&#xe9;bec/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/diagnosis/genetics/cerebrospinal fluid/blood/metabolism ; *Extracellular Vesicles/metabolism/genetics ; *MicroRNAs/cerebrospinal fluid/metabolism/blood ; Biomarkers/cerebrospinal fluid/blood/metabolism ; Animals ; }, abstract = {Given the absence of curative treatments for neurodegenerative diseases, early detection and therapeutic intervention are critical to slowing disease progression. Extracellular vesicles (EVs) have emerged as promising biomarkers for neurodegeneration, owing to their accessibility in bodily fluids and dynamic molecular cargo, including microRNAs (miRNAs). The last decade has seen accumulating evidence for miRNA dysregulation in circulating EVs from people with neurodegenerative diseases; however, assessing reproducibility between studies remains challenging, largely due to clinical and methodological heterogeneity. In this systematic review, we comprehensively searched the MEDLINE database for studies investigating miRNA expression in biofluids from people with neurodegenerative diseases. We extracted miRNA expression data from 185 peer-reviewed publications, published until June of 2025, reporting altered miRNA levels in fluid-derived EVs from people with neurodegenerative diseases. We consolidated results between studies to identify the most frequently dysregulated miRNAs across diseases, with a focus on Alzheimer's disease, Parkinson's disease, mild cognitive impairment, multiple sclerosis, amyotrophic lateral sclerosis, frontotemporal dementia, stroke, traumatic brain injury, and schizophrenia. Evaluating tissue specificity of frequently dysregulated miRNAs revealed enrichment of select miRNAs in the nervous system relative to blood and immune compartments. Summarizing miRNA regulation across biofluids emphasized consistencies between cerebrospinal fluid and plasma, but not serum. We highlight circulating miRNAs that may be reflective of neuropathology, including miR-143-3p, miR-127-3p, miR-9-5p, miR-15a-5p, and miR-125b-5p. Finally, we provide a repository of miRNA expression data from over 30 neurodegenerative conditions which can be exploited to further investigate miRNA regulation in diseases of interest.}, }
@article {pmid41571168, year = {2026}, author = {Malvandi, AM and Gerosa, L and Maroni, P and Orlando, ME and Mohammadipour, A and Lombardi, G}, title = {miRNA-206 in muscle and central nervous system crosstalk during exercise: A double-edged sword with therapeutic potential.}, journal = {Neuroscience and biobehavioral reviews}, volume = {183}, number = {}, pages = {106569}, doi = {10.1016/j.neubiorev.2026.106569}, pmid = {41571168}, issn = {1873-7528}, abstract = {Physical activity triggers complex molecular responses in skeletal muscle, with increasing evidence showing systemic signaling roles for muscle-derived microRNAs (myomiRs). Among these, miR-206 has attracted attention for its dual function: promoting muscle regeneration but potentially harming the central nervous system (CNS). This review examines how miR-206 expression is regulated during exercise and its effects on muscle biology-such as fiber-type specification, mitochondrial changes, and neuromuscular junction (NMJ) repair. It also explores the paradoxical effects of high miR-206 levels in the CNS, where it targets brain-derived neurotrophic factor (BDNF), reducing neuroplasticity and increasing vulnerability to neuropsychiatric and neurodegenerative diseases. The review highlights disease-specific aspects, showing miR-206 as harmful in Alzheimer's, stroke, and depression, but potentially protective in amyotrophic lateral sclerosis (ALS). We discuss its potential as a biomarker and therapeutic target, stressing tissue-specific regulation approaches. Overall, miR-206 plays a key role in muscle-brain communication, with important implications for exercise, aging, and CNS disorders.}, }
@article {pmid41570741, year = {2026}, author = {Genin, EC and Paquis-Flucklinger, V}, title = {ALS-related proteinopathies: From TDP-43 to mitochondrial proteinopathies.}, journal = {Current opinion in neurobiology}, volume = {97}, number = {}, pages = {103163}, doi = {10.1016/j.conb.2025.103163}, pmid = {41570741}, issn = {1873-6882}, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive loss of motor neurons. ALS often overlaps clinically and pathologically with frontotemporal dementia (FTD), the second most common form of dementia. Like many neurodegenerative disorders, both ALS and FTD share a crucial pathological hallmark, the aggregation of misfolded proteins into insoluble inclusions in degenerating neurons. This process is referred to as proteinopathy. This review focuses on the proteinopathies associated with ALS, including aggregates of TDP-43, SOD1, FUS, and CHCHD10, which disrupt critical cellular processes such as RNA metabolism, mitochondrial function, and protein homeostasis. The review highlights to the identification of new types of mitochondrial and cytosolic aggregates linked to CHCHD10-related ALS. Although the precise pathological mechanisms remain to be fully elucidated, strategies aimed at restoring proteostasis and reducing protein aggregation may be promising therapeutic approaches for treating ALS, as they directly target fundamental pathogenic mechanisms.}, }
@article {pmid41567979, year = {2025}, author = {Hamdalla, RH and Bhaskar, VB and Tian, C}, title = {Brain-derived extracellular vesicles potentially mediate crosstalk with peripheral organs in neurodegenerative diseases.}, journal = {Frontiers in cell and developmental biology}, volume = {13}, number = {}, pages = {1710150}, pmid = {41567979}, issn = {2296-634X}, abstract = {Brain-Derived Extracellular vesicles (BDEVs) are emerging mediators of intra- and interorgan communication in neurodegenerative diseases (NDs) such as Alzheimer's Disease (AD) and Parkinson's Disease (PD). A growing body of evidence suggests that BDEVs play an important role in modulating intercellular communication within the central nervous system in the pathogenesis of many NDs. By transporting non-coding RNAs (e.g., miRNAs) and important pathological proteins, BDEVs also influence peripheral organs and contribute to the progression of disease in the central nervous system (CNS). This review extends the understanding of NDs beyond solely brain dysfunction and gives a novel framework for the progression of these diseases, uniquely emphasizing the currently underexplored mechanisms by which BDEV-mediated communication exacerbates or potentially initiates peripheral dysfunction or complications. It maps and clarifies the specific and potential mechanisms by which CNS-originating EV activity proliferates systemic dysfunction, presenting new opportunities and areas for therapeutic and diagnostic treatments for NDs. These findings are contextualized across multiple NDs, including Amyotrophic Lateral Sclerosis (ALS), Huntington's Disease (HD), and Multiple Sclerosis (MS), by incorporating data on dysregulated BDEV miRNAs and toxic proteins to map the pathway of BDEV-mediated disease spread.}, }
@article {pmid41565509, year = {2026}, author = {Lee, NC and Lin, CH and Chien, YH and Hwu, WL}, title = {Genetic testing for adult-onset neurodegenerative diseases: A clinical perspective.}, journal = {Journal of the Formosan Medical Association = Taiwan yi zhi}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jfma.2026.01.021}, pmid = {41565509}, issn = {0929-6646}, abstract = {Adult-onset neurodegenerative diseases (AOND), such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and frontotemporal dementia, severely affect patients' quality of life. Pathogenic single-nucleotide variations (SNVs) and small insertions and deletions (indels) can disrupt genes involving ANOD, and expansion of short tandem repeats such as trinucleotide repeats is an important etiology of hereditary ataxia. Variations in more than one gene combined to create polygenic risk scores (PRS) for multifactorial types of AOND. Recently, genome structural variations (SVs) like copy number variations (CNVs) and expansion of long repeats are increasingly identified as the etiologies of AOND. Tools for molecular diagnosis of AOND have evolved from Sanger sequencing to next-generation sequencing (NGS) such as short-read whole-exome sequencing (WES) and whole-genome sequencing (WGS), and long-read sequencing is especially helpful in solving SVs and expansions of long repeats. Patients might have affected and/or at-risk family members at the time of diagnosis, so genetic counseling for risk handling and birth planning need to be conducted with caution. This review will help readers to better understand the genetic testing for AOND.}, }
@article {pmid41563518, year = {2026}, author = {Boomsma, A and Doyle, C and Sai, N and Rogers, ML and Lee, SH and Benyamin, B}, title = {The differences in sex ratio between sporadic and familial amyotrophic lateral sclerosis: a systematic review.}, journal = {Journal of neurology}, volume = {273}, number = {2}, pages = {92}, pmid = {41563518}, issn = {1432-1459}, support = {Research Training Program//Australian Government/ ; DIS-202303-00932//FightMND/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology/genetics ; *Sex Ratio ; Male ; Female ; *Sex Characteristics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is more prevalent in males than in females. However, it is unclear whether the difference in sex ratio is observed similarly in sporadic compared to familial ALS. Here, we conducted a systematic review to investigate the differences in sex ratio between familial and sporadic ALS. Following the meta-analysis of observational studies in epidemiology (MOOSE) guidelines, this study searched Ovid MEDLINE, Embase, Emcare, SCOPUS and Cochrane databases. We used a random-effects meta-analysis to estimate sex ratios in a total of 9269 ALS patients (4135 female, 5134 male) across 20 included studies. We confirmed that ALS is more prevalent in males than in females (sex ratio: 1.25 (95%CI 1.14-1.37). However, when we stratified the analyses, the sex ratio was only different in sporadic ALS. Male-to-female ratios were 1.29 (95% CI 1.16-1.42) for sporadic ALS and 1.05 (95% CI 0.93-1.18) for familial ALS. A further analysis showed a pooled risk ratio of 1.07 (95% CI 1.00-1.15), indicating a 7% higher likelihood of males being diagnosed with sporadic rather than familial ALS. These findings highlight the importance of considering sex-specific factors in ALS research and clinical practice.}, }
@article {pmid41562880, year = {2026}, author = {Fiorella, ML and Ballini, L and Lavermicocca, V and Ragno, MS and Restivo, DA and Marchese-Ragona, R}, title = {Dysphagia and Dysarthria in Neurodegenerative Diseases: A Multisystem Network Approach to Assessment and Management.}, journal = {Audiology research}, volume = {16}, number = {1}, pages = {}, pmid = {41562880}, issn = {2039-4330}, abstract = {Dysphagia and dysarthria are common, co-occurring manifestations in neurodegenerative diseases, resulting from damage to distributed neural networks involving cortical, subcortical, cerebellar, and brainstem regions. These disorders profoundly affect patient health and quality of life through complex sensorimotor impairments. Objective: The aims was to provide a comprehensive, evidence-based review of the neuroanatomical substrates, pathophysiology, diagnostic approaches, and management strategies for dysphagia and dysarthria in neurodegenerative diseases with emphasis on their multisystem nature and integrated treatment approaches. Methods: A narrative literature review was conducted using PubMed, Scopus, and Web of Science databases (2000-2024), focusing on Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), progressive supranuclear palsy (PSP), and multiple system atrophy (MSA). Search terms included "dysphagia", "dysarthria", "neurodegenerative diseases", "neural networks", "swallowing control" and "speech production." Studies on neuroanatomy, pathophysiology, diagnostic tools, and therapeutic interventions were included. Results: Contemporary neuroscience demonstrates that swallowing and speech control involve extensive neural networks beyond the brainstem, including bilateral sensorimotor cortex, insula, cingulate gyrus, basal ganglia, and cerebellum. Disease-specific patterns reflect multisystem involvement: PD affects basal ganglia and multiple brainstem nuclei; ALS involves cortical and brainstem motor neurons; MSA causes widespread autonomic and motor degeneration; PSP produces tau-related damage across multiple brain regions. Diagnostic approaches combining fiberoptic endoscopic evaluation, videofluoroscopy, acoustic analysis, and neuroimaging enable precise characterization. Management requires multidisciplinary Integrated teams implementing coordinated speech-swallowing therapy, pharmacological interventions, and assistive technologies. Conclusions: Dysphagia and dysarthria in neurodegenerative diseases result from multifocal brain damage affecting distributed neural networks. Understanding this multisystem pathophysiology enables more effective integrated assessment and treatment approaches, enhancing patient outcomes and quality of life.}, }
@article {pmid41562832, year = {2026}, author = {Aranda-Abreu, GE and Rojas-Durán, F and Hernández-Aguilar, ME and Herrera-Covarrubias, D and Tlapa-Monge, LR and Mestizo-Gutiérrez, SL}, title = {The Molecular Architecture of Neurodegeneration: An Integrative Overview of Convergent Mechanisms.}, journal = {NeuroSci}, volume = {7}, number = {1}, pages = {}, pmid = {41562832}, issn = {2673-4087}, abstract = {Neurodegenerative diseases such as Alzheimer's, Parkinson's, amyotrophic lateral sclerosis, and Huntington's disease represent a major challenge in neuroscience due to their complex, multifactorial nature and the absence of curative treatments. These disorders share common molecular mechanisms, including oxidative stress, mitochondrial dysfunction, proteostasis collapse, calcium dyshomeostasis, chronic neuroinflammation, and the prion-like propagation of misfolded proteins. Together, these processes trigger a cascade of cellular damage that culminates in synaptic dysfunction and programmed neuronal death. This review integrates current evidence on the sequential stages of neurodegeneration, emphasizing the convergence of oxidative, inflammatory, and proteotoxic pathways that drive neuronal vulnerability. Moreover, it explores emerging therapeutic strategies aimed at restoring cellular homeostasis, such as Nrf2 activation, modulation of the unfolded protein response (UPR), enhancement of autophagy, immunotherapy against pathological proteins, and gene therapy approaches. The dynamic interplay among mitochondria, endoplasmic reticulum, and glial cells is highlighted as a central element in disease progression. Understanding these interconnected mechanisms provides a foundation for developing multi-targeted interventions capable of halting or delaying neuronal loss and improving clinical outcomes in neurodegenerative disorders. This work provides an integrative and introductory overview of the convergent mechanisms underlying neurodegeneration rather than an exhaustive mechanistic analysis.}, }
@article {pmid41561436, year = {2025}, author = {Ishaq, SM and Russell, AP}, title = {Potential role of stress granules and myogranules in amyotrophic lateral sclerosis.}, journal = {Frontiers in molecular neuroscience}, volume = {18}, number = {}, pages = {1686230}, pmid = {41561436}, issn = {1662-5099}, abstract = {Amyotrophic lateral sclerosis (ALS) is characterized by the progressive loss of upper and lower motor neurones, leading to muscle wasting, paralysis and respiratory failure. Pathological cytoplasmic aggregation of the RNA-binding protein transactive response DNA-binding protein 43 (TDP-43) protein occurs in neural tissues in ~97% of all ALS cases, and is also observed in skeletal muscle. Cytoplasmic aggregation of TDP-43 is believed to contribute to ALS pathogenesis; however, its precise mechanistic role/s continues to elude the field. This mini review explores the potential role and regulation of two TDP-43-associated RNA-protein assemblies, stress granules (SGs) and myogranules (MGs). We review the current understanding of SG and MG formation and their potential role in ALS-related neurodegeneration and muscle pathology. We also highlight limitations and strengths and suggest future directions for research.}, }
@article {pmid41553588, year = {2026}, author = {Bjørklund, G and Butnariu, M and Caunii, A and Peana, M}, title = {Metallothioneins in Neurodegenerative Diseases: Metal Homeostasis, Autoimmunity, and Therapeutic Potential.}, journal = {Molecular neurobiology}, volume = {63}, number = {1}, pages = {373}, pmid = {41553588}, issn = {1559-1182}, mesh = {Humans ; *Homeostasis/physiology ; *Metallothionein/metabolism ; *Neurodegenerative Diseases/metabolism/immunology/drug therapy/therapy ; *Autoimmunity/physiology ; Animals ; *Metals/metabolism ; }, abstract = {Neurodegenerative diseases, including multiple sclerosis, Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis, are characterized by progressive neuronal loss and are frequently linked to metal dysregulation, oxidative stress, and immune dysfunction. Metallothioneins (MTs), a family of cysteine-rich, metal-binding proteins, are critical in maintaining metal homeostasis, mitigating oxidative damage, and modulating immune responses, functions highly relevant in these pathologies. MTs regulate essential metals like copper and iron by preventing their participation in harmful redox reactions and control zinc availability for enzymatic and signaling processes. They also detoxify neurotoxic metal(oid)s such as cadmium, mercury, lead, and arsenic, thereby reducing their adverse neurological and immunological effects. In autoimmune neurodegeneration, MTs modulate pro- and anti-inflammatory cytokines (e.g., IL-6, TNF-α, IL-10) and influence immune cell activity, particularly microglia and T cells, which are central to neuroinflammation and autoimmunity. Through these mechanisms, MTs play a dual role in sustaining immune homeostasis and counteracting oxidative stress. Their capacity to integrate metal regulation with immune modulation positions them as promising therapeutic targets, with preclinical and some clinical evidence supporting strategies to enhance MT expression or develop MT-mimetic agents to address both metal dysregulation and immune imbalance. Additionally, MTs show emerging utility as biomarkers, as alterations in MT isoform expression and metal-bound complexes in biofluids have been associated with disease onset, progression, and therapeutic response in specific neurodegenerative conditions. This article reviews the multifaceted roles of MTs in neurodegenerative diseases, emphasizing their function in metal and immune regulation and their emerging potential as therapeutic targets and clinical biomarkers.}, }
@article {pmid41552817, year = {2025}, author = {Chen, Y and Xiao, W and Qian, C and Huang, L and Lv, J and Wang, Z and Luo, Y}, title = {System Xc-pathway as a potential regulatory target in neurological disorders.}, journal = {Frontiers in pharmacology}, volume = {16}, number = {}, pages = {1701320}, pmid = {41552817}, issn = {1663-9812}, abstract = {The System Xc-pathway is composed of the 12-transmembrane transporter protein SLC7A11 (xCT) and the single-channel transmembrane protein SLC3A2 (CD98hc). We detail the pathway's characteristics and distribution within the central nervous system, as well as its canonical role in maintaining glutathione synthesis and inhibiting ferroptosis, and its emerging non-canonical functions in metabolic coupling and neuroimmunity. A core theme is the pathway's context-dependent and often paradoxical role across major neurological disorders, including ischemic stroke, Alzheimer's disease, multiple sclerosis, Parkinson's disease, and amyotrophic lateral sclerosis. Critically, we analyze how pathological activation of N-methyl-D-aspartate receptors (NMDARs) can dysregulate System Xc-through mechanisms involving calcium overload, reactive oxygen species, and specific signaling axes (e.g., Nrf2, PP2A/AMPK/HMGB1), thereby exacerbating excitotoxicity and oxidative damage. Conversely, System Xc-dysfunction can further fuel NMDAR-mediated injury, creating vicious pathogenic cycles. This analysis reveals that System Xc-is not a unitary target but a dynamic node within a complex network. Consequently, effective therapeutic strategies must move beyond broad inhibition and instead aim for nuanced, cell-type-specific, and disease-stage-precise modulation. This approach will selectively correct the dysfunction of System Xc-while preserving its essential physiological roles. It presents both a significant challenge and a promising frontier for future neuroprotective drug development.}, }
@article {pmid41552526, year = {2026}, author = {Turcatel, GA and Moura, S}, title = {Glutamate Receptor Agonists as Triggers of Neurotoxicity: Decoding Pathways of Five Neurotoxins and Potential Therapeutic Targets.}, journal = {ACS omega}, volume = {11}, number = {1}, pages = {70-81}, pmid = {41552526}, issn = {2470-1343}, abstract = {l-Glutamate (l-Glu) is one of the primary excitatory neurotransmitters in the nervous system, functioning through both ionotropic and metabotropic receptors. The release of l-Glu into the synaptic cleft, its interaction with receptors, and its reuptake are meticulously regulated by excitatory amino acid transporters. The structural similarity of various compounds to l-glutamate is crucial to their ability to interact with NMDA, AMPA, and kainate receptors. These interactions can significantly influence neural communication and function. Overstimulation of these receptors, which operate as ion channels, results in an increased level of calcium ion influx, a phenomenon known as excitotoxicity, which is often linked to neurodegeneration. Many neurodegenerative conditions are linked to both acute and chronic exposures to neurotoxins, whether they originate within the body (endogenous) or from external sources (exogenous). These neurotoxins often function as l-glutamate receptor agonists, potentially contributing to the progression of these diseases. This perspective focuses on key neurotoxins, including β-N-methylamino-l-alanine (l-BMAA), quinolinic acid (QUIN), domoic acid, β-N-oxalyl-l-α,β-diaminopropionic acid (β-ODAP), homocysteine (Hcy), and l-homocysteate, all of which exhibit complementary mechanisms of action. We will explore their structural characteristics and mechanisms through which they induce neurotoxicity. Understanding the neurotoxic mechanisms of these compounds is essential for elucidating the pathology of neurodegenerative diseases, such as amyotrophic lateral sclerosis, neurolathyrism, and amnesic shellfish poisoning. This review summarizes the findings of 64 studies to clarify these relationships involving classic events associated with neurodegeneration such as mitochondrial damage, oxidative stress, and activation of proapoptotic pathways. In summary, the distinctive properties of these neurotoxins provide valuable insights that could help in the development of future therapeutic drugs aimed at treating and alleviating the effects of neurodegenerative diseases. Understanding how these neurotoxins interact with neuronal pathways can guide researchers in designing more effective interventions.}, }
@article {pmid41548740, year = {2026}, author = {Qaisar, R}, title = {Fiber-type-specific architecture and pathophysiology of the neuromuscular junction.}, journal = {Neuroscience}, volume = {597}, number = {}, pages = {13-26}, doi = {10.1016/j.neuroscience.2026.01.015}, pmid = {41548740}, issn = {1873-7544}, abstract = {The neuromuscular junction (NMJ) is a specialized synapse essential for translating neuronal signals into muscle contraction. This review examines the complex structural, functional, and molecular differences in NMJs that innervate fast- and slow-twitch skeletal muscle fibers. Fast-twitch fibers, optimized for rapid and powerful contractions, possess elaborate NMJs with deep folds, high neurotransmitter turnover, and greater vulnerability to synaptic fatigue and degeneration. In contrast, slow-twitch fiber NMJs exhibit simpler but more stable architectures that support sustained, fatigue-resistant activity. These differences are not fixed but subject to activity-dependent plasticity and pathological remodeling. Chronic stimulation, injury, and aging influence NMJ morphology, with fast-twitch junctions more prone to degeneration in conditions such as ALS, myasthenia gravis, and diabetic neuropathy. Slow-twitch NMJs often resist early deterioration due to superior trophic support, metabolic stability, and more robust expression of synaptic organizers, such as agrin and PGC-1α. Several key signaling pathways, including agrin-MuSK-LRP4, Wnt/β-catenin, and neuregulin/ErbB, govern NMJ maintenance with fiber-type-specific nuances. These insights underscore the importance of tailoring therapeutic strategies to the muscle fiber phenotype. Gene therapies, neuromuscular electrical stimulation, and biomaterial scaffolds are emerging as promising modalities for preserving or restoring NMJ integrity, especially in fast-twitch fibers at higher risk of degeneration. Understanding fiber-type-specific NMJ biology enhances our understanding of motor control, muscle aging, and neuromuscular disease progression, and it opens pathways for precision therapeutics that target vulnerable synapses with structural and functional specificity. This review introduces a novel perspective by emphasizing fiber-type-specific NMJ differences and their implications for targeted therapies.}, }
@article {pmid41548719, year = {2026}, author = {Li, X and Wan, R and Zhao, Y and Wu, Y and Chen, X and Li, Q and Luo, C}, title = {Decoding synaptic imbalance in neurodegenerative diseases: From pathological analysis to targeted intervention.}, journal = {Ageing research reviews}, volume = {}, number = {}, pages = {103028}, doi = {10.1016/j.arr.2026.103028}, pmid = {41548719}, issn = {1872-9649}, abstract = {Synapses serve as the central functional components mediating information transmission, integration, and storage within the central nervous system (CNS). Their functionality depends on the synergistic interplay of the presynaptic membrane, synaptic cleft, and postsynaptic membrane-three structures that collectively sustain neurotransmitter secretion, postsynaptic signaling, and synaptic plasticity. Of note, synaptic impairment represents an early, shared pathological hallmark across aging and age-related neurodegenerative disorders like Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic lateral sclerosis (ALS). This damage emerges prior to the demise of neuronal cell bodies and the manifestation of clinical symptoms, with its location and severity directly shaping disease phenotypes. Importantly, such synaptic dysfunction is closely linked to the pathological proteins specific to each disorder. This review comprehensively synthesizes current research advances regarding synaptic impairment in age-related neurodegenerative diseases. It elaborates on the location-specific pathological features of synaptic damage in AD, PD, HD, and ALS, with particular emphasis on their associations with disease-related pathological markers. Additionally, the work unpacks five core mechanisms driving synaptic dysfunction: the toxic effects of pathological proteins, dysregulated synaptic protein homeostasis, excitotoxicity coupled with disrupted calcium balance, oxidative stress and inflammatory responses, and deficiencies in neurotrophic factors. Ultimately, it summarizes potential biomarkers and targeted intervention strategies, aiming to provide a systematic reference for mechanistic investigations, early diagnosis, and clinical management of neurodegenerative diseases.}, }
@article {pmid41547243, year = {2026}, author = {Dorothy Wong, ZY and Kang, X and Shi, Y and Fan, R and Zhang, C and Min, D and Sun, N and Ma, Y and Tang, ML}, title = {Autophagy-tethering compounds (ATTECs) as an emerging and potentially transformative drug discovery approach.}, journal = {European journal of medicinal chemistry}, volume = {305}, number = {}, pages = {118585}, doi = {10.1016/j.ejmech.2026.118585}, pmid = {41547243}, issn = {1768-3254}, mesh = {Humans ; *Autophagy/drug effects ; *Drug Discovery ; Lysosomes/metabolism/drug effects ; Proteolysis/drug effects ; Molecular Structure ; Animals ; }, abstract = {Targeted protein degradation (TPD) strategies leveraging the ubiquitin-proteasome system (UPS), such as proteolysis-targeting chimeras (PROTACs), have gained wide recognition. While the UPS predominantly degrades short-lived soluble proteins, the lysosome-mediated system (LMS) excels at processing larger substrates, including protein aggregates, organelles, and macromolecular complexes. Recently, autophagy-tethering compounds (ATTECs) have emerged as a promising strategy for targeted degradation, harnessing the autophagy-lysosome system (ALS) to enable proximity-induced degradation. These heterobifunctional molecules, composed of LC3-binding warheads and TOI (target of interest) ligands linked together, provide therapeutic potential against disease-causing targets. This review outlines the therapeutic applications of ATTECs in human diseases, highlights recent progress in their development, and explores future opportunities for expanding this emerging class of degradation technologies through ALS from medicinal chemistry perspective.}, }
@article {pmid41396532, year = {2025}, author = {Sabey, TB and Shanklin, BC and Colquitt, JA and Baer, MD}, title = {The approach-inhibition theory of power: A meta-analytic test and synthesis.}, journal = {Psychological bulletin}, volume = {151}, number = {10}, pages = {1245-1279}, doi = {10.1037/bul0000500}, pmid = {41396532}, issn = {1939-1455}, mesh = {Humans ; *Inhibition, Psychological ; *Psychological Theory ; *Power, Psychological ; *Cognition ; *Affect/physiology ; }, abstract = {Keltner et al. (2003) presented an integrative theory of the social implications of possessing power. Their theory-the approach-inhibition theory of power-quickly became the dominant lens for empirical investigations of how power influences a person's cognition, affect, and behavior. Despite the many benefits of Keltner et al.'s theory, the past 20 years of research have surfaced several potential issues with the theory, including empirical dissensus, mediational ambiguity, and questions about cognitive versus affective primacy. The purpose of this study is to resolve these issues by conducting the first meta-analytic synthesis of the literature on the outcomes of power. Specifically, we tested Keltner et al.'s propositions that power is positively related to the approach-oriented outcomes of attention to rewards, automatic cognition, positive affect, and disinhibited behavior and negatively related to the inhibition-oriented outcomes of attention to threats, controlled cognition, negative affect, and inhibited behavior. Our meta-analysis included a final set of 1,712 effect sizes from 813 independent samples of 432 manuscripts with 269,534 participants. Our analysis demonstrates that the theory is well-supported; approach associations are larger than inhibition associations; power influences behavior indirectly through attention, cognition, and affect; and those indirect effects are largely conveyed through affect. Based on these findings, we suggest several future directions that scholars can take as the literature on power continues to evolve. (PsycInfo Database Record (c) 2025 APA, all rights reserved).}, }
@article {pmid41365015, year = {2026}, author = {Svendsen, O and Stevens, MWR and Hamamura, T and Harpas, I and Radunz, M and King, DL}, title = {Reporting quality standards in gaming disorder treatment evidence: A systematic review.}, journal = {Acta psychologica}, volume = {262}, number = {}, pages = {106063}, doi = {10.1016/j.actpsy.2025.106063}, pmid = {41365015}, issn = {1873-6297}, mesh = {Humans ; *Video Games ; *Psychotherapy/standards ; Randomized Controlled Trials as Topic/standards ; *Internet Addiction Disorder/therapy ; *Research Design/standards ; }, abstract = {BACKGROUND: The treatment evidence base for gaming disorder (GD) has grown steadily over the past two decades. A systematic review by King et al. (2017) of 30 studies reported that GD treatment studies tended to favor psychotherapy approaches, but the research was limited by poor reporting standards as assessed by the Consolidated Standards of Reporting Trials (CONSORT) framework. This systematic review aimed to conduct a follow up evaluation of the reporting quality of subsequent GD treatment studies.<br><br>METHODS: A literature search of six databases yielded 51,056 records, which resulted in 31 eligible studies after screening. Each study's reporting quality was assessed using the CONSORT statement, and then these assessments were compared to King et al.'s (2017) review.<br><br>RESULTS: This review identified several methodological improvements since 2017: 61&#xa0;% of studies were randomized controlled trials (vs. 40&#xa0;% in 2017), 90&#xa0;% included control groups (vs. 63&#xa0;%), and follow-up duration increased to 6.1&#xa0;months (vs. 3.5&#xa0;months; p&#xa0;=&#xa0;.032). Reporting improved for participant flow (87.1&#xa0;% vs. 43.3&#xa0;%; p&#xa0;=&#xa0;.001) and group-level statistics (74.2&#xa0;% vs. 36.7&#xa0;%; p&#xa0;=&#xa0;.003), but some areas showed no improvement.<br><br>DISCUSSION: There have been several improvements in GD treatment study design and reporting, including controls, randomization and follow up, reflecting an increasing number of higher quality trials for the condition. Most of the studies with higher reporting quality (i.e., scoring &#x2265;30/46 on the CONSORT framework) were psychotherapy-based. Future research should employ designs with longer follow-ups, broader assessment of outcomes, and standardized ICD-11-aligned tools. Pharmacological treatments, including novel pharmacotherapies for other addictions (e.g., Naltrexone), are underexplored and lack high quality evidence.}, }
@article {pmid41354105, year = {2026}, author = {Mendes Araújo, L and Chianca, T and Persaud, C and Hartung, P and Soares, Y and Almirón, G and João, R}, title = {Respiratory strength training for patients with amyotrophic lateral sclerosis: A meta-analysis of randomized controlled trials.}, journal = {Respiratory medicine}, volume = {251}, number = {}, pages = {108560}, doi = {10.1016/j.rmed.2025.108560}, pmid = {41354105}, issn = {1532-3064}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/rehabilitation/therapy ; Randomized Controlled Trials as Topic ; *Breathing Exercises/methods ; Male ; Middle Aged ; Respiratory Muscles/physiopathology ; *Resistance Training/methods ; Female ; Treatment Outcome ; Aged ; Maximal Respiratory Pressures ; }, abstract = {INTRODUCTION: Respiratory strength training (RST) has been considered as a possible add-on treatment for amyotrophic lateral sclerosis (ALS). However, the benefits of RST are still controversial. We performed a meta-analysis of randomized controlled trials (RCTs) on the efficacy of RST in patients with ALS.<br><br>METHODS: PubMed, Embase and Cochrane Central were searched for RCTs comparing the use of RST with sham therapy or minimal device load in patients with ALS. The main outcomes were maximal expiratory pressure (MEP), maximal inspiratory pressure (MIP) and the ALS functioning rating scale (ALSFRS-R) score. Statistical analysis was performed using R software and heterogeneity was assessed with I[2] statistics.<br><br>RESULTS: Four RCTs were included with a total of 138 patients. RST was used to treat 69 (50&#xa0;%) patients. The mean age was 60.2&#xa0;&#xb1;&#xa0;10.4 years, with 82 (62.3&#xa0;%) male patients. Follow-up ranged from 2 to 8 months. Subgroup analysis of expiratory muscle training protocols showed a statistically significant improvement in MEP (MD 20.22 cmH2O; 95&#xa0;% CI 2.66-37.77; p&#xa0;=&#xa0;0.04). In overall analyses, there was no difference between groups regarding MEP (MD 9.40 cmH2O; 95&#xa0;% CI -11.57-30.37; p&#xa0;=&#xa0;0.25), MIP (MD 3.26 cmH2O; 95&#xa0;% CI -9.23-15.75; p&#xa0;=&#xa0;0.38), FVC (MD 4.05 %predicted; 95&#xa0;% CI -0.91-9.01; p&#xa0;=&#xa0;0.08) and ALSFRS-R score (MD 0.01 points; 95&#xa0;% CI -0.29-0.32; p&#xa0;=&#xa0;0.85).<br><br>CONCLUSION: In this meta-analysis of RCTs including patients with ALS, expiratory muscle training was associated with increased MEP compared with sham or minimal load. However, no statistically significant associations were found for overall RST in MIP, FVC, MEP, and ALSFRS-R.}, }
@article {pmid41307543, year = {2026}, author = {Macpherson, CE and Wani, DK and Li, H and Rana, V and Blacutt, M and Bello-Haas, VD and Quinn, L}, title = {Physical Therapist Interventions for People With Amyotrophic Lateral Sclerosis Across Disease Stages: A Systematic Review of Efficacy.}, journal = {Physical therapy}, volume = {106}, number = {1}, pages = {}, doi = {10.1093/ptj/pzaf142}, pmid = {41307543}, issn = {1538-6724}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/rehabilitation/therapy/physiopathology ; *Physical Therapy Modalities ; Exercise Therapy/methods ; Vital Capacity ; }, abstract = {IMPORTANCE: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease causing declines in muscular strength that affect respiratory function and functional independence. Although physical therapist interventions have been studied in ALS, their efficacy and evidence quality have not been systematically assessed across disease stages.<br><br>OBJECTIVE: The objective of this study was to examine the efficacy of physical therapist interventions on clinical outcomes across ALS disease stages.<br><br>DESIGN: This study was a systematic review using Joanna Briggs Institute methodology.<br><br>SETTING: Multiple settings were used.<br><br>PARTICIPANTS: The participants were adults (>18&#xa0;years old) with ALS or motor neuron disease.<br><br>INTERVENTIONS: Physical therapist interventions within the professional scope of practice included therapeutic exercise, pulmonary training, manual therapy, and multimodal approaches.<br><br>OUTCOME MEASURES: Outcome measures included effect sizes (ESs) and 95% CIs calculated for forced vital capacity (FVC) and the Amyotrophic Lateral Sclerosis Rating Scale (ALSFRS) or the ALSFRS revised (ALSFRS-R).<br><br>RESULTS: Six databases were searched from inception to January 2025. Thirty-nine studies were included (25 experimental, 14 observational). Outcomes were heterogeneous, with 94 measures across studies: 23 included the ALSFRS or ALSFRS-R, and 16 included FVC. Most interventions targeted early-stage ALS (n&#x2009;=&#x2009;27), limiting comparisons across stages. Multimodal training had moderate-quality evidence, with moderate effects on the ALSFRS-R (ES&#x2009;=&#x2009;0.56 [95% CI&#x2009;=&#x2009;0.09-1.03]), and low-quality evidence, with negligible effects on FVC (ES&#x2009;=&#x2009;-0.03 [95% CI&#x2009;=&#x2009;-1.47 to 1.41]). Pulmonary interventions had moderate-quality evidence, with small effects on FVC (ES&#x2009;=&#x2009;0.40 [95% CI&#x2009;=&#x2009;-0.18 to 0.98]), and low-quality evidence, with negligible effects on the ALSFRS-R (ES&#x2009;=&#x2009;0.04 [95% CI&#x2009;=&#x2009;-0.25 to 0.33]).<br><br>CONCLUSIONS: A range of physical therapist interventions for ALS were assessed, although most were early phase or low quality. Multimodal and pulmonary interventions showed modest benefits in the ALSFRS-R and FVC, respectively. However, variability in outcome measures and limited research beyond early-stage disease highlight the need for stage-specific trials using consistent functional outcomes.<br><br>RELEVANCE: This review highlights the breadth of studies of physical therapy in ALS and underscores the need for more rigorous, targeted research.}, }
@article {pmid41261682, year = {2025}, author = {Huang, X and Wang, X and Yang, Y and Chen, H}, title = {Assessing the potential causal influence of myasthenia gravis on neurodegenerative diseases via multivariable Mendelian randomization.}, journal = {Medicine}, volume = {104}, number = {44}, pages = {e45340}, pmid = {41261682}, issn = {1536-5964}, mesh = {Humans ; Alzheimer Disease/epidemiology/genetics ; Amyotrophic Lateral Sclerosis/epidemiology/genetics ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Mendelian Randomization Analysis ; *Myasthenia Gravis/epidemiology/genetics ; *Neurodegenerative Diseases/epidemiology/genetics ; Parkinson Disease/epidemiology/genetics ; Risk Factors ; }, abstract = {Myasthenia gravis (MG), an autoimmune condition known for impairing neuromuscular signaling, has increasingly been implicated in broader neurological dysfunctions. Recent studies point toward a possible connection between autoimmune and neurodegenerative processes. However, whether MG contributes causally to the onset of major neurodegenerative disorders such as Alzheimer disease (AD), Parkinson disease (PD), and amyotrophic lateral sclerosis (ALS) remains unclear. This study utilizes Mendelian randomization (MR) to explore the potential causal influence of MG on these disorders from a genetic standpoint. A univariable Mendelian randomization (UVMR) framework was employed using summary-level data from genome-wide association studies (GWAS) to evaluate the effect of MG on the risk of AD, PD, and ALS. To confirm the robustness of the association between MG and AD, 2 independent AD GWAS datasets were incorporated for external replication, followed by a meta-analysis to combine the evidence. Additionally, multivariable Mendelian randomization (MVMR) was conducted to adjust for smoking behavior as a potential confounding factor. The UVMR analysis revealed a statistically significant causal relationship between MG and increased susceptibility to AD (odds ratio (OR): 1.037; 95% confidence interval (CI): 1.007-1.068; P = .016). No significant causal effects were observed for PD (OR: 1.019; 95% CI: 0.964-1.077; P = .509) or ALS (OR: 1.055; 95% CI: 0.977-1.140; P = .171). The association between MG and AD was consistently validated in 2 independent datasets (ieu-a-297: OR = 1.084; 95% CI: 1.017-1.156; P = .013; ieu-b-2: OR = 1.054; 95% CI: 1.006-1.104; P = .027). Meta-analysis reinforced the evidence supporting MG as a risk factor for AD (OR: 1.047; 95% CI: 1.023-1.072; P < .001). Furthermore, MVMR adjusting for smoking confirmed that MG independently contributes to AD risk (OR: 1.037; 95% CI: 1.006-1.069; P = .020). This study provides robust genetic evidence suggesting that MG is a causal and independent risk factor for AD. These findings highlight a novel link between autoimmunity and neurodegeneration, offering new directions for mechanistic and therapeutic research.}, }
@article {pmid41117572, year = {2025}, author = {Soar, J and Böttiger, BW and Carli, P and Jiménez, FC and Cimpoesu, D and Cole, G and Couper, K and D'Arrigo, S and Deakin, CD and Ek, JE and Holmberg, MJ and Magliocca, A and Nikolaou, N and Paal, P and Pocock, H and Sandroni, C and Scquizzato, T and Skrifvars, MB and Verginella, F and Yeung, J and Nolan, JP}, title = {European Resuscitation Council Guidelines 2025 Adult Advanced Life Support.}, journal = {Resuscitation}, volume = {215 Suppl 1}, number = {}, pages = {110769}, doi = {10.1016/j.resuscitation.2025.110769}, pmid = {41117572}, issn = {1873-1570}, mesh = {Humans ; *Advanced Cardiac Life Support/standards/methods ; *Cardiopulmonary Resuscitation/standards/methods ; Adult ; Europe ; *Heart Arrest/therapy ; *Out-of-Hospital Cardiac Arrest/therapy ; }, abstract = {These European Resuscitation Council (ERC) Guidelines 2025 Adult Advanced Life Support (ALS) are based on the International Liaison Committee on Resuscitation (ILCOR) Consensus on Cardiopulmonary Resuscitation Science with Treatment Recommendations (CoSTR). The evidence informing the ALS Guidelines is also included. When ILCOR has not addressed a specific topic, the ERC ALS Writing Group has provided its own guidance and the evidence supporting it. This section provides recommendations for ALS for adults with in- or out-of-hospital cardiac arrest. The ERC Guidelines 2025 ALS emphasise providing early and effective ALS interventions to improve survival from cardiac arrest in adults.}, }
@article {pmid41016645, year = {2025}, author = {Thumbadoo, KM and Nementzik, LR and Swanson, MEV and Dieriks, BV and Dragunow, M and Faull, RLM and Curtis, MA and Blair, IP and Nicholson, GA and Williams, KL and Scotter, EL}, title = {A meta-analysis of genetic variant pathogenicity and sex differences in UBQLN2-linked amyotrophic lateral sclerosis and frontotemporal dementia.}, journal = {Neurobiology of disease}, volume = {216}, number = {}, pages = {107127}, doi = {10.1016/j.nbd.2025.107127}, pmid = {41016645}, issn = {1095-953X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *Frontotemporal Dementia/genetics ; *Autophagy-Related Proteins/genetics ; *Adaptor Proteins, Signal Transducing/genetics ; Male ; Female ; *Genetic Variation/genetics ; *Sex Characteristics ; *Cell Cycle Proteins/genetics ; *Ubiquitins/genetics ; }, abstract = {Ubiquilin 2, encoded by the X-linked UBQLN2 gene, is a ubiquitin-binding quality control protein. Pathogenic UBQLN2 genetic variants cause X-linked dominant amyotrophic lateral sclerosis and/or frontotemporal dementia (ALS/FTD), however, clinical phenotypes from these variants show striking inter- and intra-familial heterogeneity. Further, there are many UBQLN2 variants whose significance to disease is uncertain. Here, we examine the pathogenic potential of UBQLN2 variants reported in individuals with ALS/FTD and their non-symptomatic relatives. Meta-analysis from 27 published studies identified 186 affected individuals and 51 asymptomatic carriers, each harbouring one of 43 unique UBQLN2 coding variants. Features of identified variants, including evolutionary conservation, minor allele frequencies, localisation to protein domains, and in silico predictions of pathogenicity were compiled. Per biological sex, clinical features were compared between UBQLN2 variants segregated by pathogenicity. Pathogenic UBQLN2 variant carriers, most of whom are familial ALS cases, showed a sex-specific difference in age at onset wherein males developed disease on average 18.15 years prior to females (29.54 ± 11.9 versus 47.69 ± 13.4 years, p < 0.0001), with no change in disease duration (p = 0.2091). UBQLN2 variants of uncertain significance showed a bimodal distribution of onset age per sex suggesting a mixture of true benign and true pathogenic variants. In human brain tissue, two male UBQLN2 p.Thr487Ile (ALS-FTD and ALS) cases showed a greater burden of ubiquilin 2 aggregates than a related female case (ALS-FTD). These robust sex-specific differences in ALS/FTD presentation in carriers of pathogenic UBQLN2 variants may improve predictions of ALS/FTD risk in carriers, aiding in diagnosis and disease management.}, }
@article {pmid40983380, year = {2025}, author = {Schellenberg, KL and Caspar-Bell, G and Ellis, C and Johnston, W and King, A and King, M and Korngut, L and Kushneriuk, B and Lavoie, AJ and McGonigle, R and Newton, J and O'Connell, C and Shoesmith, C and Suchowersky, O and Warman-Chardon, J and Wunder, S and Pfeffer, G}, title = {Best practice recommendations for the clinical care of spinal bulbar muscular atrophy.}, journal = {CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne}, volume = {197}, number = {31}, pages = {E987-E999}, pmid = {40983380}, issn = {1488-2329}, mesh = {Humans ; Canada ; *Bulbo-Spinal Atrophy, X-Linked/therapy/diagnosis ; Male ; }, abstract = {BACKGROUND: Although rare in the general population, spinal bulbar muscular atrophy (SBMA) is an X-linked recessive neuromuscular condition that is highly prevalent in people identifying as First Nations and Métis in western Canada. The aim of this guideline is to improve and standardize care of SBMA, and to increase awareness of the condition.<br><br>METHODS: Our interdisciplinary working group conducted a needs assessment survey to aid in the development of guideline topic questions, followed by a literature search, evidence review, and external review by health practitioners and people with lived experience. We followed the ADAPTE framework to evaluate the only pre-existing SBMA guideline (2020 French national protocol) and the 2020 Canadian amyotrophic lateral sclerosis guideline for appropriateness of adaptation. Our process adhered to the Appraisal of Guidelines for Research and Evaluation (AGREE II) tool; used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach; and followed the Guidelines International Network-McMaster Guideline Development Checklist. Indigenous community engagement was led by the Pewaseskwan Indigenous Research Group, who participated in the development of the guideline.<br><br>RECOMMENDATIONS: We developed 41 recommendations to address the continuum of care in SBMA, including diagnosis; multidisciplinary teams; management of limb and bulbar symptoms, respiratory and cardiac complications, and multisystem symptoms; female carriers; emotional supports; and considerations for Indigenous people. Spinal bulbar muscular atrophy is best managed by multidisciplinary teams that can address both its motor and nonmotor manifestations, including cardiac involvement, sensory symptoms, and metabolic dysfunction. Concerns for female carriers may include symptom management and genetic counselling. Providers should ensure culturally appropriate care for Indigenous people.<br><br>INTERPRETATION: In this guideline, we provide health care professionals with a culturally responsive standard of care for SBMA, and hope this will translate into improved quality of life for people affected by SBMA.}, }
@article {pmid40971912, year = {2026}, author = {Zhang, G and Ma, Y and Liu, Z and Jin, L and Zheng, D and Zhang, X and Jin, G}, title = {Intraocular lens power calculation formula accuracy in 1178 eyes with short axial length: systematic review and network meta-analysis.}, journal = {Journal of cataract and refractive surgery}, volume = {52}, number = {2}, pages = {202-207}, pmid = {40971912}, issn = {1873-4502}, mesh = {Humans ; *Axial Length, Eye/pathology ; *Biometry/methods ; *Lens Implantation, Intraocular ; *Lenses, Intraocular ; *Optics and Photonics ; *Refraction, Ocular/physiology ; }, abstract = {TOPIC: To systematically review the literature and conduct a comprehensive quantitative analysis to compare the accuracy of different intraocular lens (IOL) calculation formulas in eyes with short axial lengths (ALs).<br><br>CLINICAL RELEVANCE: The precision of the IOL formulas decreases when applied in eyes with short AL (AL <22 mm), and many new formulas for calculating IOL power have been proposed in the past few decades. However, the accuracy of these formulas has not been systematically compared when applied in eyes with short AL.<br><br>METHODS: This study systematically searched PubMed, Embase, Web of Science, and Cochrane Library databases to collect relevant research literature published between January 2003 and September 2023. Included were prospective or retrospective clinical studies involving cataract patients with short AL (AL <22 mm) and reporting the following outcomes: mean absolute error, median absolute error (MedAE), and percentage of eyes with a prediction error (PE) within &#xb1;0.25 diopters (D), &#xb1;0.50 D, and &#xb1;1.00 D. A network meta-analysis was performed using R software (v. 4.2.1).<br><br>RESULTS: 15 prospective or retrospective studies involving 1178 eyes and 12 calculation formulas were included in this study. The network meta-analysis showed that compared with the widely used Haigis formula, the Kane formula had a higher percentage of eyes with PE within the range of &#xb1;0.25 D, &#xb1;0.50 D, and &#xb1;1.00 D (all odds ratio >1, but P > .05). In addition, based on the surface under the cumulative ranking area (SUCRA), the Kane formula had the highest probability of predicting the PE of the eyes within the range of &#xb1;0.25 D, with its SUCRA value of 95.74%, followed by Haigis formula (94.79%) and Olsen Standalone formula (84.04%). The Kane and Olsen Standalone formulas had the lowest MedAE.<br><br>CONCLUSIONS: The Kane, Haigis, and Olsen Standalone formulas may perform better than other formulas in calculating the IOLs power in eyes with short AL. Nonetheless, significant uncertainty remains in this area. The accuracy of these formulas in patients with short AL needs to be verified by large multicenter registry studies.}, }
@article {pmid40908696, year = {2025}, author = {Paul, S and Tiwari, P and Dubey, S}, title = {Precision Enzyme: Targeted Drug Discovery in Neurodegenerative Disorders.}, journal = {Protein and peptide letters}, volume = {32}, number = {8}, pages = {539-556}, pmid = {40908696}, issn = {1875-5305}, mesh = {Humans ; *Drug Discovery/methods ; *Neurodegenerative Diseases/drug therapy/enzymology ; Molecular Docking Simulation ; *Enzyme Inhibitors/chemistry/therapeutic use/pharmacology ; Animals ; }, abstract = {INTRODUCTION: Neurodegenerative disorders such as Alzheimer's, Parkinson's, and ALS are characterized by progressive neuronal dysfunction with limited therapeutic options. Recent advances in molecular biology and drug development have highlighted the therapeutic promise of precision enzyme targeting, offering novel strategies for disease modulation and symptom management.<br><br>METHODS: A comprehensive literature review spanning recent/current was conducted using PubMed, Scopus, and ScienceDirect. Studies focusing on enzyme-based targets, high-throughput screening, and molecular docking in neurodegeneration were included. Thematic synthesis was employed to categorize findings based on enzyme class, disease relevance, and therapeutic outcomes.<br><br>RESULTS: Key enzyme families such as kinases, proteases, and oxidoreductases were identified as pivotal modulators in disease progression. Emerging enzyme-targeted compounds demonstrated enhanced bioavailability, blood-brain barrier permeability, and disease-specific efficacy. Novel screening platforms and computational modeling enabled the precise selection of inhibitors, significantly improving the therapeutic index and reducing off-target effects.<br><br>DISCUSSION: Targeting enzymes implicated in neuroinflammation, oxidative stress, and protein misfolding has shown disease-modifying potential. Integrating precision drug discovery tools, such as AI-assisted modeling and enzyme kinetics, supports rational drug design. However, translational challenges persist due to variability in enzyme expression and disease heterogeneity.<br><br>CONCLUSION: Future research should focus on refining enzyme inhibitors and integrating biomarkers to facilitate personalized treatment strategies for neurodegenerative disorders. As the understanding of enzymatic roles in neurodegeneration deepens, precision enzyme-targeted drug discovery holds significant promise in transforming neurotherapeutic approaches.}, }
@article {pmid40875341, year = {2025}, author = {Dang, J and Xiao, S}, title = {A meta-analytic reassessment of the vicious cycle of psychopathology and stressful life events: Commentary on Rnic et al. (2023).}, journal = {Psychological bulletin}, volume = {151}, number = {7}, pages = {930-939}, doi = {10.1037/bul0000475}, pmid = {40875341}, issn = {1939-1455}, mesh = {Humans ; *Stress, Psychological/psychology ; *Life Change Events ; *Mental Disorders/psychology/epidemiology ; Psychopathology ; }, abstract = {Rnic et al. (2023) conducted a comprehensive multilevel meta-analysis examining the stress generation hypothesis across various forms of psychopathology. They utilized the bivariate correlation between psychopathology at Time 1 and stress at Time 2 to estimate effect sizes. To address potential confounding from baseline stress assessments, we reanalyzed the data by (a) using the cross-lagged association in a multilevel meta-analysis to examine longitudinal links between Time 1 psychopathology and Time 2 stress and (b) incorporating Time 1 stress as a control variable in a meta-analytic structural equation model. Based on a subset of Rnic et al.'s original data set (33 studies with 18,684 participants and 126 effect sizes), our findings revealed cross-lagged associations of rC.L = .12 for the predictive effect of baseline psychopathology, especially internalizing psychopathology, on subsequent dependent stress and rC.L = .06 for independent stress. These effects were homogeneous across diverse samples, measures, and contexts. Moreover, even after controlling for Time 1 stress, dependent stress continued to mediate the relationship between baseline psychopathology and subsequent symptoms, whereas independent stress did not mediate, underscoring the role of dependent stress in perpetuating the cycle of stress and psychopathology. (PsycInfo Database Record (c) 2025 APA, all rights reserved).}, }
@article {pmid40875336, year = {2026}, author = {Yuan, Z and Yin, J and Sun, J}, title = {The paradox of team conflict revisited: An updated meta-analysis of the team conflict-team performance relationships.}, journal = {The Journal of applied psychology}, volume = {111}, number = {2}, pages = {195-224}, doi = {10.1037/apl0001315}, pmid = {40875336}, issn = {1939-1854}, mesh = {Humans ; *Conflict, Psychological ; *Group Processes ; *Interpersonal Relations ; *Work Performance ; *Cooperative Behavior ; *Employment/psychology ; }, abstract = {The possibility that team conflict, especially task conflict, might improve team performance has stimulated a large body of empirical research that continues to grow to this day. Nevertheless, 12 years has passed since de Wit et al.'s (2012) comprehensive meta-analysis. To synthesize the even larger body of empirical evidence now available, we provide an updated meta-analysis of the team conflict-team performance relationships by revisiting the population average estimates and their effect size heterogeneity. Given the recent developments in the team conflict literature, we also incorporate status conflict into our synthesis. Moreover, to shed light on the contextual factors that may help explain the heterogeneous team conflict-team performance relationships, we examine a host of moderators pertaining to national culture, team features, and research methods. Our results based on psychometric meta-analysis indicate that all four team conflict dimensions (i.e., task conflict, relationship conflict, process conflict, and status conflict) are negatively related to team performance. Moreover, the relationships of task conflict and relationship conflict with team performance have substantial cross-situation heterogeneity. Examining the contingencies of these heterogeneous relationships, our metaregression analyses reveal that national culture (e.g., individualism), team features (e.g., team performance facet), and methodological factors (e.g., team conflict scale) all play important roles in helping to explain the mixed effects of team conflict on team performance. Based on our quantitative synthesis, we discuss the implications for the next waves of team conflict research. (PsycInfo Database Record (c) 2026 APA, all rights reserved).}, }
@article {pmid40849781, year = {2025}, author = {Kurochkina, N and Rudrabhatla, P}, title = {Role of Calmodulin in Neurodegeneration and Neuroprotection.}, journal = {Mini reviews in medicinal chemistry}, volume = {25}, number = {13}, pages = {965-974}, pmid = {40849781}, issn = {1875-5607}, support = {1142025//School of Theoretical Modeling, Washington, DC, USA/ ; }, mesh = {*Calmodulin/metabolism/chemistry/antagonists &amp; inhibitors ; Humans ; *Neurodegenerative Diseases/metabolism/drug therapy/pathology ; Animals ; *Neuroprotection ; *Neuroprotective Agents/pharmacology/chemistry ; Calcium/metabolism ; }, abstract = {Intracellular calcium (Ca[2+]) levels are critical in maintaining cellular activities and are tightly regulated. Neuronal degeneration and regeneration rely on calcium-binding proteins. Calmodulin (CaM) is a calcium sensor and the primary regulator of receptors and ion channels that maintain calcium homeostasis. The calmodulin binding domains are present in proteins that serve as risk factors and biomarkers associated with Alzheimer's disease, Parkinson's disease, Huntington's disease, Amyotrophic Lateral Sclerosis, and other neurodegenerative diseases, suggesting calmodulin ligands as emerging therapeutic targets for treatment. Inhibiting CaM to develop new therapies has drawbacks, as CaM is a ubiquitous molecule involved in many regulatory pathways. Recently, new strategies for disrupting CaM interactions with its targets have shown promising approaches to treatment. The structures of human CaM, its binding proteins, and inhibitors are well studied, with particular emphasis on the conservation of CaM amino acid sequences and the ability to bind protein fragments of high sequence variability, which exhibit common characteristics of amphipathic helices carrying basic amino acids. In this review, we discuss structural characteristics of CaM and its ligands in the context of transcriptional regulation. Specific binding of CaM to (1) basic region/helix-loop-helix/leucine zipper and (2) helix-turn-helix high mobility group box containing Sox families of transcription factors highlights common features of CaM binding sequences, which suggest their regulatory functions. We describe key proteins involved in neurodegeneration and transcription factors subject to calmodulin regulation that are candidates for the development of new approaches to treating neuronal diseases.}, }
@article {pmid40646421, year = {2025}, author = {McCormick, CR and Christie, J}, title = {Assessing Posner's theory of alerting: A meta-analysis of speed-accuracy effects.}, journal = {Attention, perception &amp; psychophysics}, volume = {87}, number = {6}, pages = {2007-2028}, pmid = {40646421}, issn = {1943-393X}, mesh = {Humans ; *Reaction Time ; *Attention ; *Pattern Recognition, Visual ; *Psychological Theory ; *Orientation ; Cues ; Psychomotor Performance ; Discrimination, Psychological ; }, abstract = {Posner and his colleagues proposed a seminal theory of how alerting influenced information processing over 50 years ago (Posner et al., Memory &amp; Cognition, 1, 2-12, 1973). In this study, participants were presented with warning signals at varying intervals before a target, and participants were asked to produce a spatial discrimination response. Trials in which participants were played a warning signal were compared to trials without a warning signal to understand the effect of phasic alerting using reaction time (RT) and error rate (ER). Posner and colleagues observed a general speed-accuracy trade-off (SAT) across conditions, in which faster RTs led to higher ER, and concluded that phasic alertness shifts response criteria without improving the efficiency of information processing. More recent research has questioned whether this theory of alerting applies generally across all time-courses and conditions. The current meta-analysis aimed to test Posner's theory of alerting (1975) using all available data in the field that closely matches the methodology used in Posner et al.'s Memory &amp; Cognition, 1, 2-12, (1973) influential study. After including data from 16 published experiments across three different signal-target foreperiod durations, our conclusions support that while a speed-accuracy trade-off is likely present at shorter foreperiods (50 ms), the longer foreperiods (200 and 400 ms) show evidence of an increase in the rate of information processing when the participant was alerted.}, }
@article {pmid40300556, year = {2025}, author = {Zhou, S and Zhou, P and Yang, T and Si, J and An, W and Jiang, Y}, title = {Glucosamine supplementation contributes to reducing the risk of type 2 diabetes: Evidence from Mendelian randomization combined with a meta-analysis.}, journal = {The Journal of international medical research}, volume = {53}, number = {4}, pages = {3000605251334460}, pmid = {40300556}, issn = {1473-2300}, mesh = {Humans ; *Diabetes Mellitus, Type 2/genetics/prevention &amp; control/epidemiology ; *Glucosamine/administration &amp; dosage/therapeutic use ; Mendelian Randomization Analysis ; *Dietary Supplements ; Genome-Wide Association Study ; Risk Factors ; Polymorphism, Single Nucleotide ; }, abstract = {ObjectiveObservational studies on glucosamine supplementation and type 2 diabetes risk have shown inconsistent results, necessitating the use of Mendelian randomization to clarify the true causal relationship.MethodsThe glucosamine supplementation-related genome-wide association study dataset was obtained from the MRC Integrative Epidemiology Unit consortium, whereas type 2 diabetes-related genome-wide association study datasets were obtained from the FinnGen consortium (discovery) and Xue et al.'s meta-analysis (validation). Two-sample Mendelian randomization analyses were performed separately in the discovery and validation datasets, followed by meta-analysis and multivariable Mendelian randomization analyses to verify the robustness of the results of two-sample Mendelian randomization. The estimation of the causal relationship was conducted through the inverse variance weighted method.ResultsGlucosamine supplementation exhibited a significant protective effect against type 2 diabetes, as identified by two-sample Mendelian randomization analysis in the FinnGen consortium (odds ratio: 0.13, 95% confidence interval: 0.02-0.89) and validated in Xue et al.'s meta-analysis (odds ratio: 0.06, 95%; confidence interval: 0.01-0.29). A combined meta-analysis (odds ratio: 0.08, 95%; confidence interval: 0.02-0.27) of the results of two-sample Mendelian randomization confirmed the robustness of these findings. Additionally, multivariable Mendelian randomization analysis (odds ratio: 0.12, 95%; confidence interval: 0.02-0.94), after adjusting for confounding factors, supported the results of two-sample Mendelian randomization. No evidence of heterogeneity or pleiotropy was observed.ConclusionOverall, our results revealed that genetically predicted glucosamine supplementation was inversely associated with the risk of type 2 diabetes, highlighting the potential importance of glucosamine supplementation in preventing type 2 diabetes.}, }
@article {pmid39904709, year = {2025}, author = {Vahey, N and Nicholson, E and Barnes-Holmes, D}, title = {A decade on: Reflecting on the limitations of the first meta-analysis of the Implicit Relational Assessment Procedure's (IRAP) criterion validity in the clinical domain.}, journal = {Journal of behavior therapy and experimental psychiatry}, volume = {87}, number = {}, pages = {102016}, doi = {10.1016/j.jbtep.2024.102016}, pmid = {39904709}, issn = {1873-7943}, mesh = {Humans ; *Meta-Analysis as Topic ; Reproducibility of Results ; }, abstract = {Hussey (in press) recently conducted a detailed critical reanalysis of Vahey, Nicholson and Barnes-Holmes' (2015) meta-analysis. Its stated purpose was to (a) examine the extent to which Vahey et al.'s (2015) meta-analysis contains errors; and (b) to test how computationally reproducible it is by current standards of best practice. Hussey identified a small number of minor numerical errors, but crucially was unable to exactly replicate the original meta-effect of r‾ = .45. Six different variations of the meta-analysis reported by Vahey et al. were used and obtained meta-effects that deviated from the original by Δr‾ = .01-.02. Hussey also reported corresponding 95% credibility intervals that were all of zero width. These discrepancies prompted the present authors to conduct a detailed audit of the original meta-analysis. This revealed one minor transposing error in addition to three identified by Hussey. Once corrected this resulted in a marginally increased Hunter and Schmidt meta-analytic effect of r‾ = .46 without a credibility interval, and a Hedges-Vevea meta-effect of r‾ = .47 with 95% confidence interval (.40, .54). This correction was too small to have any bearing on Vahey et al.'s supplementary analyses regarding publication bias or statistical power. Vahey et al. contained a much lower proportion of transposing errors than is typical of meta-analyses even still (cf. Kadlec, Sainani, &amp; Nimphius, 2023; Lakens et al., 2016; Lakens et al., 2017). Nonetheless, Hussey highlighted important ambiguities about the theoretical and practical meaning of the meta-effect reported by Vahey et al. We clarify our position on these matters in summary, and in so doing explain why we believe that the wider IRAP literature would undoubtedly benefit from increased adoption of contemporary open science standards.}, }
@article {pmid39786806, year = {2025}, author = {Yang, S and Song, J and Deng, M and Cheng, S}, title = {Identification of Drug-Targetable Genes for Eczema and Dermatitis Using Integrated Genomic and Proteomic Approaches.}, journal = {Dermatitis : contact, atopic, occupational, drug}, volume = {36}, number = {4}, pages = {369-381}, doi = {10.1089/derm.2024.0429}, pmid = {39786806}, issn = {2162-5220}, mesh = {Humans ; *Eczema/genetics/drug therapy ; Proteomics ; Polymorphism, Single Nucleotide ; Genome-Wide Association Study ; Quantitative Trait Loci ; Mendelian Randomization Analysis ; Genomics ; *Dermatitis/genetics/drug therapy ; }, abstract = {Background: Eczema and dermatitis are common inflammatory skin conditions with significant morbidity. Identifying drug-targetable genes can facilitate the development of effective treatments. Methods: This study analyzed data obtained by meta-analysis of 2 genome-wide association studies on eczema/dermatitis (57,311 cases and 896,779 controls, European ancestry). We identified drug-targetable genes from the Drug-Gene Interaction Database and Finan et al's findings. Cis-expression quantitative trait loci (eQTL) data from human blood and skin tissues were used for Mendelian randomization (MR) analysis. Bayesian colocalization, proteomic MR, and meta-analysis validated the causal relationships. Finally, protein-protein interactions (PPIs) and correlation analysis of potential drug targets and cytokines were performed. Results: We identified 2532 drug-targetable genes; 3378 Single Nucleotide Polymorphism (SNPs) were associated with 1531 genes in blood cis-eQTLs, 664 SNPs with 667 genes in sun-exposed skin eQTLs, and 572 SNPs with 574 genes in nonsun-exposed skin eQTLs. Five genes (SLC22A5, NOTCH4, AGER, HLA-DRB5, and EHMT2) showed causal relationships with eczema/dermatitis across multiple datasets. Single-variable and multi-variable Mendelian randomization (SMR) and multi-SNP SMR analysis identified 8 genes (PIK3R4, DHODH, CXCR2, Interleukin (IL)18, LGALS9, RPS6KB2, SLC22A5, and AGER) across all tissues. Functional Summary Information for Variants in the Online Network (FUSION) analysis confirmed associations for SLC22A5 and AGER. Bayesian colocalization indicated AGER (PPH4: 0.95) as a shared causal variant. Proteomic MR and meta-analysis showed that increased AGER protein levels were associated with a lower risk of eczema or dermatitis (odds ratio: 0.995, 95% confidence interval: 0.997-0.993, P = 0.0002). A PPI network revealed interactions of AGER with NOTCH4 and multiple cytokines, whereas SLC22A5 showed no cytokine interactions. Conclusions: This study identified potential drug-targetable genes, with AGER showing strong potential as a target for reducing eczema/dermatitis risk. These findings provide a basis for developing targeted therapies.}, }
@article {pmid39496035, year = {2024}, author = {Xu, W and Zhao, X and Wang, J and Guo, Y and Ren, Z and Cai, L and Wu, S and Zhou, M}, title = {Different intensities of physical activity for amyotrophic lateral sclerosis and Parkinson disease: A Mendelian randomization study and meta-analysis.}, journal = {Medicine}, volume = {103}, number = {44}, pages = {e40141}, pmid = {39496035}, issn = {1536-5964}, support = {ZYYLJRC201911//the Anhui Province Traditional Chinese Medicine Leading Talents Construction Project/ ; }, mesh = {Humans ; *Mendelian Randomization Analysis ; *Amyotrophic Lateral Sclerosis/genetics ; *Parkinson Disease/genetics/epidemiology ; *Exercise ; Genome-Wide Association Study ; }, abstract = {BACKGROUND: The causal relationships between amyotrophic lateral sclerosis (ALS), Parkinson disease and different intensities of physical activity (PA) are still inconclusive. To evaluate the causal impact of PA on ALS and Parkinson disease (PD), this study integrates evidence from Mendelian randomization (MR) using a meta-analysis approach.<br><br>METHODS: MR analyses on genetically predicted levels of PA (compose of self-reported moderate-to-vigorous physical activity [MVPA], self-reported vigorous physical activity [VPA], and strenuous sports or other exercises [SSOE]) regarding ALS and PD published up to July 27, 2024, were obtained from PubMed, Scopus, Web of Science, and Embase. De novo MR studies were analyzed utilizing publicly accessible datasets from genome-wide association studies and then meta-analyses were performed to pool the results.<br><br>RESULTS: Meta-analyses of results of 12 de novo MR studies analyses and 2 published MR studies indicated that genetic predicted levels of MVPA (odds ratio [OR]: 1.22, 95% confidence interval [CI]: 1.08-1.38), VPA (OR: 1.32, 95% CI: 1.08-1.60), and SSOE (OR: 1.35, 95% CI: 1.07-1.70) were related to a raised risk of ALS, but not causally with PD.<br><br>CONCLUSION: Our findings showed no causal relationships between MVPA, VPA, SSOE, and PD, while MVPA, VPA, and SSOE were associated with increased ALS risk, highlighting the need for targeted PA recommendations for disease management.}, }
@article {pmid39378530, year = {2025}, author = {Meng, T and Wu, W and Wang, B and Li, C and Li, J and Liu, J and Wang, J and Qie, R}, title = {Treating chronic pulmonary heart disease with traditional Chinese medicine: Systematic evaluation and mechanistic insights into the resolving phlegm and activating blood approach.}, journal = {Heart &amp; lung : the journal of critical care}, volume = {69}, number = {}, pages = {111-126}, doi = {10.1016/j.hrtlng.2024.09.017}, pmid = {39378530}, issn = {1527-3288}, mesh = {Humans ; Chronic Disease ; *Drugs, Chinese Herbal/therapeutic use/pharmacology ; *Medicine, Chinese Traditional/methods ; *Pulmonary Heart Disease/drug therapy ; Randomized Controlled Trials as Topic ; }, abstract = {BACKGROUND: Chronic Pulmonary Heart Disease (CPHD) significantly impacts global health, especially among middle-aged and older adults. In China, the Traditional Chinese Medicine (TCM) technique of Resolving Phlegm and Activating Blood (RPAB) is widely used to treat CPHD, although high-quality evidence supporting its efficacy remains limited.<br><br>OBJECTIVES: The purpose of this study was to rigorously assess the clinical efficacy of RPAB for CPHD and elucidate the mechanisms underlying its primary herbal components.<br><br>METHODS: Through a detailed search of literature in both Chinese and English and strict inclusion and exclusion criteria, 18 randomized controlled trials (RCTs) were selected for meta-analysis. We identified RPAB's core herbal combinations using association rule analysis. This method statistically analyzes the frequency and correlation of herbal medicine usage. We then analyzed the chemical components of these combinations and investigated their potential intervention mechanisms on CPHD through network pharmacology.<br><br>RESULTS: The combination of RPAB with Western medicine was superior to Western medicine alone in improving blood gas analysis and pulmonary function and reducing plasma viscosity in CPHD patients. The core herbal combination identified was Astragalus membranaceus (Fisch.) Bunge, Ligusticum chuanxiong Hort. ex S. H. Qiu &amp; al., and Stellaria alsine Grimm (ALS). This combination targeted 588 therapeutic and 27 core targets. It influenced ten core compounds across 34 pathways, primarily through the chemokine signaling pathway and the JAK-STAT signaling pathway.<br><br>CONCLUSION: RPAB with Western medicine significantly improves CPHD treatment outcomes. The study highlights the therapeutic potential of the ALS combination, which operates through multiple pathways to remodel pulmonary arteries, decrease inflammation, and lessen oxidative stress. These insights support the clinical application of RPAB in CPHD treatment and open new avenues for research and therapeutic development.}, }
@article {pmid39122262, year = {2024}, author = {Wang, S and Jiang, Q and Zheng, X and Wei, Q and Lin, J and Yang, T and Xiao, Y and Li, C and Shang, H}, title = {Genotype-phenotype correlation of SQSTM1 variants in patients with amyotrophic lateral sclerosis.}, journal = {Journal of medical genetics}, volume = {61}, number = {10}, pages = {966-972}, doi = {10.1136/jmg-2023-109569}, pmid = {39122262}, issn = {1468-6244}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Amyotrophic Lateral Sclerosis/genetics/pathology/epidemiology ; Frontotemporal Dementia/genetics/pathology ; Gene Frequency ; *Genetic Association Studies ; Genetic Predisposition to Disease ; Genotype ; Mutation ; Phenotype ; *Sequestosome-1 Protein/genetics ; Young Adult ; Aged, 80 and over ; }, abstract = {BACKGROUND: Several variants of sequestosome 1 (SQSTM1) were screened in patients with amyotrophic lateral sclerosis (ALS), while the pathogenicity and genotype-phenotype correlation remains unclear.<br><br>METHODS: We screened variants of SQSTM1 gene in 2011 Chinese patients with ALS and performed a burden analysis focusing on the rare variants. Furthermore, we conducted a comprehensive analysis of patients with variants of SQSTM1 gene in patients with ALS from our cohort and published studies.<br><br>RESULTS: In our cohort, we identified 32 patients with 25 different SQSTM1 variants with a mutant frequency of 1.6%. Notably, 26% (5/19) of the patients with ALS with SQSTM1 variant in our cohort had comorbid cognitive impairment and 43% (3/7) of them had behavioural variant frontotemporal dementia (FTD). Our meta-analysis found a total frequency of SQSTM1 variants in 7183 patients with ALS was 2.4%; burden analysis indicated that patients with ALS had enrichment of ultra-rare (minor allele frequency<0.01%) probably pathogenic variants in SQSTM1. Most variants were missense variants and distributed in various domains of p62 protein, some of which might be related to comorbidities of Paget's disease of bone and FTD.<br><br>CONCLUSION: Our study established the largest cohort of patients with ALS with SQSTM1 variants, expanded the mutation spectrum and investigated the genotype-phenotype correlations of SQSTM1 variants.}, }
@article {pmid39085618, year = {2024}, author = {Müller, KJ and Schmidbauer, ML and Schönecker, S and Kamm, K and Pelz, JO and Holzapfel, K and Papadopoulou, M and Bakola, E and Tsivgoulis, G and Naumann, M and Hermann, A and Walter, U and Dimitriadis, K and Reilich, P and Schöberl, F}, title = {Diagnostic accuracy and confounders of vagus nerve ultrasound in amyotrophic lateral sclerosis-a single-center case series and pooled individual patient data meta-analysis.}, journal = {Journal of neurology}, volume = {271}, number = {9}, pages = {6255-6263}, pmid = {39085618}, issn = {1432-1459}, support = {DFG TRR 338//Deutsche Forschungsgemeinschaft/ ; DFG TRR 274//Deutsche Forschungsgemeinschaft/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/diagnostic imaging/diagnosis ; Humans ; Male ; Aged ; Female ; Middle Aged ; *Ultrasonography ; *Vagus Nerve/diagnostic imaging ; }, abstract = {BACKGROUND: Several single-center studies proposed utility of vagus nerve (VN) ultrasound for detecting disease severity, autonomic dysfunction, and bulbar phenotype in amyotrophic lateral sclerosis (ALS). However, the resulting body of literature shows opposing results, leaving considerable uncertainty on the clinical benefits of VN ultrasound in ALS.<br><br>METHODS: Relevant studies were identified up to 04/2024 and individual patient data (IPD) obtained from the respective authors were pooled with a so far unpublished cohort (from Munich). An IPD meta-analysis of 109 patients with probable or definite ALS (El Escorial criteria) and available VN cross-sectional area (CSA) was performed, with age, sex, ALS Functional Rating Scale-revised (ALSFRS-R), disease duration, and bulbar phenotype as independent variables.<br><br>RESULTS: Mean age was 65&#xa0;years (&#xb1;&#x2009;12) and 47% of patients (&#xb1;&#x2009;12) had bulbar ALS. Mean ALSFRS-R was 38 (&#xb1;&#x2009;7), and mean duration was 18&#xa0;months (&#xb1;&#x2009;18). VN atrophy was highly prevalent [left: 67% (&#xb1;&#x2009;5), mean CSA 1.6mm[2] (&#xb1;&#x2009;0.6); right: 78% (&#xb1;&#x2009;21), mean CSA 1.8 mm[2] (&#xb1;&#x2009;0.7)]. VN CSA correlated with disease duration (mean slope: left -&#xa0;0.01; right -&#xa0;0.01), but not with ALSFRS-R (mean slope: left 0.004; mean slope: right -&#xa0;0.002). Test accuracy for phenotyping bulbar vs. non-bulbar ALS was poor (summary receiver operating characteristic area under the curve: left 0.496; right 0.572).<br><br>CONCLUSION: VN atrophy in ALS is highly prevalent and correlates with disease duration, but not with ALSFRS-R. VN CSA is insufficient to differentiate bulbar from non-bulbar ALS phenotypes. Further studies are warranted to analyze the link between VN atrophy, autonomic impairment, and survival in ALS.}, }
@article {pmid38968276, year = {2024}, author = {El Ouardi, L and Yeou, M}, title = {Are Personal and Reflexive Pronouns Dissociated in Agrammatic Comprehension? An Individual Participant Meta-Analysis With Clinical Implications.}, journal = {American journal of speech-language pathology}, volume = {33}, number = {6S}, pages = {3218-3235}, pmid = {38968276}, issn = {1558-9110}, mesh = {Humans ; Aphasia, Broca/physiopathology ; *Comprehension/physiology ; Semantics ; }, abstract = {PURPOSE: This study had three objectives: (a) to verify if Grodzinsky et al.'s (1993) findings of worse comprehension of personal than reflexive pronouns can be replicated in a larger meta-analysis of individual participant data, (b) to examine if the heterogeneity found in the patterns of pronoun comprehension in agrammatism can be attributed to task effects, and (c) to evaluate the risk of bias in the reviewed studies.<br><br>METHOD: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic literature search was performed to identify studies examining the personal-reflexive pronoun dissociation in agrammatic comprehension. Seven studies met the search criteria and were included in the meta-analysis. For each participant, individual accuracy scores for the comprehension of personal and reflexive pronouns were extracted in addition to information on the study methods. Individual accuracy data were analyzed using the Fisher's exact test and the binomial test. The risk of bias in the studies was assessed using an adapted version of the Newcastle-Ottawa Quality Assessment Scale.<br><br>RESULTS: The meta-analysis had three main findings: (a) The majority of the persons with agrammatic aphasia (89%) had no dissociation between the comprehension of personal and reflexive pronouns; (b) 8% revealed a pattern consistent with a neuropsychological dissociation, faring worse on the comprehension of personal than reflexive pronouns; and (c) 2% performed worse on reflexive than personal pronouns. The type of the task used affected pronoun comprehension accuracy and accounted for the heterogeneity in the patterns of pronoun comprehension attested across the different participants.<br><br>CONCLUSIONS: Taken together, the meta-analysis did not support a dissociation between personal and reflexive pronoun comprehension in agrammatic comprehension. When confirmed, the dissociation was driven by task effects. The clinical implications of these findings were discussed together with implications to minimize the risk of bias in future examinations of the topic.}, }
@article {pmid38937912, year = {2024}, author = {Verde, F and Licaj, S and Soranna, D and Ticozzi, N and Silani, V and Zambon, A}, title = {Cerebrospinal fluid and blood neurofilament light chain levels in amyotrophic lateral sclerosis and frontotemporal degeneration: A meta-analysis.}, journal = {European journal of neurology}, volume = {31}, number = {9}, pages = {e16371}, pmid = {38937912}, issn = {1468-1331}, support = {//Ministero della Salute/ ; //BIBLIOSAN/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/cerebrospinal fluid/blood ; Humans ; *Neurofilament Proteins/blood/cerebrospinal fluid ; *Frontotemporal Lobar Degeneration/blood/cerebrospinal fluid ; Biomarkers/cerebrospinal fluid/blood ; Frontotemporal Dementia/cerebrospinal fluid/blood ; }, abstract = {BACKGROUND AND PURPOSE: Neurofilament light chain (NFL) has been shown to be increased in amyotrophic lateral sclerosis (ALS) and, to a lesser extent, in frontotemporal dementia (FTD). A meta-analysis of NFL in ALS and FTD was performed.<br><br>METHODS: Available studies comparing cerebrospinal fluid and blood NFL levels in ALS versus neurologically healthy controls (NHCs), other neurological diseases (ONDs) and ALS mimics, as well as in FTD and related entities (behavioural variant of FTD and frontotemporal lobar degeneration syndromes) versus NHCs, ONDs and other dementias were evaluated.<br><br>RESULTS: In ALS, both cerebrospinal fluid and blood levels of NFL were higher compared to other categories. In FTD, behavioural variant of FTD and frontotemporal lobar degeneration syndromes, NFL levels were consistently higher compared to NHCs; however, several comparisons with ONDs and other dementias did not demonstrate significant differences.<br><br>DISCUSSION: Amyotrophic lateral sclerosis is characterized by higher NFL levels compared to most other conditions. In contrast, NFL is not as good at discriminating FTD from other dementias.}, }
@article {pmid38924633, year = {2024}, author = {Wolf, J and Buckley, GJ and Rozanski, EA and Fletcher, DJ and Boller, M and Burkitt-Creedon, JM and Weigand, KA and Crews, M and Fausak, ED and , }, title = {2024 RECOVER Guidelines: Advanced Life Support. Evidence and knowledge gap analysis with treatment recommendations for small animal CPR.}, journal = {Journal of veterinary emergency and critical care (San Antonio, Tex. : 2001)}, volume = {34 Suppl 1}, number = {}, pages = {44-75}, doi = {10.1111/vec.13389}, pmid = {38924633}, issn = {1476-4431}, support = {//Zoetis Animal Health/ ; //Boehringer Ingelheim Animal Health/ ; }, mesh = {Animals ; Dogs ; Cats ; *Dog Diseases/therapy/drug therapy ; Cardiopulmonary Resuscitation/veterinary/standards ; Cat Diseases/therapy/drug therapy ; Veterinary Medicine/standards ; Heart Arrest/veterinary/therapy ; }, abstract = {OBJECTIVE: To systematically review the evidence and devise clinical recommendations on advanced life support (ALS) in dogs and cats and to identify critical knowledge gaps.<br><br>DESIGN: Standardized, systematic evaluation of literature pertinent to ALS following Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Prioritized questions were each reviewed by Evidence Evaluators, and findings were reconciled by ALS Domain Chairs and Reassessment Campaign on Veterinary Resuscitation (RECOVER) Co-Chairs to arrive at treatment recommendations commensurate to quality of evidence, risk:benefit relationship, and clinical feasibility. This process was implemented using an Evidence Profile Worksheet for each question that included an introduction, consensus on science, treatment recommendations, justification for these recommendations, and important knowledge gaps. A draft of these worksheets was distributed to veterinary professionals for comment for 4&#xa0;weeks prior to finalization.<br><br>SETTING: Transdisciplinary, international collaboration in university, specialty, and emergency practice.<br><br>RESULTS: Seventeen questions pertaining to vascular access, vasopressors in shockable and nonshockable rhythms, anticholinergics, defibrillation, antiarrhythmics, and adjunct drug therapy as well as open-chest CPR were reviewed. Of the 33 treatment recommendations formulated, 6 recommendations addressed the management of patients with nonshockable arrest rhythms, 10 addressed shockable rhythms, and 6 provided guidance on open-chest CPR. We recommend against high-dose epinephrine even after prolonged CPR and suggest that atropine, when indicated, is used only once. In animals with a shockable rhythm in which initial defibrillation was unsuccessful, we recommend doubling the defibrillator dose once and suggest vasopressin (or epinephrine if vasopressin is not available), esmolol, lidocaine in dogs, and/or amiodarone in cats.<br><br>CONCLUSIONS: These updated RECOVER ALS guidelines clarify the approach to refractory shockable rhythms and prolonged CPR. Very low quality of evidence due to absence of clinical data in dogs and cats continues to compromise the certainty with which recommendations can be made.}, }
@article {pmid38924627, year = {2024}, author = {Burkitt-Creedon, JM and Boller, M and Fletcher, DJ and Brainard, BM and Buckley, GJ and Epstein, SE and Fausak, ED and Hopper, K and Lane, SL and Rozanski, EA and Wolf, J}, title = {2024 RECOVER Guidelines: Updated treatment recommendations for CPR in dogs and cats.}, journal = {Journal of veterinary emergency and critical care (San Antonio, Tex. : 2001)}, volume = {34 Suppl 1}, number = {}, pages = {104-123}, doi = {10.1111/vec.13391}, pmid = {38924627}, issn = {1476-4431}, support = {//Boehringer Ingelheim Animal Health/ ; //Zoetis Animal Health/ ; }, mesh = {Dogs ; Animals ; Cats ; *Cardiopulmonary Resuscitation/veterinary/standards/methods ; *Cat Diseases/therapy ; Dog Diseases/therapy ; Heart Arrest/veterinary/therapy ; }, abstract = {OBJECTIVE: After the 2012 Reassessment Campaign on Veterinary Resuscitation (RECOVER) CPR Guidelines, this is an update of evidence-based consensus guidelines for Basic Life Support (BLS), advanced life support (ALS), and periarrest monitoring.<br><br>DESIGN: These RECOVER CPR Guidelines were generated using a modified version of the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system for evidence evaluation and translation of this evidence into clear and actionable clinical instructions. Prioritized clinical questions in the Population, Intervention, Comparator, and Outcome (PICO) format were used as the basis to conduct systematic literature searches by information specialists, to extract information from relevant publications, to assess this evidence for quality, and finally to translate the findings into treatment recommendations. These recommendations were reviewed by the RECOVER writing group and opened for comment by veterinary professionals for 4&#xa0;weeks.<br><br>SETTING: Transdisciplinary, international collaboration in university, specialty, and emergency practice.<br><br>RESULTS: A total of 40 worksheets were prepared to evaluate questions across the 3 domains of BLS, ALS and Monitoring, resulting in 90 individual treatment recommendations. High-dose epinephrine is no longer recommended, and atropine, if used, is only administered once. Bag-mask ventilation is prioritized over mouth-to-nose ventilation in nonintubated animals. In addition, an algorithm for initial assessment, an updated CPR algorithm, a rhythm diagnosis tool, and an updated drug dosing table are provided.<br><br>CONCLUSIONS: While the majority of the BLS and ALS recommendations remain unchanged, some noteworthy changes were made due to new evidence that emerged over the past 10&#xa0;years. Indirectness of evidence remains the largest impediment to the certainty of guidelines formulation and underscores an urgent need for more studies in the target species of dogs and cats.}, }
@article {pmid38627298, year = {2024}, author = {Hamad, AA and Amer, BE}, title = {Safety of masitinib in patients with neurodegenerative diseases: a meta-analysis of randomized controlled trials.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {7}, pages = {3503-3507}, pmid = {38627298}, issn = {1590-3478}, mesh = {Humans ; *Randomized Controlled Trials as Topic ; *Thiazoles/adverse effects/administration &amp; dosage/therapeutic use ; *Neurodegenerative Diseases/drug therapy ; *Piperidines/adverse effects/therapeutic use/administration &amp; dosage ; *Benzamides/adverse effects/administration &amp; dosage ; *Pyridines/adverse effects/administration &amp; dosage/therapeutic use ; Protein Kinase Inhibitors/adverse effects/administration &amp; dosage ; }, abstract = {OBJECTIVES: This meta-analysis aimed to examine the safety of masitinib in patients with neurodegenerative diseases.<br><br>METHODS: We considered randomized controlled trials (RCTs) comparing different doses of masitinib versus placebo. We performed our analysis using the R (v.4.3.0) programming language and the incidence of adverse events was pooled using risk ratio (RR) and 95% confidence interval (CI).<br><br>RESULTS: We included five RCTs, focusing on multiple sclerosis (MS), Alzheimer's disease (AD), and amyotrophic lateral sclerosis. The meta-analysis revealed a significantly higher incidence of adverse events in the masitinib group compared to the control group, regardless of adverse event grade and masitinib dose (RR = 1.12, 95% CI [1.07 to 1.17], P < 0.01). Adverse events categorized as severe, non-fatal serious, leading to dose reduction, and leading to permanent discontinuation also showed a higher incidence in the masitinib group (P &#x2264; 0.01). Subgroup analysis for AD and MS supported these findings. The pooled incidence of adverse events, regardless of their grade, was higher in the masitinib group for both the 3 mg/kg/d dose (RR = 1.13, P = 0.01) and the 4.5 mg/kg/d dose (RR = 1.11, P < 0.01). However, there was no significant difference between masitinib 3 mg/kg/d dose and placebo regarding severe and non-fatal serious adverse events for the.<br><br>CONCLUSION: Masitinib use in neurodegenerative diseases presents safety concerns that may impact patients' quality of life and require management. Further research is recommended to determine the optimal dose with minimal safety concerns in this patient population.}, }
@article {pmid38522911, year = {2024}, author = {Urushitani, M and Warita, H and Atsuta, N and Izumi, Y and Kano, O and Shimizu, T and Nakayama, Y and Narita, Y and Nodera, H and Fujita, T and Mizoguchi, K and Morita, M and Aoki, M}, title = {The clinical practice guideline for the management of amyotrophic lateral sclerosis in Japan-update 2023.}, journal = {Rinsho shinkeigaku = Clinical neurology}, volume = {64}, number = {4}, pages = {252-271}, doi = {10.5692/clinicalneurol.cn-001946}, pmid = {38522911}, issn = {1882-0654}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/diagnosis ; Disease Progression ; Evidence-Based Medicine ; Japan ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is an adult-onset intractable motor neuron disease characterized by selective degeneration of cortical neurons in the frontotemporal lobe and motor neurons in the brainstem and spinal cord. Impairment of these neural networks causes progressive muscle atrophy and weakness that spreads throughout the body, resulting in life-threatening bulbar palsy and respiratory muscle paralysis. However, no therapeutic strategy has yet been established to halt ALS progression. Although evidence for clinical practice in ALS remains insufficient, novel research findings have steadily accumulated in recent years. To provide updated evidence-based or expert consensus recommendations for the diagnosis and management of ALS, the ALS Clinical Practice Guideline Development Committee, approved by the Japanese Society of Neurology, revised and published the Japanese clinical practice guidelines for the management of ALS in 2023. In this guideline, disease-modifying therapies that have accumulated evidence from randomized controlled trials were defined as "Clinical Questions," in which the level of evidence was determined by systematic reviews. In contrast, "Questions and Answers" were defined as issues of clinically important but insufficient evidence, according to reports of a small number of cases, observational studies, and expert opinions. Based on a literature search performed in February 2022, recommendations were reached by consensus, determined by an independent panel, reviewed by external reviewers, and submitted for public comments by Japanese Society of Neurology members before publication. In this article, we summarize the revised Japanese guidelines for ALS, highlighting the regional and cultural diversity of care processes and decision-making. The guidelines cover a broad range of essential topics such as etiology, diagnostic criteria, disease monitoring and treatments, management of symptoms, respiration, rehabilitation, nutrition, metabolism, patient instructions, and various types of care support. We believe that this summary will help improve the daily clinical practice for individuals living with ALS and their caregivers.}, }
@article {pmid38470068, year = {2024}, author = {Van Damme, P and Al-Chalabi, A and Andersen, PM and Chiò, A and Couratier, P and De Carvalho, M and Hardiman, O and Kuźma-Kozakiewicz, M and Ludolph, A and McDermott, CJ and Mora, JS and Petri, S and Probyn, K and Reviers, E and Salachas, F and Silani, V and Tysnes, OB and van den Berg, LH and Villanueva, G and Weber, M}, title = {European Academy of Neurology (EAN) guideline on the management of amyotrophic lateral sclerosis in collaboration with European Reference Network for Neuromuscular Diseases (ERN EURO-NMD).}, journal = {European journal of neurology}, volume = {31}, number = {6}, pages = {e16264}, pmid = {38470068}, issn = {1468-1331}, support = {//ERN Euro-NMD/ ; //European Academy of Neurology/ ; //ALS Liga Belgium/ ; //EUpALS/ ; //ENCALS/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/therapy ; Humans ; Europe ; Neurology/standards/methods ; Neuromuscular Diseases/therapy ; }, abstract = {BACKGROUND: This update of the guideline on the management of amyotrophic lateral sclerosis (ALS) was commissioned by the European Academy of Neurology (EAN) and prepared in collaboration with the European Reference Network for Neuromuscular Diseases (ERN EURO-NMD) and the support of the European Network for the Cure ALS (ENCALS) and the European Organization for Professionals and Patients with ALS (EUpALS).<br><br>METHODS: Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was used to assess the effectiveness of interventions for ALS. Two systematic reviewers from Cochrane Response supported the guideline panel. The working group identified a total of 26 research questions, performed systematic reviews, assessed the quality of the available evidence, and made specific recommendations. Expert consensus statements were provided where insufficient evidence was available.<br><br>RESULTS: A guideline mapping effort revealed only one other ALS guideline that used GRADE methodology (a National Institute for Health and Care Excellence [NICE] guideline). The available evidence was scarce for many research questions. Of the 26 research questions evaluated, the NICE recommendations could be adapted for 8 questions. Other recommendations required updates of existing systematic reviews or de novo reviews. Recommendations were made on currently available disease-modifying treatments, multidisciplinary care, nutritional and respiratory support, communication aids, psychological support, treatments for common ALS symptoms (e.g., muscle cramps, spasticity, pseudobulbar affect, thick mucus, sialorrhea, pain), and end-of-life management.<br><br>CONCLUSIONS: This update of the guideline using GRADE methodology provides a framework for the management of ALS. The treatment landscape is changing rapidly, and further updates will be prepared when additional evidence becomes available.}, }
@article {pmid38381392, year = {2024}, author = {Miah, MM and Zinnia, MA and Tabassum, N and Islam, ABMMK}, title = {Association between DPP6 gene rs10260404 polymorphism and increased risk of sporadic amyotrophic lateral sclerosis (sALS): a meta-analysis.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {7}, pages = {3225-3243}, pmid = {38381392}, issn = {1590-3478}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/epidemiology ; *Genetic Predisposition to Disease/genetics ; *Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/genetics ; *Polymorphism, Single Nucleotide ; Case-Control Studies ; Nerve Tissue Proteins ; Potassium Channels ; }, abstract = {BACKGROUND: Sporadic amyotrophic lateral sclerosis (sALS) is a severe neurodegenerative disease characterized by continuous diminution of motor neurons in the brain and spinal cord. Earlier studies indicated that the DPP6 gene variant has a role in the development of sALS. This meta-analysis was designed to uncover the role of rs10260404 polymorphism of the DPP6 gene and its association with sALS.<br><br>METHODS: All case-control articles published prior to October 2022 on the association between DPP6 (rs10260404) polymorphism and sALS risk were systematically extracted from different databases which include PubMed, PubMed Central, and Google Scholar. Overall odds ratios (ORs) and "95% confidence intervals (CIs)" were summarized for various genetic models. Subgroup and heterogeneity assessments were performed. Egger's and "Begg's tests were applied to evaluate publication bias. Trial sequential analysis (TSA) and false-positive report probability (FPRP) were performed.<br><br>RESULTS: Nine case-control studies containing 4202 sALS cases and 4444 healthy controls were included in the meta-analysis. A significant association of the DPP6 (rs10260404) variant with an increased sALS risk in overall pooled subjects under allelic model [C allele vs. T allele, OR&#x2009;=&#x2009;1.149, 95% CI (1.010-1.307), p-value&#x2009;=&#x2009;0.035], dominant model [CC&#x2009;+&#x2009;CT vs. TT, OR&#x2009;=&#x2009;1.165, 95% CI (1.067-1.273), p-value&#x2009;=&#x2009;0.001], and homozygote comparison [CC vs. TT, OR&#x2009;=&#x2009;1.421, 95% CI (1.003-2.011), p-value&#x2009;=&#x2009;0.048] were observed. Moreover, in subgroup analysis by nationality, remarkable associations were detected in Dutch, Irish, American, and Swedish under allelic, dominant, and homozygote models. Additionally, stratification analysis by ethnicity exhibited an association with sALS risk among Caucasians and Americans under different genetic models. Interestingly, none of the models found any significant association with Asians.<br><br>CONCLUSION: The present meta-analysis indicates that DPP6 (rs10260404) polymorphism could be a candidate risk factor for sALS predisposition.}, }
@article {pmid37930481, year = {2024}, author = {Domi, T and Schito, P and Sferruzza, G and Russo, T and Pozzi, L and Agosta, F and Carrera, P and Riva, N and Filippi, M and Quattrini, A and Falzone, YM}, title = {Unveiling the SOD1-mediated ALS phenotype: insights from a comprehensive meta-analysis.}, journal = {Journal of neurology}, volume = {271}, number = {3}, pages = {1342-1354}, pmid = {37930481}, issn = {1432-1459}, mesh = {Humans ; Superoxide Dismutase-1/genetics ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics ; Phenotype ; Genetic Testing ; Mutation ; C9orf72 Protein/genetics ; RNA-Binding Protein FUS/genetics ; }, abstract = {BACKGROUND AND OBJECTIVES: Amyotrophic lateral sclerosis associated with mutations in SOD1 (SOD1-ALS) might be susceptible to specific treatment. The aim of the study is to outline the clinical features of SOD1-ALS patients by comparing them to patients without ALS major gene variants and patients with variants in other major ALS genes. Defining SOD1-ALS phenotype may assist clinicians in identifying patients who should be prioritized for genetic testing.<br><br>METHODS: We performed an extensive literature research including original studies which reported the clinical features of SOD1-ALS and at least one of the following patient groups: C9ORF72 hexanucleotide repeat expansion (C9-ALS), TARDBP (TARDBP-ALS), FUS (FUS-ALS) or patients without a positive test for a major-ALS gene (N-ALS). A random effects meta-analytic model was applied to clinical data extracted encompassing sex, site and age of onset. To reconstruct individual patient survival data, the published Kaplan-Meier curves were digitized. Data were measured as odds ratio (OR) or standardized mean difference (SMD) as appropriate. Median survival was compared between groups.<br><br>RESULTS: Twenty studies met the inclusion criteria. We identified 721 SOD1-ALS, 470 C9-ALS, 183 TARDBP-ALS, 113 FUS-ALS and 2824 N-ALS. SOD1-ALS showed a higher rate of spinal onset compared with N-ALS and C9-ALS (OR&#x2009;=&#x2009;4.85, 95% CI&#x2009;=&#x2009;3.04-7.76; OR&#x2009;=&#x2009;10.47, 95% CI&#x2009;=&#x2009;4.32-27.87) and an earlier onset compared with N-ALS (SMD&#x2009;=&#x2009;-&#xa0;0.45, 95% CI&#x2009;=&#x2009;-&#xa0;0.72 to -&#xa0;0.18). SOD1-ALS had a similar survival compared with N-ALS (p&#x2009;=&#x2009;0.14), a longer survival compared with C9-ALS (p&#x2009;<&#x2009;0.01) and FUS-ALS (p&#x2009;=&#x2009;0.019) and a shorter survival compared with TARDBP-ALS (p&#x2009;<&#x2009;0.01).<br><br>DISCUSSION: This study indicates the presence of a specific SOD1-ALS phenotype. Insights in SOD1-ALS clinical features are important in genetic counseling, disease prognosis and support patients' stratification in clinical trials.}, }
@article {pmid37806668, year = {2023}, author = {Marchand, GJ and Masoud, A}, title = {Response to Dr. Somovilla del Saz's letter to the editor regarding "Risk of all-cause and cardiac-related mortality after vaccination against COVID-19: A meta-analysis of self-controlled case series studies".}, journal = {Human vaccines &amp; immunotherapeutics}, volume = {19}, number = {3}, pages = {2264599}, pmid = {37806668}, issn = {2164-554X}, abstract = {This is a response to Dr. Somovilla del Saz's letter to the editor regarding Marchand et al.'s article, "Risk of all-cause and cardiac-related mortality after vaccination against COVID-19: A meta-analysis of self-controlled case series studies." The response is on behalf of all authors clarifying misconceptions about the work.}, }
@article {pmid37735015, year = {2023}, author = {Corcia, P and Vourc'h, P and Bernard, E and Cassereau, J and Codron, P and Fleury, MC and Guy, N and Mouzat, K and Pradat, PF and Soriani, MH and Couratier, P}, title = {French National Protocol for genetic of amyotrophic lateral sclerosis.}, journal = {Revue neurologique}, volume = {179}, number = {9}, pages = {1020-1029}, doi = {10.1016/j.neurol.2023.05.005}, pmid = {37735015}, issn = {0035-3787}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/epidemiology/genetics ; Mutation ; }, abstract = {Relationships between genes and amyotrophic lateral sclerosis (ALS) have been widely accepted since the first studies highlighting pathogenic mutations in the SOD1 gene 30years ago. Over the last three decades, scientific literature has clearly highlighted the central role played by genetic factors in the disease, in both clinics and pathophysiology, as well as in therapeutics. This implies that health professionals who care for patients with ALS are increasingly faced with patients and relatives eager to have answers to questions related to the role of genetic factors in the occurrence of the disease and the risk for their relatives to develop ALS. In order to address these public health issues, the French ALS network FILSLAN proposed to the Haute Autorité de santé (HAS) the drafting of a French National Protocol (PNDS) on ALS genetics. This PNDS was developed according to the "method for developing a national diagnosis and care protocol for rare diseases" published by the HAS in 2012 (methodological guide for PNDS available on the HAS website: http://www.has-sante.fr/). This document aims to provide the most recent data on the role of genes in ALS and to detail the implications for diagnosis and care.}, }
@article {pmid37688479, year = {2024}, author = {Li, Z and Tian, M and Jia, H and Li, X and Liu, Q and Zhou, X and Li, R and Dong, H and Liu, Y}, title = {Genetic variation in targets of lipid-lowering drugs and amyotrophic lateral sclerosis risk: a Mendelian randomization study.}, journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration}, volume = {25}, number = {1-2}, pages = {197-206}, doi = {10.1080/21678421.2023.2255622}, pmid = {37688479}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/epidemiology/genetics ; Mendelian Randomization Analysis ; Genome-Wide Association Study ; Cholesterol, LDL ; Apolipoproteins B/genetics ; Genetic Variation ; Polymorphism, Single Nucleotide/genetics ; }, abstract = {BACKGROUND: The use of lipid-lowering drugs is still highly controversial in patients with amyotrophic lateral sclerosis (ALS). We performed a drug-target Mendelian randomization (MR) analysis to investigate the effect of targeted lipid-lowering drugs on the risk of ALS.<br><br>METHODS: First, we evaluated the causal relationship between HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase (HMGCR) inhibitors-taking trait and ALS using a bidirectional two-sample MR study. Second, we investigated the causal relationship between lipid-lowering drugs and ALS through a drug-target MR approach. The summary data for HMGCR inhibitors-taking traits were extracted from a genome-wide association study (GWAS) of medication use and associated disease in the UK Biobank. The summary data for low-density lipoprotein cholesterol and apolipoprotein B (apoB) were extracted from a meta-analysis of GWAS in individuals of European ancestry in the UKB. The GWAS summary data of ALS were obtained from the Project MinE.<br><br>RESULTS: Our bidirectional two-sample MR showed that genetically determined increased HMGCR inhibitors-taking trait was an independent risk factor for ALS (odds ratio [OR]&#x2009;=&#x2009;1.090, 95% confidence interval [CI]&#x2009;=&#x2009;1.035-1.150, p&#x2009;=&#x2009;0.001). The results of drug-target MR showed that the increased expression of the HMGCR gene in blood with the higher risk of ALS (OR = 1.21, 95% CI = 1.01-1.46; p&#x2009;=&#x2009;0.042) through SMR method and the apoB level mediated by the APOB gene increased the risk of ALS (OR = 1.15; 95% CI =1.05-1.25; p&#x2009;=&#x2009;0.001) through inverse-variance weighted MR method.<br><br>CONCLUSION: This present study provides genetic support for a positive causal effect of HMGCR inhibitors-taking trait and ALS. The reason for this may be due to the underlying disease condition behind the medication, rather than the medication itself. Our findings also suggested that HMGCR and apoB inhibitors may have potential protective effects on ALS.}, }
@article {pmid37647907, year = {2023}, author = {Gondim, FAA and Pinto, WBVR and Chieia, MAT and Correia, CDC and Cunha, FMB and Dourado, MET and França Júnior, MC and Marques Júnior, W and Oliveira, ASB and Rodrigues, CL and Silva, DJD and Dias-Tosta, E}, title = {Definitions, phenomenology, diagnosis, and management of the disorders of laughter and crying in amyotrophic lateral sclerosis (ALS): Consensus from ALS and Motor Neuron Disease Scientific Department of the Brazilian Academy of Neurology.}, journal = {Arquivos de neuro-psiquiatria}, volume = {81}, number = {8}, pages = {764-775}, pmid = {37647907}, issn = {1678-4227}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/therapy ; Brazil ; *Laughter ; Crying ; *Motor Neuron Disease ; *Neurology ; }, abstract = {The spectrum of neuropsychiatric phenomena observed in amyotrophic lateral sclerosis (ALS) is wide and not fully understood. Disorders of laughter and crying stand among the most common manifestations. The aim of this study is to report the results of an educational consensus organized by the Brazilian Academy of Neurology to evaluate the definitions, phenomenology, diagnosis, and management of the disorders of laughter and crying in ALS patients. Twelve members of the Brazilian Academy of Neurology - considered to be experts in the field - were recruited to answer 12 questions about the subject. After exchanging revisions, a first draft was prepared. A face-to-face meeting was held in Fortaleza, Brazil on 9.23.22 to discuss it. The revised version was subsequently emailed to all members of the ALS Scientific Department from the Brazilian Academy of Neurology and the final revised version submitted for publication. The prevalence of pseudobulbar affect/pathological laughter and crying (PBA/PLC) in ALS patients from 15 combined studies and 3906 patients was 27.4% (N = 1070), ranging from 11.4% to 71%. Bulbar onset is a risk factor but there are limited studies evaluating the differences in prevalence among the different motor neuron diseases subtypes, including patients with and without frontotemporal dementia. Antidepressants and a combination of dextromethorphan and quinidine (not available in Brazil) are possible therapeutic options. This group of panelists acknowledge the multiple gaps in the current literature and reinforces the need for further studies.}, }
@article {pmid37516812, year = {2023}, author = {Yin, Z and Chen, J and Xia, M and Zhang, X and Li, Y and Chen, Z and Bao, Q and Zhong, W and Yao, J and Wu, K and Zhao, L and Liang, F}, title = {Assessing causal relationship between circulating cytokines and age-related neurodegenerative diseases: a bidirectional two-sample Mendelian randomization analysis.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {12325}, pmid = {37516812}, issn = {2045-2322}, mesh = {Humans ; Cytokines/genetics ; *Neurodegenerative Diseases/genetics ; Mendelian Randomization Analysis ; *Amyotrophic Lateral Sclerosis/genetics ; Fibroblast Growth Factor 2 ; Genome-Wide Association Study ; *Alzheimer Disease ; *Parkinson Disease/genetics ; }, abstract = {Numerous studies have reported that circulating cytokines (CCs) are linked to age-related neurodegenerative diseases (ANDDs); however, there is a lack of systematic investigation for the causal association. A two-sample bidirectional Mendelian Randomisation (MR) method was utilized to evaluate the causal effect. We applied genetic variants correlated with concentrations of CCs from a genome-wide association study meta-analysis (n = 8293) as instrumental variables. Summary data of three major ANDDs [Alzheimer's disease (AD), Parkinson's disease (PD), and Amyotrophic lateral sclerosis (ALS)] were identified from the IEU OpenGWAS platform (n = 627, 266). Inverse-variance weighted method is the main approach to analyse causal effect, and MR results are verified by several sensitivity and pleiotropy analyses. In directional MR, it suggested that several CCs were nominally correlated with the risk of ANDDs, with a causal odds ratio (OR) of Interleukin (IL)-5 of 0.909 for AD; OR of IL-2 of 1.169 for PD; and OR of Beta nerve growth factor of 1.142 for ALS). In reverse MR, there were some suggestively causal effects of ANDDs on CCs (AD on increased Basic fibroblast growth factor and IL-12 and decreased Stem cell growth factor beta; PD on decreased Monokine induced by interferon-gamma; ALS on decreased Basic fibroblast growth factor and IL-17). The findings were stable across sensitivity and pleiotropy analyses. However, after Bonferroni correction, there is no statistically significant association between CCs and ANDDs. Through the genetic epidemiological approach, our study assessed the role and presented possible causal associations between CCs and ANDDs. Further studies are warranted to verify the causal associations.}, }
@article {pmid37211659, year = {2023}, author = {O'Keefe, DJ}, title = {Commentary on "Do Vaping Prevention Messages Impact Adolescents and Young Adults? A Meta-Analysis of Experimental Studies".}, journal = {Health communication}, volume = {38}, number = {8}, pages = {1723-1726}, doi = {10.1080/10410236.2023.2212467}, pmid = {37211659}, issn = {1532-7027}, mesh = {Humans ; Adolescent ; Young Adult ; *Vaping/prevention &amp; control ; }, abstract = {Preventing vaping by adolescents and young adults is unquestionably an important goal. Ma et al.'s meta-analysis invites the conclusion that vaping prevention messages are effective. This commentary discusses two concerns about that conclusion and the affiliated meta-analysis: (1) None of the analyzed effect sizes describes the effectiveness of vaping prevention messages; the effect sizes describe the difference in effectiveness (the difference on an outcome variable) between the two conditions being compared. (2) As the two conditions being compared vary, so do the relevant conclusions--but the review combines different kinds of comparisons.}, }
@article {pmid37171577, year = {2023}, author = {Zhao, B and Jiang, Q and Lin, J and Wei, Q and Li, C and Hou, Y and Cao, B and Zhang, L and Ou, R and Liu, K and Yang, T and Xiao, Y and Huang, R and Shang, H}, title = {Genetic and Phenotypic Spectrum of Amyotrophic Lateral Sclerosis Patients with CCNF Variants from a Large Chinese Cohort.}, journal = {Molecular neurobiology}, volume = {60}, number = {7}, pages = {4150-4160}, pmid = {37171577}, issn = {1559-1182}, support = {2020YJ0457//Sichuan Science and Technology Program/ ; 2022ZDZX0023//Sichuan Science and Technology Program/ ; 82101485//National Natural Science Foundation of China/ ; 2021-YF05-00242-SN//Science and Technology commission foundation of Chengdu City/ ; }, mesh = {Humans ; Male ; Female ; *Amyotrophic Lateral Sclerosis/genetics ; East Asian People ; *Frontotemporal Dementia/genetics ; Genetic Association Studies ; Mutation, Missense/genetics ; Mutation ; Cyclins ; }, abstract = {Cyclin F (CCNF) variants have been found to be associated with amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD). However, the genetic and clinical characteristics of ALS patients who carry CCNF variants are largely unknown. Genetic analysis was performed for 1587 Chinese ALS patients, and missense variants were predicted by software analyses. Additionally, we searched PubMed, Embase, and Web of Science for relevant literature and conducted a meta-analysis of the frequency of variants. In our ALS cohort, we identified 29 nonsynonymous variants in 41 ALS patients. Among these ALS patients, 18 (1.1%) were carriers of 15 rare missense variants that were considered probably pathogenic variants, and 11 of 15 variants were novel. Seven relevant studies were identified, and a total of 43 CCNF variants in 59 ALS patients with a frequency of 0.8% were reported. The ratio of males to females in our cohort (10/8) was similar to that in Caucasian populations (4/7) and significantly higher than that in Asian populations (10/1). The proportion of bulbar onset in Caucasian CCNF carriers was similar to our cohort (25.0 vs. 27.8%); however, bulbar onset had never been reported in previous Asian studies (0/11). FTD was not found in CCNF carriers in previous Asian studies and our cohort, but it has been reported in a FALS cohort (1/75) of Caucasian individuals. There were some differences in the clinical characteristics among different ethnic ALS populations. More basic scientific studies are needed to elucidate the pathogenic mechanisms and genotype-phenotype associations of CCNF variants.}, }
@article {pmid36835433, year = {2023}, author = {Vasilopoulou, C and McDaid-McCloskey, SL and McCluskey, G and Duguez, S and Morris, AP and Duddy, W}, title = {Genome-Wide Gene-Set Analysis Identifies Molecular Mechanisms Associated with ALS.}, journal = {International journal of molecular sciences}, volume = {24}, number = {4}, pages = {}, pmid = {36835433}, issn = {1422-0067}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Genome-Wide Association Study ; Genotype ; Motor Neurons ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal late-onset motor neuron disease characterized by the loss of the upper and lower motor neurons. Our understanding of the molecular basis of ALS pathology remains elusive, complicating the development of efficient treatment. Gene-set analyses of genome-wide data have offered insight into the biological processes and pathways of complex diseases and can suggest new hypotheses regarding causal mechanisms. Our aim in this study was to identify and explore biological pathways and other gene sets having genomic association to ALS. Two cohorts of genomic data from the dbGaP repository were combined: (a) the largest available ALS individual-level genotype dataset (N = 12,319), and (b) a similarly sized control cohort (N = 13,210). Following comprehensive quality control pipelines, imputation and meta-analysis, we assembled a large European descent ALS-control cohort of 9244 ALS cases and 12,795 healthy controls represented by genetic variants of 19,242 genes. Multi-marker analysis of genomic annotation (MAGMA) gene-set analysis was applied to an extensive collection of 31,454 gene sets from the molecular signatures database (MSigDB). Statistically significant associations were observed for gene sets related to immune response, apoptosis, lipid metabolism, neuron differentiation, muscle cell function, synaptic plasticity and development. We also report novel interactions between gene sets, suggestive of mechanistic overlaps. A manual meta-categorization and enrichment mapping approach is used to explore the overlap of gene membership between significant gene sets, revealing a number of shared mechanisms.}, }
@article {pmid36613659, year = {2022}, author = {Ciuro, M and Sangiorgio, M and Leanza, G and Gulino, R}, title = {A Meta-Analysis Study of SOD1-Mutant Mouse Models of ALS to Analyse the Determinants of Disease Onset and Progression.}, journal = {International journal of molecular sciences}, volume = {24}, number = {1}, pages = {}, pmid = {36613659}, issn = {1422-0067}, mesh = {Mice ; Animals ; *Amyotrophic Lateral Sclerosis/pathology ; Superoxide Dismutase-1/genetics/therapeutic use ; Superoxide Dismutase/genetics ; Mice, Transgenic ; Mutation ; Disease Models, Animal ; Disease Progression ; }, abstract = {A complex interaction between genetic and external factors determines the development of amyotrophic lateral sclerosis (ALS). Epidemiological studies on large patient cohorts have suggested that ALS is a multi-step disease, as symptom onset occurs only after exposure to a sequence of risk factors. Although the exact nature of these determinants remains to be clarified, it seems clear that: (i) genetic mutations may be responsible for one or more of these steps; (ii) other risk factors are probably linked to environment and/or to lifestyle, and (iii) compensatory plastic changes taking place during the ALS etiopathogenesis probably affect the timing of onset and progression of disease. Current knowledge on ALS mechanisms and therapeutic targets, derives mainly from studies involving superoxide dismutase 1 (SOD1) transgenic mice; therefore, it would be fundamental to verify whether a multi-step disease concept can also be applied to these animal models. With this aim, a meta-analysis study has been performed using a collection of primary studies (n = 137), selected according to the following criteria: (1) the studies should employ SOD1 transgenic mice; (2) the studies should entail the presence of a disease-modifying experimental manipulation; (3) the studies should make use of Kaplan-Meier plots showing the distribution of symptom onset and lifespan. Then, using a subset of this study collection (n = 94), the effects of treatments on key molecular mechanisms, as well as on the onset and progression of disease have been analysed in a large population of mice. The results are consistent with a multi-step etiopathogenesis of disease in ALS mice (including two to six steps, depending on the particular SOD1 mutation), closely resembling that observed in patient cohorts, and revealed an interesting relationship between molecular mechanisms and disease manifestation. Thus, SOD1 mouse models may be considered of high predictive value to understand the determinants of disease onset and progression, as well as to identify targets for therapeutic interventions.}, }
@article {pmid36504126, year = {2023}, author = {Gautam, AS and Pulivarthi, CB and Singh, RK}, title = {Proinflammatory IL-17 levels in serum/cerebrospinal fluid of patients with neurodegenerative diseases: a meta-analysis study.}, journal = {Naunyn-Schmiedeberg's archives of pharmacology}, volume = {396}, number = {3}, pages = {577-588}, pmid = {36504126}, issn = {1432-1912}, mesh = {Humans ; *Neurodegenerative Diseases ; *Alzheimer Disease ; *Amyotrophic Lateral Sclerosis ; Interleukin-17 ; Leukocytes, Mononuclear ; *Parkinson Disease ; Cytokines ; *Multiple Sclerosis ; }, abstract = {IL-17 is one of the major proinflammatory cytokine implicated in the pathophysiology of various chronic inflammatory diseases. However, a clear association between the levels of IL-17 and various neurodegenerative diseases is inconclusive due to lack of consistent results reported in several studies. Therefore, we designed and performed a meta-analysis study to assess the levels of IL-17 cytokine in various neurodegenerative diseases. The aim of this meta-analysis study was to assess the level of IL-17 in cerebrospinal fluid/serum of the patients with neurodegenerative diseases such as Alzheimer's disease, Parkinson disease, multiple sclerosis, and amyotrophic lateral sclerosis. An extensive search was performed on electronic databases including PubMed, Cochrane, and Google Scholar to find out the relevant studies for analysis. The quality of selected studies was assessed by Newcastle-Ottawa scale for cohort and case control studies. The standardized mean difference of level of IL-17 in patients with neurodegenerative diseases and control was calculated using RevMan 5 software. A significant increase in the level of serum IL-17 was found to in the patients with neurodegenerative diseases like Alzheimer's disease (p = 0.001) and amyotrophic lateral sclerosis (p = 0.009), whereas IL-17 level in serum of Parkinson's disease (p = 0.22), multiple sclerosis (p = 0.09), and in peripheral blood mononuclear cells of MS patients (p = 0.34) was not found to be significant. IL-17 may be involved in regulation of neuronal inflammation during the pathogenesis of these neurodegenerative disease, and its specific inhibition could be a potential therapeutic target.}, }
@article {pmid36460467, year = {2023}, author = {Janse van Mantgem, MR and van Rheenen, W and Hackeng, AV and van Es, MA and Veldink, JH and van den Berg, LH and van Eijk, RPA}, title = {Association Between Serum Lipids and Survival in Patients With Amyotrophic Lateral Sclerosis: A Meta-analysis and Population-Based Study.}, journal = {Neurology}, volume = {100}, number = {10}, pages = {e1062-e1071}, pmid = {36460467}, issn = {1526-632X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; Genome-Wide Association Study ; Triglycerides ; Cholesterol, HDL ; Biomarkers ; }, abstract = {BACKGROUND AND OBJECTIVE: To explore the association between lipids, polygenic profile scores (PPS) for biomarkers of lipid metabolism, markers of disease severity, and survival in patients with amyotrophic lateral sclerosis (ALS).<br><br>METHODS: We meta-analyzed the current literature on the prognostic value of lipids in patients with ALS. Subsequently, we evaluated the relationship between lipid levels at diagnosis, clinical disease stage, and survival in all consecutive patients diagnosed in the Netherlands. We determined the hazard ratio (HR) of each lipid for overall survival, defined as death from any cause. A subset of patients was matched to a previous genome-wide association study; data were used to calculate PPS for biomarkers of lipid metabolism and to determine the association between observed lipid levels at diagnosis and survival.<br><br>RESULTS: Meta-analysis of 4 studies indicated that none of the biomarkers of the lipid metabolism were statistically significantly associated with overall survival; there was, however, considerable heterogeneity between study results. Using individual patient data (N = 1,324), we found that increased high-density lipoprotein (HDL) cholesterol was associated with poorer survival (HR of 1.33 (95% CI 1.14-1.55, p < 0.001)). The correlation between BMI and HDL cholesterol (Pearson r -0.26, 95% CI -0.32 to -0.20) was negative and between BMI and triglycerides (TG) positive (Pearson r 0.18, 95% CI 0.12-0.24). Serum concentrations of total cholesterol and LDL cholesterol were lower in more advanced clinical stages (both p < 0.001). PPS for biomarkers of lipid metabolism explained 1.2%-13.1% of their variance at diagnosis. None of the PPS was significantly associated with survival (all p > 0.50).<br><br>DISCUSSION: Lipids may contain valuable information about disease severity and prognosis, but their main value may be driven as a consequence of disease progression. Our results underscore that gaining further insight into lipid metabolism and longitudinal data on serum concentrations of the lipid profile could improve the monitoring of patients and potentially further disentangle ALS pathogenesis.}, }
@article {pmid36252825, year = {2022}, author = {Román-Caballero, R and Lupiáñez, J}, title = {Suggestive but not conclusive: An independent meta-analysis on the auditory benefits of learning to play a musical instrument. Commentary on.}, journal = {Neuroscience and biobehavioral reviews}, volume = {142}, number = {}, pages = {104916}, doi = {10.1016/j.neubiorev.2022.104916}, pmid = {36252825}, issn = {1873-7528}, mesh = {Humans ; *Music ; Auditory Perception ; Learning ; }, abstract = {The literature on musical training suggests benefits of this activity on auditory skills (i.e., near transfer) and general cognitive abilities (i.e., far transfer). However, other positions have taken those results more skeptically, rather arguing that studies with positive outcomes suffer from methodological issues that impede inferences of causality. In the context of this debate, we conducted an independent meta-analysis similar to one recently published by Neves et al.'s, also showing auditory benefits of musical training. Our meta-analysis suggests that the available evidence is not sufficient to reach firm conclusions as interventions with design-quality features (randomization and active control) are still scarce. Moreover, the reviewed studies measured auditory skills with tests based on same/different judgments that rely on short-term memory, therefore being less sensitive to changes produced by musicmaking experiences. Although the evidence is not conclusive, the results are in line with those observed with other cognitively stimulating activities and suggest a positive impact of musical training on auditory skills. Thus, the available evidence does not support extreme versions of skepticism.}, }
@article {pmid36116424, year = {2022}, author = {Lu, WZ and Lin, HA and Hou, SK and Lee, CF and Bai, CH and Lin, SF}, title = {Split-hand index for amyotrophic lateral sclerosis diagnosis: A frequentist and Bayesian meta-analysis.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {143}, number = {}, pages = {56-66}, doi = {10.1016/j.clinph.2022.08.020}, pmid = {36116424}, issn = {1872-8952}, mesh = {*Amyotrophic Lateral Sclerosis/diagnosis ; Bayes Theorem ; Hand ; Humans ; Muscle, Skeletal ; ROC Curve ; }, abstract = {OBJECTIVE: Preferential wasting of the thenar muscles, the split-hand sign, may be used for early diagnosis of amyotrophic lateral sclerosis (ALS).<br><br>METHODS: Electronic databases were searched for studies assessing the split-hand index (SHI) and the compound muscle action potential (CMAP) amplitudes of abductor pollicis brevis (APB), first dorsal interosseous (FDI), and abductor digiti minimi (ADM). The SHI was obtained by multiplying CMAP amplitudes of APB and FDI and dividing the product by the CMAP amplitude of ADM. The Bayesian analysis was used for validation.<br><br>RESULTS: In total, 17 studies and 1635 patients were included. Our meta-analysis revealed that ALS patients had significantly decreased SHI (standardized mean difference [SMD], -1.60, P&#xa0;<&#xa0;0.001), CMAP of the APB (SMD, -1.67, P&#xa0;<&#xa0;0.001), FDI (SMD, -1.12, P&#xa0;<&#xa0;0.001), and ADM (SMD, -1.09, P&#xa0;<&#xa0;0.001). The binormal receiver operating characteristic curve analysis showed a threshold of&#xa0;<&#xa0;7.4 for SHI, and cutoff values of&#xa0;<&#xa0;6.4&#xa0;mV for APB and&#xa0;<&#xa0;8.4&#xa0;mV for FDI, respectively. The Bayesian analysis validated decreased SHI in ALS patients (posterior mean difference of&#xa0;-&#xa0;5.91).<br><br>CONCLUSIONS: An SHI of&#xa0;<&#xa0;7.4 can be used facilitating earlier diagnosis of ALS.<br><br>SIGNIFICANCE: SHI can be used as a standard neurophysiological biomarker for early diagnosis.}, }
@article {pmid35946434, year = {2022}, author = {Cao, MC and Scotter, EL}, title = {Transcriptional targets of amyotrophic lateral sclerosis/frontotemporal dementia protein TDP-43 - meta-analysis and interactive graphical database.}, journal = {Disease models &amp; mechanisms}, volume = {15}, number = {9}, pages = {}, pmid = {35946434}, issn = {1754-8411}, mesh = {*Amyotrophic Lateral Sclerosis/pathology ; DNA-Binding Proteins/genetics/metabolism ; *Frontotemporal Dementia/genetics/pathology ; Humans ; RNA ; }, abstract = {TDP-43 proteinopathy is the major pathology in amyotrophic lateral sclerosis (ALS) and tau-negative frontotemporal dementia (FTD). Mounting evidence implicates loss of normal TDP-43 RNA-processing function as a key pathomechanism. However, the RNA targets of TDP-43 differ by report, and have never been formally collated or compared between models and disease, hampering understanding of TDP-43 function. Here, we conducted re-analysis and meta-analysis of publicly available RNA-sequencing datasets from six TDP-43-knockdown models, and TDP-43-immunonegative neuronal nuclei from ALS/FTD brain, to identify differentially expressed genes (DEGs) and differential exon usage (DEU) events. There was little overlap in DEGs between knockdown models, but PFKP, STMN2, CFP, KIAA1324 and TRHDE were common targets and were also differentially expressed in TDP-43-immunonegative neurons. DEG enrichment analysis revealed diverse biological pathways including immune and synaptic functions. Common DEU events in human datasets included well-known targets POLDIP3 and STMN2, and novel targets EXD3, MMAB, DLG5 and GOSR2. Our interactive database (https://www.scotterlab.auckland.ac.nz/research-themes/tdp43-lof-db/) allows further exploration of TDP-43 DEG and DEU targets. Together, these data identify TDP-43 targets that can be exploited therapeutically or used to validate loss-of-function processes. This article has an associated First Person interview with the first author of the paper.}, }
@article {pmid35820692, year = {2022}, author = {de Jong, VMT and Rousset, RZ and Antonio-Villa, NE and Buenen, AG and Van Calster, B and Bello-Chavolla, OY and Brunskill, NJ and Curcin, V and Damen, JAA and Fermín-Martínez, CA and Fernández-Chirino, L and Ferrari, D and Free, RC and Gupta, RK and Haldar, P and Hedberg, P and Korang, SK and Kurstjens, S and Kusters, R and Major, RW and Maxwell, L and Nair, R and Naucler, P and Nguyen, TL and Noursadeghi, M and Rosa, R and Soares, F and Takada, T and van Royen, FS and van Smeden, M and Wynants, L and Modrák, M and ,  and Asselbergs, FW and Linschoten, M and ,  and Moons, KGM and Debray, TPA}, title = {Clinical prediction models for mortality in patients with covid-19: external validation and individual participant data meta-analysis.}, journal = {BMJ (Clinical research ed.)}, volume = {378}, number = {}, pages = {e069881}, pmid = {35820692}, issn = {1756-1833}, mesh = {*COVID-19 ; Data Analysis ; Hospital Mortality ; Humans ; *Models, Statistical ; Prognosis ; }, abstract = {OBJECTIVE: To externally validate various prognostic models and scoring rules for predicting short term mortality in patients admitted to hospital for covid-19.<br><br>DESIGN: Two stage individual participant data meta-analysis.<br><br>SETTING: Secondary and tertiary care.<br><br>PARTICIPANTS: 46&#x2009;914 patients across 18 countries, admitted to a hospital with polymerase chain reaction confirmed covid-19 from November 2019 to April 2021.<br><br>DATA SOURCES: Multiple (clustered) cohorts in Brazil, Belgium, China, Czech Republic, Egypt, France, Iran, Israel, Italy, Mexico, Netherlands, Portugal, Russia, Saudi Arabia, Spain, Sweden, United Kingdom, and United States previously identified by a living systematic review of covid-19 prediction models published in The BMJ, and through PROSPERO, reference checking, and expert knowledge.<br><br>Prognostic models identified by the living systematic review and through contacting experts. A priori models were excluded that had a high risk of bias in the participant domain of PROBAST (prediction model study risk of bias assessment tool) or for which the applicability was deemed poor.<br><br>METHODS: Eight prognostic models with diverse predictors were identified and validated. A two stage individual participant data meta-analysis was performed of the estimated model concordance (C) statistic, calibration slope, calibration-in-the-large, and observed to expected ratio (O:E) across the included clusters.<br><br>MAIN OUTCOME MEASURES: 30 day mortality or in-hospital mortality.<br><br>RESULTS: Datasets included 27 clusters from 18 different countries and contained data on 46&#x2009;914patients. The pooled estimates ranged from 0.67 to 0.80 (C statistic), 0.22 to 1.22 (calibration slope), and 0.18 to 2.59 (O:E ratio) and were prone to substantial between study heterogeneity. The 4C Mortality Score by Knight et al (pooled C statistic 0.80, 95% confidence interval 0.75 to 0.84, 95% prediction interval 0.72 to 0.86) and clinical model by Wang et al (0.77, 0.73 to 0.80, 0.63 to 0.87) had the highest discriminative ability. On average, 29% fewer deaths were observed than predicted by the 4C Mortality Score (pooled O:E 0.71, 95% confidence interval 0.45 to 1.11, 95% prediction interval 0.21 to 2.39), 35% fewer than predicted by the Wang clinical model (0.65, 0.52 to 0.82, 0.23 to 1.89), and 4% fewer than predicted by Xie et al's model (0.96, 0.59 to 1.55, 0.21 to 4.28).<br><br>CONCLUSION: The prognostic value of the included models varied greatly between the data sources. Although the Knight 4C Mortality Score and Wang clinical model appeared most promising, recalibration (intercept and slope updates) is needed before implementation in routine care.}, }
@article {pmid35789175, year = {2022}, author = {Walsh, CJ and Batt, J and Herridge, MS and Mathur, S and Bader, GD and Hu, P and Khatri, P and Dos Santos, CC}, title = {Comprehensive multi-cohort transcriptional meta-analysis of muscle diseases identifies a signature of disease severity.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {11260}, pmid = {35789175}, issn = {2045-2322}, support = {MOP-137002//CIHR/Canada ; MOP-106545//CIHR/Canada ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics ; Cohort Studies ; Humans ; *Muscular Diseases/genetics ; Quadriceps Muscle ; Severity of Illness Index ; }, abstract = {Muscle diseases share common pathological features suggesting common underlying mechanisms. We hypothesized there is a common set of genes dysregulated across muscle diseases compared to healthy muscle and that these genes correlate with severity of muscle disease. We performed meta-analysis of transcriptional profiles of muscle biopsies from human muscle diseases and healthy controls. Studies obtained from public microarray repositories fulfilling quality criteria were divided into six categories: (i) immobility, (ii) inflammatory myopathies, (iii) intensive care unit (ICU) acquired weakness (ICUAW), (iv) congenital muscle diseases, (v) chronic systemic diseases, (vi) motor neuron disease. Patient cohorts were separated in discovery and validation cohorts retaining roughly equal proportions of samples for the disease categories. To remove bias towards a specific muscle disease category we repeated the meta-analysis five times by removing data sets corresponding to one muscle disease class at a time in a "leave-one-disease-out" analysis. We used 636 muscle tissue samples from 30 independent cohorts to identify a 52 gene signature (36 up-regulated and 16 down-regulated genes). We validated the discriminatory power of this signature in 657 muscle biopsies from 12 additional patient cohorts encompassing five categories of muscle diseases with an area under the receiver operating characteristic curve of 0.91, 83% sensitivity, and 85.3% specificity. The expression score of the gene signature inversely correlated with quadriceps muscle mass (r = -0.50, p-value = 0.011) in ICUAW and shoulder abduction strength (r = -0.77, p-value = 0.014) in amyotrophic lateral sclerosis (ALS). The signature also positively correlated with histologic assessment of muscle atrophy in ALS (r = 0.88, p-value = 1.62 × 10[-3]) and fibrosis in muscular dystrophy (Jonckheere trend test p-value = 4.45 × 10[-9]). Our results identify a conserved transcriptional signature associated with clinical and histologic muscle disease severity. Several genes in this conserved signature have not been previously associated with muscle disease severity.}, }
@article {pmid35703478, year = {2022}, author = {Li, Z and Zheng, Y and Li, D and Wang, X and Cheng, S and Luo, X and Wen, A}, title = {Low-Dose NOACs Versus Standard-Dose NOACs or Warfarin on Efficacy and Safety in Asian Patients with NVAF: A Meta-Analysis.}, journal = {Anatolian journal of cardiology}, volume = {26}, number = {6}, pages = {424-433}, pmid = {35703478}, issn = {2149-2271}, mesh = {Administration, Oral ; Anticoagulants/therapeutic use ; *Atrial Fibrillation/complications ; Gastrointestinal Hemorrhage/complications/drug therapy ; Humans ; Intracranial Hemorrhages/complications/drug therapy ; *Stroke/complications/prevention &amp; control ; Treatment Outcome ; Warfarin/therapeutic use ; }, abstract = {BACKGROUND: The meta-analysis of randomized controlled trials has illustrated that the efficacy of low-dose non-vitamin K antagonist oral anticoagulants is inferior compared with standard-dose non-vitamin K antagonist oral anticoagulants, though they are still frequently prescribed for Asian patients with non-valvular atrial fibrillation. We aimed to further investigate the efficacy and safety of low-dose non-vitamin K antagonist oral anticoagulants by carrying out a meta-analysis of all relevant randomized controlled tri- als and cohort studies.<br><br>METHODS: Cochrane Central Register of Controlled Trials, Embase, and MEDLINE were sys- tematically searched from the inception to September 9, 2021, for randomized controlled trials or cohorts that compared the efficacy and/or safety of low-dose non-vitamin K antagonist oral anticoagulants in Asian patients with non-valvular atrial fibrillation. The primary outcomes were stroke and major bleeding, and the secondary outcomes were mortality, intracranial hemorrhage, and gastrointestinal hemorrhage. Hazard ratios and 95% CIs were estimated using the random-effect model.<br><br>RESULTS: Nineteen publications involving 371 574 Asian patients with non-valvular atrial fibrillation were included. Compared with standard-dose non-vitamin K antagonist oral anticoagulants, low-dose non-vitamin K antagonist oral anticoagulants showed compa- rable risks of stroke (hazard ratio, 1.18; 95% CI 0.98 to 1.42), major bleeding (hazard ratio, 1.00; 95% CI 0.83 to 1.21), intracranial hemorrhage (hazard ratio, 1.13; 95% CI 0.92 to 1.38), and gastrointestinal hemorrhage (hazard ratio, 1.07; 95% CI 0.87 to 1.31), though had a higher risk of mortality (hazard ratio, 1.34; 95% CI 1.05 to 1.71). Compared with warfarin, low-dose non-vitamin K antagonist oral anticoagulants were associated with lower risks of stroke (hazard ratio, 0.73; 95% CI 0.67 to 0.79), mortality (hazard ratio, 0.69; 95% CI 0.60 to 0.81), major bleeding (hazard ratio, 0.62; 95% CI 0.51 to 0.75), intracranial hemor- rhage (hazard ratio, 0.48; 95% CI 0.33 to 0.69), and gastrointestinal hemorrhage (hazard ratio, 0.78; 95% CI 0.65 to 0.93).<br><br>CONCLUSION: Low-dose non-vitamin K antagonist oral anticoagulants were superior to warfarin, and comparable to standard-dose non-vitamin K antagonist oral anticoagu- lants considering risks of stroke, major bleeding, intracranial hemorrhage, and gastroin- testinal hemorrhage. Further, high qualified studies are warranted.}, }
@article {pmid35363117, year = {2023}, author = {Medrano, NW and Villarreal, CL and Mann, NC and Price, MA and Nolte, KB and MacKenzie, EJ and Bixby, P and Eastridge, BJ and , }, title = {Activation and On-Scene Intervals for Severe Trauma EMS Interventions: An Analysis of the NEMSIS Database.}, journal = {Prehospital emergency care}, volume = {27}, number = {1}, pages = {46-53}, doi = {10.1080/10903127.2022.2053615}, pmid = {35363117}, issn = {1545-0066}, mesh = {Humans ; Databases, Factual ; *Emergency Medical Services ; Information Systems ; Retrospective Studies ; Time Factors ; }, abstract = {Objective: Time to care is a determinant of trauma patient outcomes, and timely delivery of trauma care to severely injured patients is critical in reducing mortality. Numerous studies have analyzed access to care using prehospital intervals from a Carr et al. meta-analysis of studies from 1975 to 2005. Carr et al.'s research sought to determine national mean activation and on-scene intervals for trauma patients using contemporary emergency medical services (EMS) records. Since the Carr et al. meta-analysis was published, the National Highway Traffic Safety Administration (NHTSA) created and refined the National Emergency Medical Services Information System (NEMSIS) database. We sought to perform a modern analysis of prehospital intervals to establish current standards and temporal patterns.Methods: We utilized NEMSIS to analyze EMS data of trauma patients from 2016 to 2019. The dataset comprises more than 94 million EMS records, which we filtered to select for severe trauma and stratified by type of transport and rurality to calculate mean activation and on-scene intervals. Furthermore, we explored the impact of basic life support (BLS) and advanced life support (ALS) of ground units on activation and on-scene time intervals.Results: Mean activation and on-scene intervals for ground transport were statistically different when stratified by rurality. Urban, suburban, and rural ground activation intervals were 2.60 ± 3.94, 2.88 ± 3.89, and 3.33 ± 4.58 minutes, respectively. On-scene intervals were 15.50 ± 10.46, 17.56 ± 11.27, and 18.07 ± 16.13 minutes, respectively. Mean helicopter transport activation time was 13.75 ± 7.44 minutes and on-scene time was 19.42 ± 16.09 minutes. This analysis provides an empirically defined mean for activation and on-scene times for trauma patients based on transport type and rurality. Results from this analysis proved to be significantly longer than the previous analysis, except for helicopter transport on-scene time. Shorter mean intervals were seen in ALS compared to BLS for activation intervals, however ALS on-scene intervals were marginally longer than BLS.Conclusions: With the increasing sophistication of geospatial technologies employed to analyze access to care, these intervals are the most accurate and up-to-date and should be included in access to care models.}, }
@article {pmid35264038, year = {2022}, author = {Erazo, D and Luna, J and Preux, PM and Medina, MT and Magne, J and Boumediene, F and Couratier, P}, title = {Amyotrophic lateral sclerosis mortality rates in Latin America and the Caribbean: a meta-analysis.}, journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration}, volume = {23}, number = {7-8}, pages = {608-619}, doi = {10.1080/21678421.2022.2048310}, pmid = {35264038}, issn = {2167-9223}, mesh = {Humans ; Latin America/epidemiology ; *Amyotrophic Lateral Sclerosis/epidemiology ; Ethnicity ; Caribbean Region ; Europe ; }, abstract = {Background: Recent studies have described a low occurrence of Amyotrophic Lateral Sclerosis (ALS) in Latin America. Significant differences in ALS risk have been reported among ethnic populations in the region. We conducted a meta-analysis using population-based data to describe ALS mortality rates in Latin America. We explored sources of heterogeneity among key covariates.Methods: National mortality registries from Latin American countries were searched to identify ALS deaths according to the International Classification of Diseases (ICD-9: code 335.2 and ICD-10: code G12.2). Crude and standardized mortality rates were calculated. A random-effect meta-analysis was conducted to estimate pooled mortality rates. Subgroup analysis was performed as a means of investigating heterogeneity.Results: Overall, 28,548 ALS deaths and 819 million person-years of follow-up (PYFU) from ten Latin American countries were considered. Standardized mortality varied among countries. The highest mortality rates were observed in Uruguay and Costa Rica at 1.3 and 1.2 per 100,000 PYFU, respectively. The pooled crude mortality rate was 0.38 (95%CI: 0.28-0.53) and the pooled standardized mortality was 0.62 (95%CI: 0.49-0.77) per 100,000 PYFU. Heterogeneity was high (I2: 99.9%, Cochran's Q p < 0.001). Subgroup analysis showed a higher mortality rate among countries with a higher proportion of Caucasian populations and higher income levels.Conclusion: There is a lower ALS occurrence in Latin America compared to Europe and North America. This meta-analysis supports the hypothesis of a higher ALS risk among the Caucasian population. Further studies are needed to investigate the role of ancestral origins in ALS, taking socioeconomic status into consideration.}, }
@article {pmid35179485, year = {2022}, author = {Lidborg, LH and Cross, CP and Boothroyd, LG}, title = {A meta-analysis of the association between male dimorphism and fitness outcomes in humans.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {35179485}, issn = {2050-084X}, mesh = {*Choice Behavior ; Female ; Humans ; Male ; Masculinity ; *Sex Characteristics ; Sexual Behavior ; Testosterone ; }, abstract = {Humans are sexually dimorphic: men and women differ in body build and composition, craniofacial structure, and voice pitch, likely mediated in part by developmental testosterone. Sexual selection hypotheses posit that, ancestrally, more 'masculine' men may have acquired more mates and/or sired more viable offspring. Thus far, however, evidence for either association is unclear. Here, we meta-analyze the relationships between six masculine traits and mating/reproductive outcomes (96 studies, 474 effects, N = 177,044). Voice pitch, height, and testosterone all predicted mating; however, strength/muscularity was the strongest and only consistent predictor of both mating and reproduction. Facial masculinity and digit ratios did not significantly predict either. There was no clear evidence for any effects of masculinity on offspring viability. Our findings support arguments that strength/muscularity may be sexually selected in humans, but cast doubt regarding selection for other forms of masculinity and highlight the need to increase tests of evolutionary hypotheses outside of industrialized populations.}, }
@article {pmid35169211, year = {2022}, author = {Zhang, L and Tang, L and Huang, T and Fan, D}, title = {Association between type 2 diabetes and amyotrophic lateral sclerosis.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {2544}, pmid = {35169211}, issn = {2045-2322}, mesh = {Amyotrophic Lateral Sclerosis/*epidemiology ; Case-Control Studies ; Diabetes Mellitus, Type 2/*epidemiology ; Genome-Wide Association Study ; Humans ; }, abstract = {Type 2 diabetes (T2D) and amyotrophic lateral sclerosis (ALS) are associated consistently. However, it is currently unknown whether this association is causal. We aimed to estimate the unconfounded, causal association between T2D on ALS using a two-sample Mendelian randomization approach both in European and East Asian ancestry. Genetic variants strongly associated with T2D and each T2D markers were used to investigate the effect of T2D on ALS risk in European (involving 20,806 ALS cases and 59,804 controls) and East Asian (involving 1234 ALS cases and 2850 controls) ancestry. We found that the OR of ALS per 1 SD increase in T2D was estimated to be 0.96 [95% confidence interval (CI) 0.92-0.996; p = 0.03] in European populations. Similarly, all 8 SNPs were associated with T2D in East Asian ancestry, the OR of ALS per 1 SD increase in T2D was estimated to be 0.83 [95% CI 0.70-0.992; p = 0.04] in East Asian populations. Examining the intercept estimates from MR-Egger regression also leads to the same conclusion, in that horizontal pleiotropy unlikely influences the results in either population. We found that genetically predicted T2D was associated with significantly lower odds of amyotrophic lateral sclerosis both in European and East Asian populations. It is now critical to identify a clear molecular explanation for this association between T2D and ALS and to focus on its potential therapeutic implications.}, }
@article {pmid34963663, year = {2022}, author = {Ziff, OJ and Clarke, BE and Taha, DM and Crerar, H and Luscombe, NM and Patani, R}, title = {Meta-analysis of human and mouse ALS astrocytes reveals multi-omic signatures of inflammatory reactive states.}, journal = {Genome research}, volume = {32}, number = {1}, pages = {71-84}, pmid = {34963663}, issn = {1549-5469}, support = {MR/S006591/1/MRC_/Medical Research Council/United Kingdom ; MR/L016311/1/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; 103760/Z/14/Z/WT_/Wellcome Trust/United Kingdom ; MR/M02492X/1/MRC_/Medical Research Council/United Kingdom ; FC010110/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics/metabolism ; Animals ; Astrocytes/metabolism ; Disease Models, Animal ; Humans ; *Induced Pluripotent Stem Cells ; Mice ; Mice, Transgenic ; Motor Neurons/metabolism ; Mutation ; }, abstract = {Astrocytes contribute to motor neuron death in amyotrophic lateral sclerosis (ALS), but whether they adopt deleterious features consistent with inflammatory reactive states remains incompletely resolved. To identify inflammatory reactive features in ALS human induced pluripotent stem cell (hiPSC)-derived astrocytes, we examined transcriptomics, proteomics, and glutamate uptake in VCP-mutant astrocytes. We complemented this by examining other ALS mutations and models using a systematic meta-analysis of all publicly-available ALS astrocyte sequencing data, which included hiPSC-derived astrocytes carrying SOD1, C9orf72, and FUS gene mutations as well as mouse ALS astrocyte models with SOD1[G93A] mutation, Tardbp deletion, and Tmem259 (also known as membralin) deletion. ALS astrocytes were characterized by up-regulation of genes involved in the extracellular matrix, endoplasmic reticulum stress, and the immune response and down-regulation of synaptic integrity, glutamate uptake, and other neuronal support processes. We identify activation of the TGFB, Wnt, and hypoxia signaling pathways in both hiPSC and mouse ALS astrocytes. ALS changes positively correlate with TNF, IL1A, and complement pathway component C1q-treated inflammatory reactive astrocytes, with significant overlap of differentially expressed genes. By contrasting ALS changes with models of protective reactive astrocytes, including middle cerebral artery occlusion and spinal cord injury, we uncover a cluster of genes changing in opposing directions, which may represent down-regulated homeostatic genes and up-regulated deleterious genes in ALS astrocytes. These observations indicate that ALS astrocytes augment inflammatory processes while concomitantly suppressing neuronal supporting mechanisms, thus resembling inflammatory reactive states and offering potential therapeutic targets.}, }
@article {pmid34874217, year = {2022}, author = {Sferruzza, G and Bosco, L and Falzone, YM and Russo, T and Domi, T and Quattrini, A and Filippi, M and Riva, N}, title = {Neurofilament light chain as a biological marker for amyotrophic lateral sclerosis: a meta-analysis study.}, journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration}, volume = {23}, number = {5-6}, pages = {446-457}, doi = {10.1080/21678421.2021.2007952}, pmid = {34874217}, issn = {2167-9223}, mesh = {*Amyotrophic Lateral Sclerosis/diagnosis ; Biomarkers ; Enzyme-Linked Immunosorbent Assay ; Humans ; Intermediate Filaments ; Neurofilament Proteins ; }, abstract = {Aim: The aim of the present metanalysis is to evaluate blood and CSF Neurofilament light chain (NfL) concentrations in ALS patients, compared to healthy controls, ALS mimic disorders (ALSmd) and other neurological diseases (OND), and to evaluate their diagnostic yield against ALSmd. Methods: Search engines were systematically investigated for relevant studies. A random effect model was applied to estimate the pooled standard mean difference in NfL levels between ALS and controls and a bivariate mixed-effects model was applied to estimate their diagnostic accuracy on blood and CSF. Results and conclusions: NfL CSF levels were higher in ALS compared with all other control groups. On blood, NfL levels were significantly higher in ALS patients compared with healthy controls and ALSmd. In a subgroup analysis, the use of SIMOA yielded to a better differentiation between ALS and controls on blood, compared with ELISA. Studies performed on CSF (AUC = 0.90) yielded to better diagnostic performances compared with those conducted on blood (AUC = 0.78). Further prospective investigations are needed to determine a diagnostic cutoff, exploitable in clinical practice.}, }
@article {pmid34864363, year = {2021}, author = {Su, WM and Cheng, YF and Jiang, Z and Duan, QQ and Yang, TM and Shang, HF and Chen, YP}, title = {Predictors of survival in patients with amyotrophic lateral sclerosis: A large meta-analysis.}, journal = {EBioMedicine}, volume = {74}, number = {}, pages = {103732}, pmid = {34864363}, issn = {2352-3964}, mesh = {Amyotrophic Lateral Sclerosis/*mortality ; Female ; Humans ; Life Style ; Male ; Prognosis ; Risk Assessment ; Survival Analysis ; Young Adult ; }, abstract = {BACKGROUND: The survival time of amyotrophic lateral sclerosis (ALS) is greatly variable and protective or risk effects of the potential survival predictors are controversial. Thus, we aim to undertake a comprehensive meta-analysis of studies investigating non-genetic prognostic and survival factors in patients with ALS.<br><br>METHODS: A search of relevant literature from PubMed, Embase, Cochrane library and other citations from 1[st] January 1966 to 1[st] December 020 was conducted. Random-effects models were conducted to pool the multivariable or adjusted hazard ratios (HR) by Stata MP 16.0. PROSPERO registration number: CRD42021256923.<br><br>FINDINGS: A total of 5717 reports were identified, with 115 studies meeting pre-designed inclusion criteria involving 55,169 ALS patients. Five dimensions, including demographic, environmental or lifestyle, clinical manifestations, biochemical index, therapeutic factors or comorbidities were investigated. Twenty-five prediction factors, including twenty non-intervenable and five intervenable factors, were associated with ALS survival. Among them, NFL (HR:3.70, 6.80, in serum and CSF, respectively), FTD (HR:2.98), ALSFRS-R change (HR:2.37), respiratory subtype (HR:2.20), executive dysfunction (HR:2.10) and age of onset (HR:1.03) were superior predictors for poor prognosis, but pLMN or pUMN (HR:0.32), baseline ALSFRS-R score (HR:0.95), duration (HR:0.96), diagnostic delay (HR:0.97) were superior predictors for a good prognosis. Our results did not support the involvement of gender, education level, diabetes, hypertension, NIV, gastrostomy, and statins in ALS survival.<br><br>INTERPRETATION: Our study provided a comprehensive and quantitative index for assessing the prognosis for ALS patients, and the identified non-intervenable or intervenable factors will facilitate the development of treatment strategies for ALS.<br><br>FUNDING: This study was supported by the National Natural Science Fund of China (Grant No. 81971188), the 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University (Grant No. 2019HXFH046), and the Science and Technology Bureau Fund of Sichuan Province (No. 2019YFS0216).}, }
@article {pmid34726989, year = {2022}, author = {Shi, G and Shao, S and Zhou, J and Huang, K and Bi, FF}, title = {Urinary p75[ECD] levels in patients with amyotrophic lateral sclerosis: a meta-analysis.}, journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration}, volume = {23}, number = {5-6}, pages = {438-445}, doi = {10.1080/21678421.2021.1990345}, pmid = {34726989}, issn = {2167-9223}, mesh = {*Amyotrophic Lateral Sclerosis/diagnosis ; Case-Control Studies ; Humans ; }, abstract = {Objective: p75 neurotrophin receptor (p75[NTR]) is associated with the pathogenesis of amyotrophic lateral sclerosis (ALS). However, its role is not fully understood. The aim of this study was to evaluate the association between ALS and the extracellular domain of p75[NTR](p75[ECD]) in urine. Methods: We conducted a comprehensive literature search using keywords in the PubMed, Embase, Science, and the Cochrane Library, and identified five case control studies, with the latest date of search being 18 April 2021. Results: The results showed that urinary p75[ECD] levels were significantly higher in patients with ALS compared to non-neurological control (weighted mean difference (WMD) = 4.18, 95% CI [2.525, 6.990], p < 0.001), and other neurological diseases (WMD = 6.005, 95% CI [1.596, 10.414], p = 0.008). Increased urinary p75[ECD] levels were inversely associated with ALSFRS-R in ALS patients (r = -0.32, 95% CI [-0.43, -0.21], p < 0.001). Conclusions: Given the associations between p75[ECD] and ALS found in this meta-analysis, urinary p75[ECD] levels have potential to be used as a diagnostic biomarker and a progression indicator in the future.}, }
@article {pmid34502460, year = {2021}, author = {Fernández-Beltrán, LC and Godoy-Corchuelo, JM and Losa-Fontangordo, M and Williams, D and Matias-Guiu, J and Corrochano, S}, title = {A Transcriptomic Meta-Analysis Shows Lipid Metabolism Dysregulation as an Early Pathological Mechanism in the Spinal Cord of SOD1 Mice.}, journal = {International journal of molecular sciences}, volume = {22}, number = {17}, pages = {}, pmid = {34502460}, issn = {1422-0067}, support = {2018-T1/BMD-10731//Consejer&#xed;a de Educaci&#xf3;n, Juventud y Deporte, Comunidad de Madrid/ ; }, mesh = {Amyotrophic Lateral Sclerosis/etiology/*metabolism ; Animals ; Disease Models, Animal ; Female ; *Lipid Metabolism ; Mice ; Spinal Cord/*metabolism ; Steroid Hydroxylases/genetics/metabolism ; *Transcriptome ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a multifactorial and complex fatal degenerative disorder. A number of pathological mechanisms that lead to motor neuron death have been identified, although there are many unknowns in the disease aetiology of ALS. Alterations in lipid metabolism are well documented in the progression of ALS, both at the systemic level and in the spinal cord of mouse models and ALS patients. The origin of these lipid alterations remains unclear. This study aims to identify early lipid metabolic pathways altered before systemic metabolic symptoms in the spinal cord of mouse models of ALS. To do this, we performed a transcriptomic analysis of the spinal cord of SOD1[G93A] mice at an early disease stage, followed by a robust transcriptomic meta-analysis using publicly available RNA-seq data from the spinal cord of SOD1 mice at early and late symptomatic disease stages. The meta-analyses identified few lipid metabolic pathways dysregulated early that were exacerbated at symptomatic stages; mainly cholesterol biosynthesis, ceramide catabolism, and eicosanoid synthesis pathways. We present an insight into the pathological mechanisms in ALS, confirming that lipid metabolic alterations are transcriptionally dysregulated and are central to ALS aetiology, opening new options for the treatment of these devastating conditions.}, }
@article {pmid34431799, year = {2021}, author = {Mavroudis, I and Knights, M and Petridis, F and Chatzikonstantinou, S and Karantali, E and Kazis, D}, title = {Diagnostic Accuracy of Anti-CN1A on the Diagnosis of Inclusion Body Myositis. A Hierarchical Bivariate and Bayesian Meta-analysis.}, journal = {Journal of clinical neuromuscular disease}, volume = {23}, number = {1}, pages = {31-38}, doi = {10.1097/CND.0000000000000353}, pmid = {34431799}, issn = {1537-1611}, mesh = {5'-Nucleotidase ; Autoantibodies ; Bayes Theorem ; Humans ; Male ; Muscle, Skeletal ; *Myositis ; *Myositis, Inclusion Body/diagnosis ; }, abstract = {Sporadic inclusion body myositis (IBM) is an acquired muscle disease and the most common idiopathic inflammatory myopathy over the age of 50. It is characterized by male predominance, with a prevalence rate between 1 and 71 cases per million, reaching 139 cases per million over the age of 50 globally. The diagnosis of IBM is based on clinical presentation and muscle biopsy findings. However, there is increasing evidence for the role of genetics and serum biomarkers in supporting a diagnosis. Antibodies against the cytosolic 5'-nucleotidase 1A (Anti-CN1A), an enzyme catalyzing the conversion of adenosine monophosphate into adenosine and phosphate and is abundant in skeletal muscle, has been reported to be present in IBM and could be of crucial significance in the diagnosis of the disease. In this study, we investigated the diagnostic accuracy of anti-CN1A antibodies for sporadic IBM in comparison with other inflammatory myopathies, autoimmune disorders, motor neurone disease, using a hierarchical bivariate approach, and a Bayesian model taking into account the variable prevalence. The results of the present analysis show that anti-CN1A antibodies have moderate sensitivity, and despite having high specificity, they are not useful biomarkers for the diagnosis of IBM, polymyositis or dermatomyositis, other autoimmune conditions, or neuromuscular disorders. Neither the hierarchical bivariate nor the Bayesian analysis showed any significant usefulness of anti-CN1A antibodies in the diagnosis of IBM.}, }
@article {pmid34397718, year = {2021}, author = {Chang, MC and Kwak, SG and Park, JS and Park, D}, title = {Relationship between statins and the risk of amyotrophic lateral sclerosis: A PRISMA-compliant meta-analysis.}, journal = {Medicine}, volume = {100}, number = {30}, pages = {e26751}, pmid = {34397718}, issn = {1536-5964}, support = {NRF-2019M3E5D1A02068106//National Research Foundation of Korea grand funded by the Korean government/ ; }, mesh = {Amyotrophic Lateral Sclerosis/*chemically induced ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/*adverse effects ; }, abstract = {OBJECTIVE: Previous studies on overlapping surveillance databases have suggested that statin use was associated with the development of amyotrophic lateral sclerosis (ALS)-like syndrome. However, the association between statin use and ALS incidence has not been clearly elucidated. To further explore this issue, we performed a systemic review and meta-analysis of all available clinical studies on the association between statin use and ALS incidence.<br><br>METHODS: A comprehensive database search on PubMed, Embase, Cochrane Library, and SCOPUS was conducted. We included studies up to January 31, 2020 that fulfilled our inclusion and exclusion criteria. Statin use between the ALS and control groups was collected for the meta-analysis.<br><br>RESULTS: Three case-control studies and 1 cohort study, that related the risk of ALS to statin use, satisfied the inclusion criteria for the meta-analysis. There was no statistically significant difference in statin use between the ALS and control groups (odds ratio, 0.75 [95% confidence interval, 0.53-1.08]).<br><br>CONCLUSION: No definite association was found between statin use and the development of ALS. Further large-scale prospective randomized control studies are necessary to draw definite conclusions.}, }
@article {pmid33706058, year = {2021}, author = {Haji, S and Sako, W and Murakami, N and Osaki, Y and Furukawa, T and Izumi, Y and Kaji, R}, title = {The value of serum uric acid as a prognostic biomarker in amyotrophic lateral sclerosis: Evidence from a meta-analysis.}, journal = {Clinical neurology and neurosurgery}, volume = {203}, number = {}, pages = {106566}, doi = {10.1016/j.clineuro.2021.106566}, pmid = {33706058}, issn = {1872-6968}, mesh = {Amyotrophic Lateral Sclerosis/*blood/*diagnosis ; Biomarkers/blood ; Humans ; Prognosis ; Sensitivity and Specificity ; Uric Acid/*blood ; }, abstract = {OBJECTIVE: To determine the value of uric acid (UA) as a prognostic biomarker for amyotrophic lateral sclerosis (ALS) using a meta-analysis of hazard ratio-based studies.<br><br>METHODS: We included data from Tokushima University (47 patients with ALS) and three previous studies (1835 patients with ALS) with a hazard ratio (HR) identified by a systematic computational search. A total of four studies and 1882 patients were enrolled in the pooled analysis. We pooled HRs of death or tracheostomy, which were estimated by a Cox proportional hazard model, using a random-effects model. Heterogeneity was assessed by Q statistic, and a p value < 0.1 was considered significant heterogeneity. Furthermore, sensitivity analysis was performed to assess the effect of each single study and the robustness of the summary effect. We evaluated publication bias by visual assessment of the funnel plot and Egger's test, and adjusted the bias using a trim-and-fill method.<br><br>RESULTS: This meta-analysis revealed that UA could be a prognostic factor for ALS (all, HR&#x202f;=&#x202f;0.87, p&#x202f;<&#x202f;0.001; men, HR&#x202f;=&#x202f;0.83, p&#x202f;<&#x202f;0.001; women, HR&#x202f;=&#x202f;0.76, p&#x202f;<&#x202f;0.001). The included studies were homogeneous (all, p&#x202f;=&#x202f;0.43; men, p&#x202f;=&#x202f;0.9; women, p&#x202f;=&#x202f;0.49). Sensitivity analysis confirmed the robustness of these summary effects. Publication bias was detected, which was adjusted for by a trim-and-fill method. The adjusted results showed significant summary effects (all, HR&#x202f;=&#x202f;0.88, p&#x202f;=&#x202f;0.002; men, HR&#x202f;=&#x202f;0.83, p&#x202f;<&#x202f;0.001; women, HR&#x202f;=&#x202f;0.77, p&#x202f;<&#x202f;0.001).<br><br>CONCLUSION: The present meta-analysis suggests that the serum UA level could be a prognostic biomarker in patients with ALS. Sensitivity analyses and the trim-and-fill method supported the robustness of these results.}, }
@article {pmid33678061, year = {2021}, author = {Spielmans, GI}, title = {Re-Analyzing Phase III Bremelanotide Trials for "Hypoactive Sexual Desire Disorder" in Women.}, journal = {Journal of sex research}, volume = {58}, number = {9}, pages = {1085-1105}, doi = {10.1080/00224499.2021.1885601}, pmid = {33678061}, issn = {1559-8519}, mesh = {Female ; Humans ; *Libido ; Peptides, Cyclic ; *Sexual Dysfunctions, Psychological/drug therapy ; alpha-MSH ; }, abstract = {Kingsberg et al. described results from two 24-week Phase III trials of bremelanotide for treating hypoactive sexual desire disorder (HSDD) in women. 72.72% of protocol-listed outcomes were not reported by Kingsberg et al., who provided results of 15 secondary measures which were not listed in the study protocols. None of their efficacy outcomes were reported in line with CONSORT data reporting standards and no secondary outcome had a stated rationale or cited evidence of validity. My meta-analysis of the trials' data, based on the FDA New Drug Application, found similar results to Kingsberg et al. However, Kingsberg et al. did not report that a) adverse event-induced study discontinuation was substantially higher on bremelanotide: OR = 11.98, 95% CI = 3.74-38.37, NNH: 6 or b) participants preferred placebo, measured by the combination of both 1) completing a clinical trial and 2) electing to participate in the follow-up open-label study (OR = 0.30, 95% CI = .24-.38, NNH: 4). Bremelanotide's modest benefits on incompletely reported post-hoc measures of questionable validity in combination with participants substantially preferring to take placebo suggest that the drug is generally not useful. Kingsberg et al.'s data reporting and measurement practices were incomplete and lacked transparency.}, }
@article {pmid33199452, year = {2020}, author = {Shoesmith, C and Abrahao, A and Benstead, T and Chum, M and Dupre, N and Izenberg, A and Johnston, W and Kalra, S and Leddin, D and O'Connell, C and Schellenberg, K and Tandon, A and Zinman, L}, title = {Canadian best practice recommendations for the management of amyotrophic lateral sclerosis.}, journal = {CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne}, volume = {192}, number = {46}, pages = {E1453-E1468}, pmid = {33199452}, issn = {1488-2329}, mesh = {Amyotrophic Lateral Sclerosis/*therapy ; Canada ; Humans ; *Patient Care Team ; Societies, Medical ; }, }
@article {pmid33113361, year = {2020}, author = {Iacoangeli, A and Lin, T and Al Khleifat, A and Jones, AR and Opie-Martin, S and Coleman, JRI and Shatunov, A and Sproviero, W and Williams, KL and Garton, F and Restuadi, R and Henders, AK and Mather, KA and Needham, M and Mathers, S and Nicholson, GA and Rowe, DB and Henderson, R and McCombe, PA and Pamphlett, R and Blair, IP and Schultz, D and Sachdev, PS and Newhouse, SJ and Proitsi, P and Fogh, I and Ngo, ST and Dobson, RJB and Wray, NR and Steyn, FJ and Al-Chalabi, A}, title = {Genome-wide Meta-analysis Finds the ACSL5-ZDHHC6 Locus Is Associated with ALS and Links Weight Loss to the Disease Genetics.}, journal = {Cell reports}, volume = {33}, number = {4}, pages = {108323}, pmid = {33113361}, issn = {2211-1247}, support = {ALCHALABI-DOBSON/APR14/829-791/MNDA_/Motor Neurone Disease Association/United Kingdom ; MC_PC_17214/MRC_/Medical Research Council/United Kingdom ; MR/L501529/1/MRC_/Medical Research Council/United Kingdom ; G0600974/MRC_/Medical Research Council/United Kingdom ; AL-CHALABI/APR15/844-791/MNDA_/Motor Neurone Disease Association/United Kingdom ; ALCHALABI-TALBOT/APR14/926-794/MNDA_/Motor Neurone Disease Association/United Kingdom ; MR/R024804/1/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; }, mesh = {Acyltransferases/*adverse effects ; Amyotrophic Lateral Sclerosis/*complications/genetics ; Genetic Predisposition to Disease ; Genome-Wide Association Study/*methods ; Humans ; Polymorphism, Single Nucleotide/*genetics ; Weight Loss/*genetics ; }, abstract = {We meta-analyze amyotrophic lateral sclerosis (ALS) genome-wide association study (GWAS) data of European and Chinese populations (84,694 individuals). We find an additional significant association between rs58854276 spanning ACSL5-ZDHHC6 with ALS (p = 8.3 × 10[-9]), with replication in an independent Australian cohort (1,502 individuals; p = 0.037). Moreover, B4GALNT1, G2E3-SCFD1, and TRIP11-ATXN3 are identified using a gene-based analysis. ACSL5 has been associated with rapid weight loss, as has another ALS-associated gene, GPX3. Weight loss is frequent in ALS patients and is associated with shorter survival. We investigate the effect of the ACSL5 and GPX3 single-nucleotide polymorphisms (SNPs), using longitudinal body composition and weight data of 77 patients and 77 controls. In patients' fat-free mass, although not significant, we observe an effect in the expected direction (rs58854276: -2.1 ± 1.3 kg/A allele, p = 0.053; rs3828599: -1.0 ± 1.3 kg/A allele, p = 0.22). No effect was observed in controls. Our findings support the increasing interest in lipid metabolism in ALS and link the disease genetics to weight loss in patients.}, }
@article {pmid32968195, year = {2020}, author = {Nakamura, R and Misawa, K and Tohnai, G and Nakatochi, M and Furuhashi, S and Atsuta, N and Hayashi, N and Yokoi, D and Watanabe, H and Watanabe, H and Katsuno, M and Izumi, Y and Kanai, K and Hattori, N and Morita, M and Taniguchi, A and Kano, O and Oda, M and Shibuya, K and Kuwabara, S and Suzuki, N and Aoki, M and Ohta, Y and Yamashita, T and Abe, K and Hashimoto, R and Aiba, I and Okamoto, K and Mizoguchi, K and Hasegawa, K and Okada, Y and Ishihara, T and Onodera, O and Nakashima, K and Kaji, R and Kamatani, Y and Ikegawa, S and Momozawa, Y and Kubo, M and Ishida, N and Minegishi, N and Nagasaki, M and Sobue, G}, title = {A multi-ethnic meta-analysis identifies novel genes, including ACSL5, associated with amyotrophic lateral sclerosis.}, journal = {Communications biology}, volume = {3}, number = {1}, pages = {526}, pmid = {32968195}, issn = {2399-3642}, mesh = {Amyotrophic Lateral Sclerosis/ethnology/*genetics ; Asian People/genetics ; Case-Control Studies ; China ; Coenzyme A Ligases/*genetics/physiology ; Female ; Genes/*genetics ; Genetic Predisposition to Disease/*genetics ; Genome-Wide Association Study ; Humans ; Japan ; Male ; Polymorphism, Single Nucleotide/genetics ; White People/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating progressive motor neuron disease that affects people of all ethnicities. Approximately 90% of ALS cases are sporadic and thought to have multifactorial pathogenesis. To understand the genetics of sporadic ALS, we conducted a genome-wide association study using 1,173 sporadic ALS cases and 8,925 controls in a Japanese population. A combined meta-analysis of our Japanese cohort with individuals of European ancestry revealed a significant association at the ACSL5 locus (top SNP p = 2.97 × 10[-8]). We validated the association with ACSL5 in a replication study with a Chinese population and an independent Japanese population (1941 ALS cases, 3821 controls; top SNP p = 1.82 × 10[-4]). In the combined meta-analysis, the intronic ACSL5 SNP rs3736947 showed the strongest association (p = 7.81 × 10[-11]). Using a gene-based analysis of the full multi-ethnic dataset, we uncovered additional genes significantly associated with ALS: ERGIC1, RAPGEF5, FNBP1, and ATXN3. These results advance our understanding of the genetic basis of sporadic ALS.}, }
@article {pmid32901053, year = {2020}, author = {Chang, MC and Kwak, SG and Park, JS and Park, D}, title = {The effectiveness of nonsteroidal anti-inflammatory drugs and acetaminophen in reduce the risk of amyotrophic lateral sclerosis? A meta-analysis.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {14759}, pmid = {32901053}, issn = {2045-2322}, mesh = {Acetaminophen/*therapeutic use ; Amyotrophic Lateral Sclerosis/metabolism/pathology/*prevention &amp; control ; Analgesics, Non-Narcotic/*therapeutic use ; Animals ; Anti-Inflammatory Agents, Non-Steroidal/*therapeutic use ; Drug Therapy, Combination ; Humans ; }, abstract = {To test the hypothesis that aspirin, non-aspirin nonsteroidal anti-infammatory drugs (NA-NSAIDs), or acetaminophen can reduce the risk of ALS, we conducted a systematic review and meta-analysis of related previous studies. A comprehensive search was conducted on the PubMed, Embase, Cochrane Library and SCOPUS databases. It included studies published up to 29 February 2020 that fulfilled our inclusion criteria. Aspirin, acetaminophen and NA-NSAIDs use information, between the ALS and control groups, was collected for the meta-analysis. Rates of aspirin, NA-NSAID, and acetaminophen use in ALS group, compared with control group were investigated. In the results, only three studies that relate the risk of ALS to aspirin, NA-NSAIDs and acetaminophen use satisfied the inclusion criteria for the meta-analysis. Regarding aspirin, the studies did not show any statistically significant difference in aspirin use between the ALS and control groups (Odds ratio, 1.04 [95% confidence interval, 0.90-1.21]). NA-NSAIDs and acetaminophen use, however, did show up statistically significant differences in between the ALS and control groups. (Odds ratio, 0.82 [95% confidence interval, 0.73-0.91]) and (Odds ratio, 0.80 [95% confidence interval, 0.69-0.93]). However, our study has some limitations. Firstly, we only included a small number of studies. Secondly, the included studies did not control for past medical history, which may have confounded their results, and in turn, could have caused bias in our study. Thirdly, in this meta-analysis, the ALS patients were not subdivided into sporadic or familial type. Lastly, the studies also did not consider the types of NSAIDs and dosages used of each drug. For more convincing evidence regarding the effectiveness of aspirin, NA-NSAIDs and acetaminophen to reduce the risk of ALS occurrence, more qualified prospective studies are required. In conclusion, the use of NA-NSAIDs and acetaminophen is associated with a decreased risk for the development of ALS. In contrast, aspirin did not have any effect on the reduction of the risk of ALS occurrence.}, }
@article {pmid32651855, year = {2021}, author = {Yang, B and Yang, C and Ren, J and Zhong, C and Liu, K and Zhao, L and Li, L and Wang, H and Zhu, M and Lin, Z}, title = {Meta-analysis of the association between CHCHD10 Pro34Ser variant and the risk of amyotrophic lateral sclerosis.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {42}, number = {2}, pages = {625-631}, pmid = {32651855}, issn = {1590-3478}, support = {20YYJC0146//Sichuan application basic research project/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/epidemiology/genetics ; Asian People ; Case-Control Studies ; Genome-Wide Association Study ; Humans ; Mitochondrial Proteins/genetics ; White People ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS), one of the motor neuron diseases, appears to be caused by genetic and environmental risk factors. However, the influence of Pro34Ser variant of CHCHD10 gene in increasing risk of ALS remains indeterminate. This study conducted a meta-analysis to establish the association between Pro34Ser variant of CHCHD10 gene and risk of ALS.<br><br>METHODS: PubMed, Web of Science, and Embase databases were systematically searched for genome-wide association studies or case-control studies published up to March 28, 2020, on the association between Pro34Ser variant and risk of ALS. Data from eligible studies were extracted and analyzed.<br><br>RESULTS: Twelve case-control studies involving 7442 patients with sporadic ALS and 75,371 controls were analyzed. The Pro34Ser variant was not associated with increased risk of ALS disease based on fixed-effects meta-analysis (Pro34Ser-positive vs Pro34Ser-negative: OR 1.23, 95% CI 0.90 to 1.69, P&#x2009;=&#x2009;0.201).<br><br>CONCLUSION: Existing evidence suggests that Pro34Ser variant in CHCHD10 is not associated with risk of ALS, particularly in Caucasian participants. However, our results ought to be validated using large, well-designed studies, especially in Asian and African populations.}, }
@article {pmid32028381, year = {2020}, author = {Lenoir, D and De Pauw, R and Van Oosterwijck, S and Cagnie, B and Meeus, M}, title = {Acupuncture Versus Sham Acupuncture: A Meta-Analysis on Evidence for Longer-term Effects of Acupuncture in Musculoskeletal Disorders.}, journal = {The Clinical journal of pain}, volume = {36}, number = {7}, pages = {533-549}, doi = {10.1097/AJP.0000000000000812}, pmid = {32028381}, issn = {1536-5409}, mesh = {*Acupuncture Therapy ; Humans ; *Musculoskeletal Diseases/therapy ; Pain ; Quality of Life ; }, abstract = {EDITORIAL NOTE: The original Letter to the Editor prepared by Jones et al was based on the initial electronic version then contained several important procedural errors that resulted in erroneous conclusions as noted by Jones et al in their original Letter. Subsequently, the authors of the Letter to the Editor were notified of the corrections and they then prepared the revised Letter to the Editor published here. Jones et al did note a remaining error in Table 5 of their corrected manuscript. Based on Jones et al's observation, Lenoir et al were notified of an error on Table 5 and have addressed this in the current version of their paper published in this issue. We appreciate the input of the authors of the letter and the positive response of the author(s) of this article. Dennis C. Turk, PhD Editor-in-Chief OBJECTIVE:: Acupuncture is a common modality in the therapy of musculoskeletal disorders. The evidence for acupuncture has been examined frequently, but a clear synthesis of previous research is currently lacking. This meta-analysis aimed to summarize the evidence for nonimmediate effects of acupuncture on pain, functionality, and quality of life in patients with musculoskeletal disorders, when compared with sham acupuncture.<br><br>METHODS: Search results from PubMed and Web of Science were brought together. All screening procedures were executed twice by 2 independent researchers. The pooled standardized mean difference (SMD) with its confidence interval (CI) was estimated at follow-up at <1 month, 1 to 3 months, 3 to 6 months, and >6 months.<br><br>RESULTS: For pain, the SMD equalled respectively -0.47 (CI -0.76 to -0.19), -0.27 (CI -0.44 to -0.11), -0.32 (CI -0.51 to -0.13) and -0.12 (CI -0.36 to 0.11) for <1 month, 1 to 3 months, 3 to 6 months, and >6 months follow-up. For functionality, the pooled SMD equalled -0.43 (CI -0.76 to -0.10), -0.41 (CI -0.76 to -0.05), 0.07 (CI -0.22 to 0.36), and -0.13 (-0.46 to 0.19). In the area of QOL, pooled SMD of respectively 0.20 (CI 0.04 to 0.35), 0.19 (CI -0.01 to 0.39), 0.02 (CI -0.09 to 0.14) and -0.04 (CI -0.25 to 0.16) were obtained.<br><br>DISCUSSION: A significant difference in therapy effect, favoring acupuncture, was found for pain at <1 month, 1 to 3 months, and 3 to 6 months, as well as on quality of life at <1 month, and on functionality at <1 month and 1 to 3 months.}, }
@article {pmid31932031, year = {2020}, author = {Corcia, P and Lumbroso, S and Cazeneuve, C and Mouzat, K and Camu, W and Vourc'h, P and , }, title = {Pre-symptomatic diagnosis in ALS.}, journal = {Revue neurologique}, volume = {176}, number = {3}, pages = {166-169}, doi = {10.1016/j.neurol.2019.07.027}, pmid = {31932031}, issn = {0035-3787}, mesh = {Amyotrophic Lateral Sclerosis/*diagnosis/epidemiology/*genetics ; Asymptomatic Diseases ; Confidentiality/standards ; DNA Mutational Analysis/methods/standards ; Disclosure/standards ; Early Diagnosis ; Gene Frequency ; Genetic Association Studies ; Genetic Counseling/methods/standards ; Genetic Predisposition to Disease ; Genetic Testing/methods/*standards ; Humans ; Molecular Diagnostic Techniques/methods/standards ; Prodromal Symptoms ; }, abstract = {Pathophysiology of amyotrophic lateral sclerosis (ALS) remains partially understood even though it is accepted worldwide that motor neuron death results from a pluri-factorial process with a variable role of genetic factors. Although not distinguishable from a clinical point of view, familial forms of ALS (fALS, 10% of cases) and sporadic forms (sALS, 90% of cases) can be described. Since the identification of superoxide dismutase 1 gene (SOD1) mutations, more than 30 genes have been linked to fALS. Among these genes, five (C9ORF72, SOD1, TARDBP, FUS, TBK1) seem predominant with mutation frequencies of 40%, 20%, 5%, <5%, <5% in fALS and 6%, 3%, and <1% for the last three in sALS, respectively. The situation that classically leads to request genetic screening is the presence of a familial history of motor neuron disorders (MND) or fronto-temporal lobar dementia (FTLD). However, this dichotomy between fALS and sALS based on familial history can lead to mistakes since illegitimacy, ignorance of MND, FTD or psychiatric disorders within the family due to a familial censorship or lack of familial relationship, or a recessive autosomal inheritance could wrongly lead to failing to recognize a familial form. The significant development of genetic research and easier access to genetic tests in fALS increase the number of situations for which gene mutations are identified. The consequence is an increase in genetic requests from relatives of ALS patients who are eager to know their own genetic status and their own individual risk to develop ALS. Pre-symptomatic testing is thus becoming a daily issue in ALS Centers. This led us to propose a framework for such pre-symptomatic genetic testing for people at risk for developing ALS.}, }
@article {pmid31673225, year = {2019}, author = {Xu, C and Wu, J and Wang, J}, title = {Associations of rs524952 and rs634990 gene polymorphisms in 15q14 with high myopia: A meta-analysis.}, journal = {Molecular vision}, volume = {25}, number = {}, pages = {603-609}, pmid = {31673225}, issn = {1090-0535}, mesh = {Adult ; Chromosomes, Human, Pair 15/*genetics ; *Genetic Association Studies ; *Genetic Predisposition to Disease ; Humans ; Middle Aged ; Models, Genetic ; Myopia/*genetics ; Polymorphism, Single Nucleotide/*genetics ; Publication Bias ; Risk Factors ; Young Adult ; }, abstract = {PURPOSE: Many studies have been conducted to investigate the association between the rs524952 and rs634990 polymorphisms and high myopia (HM). However, the results were conflicting. Thus, a meta-analysis was needed to reveal the real association between the two single nucleotide polymorphisms (SNPs) and HM.<br><br>METHODS: All eligible studies published in Pubmed, Embase, China Biologic Medicine (CBM), the China National Knowledge Infrastructure (CNKI), the Cochrane Library, and the Web of Science from 2010 to March 2019 were examined.<br><br>RESULTS: Six comparison groups in four studies with 5,293 subjects for the rs524952 polymorphism and five studies with 6,750 subjects for the rs634990 polymorphism were included. No statistically significant associations were observed between the rs524952 and rs634990 polymorphisms and HM under the allelic model, recessive genetic model, and dominant genetic model in this meta-analysis. Subgroup analysis was conducted by dividing the studies into two groups according to the case sample size, which showed that the association between the rs524952 polymorphism and HM was found only in a subgroup of fewer than 300 cases under the dominant genetic model (OR=0.64; 95% confidence interval [CI]:0.43-0.96). Sensitivity analysis for the rs524952 polymorphism suggested the results of this study were stable under all the genetic models. However, the association between the rs634990 polymorphism and HM turned out to be statistically significant in the allelic, recessive, and dominant genetic models after the omission of Qiang et al.'s study. No publication bias was found.<br><br>CONCLUSIONS: The results of this meta-analysis suggested the rs524952 and rs634990 polymorphisms may have nothing to do with the development of HM. The present results must be confirmed with larger-scale studies in the future.}, }
@article {pmid31610740, year = {2020}, author = {Zuckerman, M and Li, C and Lin, S and Hall, JA}, title = {The Negative Intelligence-Religiosity Relation: New and Confirming Evidence.}, journal = {Personality &amp; social psychology bulletin}, volume = {46}, number = {6}, pages = {856-868}, doi = {10.1177/0146167219879122}, pmid = {31610740}, issn = {1552-7433}, mesh = {Adult ; Cognition ; Educational Status ; Female ; Humans ; *Intelligence ; Male ; *Religion ; }, abstract = {Zuckerman et al. (2013) conducted a meta-analysis of 63 studies that showed a negative intelligence-religiosity relation (IRR). As more studies have become available and because some of Zuckerman et al.'s (2013) conclusions have been challenged, we conducted a new meta-analysis with an updated data set of 83 studies. Confirming previous conclusions, the new analysis showed that the correlation between intelligence and religious beliefs in college and noncollege samples ranged from -.20 to -.23. There was no support for mediation of the IRR by education but there was support for partial mediation by analytic cognitive style. Thus, one possible interpretation for the IRR is that intelligent people are more likely to use analytic style (i.e., approach problems more rationally). An alternative (and less interesting) reason for the mediation is that tests of both intelligence and analytic style assess cognitive ability. Additional empirical and theoretical work is needed to resolve this issue.}, }
@article {pmid31286297, year = {2019}, author = {Corrado, L and Brunetti, M and Di Pierro, A and Barberis, M and Croce, R and Bersano, E and De Marchi, F and Zuccalà, M and Barizzone, N and Calvo, A and Moglia, C and Mazzini, L and Chiò, A and D'Alfonso, S}, title = {Analysis of the GCG repeat length in NIPA1 gene in C9orf72-mediated ALS in a large Italian ALS cohort.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {40}, number = {12}, pages = {2537-2540}, pmid = {31286297}, issn = {1590-3478}, support = {FGBR17/2013//Arisla/ ; RF-2013-02355764//Ministero della Salute/ ; RF-2010-2309849//Ministero della Salute/ ; prin 2015//Ministero dell'Istruzione, dell'Universit&#xe0; e della Ricerca/ ; Joint Programme - Neurodegenerative Disease Research (Strength and Brain-Mend projects)//Ministero dell'Istruzione, dell'Universit&#xe0; e della Ricerca/ ; FP7/2007-2013 under grant agreement 259867//FP7 Ideas: European Research Council/ ; }, mesh = {Amyotrophic Lateral Sclerosis/*genetics ; C9orf72 Protein/*genetics ; Cohort Studies ; Genes, Modifier/*genetics ; Genetic Predisposition to Disease/*genetics ; Humans ; Italy ; Membrane Proteins/*genetics ; Trinucleotide Repeat Expansion ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of upper and lower motor neurons. The hexanucleotide repeat expansion in C9orf72 gene (C9orf72-HRE) is the most frequent genetic cause of ALS. Since many ALS pedigrees showed incomplete penetrance, several genes have been analyzed as possible modifiers. Length of the GCG repeat tract in NIPA1 (non-imprinted in Prader-Willi/Angelman syndrome 1) gene has been recently investigated as a possible modifier factor for C9orf72-HRE patients with contrasting findings. To disclose the possible role of NIPA1 GCG repeat length as modifier of the disease risk in C9orf72-HRE carriers, we analyzed a large cohort of 532 Italian ALS cases enriched in C9orf72-HRE carriers (172 cases) and 483 Italian controls. This sample size is powered (92% power, p = 0.05) to replicate the modifier effect observed in literature. We did not observe higher frequency of NIPA1 long alleles (> 8 GCG) in C9orf72-HRE carriers (3.5%) compared with C9orf72-HRE negative patients (4.1%) and healthy controls (5%). For the latter comparison, we meta-analyzed our data with currently available literature data, and no statistically significant effect was observed (p = 0.118). In conclusion, we did not confirm a role of NIPA1 repeat length as a modifier of the C9orf72 ALS disease risk.}, }
@article {pmid31201598, year = {2019}, author = {Yang, B and Jiang, H and Wang, F and Li, S and Wu, C and Bao, J and Zhu, Y and Xu, Z and Liu, B and Ren, H and Yang, X}, title = {UNC13A variant rs12608932 is associated with increased risk of amyotrophic lateral sclerosis and reduced patient survival: a meta-analysis.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {40}, number = {11}, pages = {2293-2302}, pmid = {31201598}, issn = {1590-3478}, support = {201801CH00572//Applied Basic Research Key Project of Yunnan (CN)/ ; 2018NS0102//Applied Basic Research Key Project of Yunnan (CN)/ ; 81860247//National Natural Science Foundation of China/ ; 2017BS005//Fundo de Apoio ao Ensino, &#xe0; Pesquisa e Extens&#xe3;o, Universidade Estadual de Campinas (BR)/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/ethnology/genetics/mortality ; *Genetic Predisposition to Disease/epidemiology/ethnology/genetics ; Humans ; Nerve Tissue Proteins/*genetics ; Risk ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease associated with both genetic and environmental risk factors. Previous studies trying to find an association between ALS and unc-13 homolog A (UNC13A) gene variants have shown inconsistent results. This study aimed to conduct a meta-analysis of the association between the C allele of rs12608932, a single-nucleotide polymorphism located in an intron of UNC13A, and risk of ALS and patient survival.<br><br>METHODS: PubMed, Web of Science, Embase, Chinese National Knowledge Infrastructure, Wanfang, and SinoMed databases were systematically searched for genome-wide association studies or case-control studies published up to January 2019 on the association between this variant in UNC13A and risk and/or prognosis of ALS. Data from eligible studies were extracted and analyzed.<br><br>RESULTS: The pooled data (28,072 patients with sporadic ALS and 56,545 controls) showed that rs12608932(C) was associated with an increased risk of ALS (OR&#x2009;=&#x2009;1.13, 95%CI 1.07-1.20). Subgroup analysis revealed that rs12608932(C) increased the risk of sporadic ALS in non-Asian individuals, including those from the USA and Europe (OR 1.17, 95%CI 1.10-1.25, P&#x2009;<&#x2009;0.000), but not in Japanese or Chinese subjects (OR 1.01, 95%CI 0.92-1.10, P&#x2009;=&#x2009;0.85). The available data demonstrated that the CC genotype decreased the survival time of patients with ALS (OR 1.33, 95%CI 1.19-1.49, P&#x2009;<&#x2009;0.001).<br><br>CONCLUSION: The present meta-analysis suggests that rs12608932(C) is associated with increased ALS susceptibility, especially in Caucasian and European subjects, and that the CC genotype of rs12608932 is associated with reduced ALS patient survival.}, }
@article {pmid31020811, year = {2019}, author = {Apolloni, S and Amadio, S and Fabbrizio, P and Morello, G and Spampinato, AG and Latagliata, EC and Salvatori, I and Proietti, D and Ferri, A and Madaro, L and Puglisi-Allegra, S and Cavallaro, S and Volonté, C}, title = {Histaminergic transmission slows progression of amyotrophic lateral sclerosis.}, journal = {Journal of cachexia, sarcopenia and muscle}, volume = {10}, number = {4}, pages = {872-893}, pmid = {31020811}, issn = {2190-6009}, mesh = {Amyotrophic Lateral Sclerosis/*drug therapy/genetics ; Animals ; Disease Models, Animal ; Disease Progression ; Gene Expression/*genetics ; Histamine/pharmacology/*therapeutic use ; Humans ; Mice ; }, abstract = {BACKGROUND: Histamine is an immune modulator, neuroprotective, and remyelinating agent, beneficially acting on skeletal muscles and promoting anti-inflammatory features in amyotrophic lateral sclerosis (ALS) microglia. Drugs potentiating the endogenous release of histamine are in trial for neurological diseases, with a role not systematically investigated in ALS. Here, we examine histamine pathway associations in ALS patients and the efficacy of a histamine-mediated therapeutic strategy in ALS mice.<br><br>METHODS: We adopted an integrative multi-omics approach combining gene expression profiles, copy number variants, and single nucleotide polymorphisms of ALS patients. We treated superoxide dismutase 1 (SOD1)-G93A mice that recapitulate key ALS features, with the brain-permeable histamine precursor histidine in the symptomatic phase of the disease and analysed the rescue from disease pathological signs. We examined the action of histamine in cultured SOD1-G93A motor neuron-like cells.<br><br>RESULTS: We identified 13 histamine-related genes deregulated in the spinal cord of two ALS patient subgroups, among which genes involved in histamine metabolism, receptors, transport, and secretion. Some histamine-related genes overlapped with genomic regions disrupted by DNA copy number and with ALS-linked pathogenic variants. Histidine treatment in SOD1-G93A mice proved broad efficacy in ameliorating ALS features, among which most importantly lifespan, motor performance, microgliosis, muscle atrophy, and motor neurons survival in vivo and in vitro.<br><br>CONCLUSIONS: Our gene set/pathway enrichment analyses and preclinical studies started at the onset of symptoms establish that histamine-related genes are modifiers in ALS, supporting their role as candidate biomarkers and therapeutic targets. We disclose a novel important role for histamine in the characterization of the multi-gene network responsible for ALS and, furthermore, in the drug development process.}, }
@article {pmid30982356, year = {2019}, author = {Palumbo, JM and Hubble, J and Apple, S and Takei, K and Tsuda, K and Liu, S and Zhang, J and Agnese, W}, title = {Post-hoc analyses of the edaravone clinical trials Study 16 and Study 19: a step toward more efficient clinical trial designs in amyotrophic lateral sclerosis.}, journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration}, volume = {20}, number = {5-6}, pages = {421-431}, doi = {10.1080/21678421.2019.1599955}, pmid = {30982356}, issn = {2167-9223}, mesh = {Amyotrophic Lateral Sclerosis/*diagnosis/*drug therapy ; Clinical Trials, Phase II as Topic/*methods ; Clinical Trials, Phase III as Topic/*methods ; Disease Progression ; Double-Blind Method ; Edaravone/*therapeutic use ; Humans ; Neuroprotective Agents/*therapeutic use ; Randomized Controlled Trials as Topic/*methods ; Treatment Outcome ; }, abstract = {Objectives: The edaravone development program established a study design in which a treatment effect slowing functional loss in amyotrophic lateral sclerosis (ALS) could be documented within a 24-week time frame. This report elucidates the strategic enrichment design utilized to create efficiency and precision in the development program. Methods: Post-hoc analyses describe learning, sequential iteration, and evolution in study design. Results: The first Phase 3 study of edaravone in ALS (Study MCI186-16) included a large proportion (35%) of placebo patients who were minimal progressors. These patients demonstrated high heterogeneity in change in ALSFRS-R score (-4 median with interquartile range [IQR] 7.5) and a modal distribution score of 0, suggesting evidence of minimal change in ALSFRS-R during the study. This level of variability and rate of progression may have made it difficult to detect a prospective treatment effect in the study. A strategic enrichment strategy provided the second Phase 3 study (Study MCI186-19) with the ability to detect a treatment effect. In Study MCI186-19, only 13% of the placebo patients were minimal progressors. Further, these placebo patients demonstrated less heterogeneity and greater functional progression of ALS, thereby providing greater likelihood of detecting a treatment effect. The enrichment strategy may have excluded some rapidly progressing patients, potentially supporting the detection of a treatment effect. As previously published, Study MCI186-19 prospectively documented a 33% reduction in rate of progression of ALS (p = 0.0013). Conclusions: Strategic choices in the design of Study MCI186-19 reduced the proportion of minimally progressing patients and supported detection of a treatment effect.}, }
@article {pmid30337677, year = {2018}, author = {Gorges, M and Del Tredici, K and Dreyhaupt, J and Braak, H and Ludolph, AC and Müller, HP and Kassubek, J}, title = {Corticoefferent pathology distribution in amyotrophic lateral sclerosis: in vivo evidence from a meta-analysis of diffusion tensor imaging data.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {15389}, pmid = {30337677}, issn = {2045-2322}, mesh = {Amyotrophic Lateral Sclerosis/*pathology ; Brain Mapping/*methods ; Case-Control Studies ; Cross-Sectional Studies ; Diffusion Tensor Imaging/*methods ; Disease Progression ; Humans ; Image Processing, Computer-Assisted/*methods ; Longitudinal Studies ; Pyramidal Tracts/*pathology ; }, abstract = {A sequential transaxonal disease spread of amyotrophic lateral sclerosis (ALS)-associated TDP-43 pathology in four stages has been defined by post-mortem data, which have been transferred to in vivo imaging by diffusion tensor imaging (DTI) studies. Here, we aimed to investigate whether DTI meta-data are consistent with this proposed pattern of progression in ALS. A systematic literature search using the search engines PubMed and Scopus yielded a total of 370 publications. Of these, 57 studies with cross-sectional data and 10 longitudinal studies of human whole-brain analyses of fractional anisotropy (FA) were included in the final data analysis. Statistical meta-analyses on coordinates of significant FA alterations were performed on a grand average alteration data set using a fixed-effect model. A widespread pattern of white matter impairment was identified from cross-sectional meta data (n = 2064 ALS patients vs. n = 1688 controls) and supported from longitudinal meta data (n = 266 ALS patients over 8 months). The results from cross-sectional meta-analyses corresponded to the brain regions and tract systems according to the sequential disease spread of ALS. Structural alterations in ALS patients vs. controls followed a power gradient, i.e., the most frequent alterations were observed along the corticospinal tract (CST, related to ALS stage 1), followed by frequent alterations along the corticorubral/-pontine tract (related to ALS stage 2), together with corticostriatal pathways (related to ALS stage 3), and, finally, alterations in the hippocampal regions adjacent to the proximal portion of the perforant path (related to ALS stage 4). The results from the DTI-based neuroimaging meta-analysis strongly support the model of the corticoefferent axonal disease progression in ALS and provides further in vivo evidence for the proposed staging scheme of ALS-associated pathology.}, }
@article {pmid30228876, year = {2018}, author = {Duggan, M and Tressoldi, P}, title = {Predictive physiological anticipatory activity preceding seemingly unpredictable stimuli: An update of Mossbridge et al's meta-analysis.}, journal = {F1000Research}, volume = {7}, number = {}, pages = {407}, pmid = {30228876}, issn = {2046-1402}, mesh = {Bayes Theorem ; *Forecasting ; Humans ; *Physiological Phenomena ; Publication Bias ; Regression Analysis ; }, abstract = {Background: This is an update of the Mossbridge et al's meta-analysis related to the physiological anticipation preceding seemingly unpredictable stimuli which overall effect size was 0.21; 95% Confidence Intervals: 0.13 - 0.29 Methods: Nineteen new peer and non-peer reviewed studies completed from January 2008 to June 2018 were retrieved describing a total of 27 experiments and 36 associated effect sizes. Results: The overall weighted effect size, estimated with a frequentist multilevel random model, was: 0.28; 95% Confidence Intervals: 0.18-0.38; the overall weighted effect size, estimated with a multilevel Bayesian model, was: 0.28; 95% Credible Intervals: 0.18-0.38. The weighted mean estimate of the effect size of peer reviewed studies was higher than that of non-peer reviewed studies, but with overlapped confidence intervals: Peer reviewed: 0.36; 95% Confidence Intervals: 0.26-0.47; Non-Peer reviewed: 0.22; 95% Confidence Intervals: 0.05-0.39. Similarly, the weighted mean estimate of the effect size of Preregistered studies was higher than that of Non-Preregistered studies: Preregistered: 0.31; 95% Confidence Intervals: 0.18-0.45; No-Preregistered: 0.24; 95% Confidence Intervals: 0.08-0.41. The statistical estimation of the publication bias by using the Copas selection model suggest that the main findings are not contaminated by publication bias. Conclusions: In summary, with this update, the main findings reported in Mossbridge et al's meta-analysis, are confirmed.}, }
@article {pmid30035009, year = {2018}, author = {Zhang, F and Chen, G and He, M and Dai, J and Shang, H and Gong, Q and Jia, Z}, title = {Altered white matter microarchitecture in amyotrophic lateral sclerosis: A voxel-based meta-analysis of diffusion tensor imaging.}, journal = {NeuroImage. Clinical}, volume = {19}, number = {}, pages = {122-129}, pmid = {30035009}, issn = {2213-1582}, mesh = {Adult ; Aged ; Aged, 80 and over ; Amyotrophic Lateral Sclerosis/*diagnostic imaging/physiopathology ; Anisotropy ; Corpus Callosum/pathology ; *Diffusion Tensor Imaging/methods ; Female ; Humans ; *Image Processing, Computer-Assisted/methods ; Internal Capsule/pathology ; Male ; Middle Aged ; Nerve Fibers, Myelinated/pathology ; Nerve Net/pathology ; Pyramidal Tracts/*pathology ; White Matter/*pathology ; }, abstract = {BACKGROUND: The results of recent diffusion tensor imaging (DTI) studies on amyotrophic lateral sclerosis (ALS) are inconclusive and controversial. We performed a voxel-based meta-analysis to identify a statistical consensus among published DTI studies of altered white matter (WM) microarchitecture in ALS.<br><br>METHODS: A systematic search was conducted for relevant studies that used voxel-wise analyses of WM microarchitecture in patients with ALS. Anisotropic effect size-signed differential mapping (AES-SDM) was applied to analyze fractional anisotropy (FA) differences between ALS patients and healthy controls. Meta-regression analysis was used to explore the effects of clinical characteristics on WM integrity in patients with ALS.<br><br>RESULTS: A total of 14 studies with 16 datasets that included 396 patients and 360 healthy controls were identified. The pooled meta-analysis revealed that patients with ALS exhibited significant FA reductions in two clusters relative to healthy controls. The largest cluster exhibited a peak coordinate in the left corona radiata, extending to the body and splenium of the corpus callosum, left superior longitudinal fasciculus, posterior limb of the internal capsule, right corona radiata, and bilateral cingulate gyrus. The other cluster exhibited decreased FA in the right corticospinal tract that extended to the right cerebral peduncle. The Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score was positively correlated with the FA reduction in the left corona radiata. Mean age and illness duration were not linearly correlated with the FA reductions.<br><br>CONCLUSIONS: This study provides a thorough profile of WM microarchitecture alterations in patients with ALS and further evidence that the neuronal degeneration is not limited to the corticospinal tract but also includes extra-motor areas, which supports the view that ALS is a multisystem degenerative disorder that involves the white matter.}, }
@article {pmid29943172, year = {2018}, author = {Trippas, D and Kellen, D and Singmann, H and Pennycook, G and Koehler, DJ and Fugelsang, JA and Dubé, C}, title = {Characterizing belief bias in syllogistic reasoning: A hierarchical Bayesian meta-analysis of ROC data.}, journal = {Psychonomic bulletin &amp; review}, volume = {25}, number = {6}, pages = {2141-2174}, pmid = {29943172}, issn = {1531-5320}, mesh = {*Bayes Theorem ; Humans ; *Logic ; *ROC Curve ; *Thinking ; }, abstract = {The belief-bias effect is one of the most-studied biases in reasoning. A recent study of the phenomenon using the signal detection theory (SDT) model called into question all theoretical accounts of belief bias by demonstrating that belief-based differences in the ability to discriminate between valid and invalid syllogisms may be an artifact stemming from the use of inappropriate linear measurement models such as analysis of variance (Dube et al., Psychological Review, 117(3), 831-863, 2010). The discrepancy between Dube et al.'s, Psychological Review, 117(3), 831-863 (2010) results and the previous three decades of work, together with former's methodological criticisms suggests the need to revisit earlier results, this time collecting confidence-rating responses. Using a hierarchical Bayesian meta-analysis, we reanalyzed a corpus of 22 confidence-rating studies (N = 993). The results indicated that extensive replications using confidence-rating data are unnecessary as the observed receiver operating characteristic functions are not systematically asymmetric. These results were subsequently corroborated by a novel experimental design based on SDT's generalized area theorem. Although the meta-analysis confirms that believability does not influence discriminability unconditionally, it also confirmed previous results that factors such as individual differences mediate the effect. The main point is that data from previous and future studies can be safely analyzed using appropriate hierarchical methods that do not require confidence ratings. More generally, our results set a new standard for analyzing data and evaluating theories in reasoning. Important methodological and theoretical considerations for future work on belief bias and related domains are discussed.}, }
@article {pmid29932266, year = {2018}, author = {Nobili, F and Arbizu, J and Bouwman, F and Drzezga, A and Agosta, F and Nestor, P and Walker, Z and Boccardi, M and , }, title = {European Association of Nuclear Medicine and European Academy of Neurology recommendations for the use of brain [18] F-fluorodeoxyglucose positron emission tomography in neurodegenerative cognitive impairment and dementia: Delphi consensus.}, journal = {European journal of neurology}, volume = {25}, number = {10}, pages = {1201-1217}, doi = {10.1111/ene.13728}, pmid = {29932266}, issn = {1468-1331}, mesh = {Brain/*diagnostic imaging ; Cognitive Dysfunction/*diagnostic imaging ; Dementia/*diagnostic imaging ; Diagnosis, Differential ; *Fluorodeoxyglucose F18 ; Humans ; Neurodegenerative Diseases/*diagnostic imaging ; Nuclear Medicine ; Positron-Emission Tomography/*methods ; Sensitivity and Specificity ; }, abstract = {BACKGROUND AND PURPOSE: Recommendations for using fluorodeoxyglucose positron emission tomography (FDG-PET) to support the diagnosis of dementing neurodegenerative disorders are sparse and poorly structured.<br><br>METHODS: Twenty-one questions on diagnostic issues and on semi-automated analysis to assist visual reading were defined. Literature was reviewed to assess study design, risk of bias, inconsistency, imprecision, indirectness and effect size. Critical outcomes were sensitivity, specificity, accuracy, positive/negative predictive value, area under the receiver operating characteristic curve, and positive/negative likelihood ratio of FDG-PET in detecting the target conditions. Using the Delphi method, an expert panel voted for/against the use of FDG-PET based on published evidence and expert opinion.<br><br>RESULTS: Of the 1435 papers, 58 papers provided proper quantitative assessment of test performance. The panel agreed on recommending FDG-PET for 14 questions: diagnosing mild cognitive impairment due to Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD) or dementia with Lewy bodies (DLB); diagnosing atypical AD and pseudo-dementia; differentiating between AD and DLB, FTLD or vascular dementia, between DLB and FTLD, and between Parkinson's disease and progressive supranuclear palsy; suggesting underlying pathophysiology in corticobasal degeneration and progressive primary aphasia, and cortical dysfunction in Parkinson's disease; using semi-automated assessment to assist visual reading. Panellists did not support FDG-PET use for pre-clinical stages of neurodegenerative disorders, for amyotrophic lateral sclerosis and Huntington disease diagnoses, and for amyotrophic lateral sclerosis or Huntington-disease-related cognitive decline.<br><br>CONCLUSIONS: Despite limited formal evidence, panellists deemed FDG-PET useful in the early and differential diagnosis of the main neurodegenerative disorders, and semi-automated assessment helpful to assist visual reading. These decisions are proposed as interim recommendations.}, }
@article {pmid29687175, year = {2018}, author = {Marin, B and Fontana, A and Arcuti, S and Copetti, M and Boumédiene, F and Couratier, P and Beghi, E and Preux, PM and Logroscino, G}, title = {Age-specific ALS incidence: a dose-response meta-analysis.}, journal = {European journal of epidemiology}, volume = {33}, number = {7}, pages = {621-634}, pmid = {29687175}, issn = {1573-7284}, mesh = {Adolescent ; Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Amyotrophic Lateral Sclerosis/*epidemiology ; Child ; Child, Preschool ; Humans ; Incidence ; Infant ; Internationality ; Middle Aged ; Young Adult ; }, abstract = {To evaluate the association between worldwide ALS incidence rates and age, using a dose-response meta-analysis. We reviewed Medline and Embase up to July 2016 and included all population-based studies of newly-diagnosed cases, using multiple sources for case ascertainment. A dose-response meta-analysis was performed. A meta-regression investigated potential sources of heterogeneity. Of 3254 articles identified in the literature, we included 41 incidence studies covering 42 geographical areas. Overall, the fit between observed and predicted age-specific rates was very good. The expected variation of ALS incidence with age was characterized, in each study, by a progressive increase in the incidence from the 40s leading to a peak in the 60s or 70s, followed by a sharp decrease. Cochran's Q test suggested a significant heterogeneity between studies. Overall, estimated patterns of ALS age-specific incidence (at which the peak was reached) were similar among subcontinents of Europe and North America: peak of ALS incidence ranged in these areas between 6.98 and 8.17/100,000 PYFU, which referred to age in the range 71.6-77.4 years. The relationship between age and ALS incidence appeared different for Eastern Asia which was characterized by a peak of ALS incidence at 2.20/100,000 PYFU around 75 years of age. This study confirms the consistency of the age-specific ALS incidence pattern within different subcontinents. Age-specific incidence appears lower in Eastern Asia as compared to Europe and North America.}, }
@article {pmid29408898, year = {2018}, author = {Cui, F and Sun, L and Xiong, J and Li, J and Zhao, Y and Huang, X}, title = {Therapeutic effects of percutaneous endoscopic gastrostomy on survival in patients with amyotrophic lateral sclerosis: A meta-analysis.}, journal = {PloS one}, volume = {13}, number = {2}, pages = {e0192243}, pmid = {29408898}, issn = {1932-6203}, mesh = {Aged ; Amyotrophic Lateral Sclerosis/physiopathology/*surgery ; Endoscopy/*methods ; Female ; Gastrostomy/*methods ; Humans ; Male ; Middle Aged ; Survival Rate ; }, abstract = {Percutaneous endoscopic gastrostomy (PEG) is a method widely used for patients with amyotrophic lateral sclerosis (ALS); nevertheless, its effect on survival remains unclear. The purpose of this meta-analysis study was to determine the effects of PEG on survival in ALS patients. Relevant studies were retrieved from PubMed, EmBase, and the Cochrane Library databases, from inception to June 2017. Studies comparing PEG with other procedures in ALS patients were included. Odds ratios (ORs) in a random-effects model were used to assess the survival at different follow-up periods. Briefly, ten studies involving a total of 996 ALS patients were included. Summary ORs indicated that PEG administration was not associated with 30-day (OR = 1.59; 95%CI 0.93-2.71; P = 0.092), 10-month (OR = 1.25; 95%CI 0.72-2.17; P = 0.436), and 30-month (OR = 1.28; 95% CI 0.77-2.11; P = 0.338) survival rates, while they showed a beneficial effect in 20-month survival rate (OR = 1.97; 95%CI 1.21-3.21; P = 0.007). The survival rate was significantly prominent in reports published before 2005, and in studies with a retrospective design, sample size <100, mean age <60.0 years, and percentage male ≥50.0%. To sum up, these findings suggested that ALS patients administered with PEG had an increased 20-month survival rates, while there was no significant effect in 30-day, 10-month, and 30-month survival rates.}, }
@article {pmid29348425, year = {2018}, author = {Zhang, F and Zhang, Q and Ke, Y and Hao, J and Lu, L and Lu, N and Chen, X}, title = {Serum uric acid levels in patients with amyotrophic lateral sclerosis: a meta-analysis.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {1100}, pmid = {29348425}, issn = {2045-2322}, mesh = {Amyotrophic Lateral Sclerosis/*blood/diagnosis/mortality ; Biomarkers ; Case-Control Studies ; Cause of Death ; Humans ; Prognosis ; Publication Bias ; Uric Acid/*blood ; }, abstract = {The pathogenic mechanism of ALS remains unclear. However, increasing evidence has indicated that uric acid (UA) may play a protective role in the pathogenesis of ALS. The aim of this study was to evaluate the association between serum UA levels and ALS. A comprehensive literature search in PubMed, Embase, Web of Science, and Cochrane Library was conducted up to 31st August, 2017, using keywords. A random-effects model or fixed-effects model was used to calculate the pooled estimate according to the inter-group heterogeneity. Finally, we indentified 8 case-control and 3 cohort studies. The results indicated that patients with ALS had significant decreased levels of serum UA compared to healthy controls (standardized mean difference (SMD) = -0.72, 95% CI [-0.98,-0.46], P < 0.001). Increased serum UA levels were associated with lower all-cause mortality risk among ALS patients (risk ratio (RR) = 0.70, 95% CI [0.57, 0.87], P = 0.001). To summarize, there is an inverse association between serum UA levels and risk of death among ALS patients. Randomized controlled trials with high quality are required to elucidate the role of UA on ALS.}, }
@article {pmid29274834, year = {2018}, author = {Burgos, R and Bretón, I and Cereda, E and Desport, JC and Dziewas, R and Genton, L and Gomes, F and Jésus, P and Leischker, A and Muscaritoli, M and Poulia, KA and Preiser, JC and Van der Marck, M and Wirth, R and Singer, P and Bischoff, SC}, title = {ESPEN guideline clinical nutrition in neurology.}, journal = {Clinical nutrition (Edinburgh, Scotland)}, volume = {37}, number = {1}, pages = {354-396}, doi = {10.1016/j.clnu.2017.09.003}, pmid = {29274834}, issn = {1532-1983}, mesh = {Deglutition Disorders/diagnosis/diet therapy/physiopathology ; Humans ; *Nervous System Diseases/diagnosis/diet therapy/physiopathology ; *Nutrition Policy ; Nutritional Status ; Prognosis ; Stroke/diagnosis/diet therapy/physiopathology ; }, abstract = {Neurological diseases are frequently associated with swallowing disorders and malnutrition. Moreover, patients with neurological diseases are at increased risk of micronutrient deficiency and dehydration. On the other hand, nutritional factors may be involved in the pathogenesis of neurological diseases. Multiple causes for the development of malnutrition in patients with neurological diseases are known including oropharyngeal dysphagia, impaired consciousness, perception deficits, cognitive dysfunction, and increased needs. The present evidence- and consensus-based guideline addresses clinical questions on best medical nutrition therapy in patients with neurological diseases. Among them, management of oropharyngeal dysphagia plays a pivotal role. The guideline has been written by a multidisciplinary team and offers 88 recommendations for use in clinical practice for amyotrophic lateral sclerosis, Parkinson's disease, stroke and multiple sclerosis.}, }
@article {pmid29092835, year = {2017}, author = {Grafton, B and MacLeod, C and Rudaizky, D and Holmes, EA and Salemink, E and Fox, E and Notebaert, L}, title = {Confusing procedures with process when appraising the impact of cognitive bias modification on emotional vulnerability[†].}, journal = {The British journal of psychiatry : the journal of mental science}, volume = {211}, number = {5}, pages = {266-271}, doi = {10.1192/bjp.bp.115.176123}, pmid = {29092835}, issn = {1472-1465}, mesh = {Affective Symptoms/*therapy ; Cognitive Behavioral Therapy/*methods ; Humans ; *Meta-Analysis as Topic ; *Psychotherapeutic Processes ; }, abstract = {If meta-analysis is to provide valuable answers, then it is critical to ensure clarity about the questions being asked. Here, we distinguish two important questions concerning cognitive bias modification research that are not differentiated in the meta-analysis recently published by Cristea et al (2015) in this journal: (1) do the varying procedures that investigators have employed with the intention of modifying cognitive bias, on average, significantly impact emotional vulnerability?; and (2) does the process of successfully modifying cognitive bias, on average, significantly impact emotional vulnerability? We reanalyse the data from Cristea et al to address this latter question. Our new analyses demonstrate that successfully modifying cognitive bias does significantly alter emotional vulnerability. We revisit Cristea et al's conclusions in light of these findings.}, }
@article {pmid29080013, year = {2017}, author = {Watanabe, Y and Watanabe, T}, title = {Meta-analytic evaluation of the association between head injury and risk of amyotrophic lateral sclerosis.}, journal = {European journal of epidemiology}, volume = {32}, number = {10}, pages = {867-879}, pmid = {29080013}, issn = {1573-7284}, support = {656161//Horizon 2020/International ; }, mesh = {Amyotrophic Lateral Sclerosis/*diagnosis/*epidemiology/etiology ; Craniocerebral Trauma/complications/*diagnosis/*epidemiology ; Female ; Humans ; Risk Assessment ; Risk Factors ; }, abstract = {Head injury is considered as a potential risk factor for amyotrophic lateral sclerosis (ALS). However, several recent studies have suggested that head injury is not a cause, but a consequence of latent ALS. We aimed to evaluate such a possibility of reverse causation with meta-analyses considering time lags between the incidence of head injuries and the occurrence of ALS. We searched Medline and Web of Science for case-control, cross-sectional, or cohort studies that quantitatively investigated the head-injury-related risk of ALS and were published until 1 December 2016. After selecting appropriate publications based on PRISMA statement, we performed random-effects meta-analyses to calculate odds ratios (ORs) and 95% confidence intervals (CI). Sixteen of 825 studies fulfilled the eligibility criteria. The association between head injuries and ALS was statistically significant when the meta-analysis included all the 16 studies (OR 1.45, 95% CI 1.21-1.74). However, in the meta-analyses considering the time lags between the experience of head injuries and diagnosis of ALS, the association was weaker (OR 1.21, 95% CI 1.01-1.46, time lag ≥ 1 year) or not significant (e.g. OR 1.16, 95% CI 0.84-1.59, time lag ≥ 3 years). Although it did not deny associations between head injuries and ALS, the current study suggests a possibility that such a head-injury-oriented risk of ALS has been somewhat overestimated. For more accurate evaluation, it would be necessary to conduct more epidemiological studies that consider the time lags between the occurrence of head injuries and the diagnosis of ALS.}, }
@article {pmid28984793, year = {2017}, author = {Liu, J and Lu, SY and Wang, YG and Wei, ZY and Zhang, HX}, title = {SPINK1 Gene is Significantly Associated With Pancreatitis: A Comprehensive Meta-Analysis.}, journal = {Pancreas}, volume = {46}, number = {10}, pages = {1373-1380}, doi = {10.1097/MPA.0000000000000947}, pmid = {28984793}, issn = {1536-4828}, mesh = {Case-Control Studies ; Genetic Predisposition to Disease/*genetics ; Humans ; Mutation ; Odds Ratio ; Pancreatitis/*genetics ; Trypsin Inhibitor, Kazal Pancreatic/*genetics ; }, abstract = {OBJECTIVES: This research was applied to case-control studies of the association between pancreatitis and SPINK1 gene to assess the joint evidence for the association, the influence of individual studies, and evidence for publication bias.<br><br>METHODS: MEDLINE and Embase were searched to identify longitudinal studies evaluating pancreatitis and SPINK1. Odds ratios (ORs) and 95% confidence interval (CI) were pooled using random-effect models and calculated using Carlin method. Publication bias was assessed using Egger et al's approach (A famous statistic method by Egger et al). Sensitivity, heterogeneity, and trim and fill analyses were conducted.<br><br>RESULTS: Based on the results, we found that (1) the results support for the association between pancreatitis and SPINK1, when analyzed totally and by subdivision (total [OR, 7.771; 95% CI, 5.232-11.543; P < 0.000]; European [OR,6.400; 95% CI, 4.346-9.426; P < 0.000]; Asian [OR, 11.823; 95% CI, 4.612-30.310; P < 0.000]; American [OR, 3.777; 95% CI, 1.596-8.939; P = 0.002]; mixed: [OR, 13.566; 95% CI, 2.322-79.252, P = 0.004]); (2) no evidence indicates that this association is accounted for by any one study, and no evidence indicates any publication bias exists.<br><br>CONCLUSIONS: The results indicated that SPINK1 gene, particularly the N34S mutation, has a genetic association with the development of pancreatitis.}, }
@article {pmid28931804, year = {2017}, author = {Benyamin, B and He, J and Zhao, Q and Gratten, J and Garton, F and Leo, PJ and Liu, Z and Mangelsdorf, M and Al-Chalabi, A and Anderson, L and Butler, TJ and Chen, L and Chen, XD and Cremin, K and Deng, HW and Devine, M and Edson, J and Fifita, JA and Furlong, S and Han, YY and Harris, J and Henders, AK and Jeffree, RL and Jin, ZB and Li, Z and Li, T and Li, M and Lin, Y and Liu, X and Marshall, M and McCann, EP and Mowry, BJ and Ngo, ST and Pamphlett, R and Ran, S and Reutens, DC and Rowe, DB and Sachdev, P and Shah, S and Song, S and Tan, LJ and Tang, L and van den Berg, LH and van Rheenen, W and Veldink, JH and Wallace, RH and Wheeler, L and Williams, KL and Wu, J and Wu, X and Yang, J and Yue, W and Zhang, ZH and Zhang, D and Noakes, PG and Blair, IP and Henderson, RD and McCombe, PA and Visscher, PM and Xu, H and Bartlett, PF and Brown, MA and Wray, NR and Fan, D}, title = {Cross-ethnic meta-analysis identifies association of the GPX3-TNIP1 locus with amyotrophic lateral sclerosis.}, journal = {Nature communications}, volume = {8}, number = {1}, pages = {611}, pmid = {28931804}, issn = {2041-1723}, support = {ALCHALABI-DOBSON/APR14/829-791/MNDA_/Motor Neurone Disease Association/United Kingdom ; MR/L501529/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Amyotrophic Lateral Sclerosis/ethnology/*genetics ; Asian People/*genetics ; Australia ; China ; DNA-Binding Proteins/*genetics ; Genome-Wide Association Study ; Glutathione Peroxidase/*genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Sequence Analysis, DNA ; White People/*genetics ; }, abstract = {Cross-ethnic genetic studies can leverage power from differences in disease epidemiology and population-specific genetic architecture. In particular, the differences in linkage disequilibrium and allele frequency patterns across ethnic groups may increase gene-mapping resolution. Here we use cross-ethnic genetic data in sporadic amyotrophic lateral sclerosis (ALS), an adult-onset, rapidly progressing neurodegenerative disease. We report analyses of novel genome-wide association study data of 1,234 ALS cases and 2,850 controls. We find a significant association of rs10463311 spanning GPX3-TNIP1 with ALS (p = 1.3 × 10[-8]), with replication support from two independent Australian samples (combined 576 cases and 683 controls, p = 1.7 × 10[-3]). Both GPX3 and TNIP1 interact with other known ALS genes (SOD1 and OPTN, respectively). In addition, GGNBP2 was identified using gene-based analysis and summary statistics-based Mendelian randomization analysis, although further replication is needed to confirm this result. Our results increase our understanding of genetic aetiology of ALS.Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease. Here, Wray and colleagues identify association of the GPX3-TNIP1 locus with ALS using cross-ethnic meta-analyses.}, }
@article {pmid28864407, year = {2017}, author = {Tai, H and Cui, L and Shen, D and Li, D and Cui, B and Fang, J}, title = {Military service and the risk of amyotrophic lateral sclerosis: A meta-analysis.}, journal = {Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia}, volume = {45}, number = {}, pages = {337-342}, doi = {10.1016/j.jocn.2017.08.035}, pmid = {28864407}, issn = {1532-2653}, mesh = {Amyotrophic Lateral Sclerosis/*epidemiology ; Female ; Humans ; Military Personnel/*statistics &amp; numerical data ; Risk Factors ; }, abstract = {To explore the relationship between the risk of amyotrophic lateral sclerosis and exposure to overall military service, we conducted a search of articles relevant to military service and the risk of ALS that used human subjects and were published in English through 20 May 2016, using Ovid Medline and Embase databases. Studies specially investigating the risk of ALS for Gulf war veterans were excluded. Quality of the cohort and case-control studies was assessed according to the Newcastle-Ottawa Scale (NOS). Analysis of data and publication bias were performed with Review Manager 5.3. A total of 8 case-control studies and 3 cohort studies were included in the meta-analysis. Only two case-control studies were conducted in Japan, comparing to 9 studies conducted in Europe/USA. The NOS scores of all studies were ≥6/9. The risk of ALS was significantly increased in military personnel compared to non-military personnel (pooled OR=1.29, 95% CI: 1.08-1.54, by random-effects model), with a moderate heterogeneity (P=0.01, I[2]=55%) due to some studies with lower quality, conformed by subgroup and sensitivity analysis. The present meta-analysis supports a positive association between overall military service and the risk of ALS. Additional studies are needed to find out related factors influencing the ALS risk of veterans, especially by gender and for specific geographic regions such as Asia. That would also do some favor to explore the etiology and mechanism of ALS.}, }
@article {pmid28795874, year = {2018}, author = {Yang, X and Li, S and Xing, D and Li, P and Li, C and Qi, L and Xu, Y and Ren, H}, title = {Lack of association between the P413L variant of chromogranin B and ALS risk or age at onset: a meta-analysis.}, journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration}, volume = {19}, number = {1-2}, pages = {80-86}, doi = {10.1080/21678421.2017.1361444}, pmid = {28795874}, issn = {2167-9223}, mesh = {Age of Onset ; Amyotrophic Lateral Sclerosis/*genetics ; Asian People ; Case-Control Studies ; Chromogranin B/*genetics ; Female ; Gene Frequency/genetics ; *Genetic Predisposition to Disease ; Genetic Testing/methods ; Genotype ; Heterozygote ; Humans ; Male ; Polymorphism, Single Nucleotide/genetics ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS), the most common motor neuron disease, is thought to result from interaction of genetic and environmental risk factors. Whether the potentially functional exonic P413L variant in the chromogranin B gene influences ALS risk and age at onset is controversial.<br><br>METHOD: We meta-analysed or other studies assessing the association between the P413L variant and ALS risk or age at ALS onset indexed in Web of Science, PubMed, Embase, Chinese National Knowledge Infrastructure, Wanfang, and SinoMed databases.<br><br>RESULTS: Five case-control studies were analysed, involving 2639 patients with sporadic ALS, 201 with familial ALS and 3381 controls. No association was detected between risk of either ALS type and the CT + TT genotype or T-allele of the P413L variant. Age at ALS onset was similar between carriers and non-carriers of the T-allele.<br><br>CONCLUSION: The available evidence suggests that the P413L variant of chromogranin B is not associated with ALS risk or age at ALS onset. These results should be validated in large, well-designed studies.}, }
@article {pmid28427253, year = {2017}, author = {Su, M and Guo, J and Huang, J}, title = {Meta-analysis of the correlation between the rs17401966 polymorphism in kinesin family member 1B and susceptibility to hepatitis B virus related hepatocellular carcinoma.}, journal = {Clinical and molecular hepatology}, volume = {23}, number = {2}, pages = {138-146}, pmid = {28427253}, issn = {2287-285X}, mesh = {Alleles ; Carcinoma, Hepatocellular/complications/*diagnosis/genetics ; Case-Control Studies ; Databases, Factual ; Gene Frequency ; *Genetic Predisposition to Disease ; Hepatitis B virus/isolation &amp; purification ; Hepatitis B, Chronic/complications/*diagnosis/virology ; Humans ; Kinesins/*genetics ; Liver Neoplasms/complications/*diagnosis/genetics ; Odds Ratio ; Polymorphism, Single Nucleotide ; Risk Factors ; }, abstract = {BACKGROUND/AIMS: The association between the kinesin family member 1B (KIF1B) gene polymorphism and the risk of hepatitis B virus-related hepatocellular carcinoma (HCC) has been investigated in many peer-reviewed studies. However, scholars have failed to replicate these results in validation tests. The purpose of the present study was to explore whether the KIF1B rs17401966 polymorphism was associated with susceptibility to HCC.<br><br>METHODS: The results of case-controlled studies on the correlation between the KIF1B rs17401966 polymorphism and HCC susceptibility were collected using Google Scholar and the EMBASE, PubMed and CNKI databases. Based on inclusion and exclusion criteria, 5 papers with a total of 12 cohorts were included in this study.<br><br>RESULTS: The 12 cohorts were integrated, and the results showed that the rs17401966 polymorphism reduced the risk for HCC under the allele, heterozygous, homozygous, and dominant models but not under the additive or recessive models. Moreover, the merged results showed strong heterogeneity, and the cumulative meta-analysis results were unreliable. A genetic differentiation analysis of the 12 cohorts found different degrees of genetic differentiation between the 5 cohorts in Zhang et al.'s study and the cohorts in the other studies. We further divided the 12 study cohorts into 2 subgroups based on fixation index value; however, the results of that analysis were inconsistent.<br><br>CONCLUSIONS: The results of this meta-analysis were not able to verify the association between the KIF1B rs1740199 polymorphism and HCC risk. Therefore, a well-designed, large-scale, multicenter validation study is needed to confirm the relationship.}, }
@article {pmid28236105, year = {2017}, author = {Morello, G and Spampinato, AG and Conforti, FL and D'Agata, V and Cavallaro, S}, title = {Selection and Prioritization of Candidate Drug Targets for Amyotrophic Lateral Sclerosis Through a Meta-Analysis Approach.}, journal = {Journal of molecular neuroscience : MN}, volume = {61}, number = {4}, pages = {563-580}, pmid = {28236105}, issn = {1559-1166}, mesh = {Amyotrophic Lateral Sclerosis/drug therapy/*genetics/metabolism ; Animals ; Antioxidants/*pharmacology/therapeutic use ; Drug Discovery ; Humans ; Mice ; Molecular Targeted Therapy ; Motor Cortex/drug effects/metabolism ; Neuroprotective Agents/*pharmacology/therapeutic use ; Species Specificity ; Superoxide Dismutase/genetics/metabolism ; Transcriptome ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive and incurable neurodegenerative disease. Although several compounds have shown promising results in preclinical studies, their translation into clinical trials has failed. This clinical failure is likely due to the inadequacy of the animal models that do not sufficiently reflect the human disease. Therefore, it is important to optimize drug target selection by identifying those that overlap in human and mouse pathology. We have recently characterized the transcriptional profiles of motor cortex samples from sporadic ALS (SALS) patients and differentiated these into two subgroups based on differentially expressed genes, which encode 70 potential therapeutic targets. To prioritize drug target selection, we investigated their degree of conservation in superoxide dismutase 1 (SOD1) G93A transgenic mice, the most widely used ALS animal model. Interspecies comparison of our human expression data with those of eight different SOD1[G93A] datasets present in public repositories revealed the presence of commonly deregulated targets and related biological processes. Moreover, deregulated expression of the majority of our candidate targets occurred at the onset of the disease, offering the possibility to use them for an early and more effective diagnosis and therapy. In addition to highlighting the existence of common key drivers in human and mouse pathology, our study represents the basis for a rational preclinical drug development.}, }
@article {pmid28187987, year = {2017}, author = {Żur-Wyrozumska, K and Pera, J and Dziubek, A and Sado, M and Golenia, A and Słowik, A and Dziedzic, T}, title = {Association between C677T polymorphism of MTHFR gene and risk of amyotrophic lateral sclerosis: Polish population study and a meta-analysis.}, journal = {Neurologia i neurochirurgia polska}, volume = {51}, number = {2}, pages = {135-139}, doi = {10.1016/j.pjnns.2017.01.008}, pmid = {28187987}, issn = {0028-3843}, mesh = {Adult ; Aged ; *Alleles ; Amyotrophic Lateral Sclerosis/*genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease/*genetics ; Genotype ; Humans ; Male ; Methylenetetrahydrofolate Reductase (NADPH2)/*genetics ; Middle Aged ; Poland ; Polymorphism, Genetic/*genetics ; Risk ; }, abstract = {OBJECTIVE: Genetic factors play a role in pathogenesis of amyotrophic lateral sclerosis (ALS). A few studies demonstrated that the TT genotype of C677T polymorphism of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene can increase the risk of sporadic ALS. The aim of our study was to determine the relationship between C677T polymorphism of MTHFR gene and the risk of sporadic ALS in Polish population and to perform the meta-analysis assessing the significance this polymorphism for the risk of ALS in Caucasian population.<br><br>METHODS: We included 251 patients with ALS and 500 control subjects recruited from Polish population and performed the meta-analysis of published data from Caucasian population. MTHFR C677T polymorphism was genotyped using a TaqMan assay and 7900HT Fast real Time PCR System.<br><br>RESULTS: The frequency of genotypes did not differ significantly between Polish ALS patients and control subjects (CC: 45.0 vs 45.8%, CT: 48.2 vs 45.0%, TT: 6.8 vs 9.2%, P=0.46). The meta-analysis including 863 ALS patients and 1362 controls revealed that TT genotype increases the risk of sporadic ALS in Caucasian population.<br><br>CONCLUSION: Although we did not find the association between C677T polymorphism of MTHRF gene and risk of ALS in Polish population, the results of meta-analysis suggest that the TT genotype can be a genetic risk factor for ALS in Caucasian population.}, }
@article {pmid28104502, year = {2017}, author = {Margeta, MA and Kuo, AN and Proia, AD and Freedman, SF}, title = {Staying away from the optic nerve: a formula for modifying glaucoma drainage device surgery in pediatric and other small eyes.}, journal = {Journal of AAPOS : the official publication of the American Association for Pediatric Ophthalmology and Strabismus}, volume = {21}, number = {1}, pages = {39-43.e1}, doi = {10.1016/j.jaapos.2016.09.027}, pmid = {28104502}, issn = {1528-3933}, mesh = {Adolescent ; Axial Length, Eye/pathology ; Child ; Child, Preschool ; *Decision Support Techniques ; Drainage/instrumentation ; Female ; Glaucoma/physiopathology/*surgery ; *Glaucoma Drainage Implants ; Humans ; Infant ; Infant, Newborn ; Intraocular Pressure/physiology ; Limbus Corneae/*pathology ; Male ; Microphthalmos/physiopathology/*surgery ; Optic Nerve/*pathology ; Prosthesis Implantation/*standards ; }, abstract = {PURPOSE: To provide guidelines for safe implantation of glaucoma drainage devices (GDDs) in small and pediatric eyes to avoid contact between the optic nerve (ON) and the posterior edge of the GDD plate.<br><br>METHODS: We developed a formula for calculating limbus-to-ON distance to estimate the available "real estate" for GDD placement in small eyes. The formula was validated using eyes of pediatric decedents undergoing clinical autopsy, with axial lengths (AL) of 15-24&#xa0;mm. For each autopsy eye, we measured AL, anterior chamber depth, corneal diameter, and limbus-to-ON distances for the four eye quadrants. The main outcome measure was the degree of agreement between measured and calculated limbus-to-ON distances.<br><br>RESULTS: A total of 15 autopsy eyes were divided into derivation (n&#xa0;=&#xa0;10) and validation (n&#xa0;=&#xa0;5) groups. A formula was derived to estimate superotemporal limbus-to-ON distance (DST) using AL and corneal diameter data. Linear regression showed excellent correlation between the measured DST and AL (R[2]&#xa0;=&#xa0;0.98). There was excellent agreement between measured and calculated limbus-to-ON values for all four eye quadrants (R[2] range, 0.92-0.98).<br><br>CONCLUSIONS: Our formula accurately predicts limbus-to-ON distances across a wide range of clinically relevant ALs. Based on this information, GDD surgery in small eyes can be adjusted by positioning the GDD closer to the limbus or by trimming the posterior edge of the GDD plate. To our knowledge, this is the first set of guidelines developed to promote safe implantation of GDDs in small eyes.}, }
@article {pmid28004338, year = {2018}, author = {Monti, C and Colugnat, I and Lopiano, L and Chiò, A and Alberio, T}, title = {Network Analysis Identifies Disease-Specific Pathways for Parkinson's Disease.}, journal = {Molecular neurobiology}, volume = {55}, number = {1}, pages = {370-381}, pmid = {28004338}, issn = {1559-1182}, mesh = {Animals ; *Databases, Genetic/trends ; Gene Regulatory Networks/*physiology ; Humans ; Parkinson Disease/*genetics/metabolism/pathology ; Proteomics/*methods/trends ; Signal Transduction/*physiology ; }, abstract = {Neurodegenerative diseases are characterized by the progressive loss of specific neurons in selected regions of the central nervous system. The main clinical manifestation (movement disorders, cognitive impairment, and/or psychiatric disturbances) depends on the neuron population being primarily affected. Parkinson's disease is a common movement disorder, whose etiology remains mostly unknown. Progressive loss of dopaminergic neurons in the substantia nigra causes an impairment of the motor control. Some of the pathogenetic mechanisms causing the progressive deterioration of these neurons are not specific for Parkinson's disease but are shared by other neurodegenerative diseases, like Alzheimer's disease and amyotrophic lateral sclerosis. Here, we performed a meta-analysis of the literature of all the quantitative proteomic investigations of neuronal alterations in different models of Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis to distinguish between general and Parkinson's disease-specific pattern of neurodegeneration. Then, we merged proteomics data with genetics information from the DisGeNET database. The comparison of gene and protein information allowed us to identify 25 proteins involved uniquely in Parkinson's disease and we verified the alteration of one of them, i.e., transaldolase 1 (TALDO1), in the substantia nigra of 5 patients. By using open-source bioinformatics tools, we identified the biological processes specifically affected in Parkinson's disease, i.e., proteolysis, mitochondrion organization, and mitophagy. Eventually, we highlighted four cellular component complexes mostly involved in the pathogenesis: the proteasome complex, the protein phosphatase 2A, the chaperonins CCT complex, and the complex III of the respiratory chain.}, }
@article {pmid28002755, year = {2017}, author = {Bora, E}, title = {Meta-analysis of social cognition in amyotrophic lateral sclerosis.}, journal = {Cortex; a journal devoted to the study of the nervous system and behavior}, volume = {88}, number = {}, pages = {1-7}, doi = {10.1016/j.cortex.2016.11.012}, pmid = {28002755}, issn = {1973-8102}, mesh = {Amyotrophic Lateral Sclerosis/*psychology ; Cognition/*physiology ; Emotions/*physiology ; Executive Function/physiology ; Facial Recognition/*physiology ; Humans ; *Social Perception ; Theory of Mind/*physiology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is associated with executive dysfunction and behavioural impairment. Recent studies suggested that social cognitive deficits might also be a prominent feature of ALS. Current meta-analysis aimed to summarize available evidence for deficits in social cognition including theory of mind (ToM) and emotion recognition in ALS. In this meta-analysis of 15 studies, facial emotion recognition and ToM performances of 389 patients with ALS and 471 healthy controls were compared. ALS was associated with significant impairments with medium effect sizes in ToM (d = .65) and facial emotion recognition (d = .69). Among individual emotions recognition of disgust and surprise were particularly impaired. Deficits in perspective taking (d = .73) aspects of ToM (ToM-PT) was more pronounced in comparison to decoding (d = .28) aspects of ToM (ToM-decoding). The severity of social cognitive impairment was similar to level of executive dysfunction and there was a significant relationship between social cognition and executive dysfunction. Deficits in social cognition are part of the cognitive phenotype of ALS.}, }
@article {pmid27642606, year = {2016}, author = {Bernabò, N and Ordinelli, A and Ramal Sanchez, M and Mattioli, M and Barboni, B}, title = {Networks Models of Actin Dynamics during Spermatozoa Postejaculatory Life: A Comparison among Human-Made and Text Mining-Based Models.}, journal = {BioMed research international}, volume = {2016}, number = {}, pages = {9795409}, pmid = {27642606}, issn = {2314-6141}, mesh = {Actins/*metabolism ; Ejaculation/physiology ; Fertilization/*physiology ; Humans ; Male ; Spermatozoa/*physiology ; }, abstract = {Here we realized a networks-based model representing the process of actin remodelling that occurs during the acquisition of fertilizing ability of human spermatozoa (HumanMade_ActinSpermNetwork, HM_ASN). Then, we compared it with the networks provided by two different text mining tools: Agilent Literature Search (ALS) and PESCADOR. As a reference, we used the data from the online repository Kyoto Encyclopaedia of Genes and Genomes (KEGG), referred to the actin dynamics in a more general biological context. We found that HM_ALS and the networks from KEGG data shared the same scale-free topology following the Barabasi-Albert model, thus suggesting that the information is spread within the network quickly and efficiently. On the contrary, the networks obtained by ALS and PESCADOR have a scale-free hierarchical architecture, which implies a different pattern of information transmission. Also, the hubs identified within the networks are different: HM_ALS and KEGG networks contain as hubs several molecules known to be involved in actin signalling; ALS was unable to find other hubs than "actin," whereas PESCADOR gave some nonspecific result. This seems to suggest that the human-made information retrieval in the case of a specific event, such as actin dynamics in human spermatozoa, could be a reliable strategy.}, }
@article {pmid27613758, year = {2016}, author = {Goldstein, B and Speth, RC and Trivedi, M}, title = {Renin-angiotensin system gene expression and neurodegenerative diseases.}, journal = {Journal of the renin-angiotensin-aldosterone system : JRAAS}, volume = {17}, number = {3}, pages = {}, pmid = {27613758}, issn = {1752-8976}, mesh = {*Gene Expression Regulation ; Genome-Wide Association Study ; Humans ; Neurodegenerative Diseases/*genetics ; Renin-Angiotensin System/*genetics ; }, abstract = {HYPOTHESIS: Single nucleotide polymorphisms and altered gene expression of components of the renin-angiotensin system (RAS) are associated with neurodegenerative diseases.<br><br>INTRODUCTION: Drugs that interact with the RAS have been shown to affect the course of neurodegenerative disease, suggesting that abnormalities in the RAS may contribute to neurodegenerative disease.<br><br>MATERIALS AND METHODS: A meta-analysis of genome-wide association studies and gene expression data for 14 RAS-related proteins was carried out for five neurodegenerative diseases: Alzheimer's disease, Parkinson's disease, narcolepsy, amyotrophic lateral sclerosis and multiple sclerosis.<br><br>RESULTS: No single nucleotide polymorphisms in any of the 14 RAS-related protein genes were significantly associated with the five neurodegenerative diseases investigated. There was an inverse association between expression of ATP6AP2, which encodes the (pro)renin receptor, and multiple sclerosis, Alzheimer's disease and Parkinson's disease. An association of AGTR, which encodes the AT1 angiotensin II receptor, and Parkinson's disease and Alzheimer's disease was also observed.<br><br>CONCLUSIONS: To date, no single nucleotide polymorphisms in components of the RAS can be definitively linked to the neurodegenerative diseases evaluated in this study. However, altered gene expression of several components of the RAS is associated with several neurodegenerative diseases, which may indicate that the RAS contributes to the pathology of these diseases.}, }
@article {pmid27515846, year = {2016}, author = {de Vries, YA and Roest, AM and Franzen, M and Munafò, MR and Bastiaansen, JA}, title = {Citation bias and selective focus on positive findings in the literature on the serotonin transporter gene (5-HTTLPR), life stress and depression.}, journal = {Psychological medicine}, volume = {46}, number = {14}, pages = {2971-2979}, doi = {10.1017/S0033291716000805}, pmid = {27515846}, issn = {1469-8978}, support = {//British Heart Foundation/United Kingdom ; //Cancer Research UK/United Kingdom ; //Medical Research Council/United Kingdom ; //Department of Health/United Kingdom ; }, mesh = {*Bibliometrics ; *Depressive Disorder, Major/etiology/genetics ; Humans ; Publication Bias/*statistics &amp; numerical data ; Serotonin Plasma Membrane Transport Proteins/*physiology ; *Stress, Psychological/complications ; }, abstract = {BACKGROUND: Caspi et al.'s 2003 report that 5-HTTLPR genotype moderates the influence of life stress on depression has been highly influential but remains contentious. We examined whether the evidence base for the 5-HTTLPR-stress interaction has been distorted by citation bias and a selective focus on positive findings.<br><br>METHOD: A total of 73 primary studies were coded for study outcomes and focus on positive findings in the abstract. Citation rates were compared between studies with positive and negative results, both within this network of primary studies and in Web of Science. In addition, the impact of focus on citation rates was examined.<br><br>RESULTS: In all, 24 (33%) studies were coded as positive, but these received 48% of within-network and 68% of Web of Science citations. The 38 (52%) negative studies received 42 and 23% of citations, respectively, while the 11 (15%) unclear studies received 10 and 9%. Of the negative studies, the 16 studies without a positive focus (42%) received 47% of within-network citations and 32% of Web of Science citations, while the 13 (34%) studies with a positive focus received 39 and 51%, respectively, and the nine (24%) studies with a partially positive focus received 14 and 17%.<br><br>CONCLUSIONS: Negative studies received fewer citations than positive studies. Furthermore, over half of the negative studies had a (partially) positive focus, and Web of Science citation rates were higher for these studies. Thus, discussion of the 5-HTTLPR-stress interaction is more positive than warranted. This study exemplifies how evidence-base-distorting mechanisms undermine the authenticity of research findings.}, }
@article {pmid27094521, year = {2016}, author = {Hu, X and Yang, Y and Su, J and Yao, C}, title = {Meta-analysis of the relationship between amyotrophic lateral sclerosis and susceptibility to serum ferritin level elevation.}, journal = {Neurosciences (Riyadh, Saudi Arabia)}, volume = {21}, number = {2}, pages = {120-125}, pmid = {27094521}, issn = {1319-6138}, mesh = {Aged ; Amyotrophic Lateral Sclerosis/*blood ; Case-Control Studies ; Female ; Ferritins/*blood ; Humans ; Male ; Middle Aged ; }, abstract = {OBJECTIVE: To study the possible relationship between amyotrophic lateral sclerosis (ALS) patients and their susceptibility to serum ferritin level elevation.<br><br>METHODS: We searched the PubMed, Springer, Medline, and OVID databases for any-language original research articles relating to serum ferritin levels in ALS patients published between June 2005 and June 2015. The search term used with `amyotrophic lateral sclerosis`, `ferritins`, `ferritin`, `iron`, `iron stores, `iron status, `iron intake`, and `iron consumption`. The meta-analysis software RevMan 5.0 was used for the heterogeneity test, and to test for the overall effect.<br><br>RESULTS: Six case-control studies met our inclusion criteria including data from a total of 1813 participants. The mean difference of serum ferritin levels comparing ALS to healthy controls was 69.05 (95% confidence interval: 52.56-85.54; p<0.00001); heterogeneity: p=0.03; I2=50%. The findings indicate homology in the sensitivity analysis. Funnel plot assessment indicated publication bias.<br><br>CONCLUSION: Our results suggest that ALS is positively associated with susceptibility to the elevation of serum ferritin levels; however, further evidence is required to support this.}, }
@article {pmid26919175, year = {2016}, author = {von Grabowiecki, Y and Abreu, P and Blanchard, O and Palamiuc, L and Benosman, S and Mériaux, S and Devignot, V and Gross, I and Mellitzer, G and Gonzalez de Aguilar, JL and Gaiddon, C}, title = {Transcriptional activator TAp63 is upregulated in muscular atrophy during ALS and induces the pro-atrophic ubiquitin ligase Trim63.}, journal = {eLife}, volume = {5}, number = {}, pages = {}, pmid = {26919175}, issn = {2050-084X}, mesh = {Amyotrophic Lateral Sclerosis/*physiopathology ; Animals ; Disease Models, Animal ; Gene Expression Profiling ; Humans ; Mice ; Muscle Proteins/*biosynthesis ; Muscles/pathology ; Transcription Factors/*biosynthesis ; Tripartite Motif Proteins ; Tumor Suppressor Protein p53/biosynthesis ; Tumor Suppressor Proteins/*biosynthesis ; Ubiquitin-Protein Ligases/*biosynthesis ; Up-Regulation ; }, abstract = {Mechanisms of muscle atrophy are complex and their understanding might help finding therapeutic solutions for pathologies such as amyotrophic lateral sclerosis (ALS). We meta-analyzed transcriptomic experiments of muscles of ALS patients and mouse models, uncovering a p53 deregulation as common denominator. We then characterized the induction of several p53 family members (p53, p63, p73) and a correlation between the levels of p53 family target genes and the severity of muscle atrophy in ALS patients and mice. In particular, we observed increased p63 protein levels in the fibers of atrophic muscles via denervation-dependent and -independent mechanisms. At a functional level, we demonstrated that TAp63 and p53 transactivate the promoter and increased the expression of Trim63 (MuRF1), an effector of muscle atrophy. Altogether, these results suggest a novel function for p63 as a contributor to muscular atrophic processes via the regulation of multiple genes, including the muscle atrophy gene Trim63.}, }
@article {pmid26700797, year = {2016}, author = {Lu, Y and Liu, W and Tan, K and Peng, J and Zhu, Y and Wang, X}, title = {Genetic association of CALHM1 rs2986017 polymorphism with risk of Alzheimer's disease: a meta-analysis.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {37}, number = {4}, pages = {525-532}, pmid = {26700797}, issn = {1590-3478}, mesh = {Alzheimer Disease/ethnology/*genetics ; Asian People/genetics ; Calcium Channels/*genetics ; Genetic Association Studies ; *Genetic Predisposition to Disease ; Humans ; Membrane Glycoproteins/*genetics ; *Polymorphism, Single Nucleotide ; Risk ; White People/genetics ; }, abstract = {Recent studies investigating the association of Calcium homeostasis modulator 1 (CALHM1) p.P86L polymorphism (rs2986017) with Alzheimer's disease (AD) are controversial. Herein, we performed a meta-analysis to investigate the association between CALHM1 rs2986017 and AD risk. Literature searches of PubMed, Alzgene, and Embase were carried out up to 24 Nov 2015. The strength of the association between rs2986017 and AD was evaluated by odds ratio (OR) and 95 % confidence interval (CI). A total of 19 studies between 2008 and 2014 comprising 8777 AD cases and 8487 controls were included. Significant association of rs2986017 with AD was found in Caucasian population in allelic model (T vs. C: OR 1.13, 95 % CI 1.02-1.26, P = 0.022), and dominant model (TT + TC vs. CC: OR 1.15, 95 % CI 1.04-1.29, P = 0.018). No significant association was found in Asian population in any genetic model. Sensitivity analysis found that Dreses-Werringloer et al.'s might affect the overall result. The current meta-analysis suggested that CALHM1 rs2986017 might be associated with increased AD risk in Caucasian, but not Asian population.}, }
@article {pmid26362941, year = {2015}, author = {Sheng, L and Ma, H and Zhong, J and Shang, H and Shi, H and Pan, P}, title = {Motor and extra-motor gray matter atrophy in amyotrophic lateral sclerosis: quantitative meta-analyses of voxel-based morphometry studies.}, journal = {Neurobiology of aging}, volume = {36}, number = {12}, pages = {3288-3299}, doi = {10.1016/j.neurobiolaging.2015.08.018}, pmid = {26362941}, issn = {1558-1497}, mesh = {Aging/pathology ; Amyotrophic Lateral Sclerosis/*pathology ; Anisotropy ; Atrophy ; Brain Mapping ; Gray Matter/*pathology ; Humans ; Motor Cortex/*pathology ; Regression Analysis ; }, abstract = {Considerable evidence from previous voxel-based morphometry studies indicates widespread but heterogeneous gray matter (GM) deficits in amyotrophic lateral sclerosis (ALS). Here, we aimed to investigate the concurrence across voxel-based morphometry studies to help clarify the spatial pattern of GM abnormalities that underlie this condition. Comprehensive meta-analyses to assess regional GM anomalies in ALS were conducted with the Anisotropic Effect Size version of Signed Differential Mapping software package. Twenty studies, which reported 22 comparisons and were composed of 454 ALS patients and 426 healthy controls, were included in the meta-analyses. Regional GM atrophy in ALS was consistently found in the frontal, temporal, and somatosensory areas. Meta-regression demonstrated that the disease duration, disease severity, and age were significantly related to GM deficits in ALS patients. The present meta-analysis provides convergent evidence that ALS is a multisystem degenerative disorder that is accompanied by a unique and widespread pattern of robust cortical GM atrophy. Future studies should investigate whether this atrophy pattern is a diagnostic and prognostic marker.}, }
@article {pmid26255299, year = {2015}, author = {Pan, L and Deng, X and Ding, D and Leng, H and Zhu, X and Wang, Z}, title = {Association between the Angiogenin (ANG) K17I variant and amyotrophic lateral sclerosis risk in Caucasian: a meta-analysis.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {36}, number = {12}, pages = {2163-2168}, pmid = {26255299}, issn = {1590-3478}, mesh = {Amyotrophic Lateral Sclerosis/*genetics ; Case-Control Studies ; Female ; *Genetic Predisposition to Disease ; Humans ; Male ; Mutation/*genetics ; Polymorphism, Single Nucleotide/*genetics ; Ribonuclease, Pancreatic/*genetics ; Risk ; White People ; }, abstract = {The study purpose is to perform a meta-analysis to help resolve the debate of whether the Angiogenin (ANG) K17I variant is associated with amyotrophic lateral sclerosis (ALS) risk in Caucasian. Three literature databases were searched for eligible studies published up to January 8, 2015: PubMed, Embase and Web of Science using the following search terms: amyotrophic lateral sclerosis or ALS and Angiogenin or ANG. Five eligible articles were identified, which reported 6 case-control studies and a total of 2326 cases and 3799 controls. The overall results suggested low frequencies of the K17I variant in Caucasian patients (10/2326, 0.43 %) and controls (6/3799, 0.16 %). There is no difference in the variant frequencies between patients with FALS or SALS (p = 0.069). Analysis of pooled odds ratios (ORs) and 95 % confidence intervals (CIs) revealed that the ANG K17I variant increases the risk for ALS (AT vs. AA: OR 2.65, 95 % CI 1.05-6.66, p = 0.038) and familial ALS (FALS) (AT vs. AA: OR 11.81, 95 % CI 2.11-66.15, p = 0.005) but not for sporadic ALS (SALS) (AT vs. AA: OR 1.63, 95 % CI 0.55-4.82, p = 0.378). The ANG K17I variant is rare in Caucasian patients and controls and increases the risk for ALS and FALS but not for SALS in Caucasian populations. Further well-designed studies with larger samples are needed to validate these results.}, }
@article {pmid26001565, year = {2015}, author = {Holtman, IR and Raj, DD and Miller, JA and Schaafsma, W and Yin, Z and Brouwer, N and Wes, PD and Möller, T and Orre, M and Kamphuis, W and Hol, EM and Boddeke, EW and Eggen, BJ}, title = {Induction of a common microglia gene expression signature by aging and neurodegenerative conditions: a co-expression meta-analysis.}, journal = {Acta neuropathologica communications}, volume = {3}, number = {}, pages = {31}, pmid = {26001565}, issn = {2051-5960}, mesh = {Aging/*genetics/immunology ; Alzheimer Disease/genetics ; Animals ; Humans ; Inflammation/*genetics ; Mice ; Microglia/*immunology ; NF-kappa B/genetics ; Neurodegenerative Diseases/*genetics/immunology ; Signal Transduction/*genetics ; Transcriptome/*genetics ; Up-Regulation ; }, abstract = {INTRODUCTION: Microglia are tissue macrophages of the central nervous system that monitor brain homeostasis and react upon neuronal damage and stress. Aging and neurodegeneration induce a hypersensitive, pro-inflammatory phenotype, referred to as primed microglia. To determine the gene expression signature of priming, the transcriptomes of microglia in aging, Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS) mouse models were compared using Weighted Gene Co-expression Network Analysis (WGCNA).<br><br>RESULTS: A highly consistent consensus transcriptional profile of up-regulated genes was identified, which prominently differed from the acute inflammatory gene network induced by lipopolysaccharide (LPS). Where the acute inflammatory network was significantly enriched for NF-&#x3ba;B signaling, the primed microglia profile contained key features related to phagosome, lysosome, antigen presentation, and AD signaling. In addition, specific signatures for aging, AD, and ALS were identified.<br><br>CONCLUSION: Microglia priming induces a highly conserved transcriptional signature with aging- and disease-specific aspects.}, }
@article {pmid25881952, year = {2015}, author = {Slade, A and Stanic, S}, title = {Managing excessive saliva with salivary gland irradiation in patients with amyotrophic lateral sclerosis.}, journal = {Journal of the neurological sciences}, volume = {352}, number = {1-2}, pages = {34-36}, doi = {10.1016/j.jns.2015.02.008}, pmid = {25881952}, issn = {1878-5883}, mesh = {Adult ; Amyotrophic Lateral Sclerosis/complications/physiopathology/*radiotherapy ; Female ; Humans ; Male ; Middle Aged ; Parotid Gland/radiation effects ; Salivary Glands/*radiation effects ; Salivation/*radiation effects ; Sialorrhea/etiology/*radiotherapy ; Treatment Outcome ; }, abstract = {OBJECTIVE: A significant fraction of patients with amyotrophic lateral sclerosis (ALS) are unable to swallow saliva, which may result in the spillage of saliva outside of the oral cavity. Although anticholinergic agents and botulin toxin injections are considered the first line of treatment, they have not been effective for all patients. We performed a literature search on therapeutic salivary gland irradiation in patients with ALS.<br><br>METHODS: We searched the PubMed for English language publications up to December 2014 on therapeutic salivary gland irradiation in patients with ALS. The search was performed using the following key words: amyotrophic lateral sclerosis, excessive salivation, sialorrhea, and radiation therapy.<br><br>RESULTS: The majority of ALS patients with excessive salivation respond well to salivary gland irradiation. The whole bilateral submandibular, and whole or partial bilateral parotid glands have been the target tissue for radiation therapy in most of the published studies. Various radiation therapy regimens have been utilized. The response to radiation therapy lasts for several months.<br><br>CONCLUSIONS: The majority of ALS patients with excessive salivation respond well to salivary gland irradiation. Neurologists should consider this treatment option for select patients with ALS and excessive salivation.}, }
@article {pmid25806521, year = {2015}, author = {Sun, X and Xu, D and Luo, F and Wei, Z and Wei, C and Xue, G}, title = {A cross-cultural perspective on the preference for potential effect: an individual participant data (IPD) meta-analysis approach.}, journal = {PloS one}, volume = {10}, number = {3}, pages = {e0124170}, pmid = {25806521}, issn = {1932-6203}, mesh = {China ; *Choice Behavior ; *Cross-Cultural Comparison ; Humans ; *Social Behavior ; United States ; }, abstract = {A recent paper [Tormala ZL, Jia JS, Norton MI (2012). The preference for potential. Journal of personality and social psychology, 103: 567-583] demonstrated that persons often prefer potential rather than achievement when evaluating others, because information regarding potential evokes greater interest and processing, resulting in more favorable evaluations. This research aimed to expand on this finding by asking two questions: (a) Is the preference for potential effect replicable in other cultures? (b) Is there any other mechanism that accounts for this preference for potential? To answer these two questions, we replicated Tormala et al.'s study in multiple cities (17 studies with 1,128 participants) in China using an individual participant data (IPD) meta-analysis approach to test our hypothesis. Our results showed that the preference for potential effect found in the US is also robust in China. Moreover, we also found a pro-youth bias behind the preference for potential effect. To be specific, persons prefer a potential-oriented applicant rather than an achievement-oriented applicant, partially because they believe that the former is younger than the latter.}, }
@article {pmid25654401, year = {2015}, author = {Kivimäki, M and Singh-Manoux, A and Virtanen, M and Ferrie, JE and Batty, GD and Rugulies, R}, title = {IPD-Work consortium: pre-defined meta-analyses of individual-participant data strengthen evidence base for a link between psychosocial factors and health.}, journal = {Scandinavian journal of work, environment &amp; health}, volume = {41}, number = {3}, pages = {312-321}, doi = {10.5271/sjweh.3485}, pmid = {25654401}, issn = {1795-990X}, support = {MR/K013351/1/MRC_/Medical Research Council/United Kingdom ; K013351/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*Evidence-Based Practice ; *Health Status ; Humans ; *Psychology ; }, abstract = {Established in 2008 and comprising over 60 researchers, the IPD-Work (individual-participant data meta-analysis in working populations) consortium is a collaborative research project that uses pre-defined meta-analyses of individual-participant data from multiple cohort studies representing a range of countries. The aim of the consortium is to estimate reliably the associations of work-related psychosocial factors with chronic diseases, disability, and mortality. Our findings are highly cited by the occupational health, epidemiology, and clinical medicine research community. However, some of the IPD-Work's findings have also generated disagreement as they challenge the importance of job strain as a major target for coronary heart disease (CHD) prevention, this is reflected in the critical discussion paper by Choi et al (1). In this invited reply to Choi et al, we aim to (i) describe how IPD-Work seeks to advance research on associations between work-related psychosocial risk factors and health; (ii) demonstrate as unfounded Choi et al's assertion that IPD-Work has underestimated associations between job strain and health endpoints; these include the dichotomous measurement of job strain, potential underestimation of the population attributable risk (PAR) of job strain for CHD, and policy implications arising from the findings of the IPD-Work consortium; and (iii) outline general principles for designing evidence-based policy and prevention from good-quality evidence, including future directions for research on psychosocial factors at work and health. In addition, we highlight some problems with Choi et al's approach.}, }
@article {pmid25597926, year = {2015}, author = {Jang, JS and Bae, JS}, title = {AWAJI criteria are not always superior to the previous criteria: A meta-analysis.}, journal = {Muscle &amp; nerve}, volume = {51}, number = {6}, pages = {822-829}, doi = {10.1002/mus.24575}, pmid = {25597926}, issn = {1097-4598}, mesh = {Amyotrophic Lateral Sclerosis/*diagnosis/epidemiology ; Databases, Bibliographic/statistics &amp; numerical data ; Demography ; Early Diagnosis ; Electromyography ; Humans ; ROC Curve ; }, abstract = {INTRODUCTION: Recently, some authors have claimed that the Awaji criteria (AC) are not always more sensitive than the revised El Escorial criteria (rEEC) in amyotrophic lateral sclerosis (ALS).<br><br>METHODS: A meta-analysis examined 2 prospective and 7 retrospective studies, which included 1,121 ALS patients, to compare AC and rEEC for early diagnosis of ALS.<br><br>RESULTS: AC led to an 11% greater likelihood of being classified into the categories "clinically definite" or "clinically probable", while if confined to the "clinically probable - laboratory supported (LS)" category, this effect was 40% higher with the rEEC (95% cnfidence interval, 3-82%; I2=98%). Specifically, AC downgraded 20% of the rEEC "clinically probable - LS" category to the AC "clinically possible".<br><br>CONCLUSIONS: Despite overall superiority of AC, this meta-analysis shows that it is not always more sensitive than rEEC. These results are related to the requirement for 2 upper motor neuron signs in the AC "clinically probable" category.}, }
@article {pmid25578179, year = {2015}, author = {Chen, Y and Li, S and Su, L and Sheng, J and Lv, W and Chen, G and Xu, Z}, title = {Association of progranulin polymorphism rs5848 with neurodegenerative diseases: a meta-analysis.}, journal = {Journal of neurology}, volume = {262}, number = {4}, pages = {814-822}, pmid = {25578179}, issn = {1432-1459}, mesh = {Alzheimer Disease/*genetics ; Amyotrophic Lateral Sclerosis/*genetics ; Frontotemporal Lobar Degeneration/*genetics ; Humans ; Intercellular Signaling Peptides and Proteins/*genetics ; Parkinson Disease/*genetics ; Polymorphism, Single Nucleotide ; Progranulins ; }, abstract = {The purpose of this meta-analysis was to investigate the association between progranulin polymorphism rs5848 and risk of the neurodegenerative diseases frontotemporal lobar degeneration (FTLD), Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Published literature from PubMed and other databases were retrieved, and 16 case-control studies were identified as eligible: 5 on FTLD (1,439 cases, 4,461 controls), 5 on AD (2,502 cases, 2,162 controls), 3 on PD (1,605 cases, 1,591 controls), and 3 on ALS (663 cases, 811 controls). The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated. We found that rs5848 was associated with an increased risk of neurodegenerative diseases in the homozygous (TT vs. CC: OR, 1.24; 95% CI, 1.10-1.39; P < 0.001) and recessive models (TT vs. CC + CT: OR, 1.23; 95% CI, 1.10-1.37; P < 0.001). Stratified analyses showed associations of rs5848 with increased risk of AD and PD in the homozygous and recessive models. Our data indicate that rs5848 is associated with risk of AD and PD, suggesting important roles of progranulin in neurodegenerative processes.}, }
@article {pmid25449558, year = {2015}, author = {Marchetti, M and Priftis, K}, title = {Brain-computer interfaces in amyotrophic lateral sclerosis: A metanalysis.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {126}, number = {6}, pages = {1255-1263}, doi = {10.1016/j.clinph.2014.09.017}, pmid = {25449558}, issn = {1872-8952}, mesh = {Amyotrophic Lateral Sclerosis/diagnosis/*physiopathology/*therapy ; *Brain-Computer Interfaces/trends ; *Communication Devices for People with Disabilities/trends ; Electroencephalography/methods/trends ; Humans ; }, abstract = {OBJECTIVE: Despite recent groundbreaking findings on the genetic causes of amyotrophic lateral sclerosis (ALS), and improvements on neuroimaging techniques for ALS diagnosis have been reported, the main clinical intervention in ALS remains palliative care. Brain-computer interfaces (BCIs) have been proposed as a channel of communication and control for ALS patients. The present metanalysis was performed to test the evidence of BCI effectiveness in ALS, and to investigate whether the promising aims emerged from the first studies have been reached.<br><br>METHODS: Studies on ALS patients tested with BCIs, until June 2013, were searched in PubMed and PsychInfo. The random-effect approach was used to compute the pooled effectiveness of BCI in ALS. A meta-regression was performed to test whether there was a BCI performance improvement as a function of time. Finally, BCI effectiveness for complete paralyzed ALS patients was tested. Twenty-seven studies were eligible for metanalysis.<br><br>RESULTS: The pooled classification accuracy (C.A.) of ALS patients with BCI was about 70%, but this estimation was affected by significant heterogeneity and inconsistency. C.A. did not significantly increase as a function of time. C.A. of completely paralyzed ALS patients with BCI did not differ from that obtained by chance.<br><br>CONCLUSIONS: After 15 years of studies, it is as yet not possible to reliably establish the effectiveness of BCIs.<br><br>SIGNIFICANCE: Methodological issues among the retrieved studies should be addressed and new well-powered studies should be conducted to confirm BCI effectiveness for ALS patients.}, }
@article {pmid25405377, year = {2014}, author = {Capozzella, A and Sacco, C and Chighine, A and Loreti, B and Scala, B and Casale, T and Sinibaldi, F and Tomei, G and Giubilati, R and Tomei, F and Rosati, MV}, title = {Work related etiology of amyotrophic lateral sclerosis (ALS): a meta-analysis.}, journal = {Annali di igiene : medicina preventiva e di comunita}, volume = {26}, number = {5}, pages = {456-472}, doi = {10.7416/ai.2014.2005}, pmid = {25405377}, issn = {1120-9135}, mesh = {Amyotrophic Lateral Sclerosis/epidemiology/*etiology ; Electromagnetic Fields/adverse effects ; Female ; Humans ; Male ; Metals, Heavy/toxicity ; Occupational Diseases/epidemiology/*etiology/physiopathology ; Occupational Exposure/*adverse effects ; Pesticides/toxicity ; Research Design ; Risk Factors ; Sex Factors ; Solvents/toxicity ; }, abstract = {BACKGROUND: The aim of this meta-analysis was to evaluate the association between ALS and occupational exposure to physical (ELF-EMF) and chemicals (solvents, heavy metals and pesticides) agents.<br><br>METHODS: We considered articles published from 1980 up to April 2013; in total, 750 publications were evaluated. The studies had to satisfy the following criteria: 1) cohort or case-control studies; 2) the presence of individual exposures; 3) clinical diagnosis of sporadic ALS or sporadic ALS on the death certificate. We followed the evaluation of quality in two steps. The first step classified studies according to a rating system based on a mix of criteria developed by scientific organizations, especially developed for studies of risk factors for ALS. The ratings obtained range from I (highest) to V (lowest). The data on risk factors derived from studies with Armon ratings of I, II, and III can reach levels of evidence A (established risk factor), B (likely risk factor), or C (possible risk factor). The second step evaluated the exposure and a score from 1 to 4 was assigned to each item; an exposure with a score of 3 or 4 was considered sufficient. Different analyses were performed on ALS and exposure to metals, solvents, pesticides and electromagnetic fields. In our study the heterogeneity was assessed both by &#x3c7;2-based Q-tests and through the index of inconsistency I&#xb2; while the measure RR/OR and CI of 95% to estimate the relationship between ALS and the various considered risk factors was employed.<br><br>RESULTS: The association between exposure to pesticides and ALS as a whole is weak and not significant. With regard to the results of individual studies the following critical synthesis can be reported: 1) the selected studies showed a low level of association between ALS and electromagnetic fields; 2) as regards the solvents, the association with ALS in some studies is combined with a slightly increased risk, particularly in women, and in others a slight but significant linear association is observed; 3) for the metals, in some cases there was a stronger association in women than in men; for individual metals, there was an association especially with chromium and lead; 4) lastly, with regard to the products of agricultural pesticides in general, there was an association with ALS in men but not in women, with a dose-response relationship.<br><br>CONCLUSIONS: The lack of statistically significant association between occupational exposure and ALS is mainly due to the methodological diversity of the studies and the lack of prospective studies at the workplace.}, }
@article {pmid25238455, year = {2014}, author = {Marcus, DK and O'Connell, D and Norris, AL and Sawaqdeh, A}, title = {Is the Dodo bird endangered in the 21st century? A meta-analysis of treatment comparison studies.}, journal = {Clinical psychology review}, volume = {34}, number = {7}, pages = {519-530}, doi = {10.1016/j.cpr.2014.08.001}, pmid = {25238455}, issn = {1873-7811}, mesh = {Adult ; Cognitive Behavioral Therapy/*statistics &amp; numerical data ; *Data Interpretation, Statistical ; Female ; Humans ; Male ; Outcome Assessment, Health Care/*statistics &amp; numerical data ; Randomized Controlled Trials as Topic/*statistics &amp; numerical data ; }, abstract = {The Dodo bird hypothesis asserts that when bona fide treatments are compared they yield similar outcomes and this hypothesis is consistent with a common factors or contextual model of psychotherapy. Wampold et al. (1997), the most recent comprehensive meta-analysis to test the Dodo bird hypothesis, yielded consistent evidence of treatment equivalence. However, some of Wampold et al.'s analytic strategies, such as using multiple effect sizes from the same study and prioritizing long-term follow-up, may have obscured treatment differences. The current meta-analysis updated Wampold et al. by analyzing studies published in the subsequent 16 years (k=51). Separate effect sizes were calculated for primary outcomes versus secondary outcomes, at termination and follow-up. Contrary to the Dodo bird hypothesis, there was evidence of treatment differences for primary outcomes at termination. Furthermore, cognitive-behavioral treatments may be incrementally more effective than alternative treatments for primary outcomes. Consistent with the Dodo bird hypothesis, there was little evidence of treatment differences for the secondary outcomes at termination and follow-up. There are small, statistically significant differences between bona-fide treatments when the specific targets of those treatments are assessed, but not when secondary outcomes are assessed, providing mixed support for both specific factors and contextual models of psychotherapy.}, }
@article {pmid24918518, year = {2014}, author = {Govone, F and Vacca, A and Rubino, E and Gai, A and Boschi, S and Gentile, S and Orsi, L and Pinessi, L and Rainero, I}, title = {Lack of association between APOE gene polymorphisms and amyotrophic lateral sclerosis: a comprehensive meta-analysis.}, journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration}, volume = {15}, number = {7-8}, pages = {551-556}, doi = {10.3109/21678421.2014.918149}, pmid = {24918518}, issn = {2167-9223}, mesh = {Amyotrophic Lateral Sclerosis/*genetics ; Apolipoproteins E/*genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease/*genetics ; Genotype ; Humans ; Male ; Odds Ratio ; Polymorphism, Single Nucleotide/*genetics ; }, abstract = {Several studies have evaluated the association between APOE gene polymorphisms and the risk for amyotrophic lateral sclerosis (ALS), with inconclusive results. The aim of our study was to further define the risk associated with carriage of the APOE alleles and development and clinical characteristics of ALS. We performed a comprehensive meta-analysis of all existing studies investigating the association between the APOE gene and ALS published up to September 2013, comprising a total of 4249 ALS patients and 10,397 controls. Pooled odds ratios (OR) were estimated using the random effect (RE) model. Results showed that the carriage of different APOE alleles had no effect on disease risk. In particular, the ϵ4 allele was not associated with a significantly increased disease risk (ϵ4 carriers vs. non-ϵ4 carriers: RE OR 1.18; 95% CI 0.91-1.53). In conclusion, our study suggests that the APOE gene does not have a significant effect in ALS aetiopathogenesis.}, }
@article {pmid24699859, year = {2014}, author = {Abraham, A and Drory, VE}, title = {Influence of serum uric acid levels on prognosis and survival in amyotrophic lateral sclerosis: a meta-analysis.}, journal = {Journal of neurology}, volume = {261}, number = {6}, pages = {1133-1138}, pmid = {24699859}, issn = {1432-1459}, mesh = {Amyotrophic Lateral Sclerosis/*blood/*mortality ; Female ; Humans ; Male ; Prognosis ; PubMed/statistics &amp; numerical data ; Sex Factors ; Uric Acid/*blood ; }, abstract = {Uric acid (UA) is considered to be one of the most important antioxidants in the blood. While high UA levels are found in many disease states, low UA levels are reported in many neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis (ALS). Various studies showed consistently that ALS patients have lower serum UA levels than healthy individuals, more prominently in cases with bulbar onset and longer disease duration. A systematic search of PubMed was conducted to retrieve published studies on UA levels in ALS patients. A meta-analysis was performed on published studies comparing UA levels between ALS patients and controls. This meta-analysis revealed highly statistically significant (p < 0.0001) lower UA levels and a very large size effect in 311 ALS patients compared to 515 controls as a group, as well as calculated for men and women separately. Many studies indicate that patients with neurodegenerative diseases, including ALS, have low UA levels. Our meta-analysis strengthens these findings in ALS patients, demonstrating highly statistically significant (p < 0.0001) lower UA levels in patients compared to controls, with very large total size effect, more prominent in men.}, }
@article {pmid24672220, year = {2014}, author = {Liu, J and Zhang, HX}, title = {Polymorphism in the 11q24.1 genomic region is associated with myopia: a comprehensive genetic study in Chinese and Japanese populations.}, journal = {Molecular vision}, volume = {20}, number = {}, pages = {352-358}, pmid = {24672220}, issn = {1090-0535}, mesh = {Asian People/*genetics ; China ; Chromosomes, Human, Pair 11/*genetics ; Female ; Genetic Association Studies ; Genetic Heterogeneity ; *Genetic Predisposition to Disease ; Genome, Human/*genetics ; Humans ; Japan ; Male ; Myopia/*genetics ; Polymorphism, Single Nucleotide/*genetics ; Publication Bias ; }, abstract = {PURPOSE: To evaluate the association of polymorphisms in the 11q24.1 genomic region and the CTNND2 gene with myopia.<br><br>METHODS: We conducted a comprehensive meta-analysis included 6,954 cases and 9,346 controls. Odds ratios (ORs) were calculated using Carlin's method. Publication bias was assessed using Egger et al.'s approach. Sensitivity, heterogeneity, and trim and fill analyses were also conducted.<br><br>RESULTS: For the 11q24.1 genomic region, the rs11218544 polymorphism showed significant association with myopia [OR and 95% confidence interval (CI): 1.167 (1.032-1.319), p=0.013], while rs577948 showed no association with the disease [OR and 95%CI: 0.988 (0.727-1.342), p=0.936]. For the CTNND2 gene, neither rs6885224 nor rs12716080 was significantly associated with myopia {rs6885224: [OR and 95%CI: 1.051 (0.795-1.391), p=0.725], rs12716080: [OR and 95%CI: 1.173 (0.990-1.390), p=0.065]}.<br><br>CONCLUSIONS: Our study indicated that the 11q24.1 genomic region, and particularly the rs11218544 polymorphism, has a genetic association with the development of myopia.}, }
@article {pmid24630593, year = {2014}, author = {Wang, XB and Cui, NH and Gao, JJ and Qiu, XP and Zheng, F}, title = {SMN1 duplications contribute to sporadic amyotrophic lateral sclerosis susceptibility: evidence from a meta-analysis.}, journal = {Journal of the neurological sciences}, volume = {340}, number = {1-2}, pages = {63-68}, doi = {10.1016/j.jns.2014.02.026}, pmid = {24630593}, issn = {1878-5883}, mesh = {Amyotrophic Lateral Sclerosis/*genetics ; DNA Copy Number Variations ; Databases, Factual/statistics &amp; numerical data ; *Genetic Predisposition to Disease ; Humans ; Survival of Motor Neuron 1 Protein/*genetics ; }, abstract = {OBJECTIVE: To investigate the association between SMN1 and SMN2 copy number variations (CNVs) and sporadic amyotrophic lateral sclerosis (SALS) by a meta-analysis.<br><br>METHODS: Through searching PubMed and EMBASE database (or manual searching) up to November 2013 using the following keywords: "survival motor neuron gene", "SMN", and "amyotrophic lateral sclerosis", "ALS" or "motor neuron disease". Nine studies were identified as eligible for this meta-analysis. The association between SMN genes and the SALS risk was investigated based on SMN1 and SMN2 CNVs. The heterogeneity across the studies was tested, as was publication bias.<br><br>RESULTS: The analysis showed significant association for SMN1 duplications in SALS risk: the risk estimates were OR=1.76, 95%CI=1.33-2.32, p<0.0001 (still significant when the p value was Bonferroni adjusted to 0.01). However, there was no significant association between SMN1 deletions and SALS risk after Bonferroni correction (OR=1.78, 95%CI=1.02-3.11, p=0.04). In addition, SMN2 copy number statuses were not associated with SALS in our pooled study. No evidence of publication bias was observed.<br><br>CONCLUSION: Our meta-analysis suggested that SMN1 duplications are a genetic risk factor in SALS, while there was no modulator effect of the SMN2 gene. In addition, it was possible that SMN1 deletions in predisposition to SALS vary across different countries. More studies were required to warrant the findings of this study.}, }
@article {pmid24458030, year = {2014}, author = {Catalá-López, F and Suárez-Pinilla, M and Suárez-Pinilla, P and Valderas, JM and Gómez-Beneyto, M and Martinez, S and Balanzá-Martínez, V and Climent, J and Valencia, A and McGrath, J and Crespo-Facorro, B and Sanchez-Moreno, J and Vieta, E and Tabarés-Seisdedos, R}, title = {Inverse and direct cancer comorbidity in people with central nervous system disorders: a meta-analysis of cancer incidence in 577,013 participants of 50 observational studies.}, journal = {Psychotherapy and psychosomatics}, volume = {83}, number = {2}, pages = {89-105}, doi = {10.1159/000356498}, pmid = {24458030}, issn = {1423-0348}, support = {NIHR/CS/010/024/DH_/Department of Health/United Kingdom ; }, mesh = {Alzheimer Disease/epidemiology ; Amyotrophic Lateral Sclerosis/epidemiology ; Central Nervous System Diseases/*epidemiology ; Child Development Disorders, Pervasive/epidemiology ; Comorbidity ; Down Syndrome/epidemiology ; Humans ; Huntington Disease/epidemiology ; Incidence ; Multiple Sclerosis/epidemiology ; Neoplasms/*epidemiology ; Observational Studies as Topic ; Parkinson Disease/epidemiology ; Schizophrenia/epidemiology ; }, abstract = {BACKGROUND: There is a lack of scientific consensus about cancer comorbidity in people with central nervous system (CNS) disorders. This study assesses the co-occurrence of cancers in patients with CNS disorders, including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), autism spectrum disorders, Down's syndrome (DS), Huntington's disease (HD), multiple sclerosis (MS), Parkinson's disease (PD) and schizophrenia (SCZ).<br><br>METHOD: Comprehensive search in PubMed/MEDLINE, Scopus and ISI Web of Knowledge of the literature published before March 2013. We identified 51 relevant articles from 2,229 discrete references, 50 of which contained data suitable for quantitative synthesis (577,013 participants). Pooled effect sizes (ES) were calculated using multiple random-effects meta-analyses. Sources of heterogeneity and uncertainty were explored by means of subgroup and sensitivity analyses, respectively.<br><br>RESULTS: The presence of CNS disorders was associated with a reduced co-occurrence of cancer (ES = 0.92; 95% confidence interval, CI: 0.87-0.98; I(2) = 94.5%). A consistently lower overall co-occurrence of cancer was detected in patients with neurodegenerative disorders (ES = 0.80; 95% CI: 0.75- 0.86; I(2) = 82.8%), and in those with AD (ES = 0.32; 95% CI: 0.22-0.46; I(2) = 0.0%), PD (ES = 0.83; 95% CI: 0.76-0.91; I(2) = 80.0%), MS (ES = 0.91; 95% CI: 0.87-0.95; I(2) = 30.3%) and HD (ES = 0.53; 95% CI: 0.42-0.67; I(2) = 56.4%). Patients with DS had a higher overall co-occurrence of cancer (ES = 1.46; 95% CI: 1.08-1.96; I(2) = 87.9%). No association was observed between cancer and ALS (ES = 0.97; 95% CI: 0.76-1.25; I(2) = 0.0%) or SCZ (ES = 0.98; 95% CI: 0.90-1.07; I(2) = 96.3%). Patients with PD, MS and SCZ showed (a) higher co-occurrence of some specific cancers (e.g. PD with melanoma, MS with brain cancers and SCZ with breast cancer), and (b) lower co-occurrence of other specific cancers (e.g. lung, prostate and colorectal cancers in PD; lung and prostate cancers in MS; and melanoma and prostate cancer in SCZ).<br><br>CONCLUSION: Increased and decreased co-occurrence of cancer in patients with CNS disorders represents an opportunity to discover biological and non-biological connections between these complex disorders.}, }
@article {pmid24238842, year = {2014}, author = {Vaa, T}, title = {ADHD and relative risk of accidents in road traffic: a meta-analysis.}, journal = {Accident; analysis and prevention}, volume = {62}, number = {}, pages = {415-425}, doi = {10.1016/j.aap.2013.10.003}, pmid = {24238842}, issn = {1879-2057}, mesh = {Accidents, Traffic/*statistics &amp; numerical data ; Attention Deficit Disorder with Hyperactivity/*epidemiology ; Attention Deficit and Disruptive Behavior Disorders/epidemiology ; Automobile Driving/*statistics &amp; numerical data ; Comorbidity ; Conduct Disorder/epidemiology ; Female ; Humans ; Male ; Risk ; }, abstract = {The present meta-analysis is based on 16 studies comprising 32 results. These studies provide sufficient data to estimate relative accident risks of drivers with ADHD. The overall estimate of relative risk for drivers with ADHD is 1.36 (95% CI: 1.18; 1.57) without control for exposure, 1.29 (1.12; 1.49) when correcting for publication bias, and 1.23 (1.04; 1.46) when controlling for exposure. A relative risk (RR) of 1.23 is exactly the same as found for drivers with cardiovascular diseases. The long-lasting assertion that "ADHD-drivers have an almost fourfold risk of accident compared to non-ADHD-drivers", which originated from Barkley et al.'s study of 1993, is rebutted. That estimate was associated with comorbid Oppositional Defiant Disorder (ODD) and/or Conduct Disorder (CD), not with ADHD, but the assertion has incorrectly been maintained for two decades. The present study provides some support for the hypothesis that the relative accident risk of ADHD-drivers with comorbid ODD, CD and/or other conduct problems, is higher than that of ADHD-drivers without these comorbidities. The estimated RRs were 1.86 (1.27; 2.75) in a sample of ADHD-drivers in which a majority had comorbid ODD and/or CD compared to 1.31 (0.96; 1.81) in a sample of ADHD-drivers with no comorbidity. Given that ADHD-drivers most often seem to drive more than controls, and the fact that a majority of the present studies lack information about exposure, it seems more probable that the true RR is lower rather than higher than 1.23. Also the assertion that ADHD-drivers violate traffic laws more often than other drivers should be modified: ADHD-drivers do have more speeding violations, but no more drunk or reckless driving citations than drivers without ADHD. All accident studies included in the meta-analysis fail to acknowledge the distinction between deliberate violations and driving errors. The former are known to be associated with accidents, the latter are not. A hypothesis that ADHD-drivers speed more frequently than controls because it stimulates attention and reaction time is suggested.}, }
@article {pmid24044580, year = {2013}, author = {Huang, M and Wang, L and Ma, H and Wang, J and Xiang, M}, title = {Lack of an association between interleukin-6 -174G/C polymorphism and circulating interleukin-6 levels in normal population: a meta-analysis.}, journal = {DNA and cell biology}, volume = {32}, number = {11}, pages = {654-664}, doi = {10.1089/dna.2013.2148}, pmid = {24044580}, issn = {1557-7430}, mesh = {Coronary Disease/genetics ; Genetic Predisposition to Disease ; Heterozygote ; Humans ; Interleukin-6/*blood/*genetics ; *Polymorphism, Single Nucleotide ; Reference Values ; }, abstract = {Interleukin-6 (IL-6) signaling may play a causal role in the development of coronary heart disease. However, the relationship between IL-6 genotypes and plasma levels of IL-6 appears to be complex. To help clarify the inconsistent findings, we conducted a meta-analysis of the published genetic association studies of the -174 G/C polymorphisms in the IL-6 gene and the circulating IL-6 levels in a normal population. In this meta-analysis, no significant association of IL-6 -174G/C polymorphism and circulating IL-6 levels in a normal population was observed. However, when compared among GG, GC, and CC genotypes, heterogeneity existed among the studies. Sensitivity analysis revealed that, the independent study by Shen et al. influenced the heterogeneity in the homozygous and heterozygous comparison. Although Shen et al.'s study was excluded, no significant association was observed between IL-6 -174G/C polymorphism and circulating IL-6 levels in a normal population [homozygous comparison (GG vs. CC): the pooled standard mean difference (SMD) was -0.01, 95% confidence interval (CI): -0.1-0.08; heterozygous comparison (GC vs. GG or CC): the pooled SMD (GG vs. GC) was -0.05, 95%CI: -0.11-0.01, and the pooled SMD (CC vs. GC) was 0.03, 95%CI: -0.03-0.1]. Under the dominant model, the pooled SMD was -0.05, 95%CI: -0.11-0.01). The meta-analysis provides evidence that the -174G/C polymorphism in the IL-6 gene is not significantly associated with circulating IL-6 levels in a normal population.}, }
@article {pmid23856242, year = {2013}, author = {Bowen, RC and Wang, Y and Balbuena, L and Houmphan, A and Baetz, M}, title = {The relationship between mood instability and depression: implications for studying and treating depression.}, journal = {Medical hypotheses}, volume = {81}, number = {3}, pages = {459-462}, doi = {10.1016/j.mehy.2013.06.010}, pmid = {23856242}, issn = {1532-2777}, mesh = {Depression/complications/*diagnosis/*physiopathology ; Factor Analysis, Statistical ; Humans ; Mood Disorders/complications/*physiopathology ; Surveys and Questionnaires ; United Kingdom ; }, abstract = {BACKGROUND: Most individuals with depressed mood report mood fluctuations (Mood Instability) within hours or days. This is not recognized in diagnostic criteria or standard rating scales for depression.<br><br>HYPOTHESIS: That mood instability is a distinct component of the development of depression that has been omitted from criteria for depression because of reliance on retrospective recall and structured interviews. The inclusion of Mood Instability would enhance research into causes and treatment of depression.<br><br>STUDIES: We examined three datasets that used retrospective and prospective measures of depressed symptom ratings and mood instability to determine the relationship between the two. Study 1 used data from the 1991 UK Health and Lifestyle Surveys (HALS). Studies 2 and 3 used clinical samples. The scales used to assess mood instability were the mood instability factor from the Eysenck Personality Inventory Neuroticism Scale, the Affective Lability Scale (ALS), and the Visual Analogue Depression Scale (VAS). The depression scales (depressive symptoms) were the General Health Questionnaire (GHQ) depression factor, the Beck Depression Inventory IA (BDI) and the mean from the Visual Analogue Depression Scale (VAS). We used partial correlation analysis to assess the association between mood instability and depression and exploratory factor analysis to determine the factor structure of items pooled from the mood instability and depression scales from studies 1 and 2.<br><br>RESULTS: Mood Instability was found to be moderately associated with depressive symptoms. The Pearson's r-values ranged from 0.49 to 0.57. The correlation was lower when recalling mood in the past. The factor analytic solution supported the hypothesis that MI and depressive symptoms are related but distinct constructs.<br><br>CONCLUSIONS: Reliance exclusively on the retrospective assessment of depressive symptoms has occluded the widespread occurrence of mood instability. Including Mood Instability in diagnostic and assessment criteria would enhance causal and treatment research in depression.}, }
@article {pmid23286751, year = {2013}, author = {Saris, CG and Groen, EJ and Koekkoek, JA and Veldink, JH and van den Berg, LH}, title = {Meta-analysis of gene expression profiling in amyotrophic lateral sclerosis: a comparison between transgenic mouse models and human patients.}, journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration}, volume = {14}, number = {3}, pages = {177-189}, doi = {10.3109/21678421.2012.729842}, pmid = {23286751}, issn = {2167-9223}, mesh = {Amyotrophic Lateral Sclerosis/diagnosis/*genetics ; Animals ; *Disease Models, Animal ; Gene Expression Profiling/*methods ; *Gene Expression Regulation ; Humans ; Mice ; Mice, Transgenic ; }, abstract = {The exact pathogenic cascade leading to motor neuron degeneration in amyotrophic lateral sclerosis (ALS) is unknown. Gene expression profiles of ALS-affected spinal cord and motor neurons have been well established in mice and man. We provide a meta-analysis of the reported significant gene lists of gene expression studies in ALS, and compare results between mouse models and human post mortem tissue. In total, 12 articles met inclusion criteria. Twenty-nine genes were found to be differentially expressed at least twice in studies using human post mortem tissue, enriched for the functions 'immune response', 'apoptosis' and 'protein metabolism'. In mouse studies, 86 genes were reported at least two times and were enriched for 'immune response', 'lysosome', 'metal ion binding' and 'mitochondrion'. Next, all differentially expressed genes from the mouse studies were translated to human homologous genes. Seventy-four differentially expressed genes in mouse tissue were also found to be differentially expressed in human tissue. In conclusion, evidence was found for shared dysfunction in protein turnover in the ubiquitin-proteasome system. Differential expression of Cathepsin B and D, GFAP and SERPINA3 was repeatedly found to be significant in both the mouse model and ALS patients.}, }
@article {pmid23267027, year = {2016}, author = {Combescure, C and Courvoisier, DS and Haller, G and Perneger, TV}, title = {Meta-analysis of two-arm studies: Modeling the intervention effect from survival probabilities.}, journal = {Statistical methods in medical research}, volume = {25}, number = {2}, pages = {857-871}, doi = {10.1177/0962280212469716}, pmid = {23267027}, issn = {1477-0334}, mesh = {Breast Neoplasms/diagnosis/mortality ; Disease-Free Survival ; Early Detection of Cancer ; Female ; Humans ; Leukemia, Myeloid, Acute/drug therapy/surgery ; Neoplasm Recurrence, Local/diagnosis/mortality ; *Proportional Hazards Models ; Time Factors ; }, abstract = {Pooling the hazard ratios is not always feasible in meta-analyses of two-arm survival studies, because the measure of the intervention effect is not systematically reported. An alternative approach proposed by Moodie et al. is to use the survival probabilities of the included studies, all collected at a single point in time: the intervention effect is then summarised as the pooled ratio of the logarithm of survival probabilities (which is an estimator of the hazard ratios when hazards are proportional). In this article, we propose a generalization of this method. By using survival probabilities at several points in time, this generalization allows a flexible modeling of the intervention over time. The method is applicable to partially proportional hazards models, with the advantage of not requiring the specification of the baseline survival. As in Moodie et al.'s method, the study-level factors modifying the survival functions can be ignored as long as they do not modify the intervention effect. The procedures of estimation are presented for fixed and random effects models. Two illustrative examples are presented.}, }
@article {pmid23189129, year = {2012}, author = {Zhou, H and Chen, G and Chen, C and Yu, Y and Xu, Z}, title = {Association between extremely low-frequency electromagnetic fields occupations and amyotrophic lateral sclerosis: a meta-analysis.}, journal = {PloS one}, volume = {7}, number = {11}, pages = {e48354}, pmid = {23189129}, issn = {1932-6203}, mesh = {Amyotrophic Lateral Sclerosis/epidemiology/*etiology ; Electromagnetic Fields/*adverse effects ; Humans ; Occupational Exposure ; Odds Ratio ; Publication Bias ; }, abstract = {OBJECTIVES: To estimate the relationship between exposure to extremely low-frequency electromagnetic fields (ELF-EMF) and the risk of amyotrophic lateral sclerosis (ALS) by a meta-analysis.<br><br>METHODS: Through searching PubMed databases (or manual searching) up to April 2012 using the following keywords: "occupational exposure", "electromagnetic fields" and "amyotrophic lateral sclerosis" or "motor neuron disease", seventeen studies were identified as eligible for this meta-analysis. The associations between ELF-EMF exposure and the ALS risk were estimated based on study design (case-control or cohort study), and ELF-EMF exposure level assessment (job title or job-exposure matrix). The heterogeneity across the studies was tested, as was publication bias.<br><br>RESULTS: Occupational exposure to ELF-EMF was significantly associated with increased risk of ALS in pooled studies (RR&#x200a;=&#x200a;1.29, 95%CI&#x200a;=&#x200a;1.02-1.62), and case-control studies (OR&#x200a;=&#x200a;1.39, 95%CI&#x200a;=&#x200a;1.05-1.84), but not cohort studies (RR&#x200a;=&#x200a;1.16, 95% CI&#x200a;=&#x200a;0.80-1.69). In sub-analyses, similar significant associations were found when the exposure level was defined by the job title, but not the job-exposure matrix. In addition, significant associations between occupational exposure to ELF-EMF and increased risk of ALS were found in studies of subjects who were clinically diagnosed but not those based on the death certificate. Moderate heterogeneity was observed in all analyses.<br><br>CONCLUSIONS: Our data suggest a slight but significant ALS risk increase among those with job titles related to relatively high levels of ELF-EMF exposure. Since the magnitude of estimated RR was relatively small, we cannot deny the possibility of potential biases at work. Electrical shocks or other unidentified variables associated with electrical occupations, rather than magnetic-field exposure, may be responsible for the observed associations with ALS.}, }
@article {pmid23063643, year = {2013}, author = {van Rheenen, W and Diekstra, FP and van Doormaal, PT and Seelen, M and Kenna, K and McLaughlin, R and Shatunov, A and Czell, D and van Es, MA and van Vught, PW and van Damme, P and Smith, BN and Waibel, S and Schelhaas, HJ and van der Kooi, AJ and de Visser, M and Weber, M and Robberecht, W and Hardiman, O and Shaw, PJ and Shaw, CE and Morrison, KE and Al-Chalabi, A and Andersen, PM and Ludolph, AC and Veldink, JH and van den Berg, LH}, title = {H63D polymorphism in HFE is not associated with amyotrophic lateral sclerosis.}, journal = {Neurobiology of aging}, volume = {34}, number = {5}, pages = {1517.e5-7}, doi = {10.1016/j.neurobiolaging.2012.07.020}, pmid = {23063643}, issn = {1558-1497}, support = {089701/WT_/Wellcome Trust/United Kingdom ; G0500289/MRC_/Medical Research Council/United Kingdom ; G0900688/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adult ; Aged ; Amyotrophic Lateral Sclerosis/*epidemiology/*genetics ; Europe/epidemiology ; Female ; Genetic Markers/*genetics ; Genetic Predisposition to Disease/*epidemiology/*genetics ; Hemochromatosis Protein ; Histocompatibility Antigens Class I/*genetics ; Humans ; Male ; Membrane Proteins/*genetics ; Middle Aged ; Polymorphism, Single Nucleotide/*genetics ; Prevalence ; Risk Factors ; }, abstract = {The H63D polymorphism in HFE has frequently been associated with susceptibility to amyotrophic lateral sclerosis (ALS). Regarding the role of HFE in iron homeostasis, iron accumulation is considered an important process in ALS. Furthermore, novel therapeutic strategies are being developed targeting this process. Evidence for this genetic association is, however, limited to several small studies. For this reason we studied the H63D polymorphism in a large European cohort including 3962 ALS patients and 5072 control subjects from 7 countries. After meta-analysis of previous studies and current findings we conclude that the H63D polymorphism in HFE is not associated with susceptibility to ALS, age at disease onset, or survival.}, }
@article {pmid22819005, year = {2012}, author = {Malek, AM and Barchowsky, A and Bowser, R and Youk, A and Talbott, EO}, title = {Pesticide exposure as a risk factor for amyotrophic lateral sclerosis: a meta-analysis of epidemiological studies: pesticide exposure as a risk factor for ALS.}, journal = {Environmental research}, volume = {117}, number = {}, pages = {112-119}, doi = {10.1016/j.envres.2012.06.007}, pmid = {22819005}, issn = {1096-0953}, mesh = {*Agriculture ; Amyotrophic Lateral Sclerosis/*chemically induced/*epidemiology ; Humans ; Male ; Models, Statistical ; Occupational Exposure/*adverse effects ; Odds Ratio ; Pesticides/*toxicity ; Risk Factors ; }, abstract = {BACKGROUND: Exposure to pesticides and agricultural chemicals has been linked to amyotrophic lateral sclerosis (ALS) although findings have been inconsistent. A meta-analysis of studies published through May, 2011 was conducted to investigate the association of pesticide exposure and risk of ALS.<br><br>METHODS: Six peer-reviewed studies that met criteria were included in a meta-analysis of men involving 1,517 ALS deaths from one retrospective cohort study and 589 ALS or motor neuron disease cases from five case-control studies. A random effects model was used to calculate sex-specific pooled odds ratios (ORs).<br><br>RESULTS: Evidence was found for an association of exposure to pesticides and risk of ALS in male cases compared to controls (OR=1.88, 95% CI: 1.36-2.61), although the chemical or class of pesticide was not specified by the majority of studies.<br><br>CONCLUSION: This meta-analysis supports the relationship of exposure to pesticides and development of ALS among male cases compared to controls. The weight of evidence links pesticide exposure to ALS; however, additional prospective studies with a target exposure group are necessary to better elucidate the relationship. Future research should focus on more accurate exposure assessment and the use of job exposure matrices.}, }
@article {pmid22059178, year = {2011}, author = {McKim, DA and Road, J and Avendano, M and Abdool, S and Cote, F and Duguid, N and Fraser, J and Maltais, F and Morrison, DL and O'Connell, C and Petrof, BJ and Rimmer, K and Skomro, R and , }, title = {Home mechanical ventilation: a Canadian Thoracic Society clinical practice guideline.}, journal = {Canadian respiratory journal}, volume = {18}, number = {4}, pages = {197-215}, pmid = {22059178}, issn = {1916-7245}, mesh = {Adult ; *Airway Management/instrumentation/methods/standards ; Clinical Trials as Topic ; *Home Care Services ; Humans ; *Monitoring, Physiologic/methods/standards ; Musculoskeletal Diseases/complications ; Nervous System Diseases/complications ; Obesity Hypoventilation Syndrome/complications ; Patient Discharge/standards ; Pulmonary Disease, Chronic Obstructive/complications ; *Respiration, Artificial/instrumentation/methods/standards ; Respiratory Function Tests ; *Respiratory Insufficiency/diagnosis/etiology/physiopathology/therapy ; Risk Assessment ; }, abstract = {Increasing numbers of patients are surviving episodes of prolonged mechanical ventilation or benefitting from the recent availability of userfriendly noninvasive ventilators. Although many publications pertaining to specific aspects of home mechanical ventilation (HMV) exist, very few comprehensive guidelines that bring together all of the current literature on patients at risk for or using mechanical ventilatory support are available. The Canadian Thoracic Society HMV Guideline Committee has reviewed the available English literature on topics related to HMV in adults, and completed a detailed guideline that will help standardize and improve the assessment and management of individuals requiring noninvasive or invasive HMV. The guideline provides a disease-specific review of illnesses including amyotrophic lateral sclerosis, spinal cord injury, muscular dystrophies, myotonic dystrophy, kyphoscoliosis, post-polio syndrome, central hypoventilation syndrome, obesity hypoventilation syndrome, and chronic obstructive pulmonary disease as well as important common themes such as airway clearance and the process of transition to home. The guidelines have been extensively reviewed by international experts, allied health professionals and target audiences. They will be updated on a regular basis to incorporate any new information.}, }
@article {pmid21914052, year = {2012}, author = {,  and Andersen, PM and Abrahams, S and Borasio, GD and de Carvalho, M and Chio, A and Van Damme, P and Hardiman, O and Kollewe, K and Morrison, KE and Petri, S and Pradat, PF and Silani, V and Tomik, B and Wasner, M and Weber, M}, title = {EFNS guidelines on the clinical management of amyotrophic lateral sclerosis (MALS)--revised report of an EFNS task force.}, journal = {European journal of neurology}, volume = {19}, number = {3}, pages = {360-375}, doi = {10.1111/j.1468-1331.2011.03501.x}, pmid = {21914052}, issn = {1468-1331}, mesh = {Advisory Committees ; Amyotrophic Lateral Sclerosis/*diagnosis/*therapy ; Evidence-Based Medicine ; Humans ; }, abstract = {BACKGROUND: The evidence base for the diagnosis and management of amyotrophic lateral sclerosis (ALS) is weak.<br><br>OBJECTIVES: To provide evidence-based or expert recommendations for the diagnosis and management of ALS based on a literature search and the consensus of an expert panel.<br><br>METHODS: All available medical reference systems were searched, and original papers, meta-analyses, review papers, book chapters and guidelines recommendations were reviewed. The final literature search was performed in February 2011. Recommendations were reached by consensus.<br><br>RECOMMENDATIONS: Patients with symptoms suggestive of ALS should be assessed as soon as possible by an experienced neurologist. Early diagnosis should be pursued, and investigations, including neurophysiology, performed with a high priority. The patient should be informed of the diagnosis by a consultant with a good knowledge of the patient and the disease. Following diagnosis, the patient and relatives/carers should receive regular support from a multidisciplinary care team. Medication with riluzole should be initiated as early as possible. Control of symptoms such as sialorrhoea, thick mucus, emotional lability, cramps, spasticity and pain should be attempted. Percutaneous endoscopic gastrostomy feeding improves nutrition and quality of life, and gastrostomy tubes should be placed before respiratory insufficiency develops. Non-invasive positive-pressure ventilation also improves survival and quality of life. Maintaining the patient's ability to communicate is essential. During the entire course of the disease, every effort should be made to maintain patient autonomy. Advance directives for palliative end-of-life care should be discussed early with the patient and carers, respecting the patient's social and cultural background.}, }
@article {pmid21644273, year = {2011}, author = {Hunyadi-Anticević, S and Colak, Z and Funtak, IL and Lukić, A and Filipović-Grcić, B and Tomljanović, B and Kniewald, H and Protić, A and Pandak, T and Poljaković, Z and Canadija, M and , }, title = {[European Resuscitation Council guidelines for resuscitation 2010].}, journal = {Lijecnicki vjesnik}, volume = {133}, number = {1-2}, pages = {1-14}, pmid = {21644273}, issn = {0024-3477}, mesh = {Acute Coronary Syndrome/therapy ; Adult ; Cardiopulmonary Resuscitation/*methods/standards ; Child ; *Emergency Medical Services ; Humans ; Infant, Newborn ; Myocardial Infarction/therapy ; }, abstract = {All rescuers trained or not, should provide chest compressions to victims of cardiac arrest. The aim should be to push to a depth of at least 5 cm at a rate of at least 100 compressions per minute, to allow full chest recoil, and to minimise interruptions in chest compressions. Trained rescuers should also provide ventilations with a compression-ventilation ratio of 30:2. ELECTRICAL THERAPIES: Much greater emphasis on minimising the duration of the pre-shock and post-shock pauses; the continuation of compressions during charging of the defibrillator is recommended. Further development of AED programmes is encouraged. ADULT ADVANCED LIFE SUPPORT: Increased emphasis on high-quality chest compressions throughout any ALS intervention paused briefly only to enable specific interventions. Removal of the recommendation for a pre-specified period of cardiopulmonary resuscitation before out-of-hospital defibrillation following cardiac arrest unwitnessed by the EMS. The role of precordial thump is de-emphasized. Delivery of drugs via a tracheal tube is no longer recommended, drugs should be given by the intraosseous (IO) route. Atropine is no longer recommended for routine use in asystole or pulseless electrical activity. Reduced emphasis on early tracheal intubation unless achieved by highly skilled individuals with minimal interruptions in chest compressions. Increased emphasis on the use of capnography. Recognition of potential harm caused by hyperoxaemia. Revision of the recommendation of glucose control. Use of therapeutic hypothermia to include comatose survivors of cardiac arrest associated initially with shockable rhythms, as well as non-shockable rhythms, with a lower level of evidence acknowledged for the latter. INITIAL MANAGEMENT OF ACUTE CORONARY SYNDROMES: The term non-ST-elevation myocardial infarction-acute coronary syndrome (non-STEMI-ACS) has been introduced for both NSTEMI and unstable angina pectoris. Primary PCI (PPCI) is the preferred reperfusion strategy provided it is performed in a timely manner by an experienced team. Non-steroidal anti-inflammatory drugs should be avoided, as well as routine use of intravenous beta-blockers; oxygen is to be given only to those patients with hypoxaemia, breathlessness or pulmonary congestion. PAEDIATRIC LIFE SUPPORT: The decision to begin resuscitation must be taken in less than 10 seconds. Lay rescuers should be taught to use a ratio of 30 compressions to 2 ventilations, rescuers with a duty to respond should learn and use a 15:2 ratio; however, they can use the 30:2 compression-ventilation ratio if they are alone. Ventilation remains a very important component of resuscitation in asphyxial arrest. The emphasis is on achieving quality compressions with the rate of at least 100 but not greater than 120 per minute, with minimal interruptions. AEDs are safe and successful when used in children older than 1 year. A single shock strategy using a non-escalating dose of 4 J/kg is recommended for defibrillation in children. Cuffed tubes can be used safely in infants and young children. Monitoring exhaled carbon dioxide (CO2), ideally by capnography, is recommended during resuscitation. RESUSCITATION OF BABIES AT BIRTH: For uncompromised babies, a delay in cord clamping of at least one minute from the complete delivery is now recommended. For term infants, air should be used fro resuscitation at birth. For preterm babies less than 32 weeks gestation blended oxygen and air should be given judiciously and its use guided by pulse oximetry. Preterm babies of less than 28 weeks gestation should be completely covered in a plastic wrap up to their necks, without drying, immediately after birth. The recommended compression: ventilation ratio remains at 3:1 for newborn resuscitation. Attempts to aspirate meconium from the nose and mouth of the unborn baby, while the head is still on the perineum, are not recommended. If adrenaline is given the n the intravenous route is recommended using a dose of 10-30 microg/kg. Newly born infants born at term or near-term with moderate to severe hypoxic-ischaemic encephalopathy should be treated with therapeutic hypothermia. PRINCIPLES OF EDUCATION IN RESUSCITATION: The aim is to ensure that learners acquire and retain skill and knowledge that will enable them to act correctly in actual cardiac arrest and improve patient outcome. Short video/computer self-instruction courses, with minimal or no instructor coaching, combined with hands-on practice can be considered as an effective alternative to instructor-led basic life support (BLS and AED) courses. Ideally all citizens should be trained in standard CPR that includes compressions and ventilations. Basic and advanced life support knowledge and skills deteriorate in as little as three to six months. CPR prompt or feedback devices improve CPR skill acquisition and retention.}, }
@article {pmid21456887, year = {2011}, author = {Iwamoto, J and Takeda, T and Matsumoto, H}, title = {Efficacy of oral bisphosphonates for preventing hip fracture in disabled patients with neurological diseases: a meta-analysis of randomized controlled trials among the Japanese population.}, journal = {Current medical research and opinion}, volume = {27}, number = {6}, pages = {1141-1148}, doi = {10.1185/03007995.2011.570747}, pmid = {21456887}, issn = {1473-4877}, mesh = {Administration, Oral ; Aged ; Bone Density Conservation Agents/administration &amp; dosage/adverse effects/*therapeutic use ; Diphosphonates/administration &amp; dosage/adverse effects/*therapeutic use ; *Persons with Disabilities ; Female ; Hip Fractures/complications/*prevention &amp; control ; Humans ; Japan ; Male ; Nervous System Diseases/*complications ; *Randomized Controlled Trials as Topic ; }, abstract = {OBJECTIVE: Neurological diseases such as amyotrophic lateral sclerosis (ALS), stroke, and Parkinson's disease cause disability and immobilization that increases the risk of hip fracture. The purpose of the present study was to clarify the efficacy of oral bisphosphonates for preventing hip fracture in disabled patients with such neurological diseases.<br><br>METHODS: A literature search (PubMed) was done from 1995 to the present for randomized controlled trials (RCTs), and a meta-analysis was conducted.<br><br>RESULTS: Seven RCTs met the criteria, including two of etidronate (ALS and stroke), two of alendronate (stroke and Parkinson's disease), and three of risedronate (stroke and Parkinson's disease). All of the RCTs were performed on Japanese patients. According to the results of pooled data analysis, the relative risk (95% confidence interval) of hip fracture in patients receiving etidronate, alendronate, and risedronate treatment compared with placebo or active control treatment was 0.16 (0.03-0.87), 0.29 (0.10-0.80), and 0.24 (0.10-0.58), respectively, suggesting a reduction of risk by more than 70% with oral bisphosphonates. There was no statistical evidence of heterogeneity among RCTs, and publication bias was not identified by the funnel plot and Begg's rank correlation test. No severe adverse events due to oral bisphosphonate treatment were reported.<br><br>LIMITATION: It remains uncertain whether the findings are relevant for Western patients with an increased risk of hip fracture due to neurological diseases.<br><br>CONCLUSION: A meta-analysis of RCTs suggested that oral bisphosphonate treatment prevents hip fracture in disabled Japanese patients with neurological diseases, including ALS, stroke, and Parkinson's disease. Oral bisphosphonate treatment was well tolerated by such patients.}, }
@article {pmid20929296, year = {2010}, author = {Chen, Z and Ma, L}, title = {Grey matter volume changes over the whole brain in amyotrophic lateral sclerosis: A voxel-wise meta-analysis of voxel based morphometry studies.}, journal = {Amyotrophic lateral sclerosis : official publication of the World Federation of Neurology Research Group on Motor Neuron Diseases}, volume = {11}, number = {6}, pages = {549-554}, doi = {10.3109/17482968.2010.516265}, pmid = {20929296}, issn = {1471-180X}, mesh = {Amyotrophic Lateral Sclerosis/*pathology ; Brain/*pathology ; Brain Mapping/*methods ; Humans ; Image Processing, Computer-Assisted/*methods ; Sensitivity and Specificity ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with selected both upper and lower motor neuron involvement. Although some inconsistent results exist, both pathological studies and many structural neuroimaging studies have revealed brain volume changes in ALS. To provide an objective overview of structural changes in ALS, a voxel-wise meta-analysis was performed in published voxel based morphometry (VBM) studies. A systematic search of VBM studies was applied in ALS. Five studies met the inclusion criteria, comprising 84 ALS patients and 81 normal controls. A voxel-wise meta-analysis was performed on the retrieved VBM studies using signed differential mapping. Descriptive analysis showed that 25% of ALS patients had right precentral gyrus atrophy (2373 voxels). Group analysis demonstrated regional grey matter loss over the whole brain in the right precentral gyrus (p = 7.96 × 10(-4)). Sensitivity analysis showed good sensitivity (157 voxels). In conclusion, right precentral grey matter atrophy was a common finding and prominent feature of brain structural changes in ALS.}, }
@article {pmid20861059, year = {2010}, author = {Al-Chalabi, A and Fang, F and Hanby, MF and Leigh, PN and Shaw, CE and Ye, W and Rijsdijk, F}, title = {An estimate of amyotrophic lateral sclerosis heritability using twin data.}, journal = {Journal of neurology, neurosurgery, and psychiatry}, volume = {81}, number = {12}, pages = {1324-1326}, pmid = {20861059}, issn = {1468-330X}, support = {089701/WT_/Wellcome Trust/United Kingdom ; G0600974/MRC_/Medical Research Council/United Kingdom ; G0900688/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Amyotrophic Lateral Sclerosis/diagnosis/*genetics ; Diseases in Twins/diagnosis/*genetics ; Genetic Predisposition to Disease/genetics ; Humans ; Models, Genetic ; Registries ; Sweden ; Twin Studies as Topic ; Twins, Dizygotic ; Twins, Monozygotic ; United Kingdom ; }, abstract = {BACKGROUND: Causative gene mutations have been identified in about 2% of those with amyotrophic lateral sclerosis (ALS), often, but not always, when there is a strong family history. There is an assumption that there is a genetic component to all ALS, but genome-wide association studies have yet to produce a robustly replicated result. A definitive estimate of ALS heritability is therefore required to determine whether ongoing efforts to find susceptibility genes are worth while.<br><br>METHODS: The authors performed two twin studies, one population- and one clinic-based. The authors used structural equation modelling to perform a meta-analysis of data from these studies and an existing twin study to estimate ALS heritability, and identified 171 twin pairs in which at least one twin had ALS.<br><br>RESULTS AND DISCUSSION: Five monozygotic twin pairs were concordant-affected, and 44 discordant-affected. No dizygotic twin pairs were concordant-affected, and 122 discordant-affected. The heritability of sporadic ALS was estimated as 0.61 (0.38 to 0.78) with the unshared environmental component 0.39 (0.22 to 0.62). ALS has a high heritability, and efforts to find causative genes should continue.}, }
@article {pmid20500522, year = {2011}, author = {Burgunder, JM and Schöls, L and Baets, J and Andersen, P and Gasser, T and Szolnoki, Z and Fontaine, B and Van Broeckhoven, C and Di Donato, S and De Jonghe, P and Lynch, T and Mariotti, C and Spinazzola, A and Tabrizi, SJ and Tallaksen, C and Zeviani, M and Harbo, HF and Finsterer, J}, title = {EFNS guidelines for the molecular diagnosis of neurogenetic disorders: motoneuron, peripheral nerve and muscle disorders.}, journal = {European journal of neurology}, volume = {18}, number = {2}, pages = {207-217}, doi = {10.1111/j.1468-1331.2010.03069.x}, pmid = {20500522}, issn = {1468-1331}, mesh = {Humans ; *Molecular Diagnostic Techniques ; Motor Neuron Disease/*diagnosis/genetics ; Muscular Diseases/*diagnosis/genetics ; Peripheral Nervous System Diseases/*diagnosis/genetics ; }, abstract = {OBJECTIVES: These EFNS guidelines on the molecular diagnosis of motoneuron disorders, neuropathies and myopathies are designed to summarize the possibilities and limitations of molecular genetic techniques and to provide diagnostic criteria for deciding when a molecular diagnostic work-up is indicated.<br><br>SEARCH STRATEGY: To collect data about planning, conditions and performance of molecular diagnosis of these disorders, a literature search in various electronic databases was carried out and original papers, meta-analyses, review papers and guideline recommendations reviewed.<br><br>RESULTS: The best level of evidence for genetic testing recommendation (B) can be found for the disorders with specific presentations, including familial amyotrophic lateral sclerosis, spinal and bulbar muscular atrophy, Charcot-Marie-Tooth 1A, myotonic dystrophy and Duchenne muscular dystrophy. For a number of less common disorders, a precise description of the phenotype, including the use of immunologic methods in the case of myopathies, is considered as good clinical practice to guide molecular genetic testing.<br><br>CONCLUSION: These guidelines are provisional and the future availability of molecular-genetic epidemiological data about the neurogenetic disorders under discussion in this article will allow improved recommendation with an increased level of evidence.}, }
@article {pmid20107424, year = {2010}, author = {Song, WA and Zhou, NK and Wang, W and Chu, XY and Liang, CY and Tian, XD and Guo, JT and Liu, X and Liu, Y and Dai, WM}, title = {Survival benefit of neoadjuvant chemotherapy in non-small cell lung cancer: an updated meta-analysis of 13 randomized control trials.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {5}, number = {4}, pages = {510-516}, doi = {10.1097/JTO.0b013e3181cd3345}, pmid = {20107424}, issn = {1556-1380}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Carcinoma, Non-Small-Cell Lung/*drug therapy/*mortality/pathology ; Chemotherapy, Adjuvant ; Humans ; Lung Neoplasms/*drug therapy/*mortality/pathology ; *Neoadjuvant Therapy ; Randomized Controlled Trials as Topic ; Survival Rate ; Treatment Outcome ; }, abstract = {INTRODUCTION: The survival effectiveness of neoadjuvant chemotherapy in non-small cell lung cancer (NSCLC) is still unclear based on the study of most up-to-date literatures. This article contributes to this problem by conducting an updated meta-analysis.<br><br>METHODS: Based on Burdett et al's (J Thorac Oncol 2006;1:611-621) systematic review, this meta-analysis was conducted. Articles were searched electrically. The possible survival benefit of neoadjuvant chemotherapy was assessed by hazard ratio (HR) in terms of overall survival. A subgroup meta-analysis with only stage III NSCLC was also conducted. The software of Review Manager was used for data management.<br><br>RESULTS: Thirteen randomized control trials, 6 of which were new ones, were included into this meta-analysis. The overall survival of NSCLC patients in neoadjuvant chemotherapy arm were improved significantly, comparing with those in surgery-alone arm (combined HR = 0.84; 95% confidence interval, 0.77-0.92; p = 0.0001). When only patients with stage III NSCLC were considered, the result was similar (combined HR = 0.84; 95% confidence interval, 0.75-0.95; p = 0.005).<br><br>CONCLUSION: Neoadjuvant chemotherapy, as an addition of surgery, would significantly improve the overall survival of operable NSCLC patients, including patients with stage III NSCLC.}, }
@article {pmid19371564, year = {2008}, author = {Rutten, AL and Stolper, CF}, title = {The 2005 meta-analysis of homeopathy: the importance of post-publication data.}, journal = {Homeopathy : the journal of the Faculty of Homeopathy}, volume = {97}, number = {4}, pages = {169-177}, doi = {10.1016/j.homp.2008.09.008}, pmid = {19371564}, issn = {1476-4245}, mesh = {History, 21st Century ; Homeopathy/*history ; Humans ; Randomized Controlled Trials as Topic ; }, abstract = {BACKGROUND: There is a discrepancy between the outcome of a meta-analysis published in 1997 of 89 trials of homeopathy by Linde et al and an analysis of 110 trials by Shang et al published in 2005, these reached opposite conclusions. Important data were not mentioned in Shang et al's paper, but only provided subsequently.<br><br>QUESTIONS: What was the outcome of Shang et al's predefined hypotheses? Were the homeopathic and conventional trials comparable? Was subgroup selection justified? The possible role of ineffective treatments. Was the conclusion about effect justified? Were essential data missing in the original article?<br><br>METHODS: Analysis of post-publication data. Re-extraction and analysis of 21 higher quality trials selected by Shang et al with sensitivity analysis for the influence of single indications. Analysis of comparability. Sensitivity analysis of influence of subjective choices, like quality of single indications and of cut-off values for 'larger samples'.<br><br>RESULTS: The quality of trials of homeopathy was better than of conventional trials. Regarding smaller trials, homeopathy accounted for 14 out of 83 and conventional medicine 2 out of 78 good quality trials with n<100. There was selective inclusion of unpublished trials only for homeopathy. Quality was assessed differently from previous analyses. Selecting subgroups on sample size and quality caused incomplete matching of homeopathy and conventional trials. Cut-off values for larger trials differed between homeopathy and conventional medicine without plausible reason. Sensitivity analyses for the influence of heterogeneity and the cut-off value for 'larger higher quality studies' were missing. Homeopathy is not effective for muscle soreness after long distance running, OR=1.30 (95% CI 0.96-1.76). The subset of homeopathy trials on which the conclusion was based was heterogeneous, comprising 8 trials on 8 different indications, and was not matched on indication with those of conventional medicine. Essential data were missing in the original paper.<br><br>CONCLUSION: Re-analysis of Shang's post-publication data did not support the conclusion that homeopathy is a placebo effect. The conclusion that homeopathy is and that conventional is not a placebo effect was not based on comparative analysis and not justified because of heterogeneity and lack of sensitivity analysis. If we confine ourselves to the predefined hypotheses and the part of the analysis that is indeed comparative, the conclusion should be that quality of homeopathic trials is better than of conventional trials, for all trials (p=0.03) as well as for smaller trials (p=0.003).}, }
@article {pmid18215701, year = {2008}, author = {Jaffer, Y and Selby, NM and Taal, MW and Fluck, RJ and McIntyre, CW}, title = {A meta-analysis of hemodialysis catheter locking solutions in the prevention of catheter-related infection.}, journal = {American journal of kidney diseases : the official journal of the National Kidney Foundation}, volume = {51}, number = {2}, pages = {233-241}, doi = {10.1053/j.ajkd.2007.10.038}, pmid = {18215701}, issn = {1523-6838}, mesh = {Adult ; Aged ; Anti-Bacterial Agents/*therapeutic use ; Anticoagulants/therapeutic use ; Bacterial Infections/*etiology/mortality/*prevention &amp; control ; Catheterization, Peripheral/*instrumentation ; Catheters, Indwelling/*adverse effects ; Drug Resistance, Bacterial ; Female ; Hemodiafiltration/*instrumentation ; Heparin/therapeutic use ; Humans ; Male ; Middle Aged ; Randomized Controlled Trials as Topic ; Renal Dialysis/mortality ; Research Design ; Thrombosis/etiology/prevention &amp; control ; Time Factors ; }, abstract = {BACKGROUND: Catheter-related infection (CRI) is associated with increased all-cause mortality and morbidity in hemodialysis patients and may be reduced by using antimicrobial lock solutions (ALSs).<br><br>STUDY DESIGN: We performed a meta-analysis of studies identified from a search conducted in February 2007 of the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, databases of ongoing trials, major renal journals, and reference lists of relevant reports.<br><br>SETTING &amp; POPULATION: Patients receiving acute or long-term hemodialysis through a tunneled or nontunneled central venous catheter.<br><br>We included all prospective randomized studies that compared ALS with heparin.<br><br>INTERVENTION: Administration of antibiotic and/or antimicrobial catheter locking solution.<br><br>OUTCOME MEASURES: Primary outcome was CRI rate in patients using ALSs compared with those using heparin alone. We also examined effects of ALS use on mortality, adverse events, and catheter thrombosis.<br><br>RESULTS: 7 studies were identified with a total of 624 patients and 819 catheters (448 tunneled, 371 nontunneled). CRI was 7.72 (95% confidence interval, 5.11 to 10.33) times less likely when using ALS. There were no consistent suggestions of adverse outcomes with ALS use; in particular, rates of catheter thrombosis did not increase. There was no evidence of antibiotic resistance developing during a maximum follow-up of 12 months.<br><br>LIMITATIONS: The major limitation of this review is the relatively short duration of follow-up of the included studies, which does not allow complete reassurance regarding the development of antibiotic resistance. Lack of direct comparisons means that determination of the most efficient ALS is not possible.<br><br>CONCLUSIONS: This review confirms that antibiotic locking solutions reduce the frequency of CRI without significant side effects.}, }
@article {pmid16749880, year = {2006}, author = {Morley, PT and Walker, T and , }, title = {Australian Resuscitation Council: adult advanced life support (ALS) guidelines 2006.}, journal = {Critical care and resuscitation : journal of the Australasian Academy of Critical Care Medicine}, volume = {8}, number = {2}, pages = {129-131}, pmid = {16749880}, issn = {1441-2772}, mesh = {Adult ; Australia ; Cardiopulmonary Resuscitation/standards ; Electric Countershock/methods/standards ; Humans ; Life Support Care/*standards ; }, }
@article {pmid16324086, year = {2005}, author = {Andersen, PM and Borasio, GD and Dengler, R and Hardiman, O and Kollewe, K and Leigh, PN and Pradat, PF and Silani, V and Tomik, B and , }, title = {EFNS task force on management of amyotrophic lateral sclerosis: guidelines for diagnosing and clinical care of patients and relatives.}, journal = {European journal of neurology}, volume = {12}, number = {12}, pages = {921-938}, doi = {10.1111/j.1468-1331.2005.01351.x}, pmid = {16324086}, issn = {1351-5101}, mesh = {Amyotrophic Lateral Sclerosis/*diagnosis/genetics/therapy ; Evidence-Based Medicine ; Humans ; Physician-Patient Relations ; }, abstract = {Despite being one of the most devastating diseases known, there is little evidence for diagnosing and managing patients with amyotrophic lateral sclerosis (ALS). Although specific therapy is lacking, correct early diagnosis and introduction of symptomatic and specific therapy can have a profound influence on the care and quality of life of the patient and may increase survival time. This document addresses the optimal clinical approach to ALS. The final literature search was performed in the spring of 2005. Consensus recommendations are given graded according to the EFNS guidance regulations. Where there was lack of evidence but consensus was clear we have stated our opinion as good practice points. People affected with possible ALS should be examined as soon as possible by an experienced neurologist. Early diagnosis should be pursued and a number of investigations should be performed with high priority. The patient should be informed of the diagnosis by a consultant with a good knowledge of the patient and the disease. Following diagnosis, the patient and relatives should receive regular support from a multidisciplinary care team. Medication with riluzole should be initiated as early as possible. PEG is associated with improved nutrition and should be inserted early. The operation is hazardous in patients with vital capacity < 50%. Non-invasive positive pressure ventilation improves survival and quality of life but is underused. Maintaining the patients ability to communicate is essential. During the entire course of the disease, every effort should be made to maintain patient autonomy. Advance directives for palliative end of life care are important and should be fully discussed early with the patient and relatives respecting the patients social and cultural background.}, }
@article {pmid16262458, year = {2005}, author = {Shafer, A}, title = {Meta-analysis of the brief psychiatric rating scale factor structure.}, journal = {Psychological assessment}, volume = {17}, number = {3}, pages = {324-335}, doi = {10.1037/1040-3590.17.3.324}, pmid = {16262458}, issn = {1040-3590}, mesh = {Brief Psychiatric Rating Scale/*statistics &amp; numerical data ; *Factor Analysis, Statistical ; Humans ; Psychometrics/methods ; Reproducibility of Results ; }, abstract = {A meta-analysis (N=17,620; k=26) of factor analyses of the Brief Psychiatric Rating Scale (BPRS) was conducted. Analysis of the 12 items from Overall et al.'s (J. E. Overall, L. E. Hollister, &amp; P. Pichot, 1974) 4 subscales found support for his 4 subscales. Analysis of all 18 BPRS items found 4 components similar to those of Overall et al. In a 5-component solution, a 5th activation component emerged but was best supported among samples of schizophrenic patients. The first 4 components appear to form the core of the BPRS factor structure. Results of the meta-analysis suggest 5 subscales (with items in parentheses): Affect (anxiety, guilt, depression, somatic); Positive Symptoms (thought content, conceptual disorganization, hallucinatory behavior, grandiosity); Negative Symptoms (blunted affect, emotional withdrawal, motor retardation); Resistance (hostility, uncooperativeness, suspiciousness); and Activation (excitement, tension, mannerisms-posturing).}, }
@article {pmid16013929, year = {2005}, author = {Giménez Poderós, T and Gaminde Inda, I and Iruin Sanz, A and Napal Lecumberri, V}, title = {[Taxanes in the adjuvant therapy of breastcancer with positive nodes: a meta-analysis].}, journal = {Farmacia hospitalaria : organo oficial de expresion cientifica de la Sociedad Espanola de Farmacia Hospitalaria}, volume = {29}, number = {2}, pages = {75-85}, doi = {10.1016/s1130-6343(05)73642-4}, pmid = {16013929}, issn = {1130-6343}, mesh = {Breast Neoplasms/*drug therapy ; Chemotherapy, Adjuvant ; Female ; Humans ; Lymphatic Metastasis ; Randomized Controlled Trials as Topic ; Taxoids/*therapeutic use ; Treatment Outcome ; }, abstract = {INTRODUCTION: Taxanes have demonstrated high activity in the treatment of metastatic breast cancer. Based on these promising results, clinical trials were initiated to assess their efficacy in non-metastatic breast cancer both in the adjuvant and neoadjuvant setting.<br><br>OBJECTIVE: To collect scientific evidence as needed for future decision making on the use of taxanes in the adjuvant therapy of breast cancer with positive nodes, and to assess the efficacy of chemotherapy regimens including a taxane using a meta-analysis.<br><br>SEARCH STRATEGY: a systematic search of randomized controlled phase-Ill trials comparing poly-chemotherapy with taxanes versus other drug combinations with-out taxanes was performed. Patients were to have non-metastatic breast cancer with positive nodes, and should have received chemotherapy following surgery. The search was performed by two investigators separately.<br><br>DATA COLLECTION AND ANALYSIS: data(relapses and mortality) were separately collected from clinical tri-als by two investigators to assess disease-free survival and overall survival at 5 years. Selected data underwent a meta-analysis using Peto's method. Peto odds ratio (ORp) and 95% confidence interval were calculated for each measured variable.<br><br>RESULTS: Only 3 clinical trials met inclusion criteria; 7,671 patients were studied. Combined OR was ORp 0.79 (95% Cl:0.71-0.87) for disease-free survival and OR, 0.82 (95% Cl: 0.73-0.92) for overall survival.<br><br>CONCLUSIONS: Chemotherapy regimens including a taxane in the adjuvant therapy setting for breast cancer with positive nodes provide a significant improvement regarding increased disease-free survival and overall survival at 5 years.}, }
@article {pmid15919576, year = {2005}, author = {Zafren, K and Durrer, B and Herry, JP and Brugger, H and , }, title = {Lightning injuries: prevention and on-site treatment in mountains and remote areas. Official guidelines of the International Commission for Mountain Emergency Medicine and the Medical Commission of the International Mountaineering and Climbing Federation (ICAR and UIAA MEDCOM).}, journal = {Resuscitation}, volume = {65}, number = {3}, pages = {369-372}, doi = {10.1016/j.resuscitation.2004.12.014}, pmid = {15919576}, issn = {0300-9572}, mesh = {Camping ; Emergency Medical Services/*methods ; Humans ; Lightning Injuries/prevention &amp; control/*therapy ; *Mountaineering ; }, abstract = {Lightning is a hazard during outdoor activities, especially for hikers and mountaineers. Specific preventive measures include staying off ridges and summits, and away from single trees. If possible, stay close to a wall but keeping a distance of at least 1m away from the wall. All metal objects (carabiners, crampons, ice-axe, ski poles, etc.) should be removed and stored away safely. Lightning currents can follow wet ropes. To prevent blunt trauma the helmet should not be removed. Move as quickly as possible away from wire ropes and iron ladders. The crouch position should be adopted immediately if there is a sensation of hair "standing on end". Crackling noises or a visible glow indicate an imminent lightning strike. Rescue of lightning victims may be hazardous. Airborne helicopters can be struck by lightning with disastrous effects. It is prudent to wait until the danger of further strikes has passed. Treatment of lightning victims is based upon the ABCs - (Assessment) airway, breathing and circulation. Victims who are not breathing can often be resuscitated and should be helped first. Respiratory arrest may be prolonged, but the prognosis can be excellent if breathing is supported. Standard Advanced Life Support (ALS), if necessary, should be given at the scene.}, }
@article {pmid14765142, year = {2004}, author = {Esik, O and Vönöczky, K and Lengyel, Z and Sáfrány, G and Trón, L}, title = {Characteristics of radiogenic lower motor neurone disease, a possible link with a preceding viral infection.}, journal = {Spinal cord}, volume = {42}, number = {2}, pages = {99-105}, doi = {10.1038/sj.sc.3101552}, pmid = {14765142}, issn = {1362-4393}, mesh = {Adolescent ; Adult ; Age Factors ; Anterior Horn Cells/physiopathology/*radiation effects/*virology ; Causality ; Central Nervous System Viral Diseases/*complications ; Drug-Related Side Effects and Adverse Reactions ; Enterovirus Infections/complications ; Female ; Humans ; Male ; Middle Aged ; Motor Neuron Disease/epidemiology/physiopathology/*virology ; Neoplasms/radiotherapy ; Poliomyelitis/complications ; Radiation Dosage ; Radiotherapy/*adverse effects ; Reaction Time/physiology/radiation effects ; Sex Factors ; }, abstract = {OBJECTIVE: To investigate the pathogenesis of the rare radiogenic lower motor neurone disease (LMND) on the basis of a meta-analysis of the published case histories.<br><br>MATERIALS AND METHODS: The authors reviewed 47 well-documented radiogenic LMND cases from the English literature.<br><br>RESULTS: The disease typically occurs following the irradiation of radiosensitive cancers situated near the spinal cord. It arises predominantly (46 cases) in the lower extremities; only one case involved the upper extremities. There is a male predominance (male:female ratio 7.8:1), and the patients are characteristically young (13-40 years, with four exceptions). An overdose does not seem to be a particular risk factor for the development of the disease, as total dose, fraction size and biologically effective dose are typically below 50 Gy, 2 Gy and 128 Gy2, respectively, which are regarded as safe doses. Other risk factors (chemotherapy, operations, etc) have been identified only rarely. Radiogenic LMND is manifested in an apparently random manner, 4-312 (mean 48.7) months after the completion of radiotherapy.<br><br>DISCUSSION: The complete lack of a dose-effect relationship argues strongly against a pure radiogenic nature of the pathological process. The latency period is typically several years and it varies extremely, which excludes a direct and complete causal relationship between radiotherapy and LMND. As the interaction of ionizing radiation with living tissues is highly unspecific, thus a selective motor injury due to irradiation alone, without comparable effects on the sensory and vegetative fibers, seems improbable.<br><br>CONCLUSIONS: On analogy with the viral motor neurone diseases, we suppose that radiogenic LMND may be preceded by viral (enterovirus/poliovirus) infection. Based on the meta-analysis, it is suggested that irradiation may be only a single component of the set of factors jointly resulting in the clinical state regarded as radiogenic LMND.}, }
@article {pmid12847526, year = {2003}, author = {Lambrechts, D and Storkebaum, E and Morimoto, M and Del-Favero, J and Desmet, F and Marklund, SL and Wyns, S and Thijs, V and Andersson, J and van Marion, I and Al-Chalabi, A and Bornes, S and Musson, R and Hansen, V and Beckman, L and Adolfsson, R and Pall, HS and Prats, H and Vermeire, S and Rutgeerts, P and Katayama, S and Awata, T and Leigh, N and Lang-Lazdunski, L and Dewerchin, M and Shaw, C and Moons, L and Vlietinck, R and Morrison, KE and Robberecht, W and Van Broeckhoven, C and Collen, D and Andersen, PM and Carmeliet, P}, title = {VEGF is a modifier of amyotrophic lateral sclerosis in mice and humans and protects motoneurons against ischemic death.}, journal = {Nature genetics}, volume = {34}, number = {4}, pages = {383-394}, doi = {10.1038/ng1211}, pmid = {12847526}, issn = {1061-4036}, mesh = {Aged ; Alleles ; Amyotrophic Lateral Sclerosis/drug therapy/etiology/*genetics/pathology ; Animals ; Cell Death/drug effects ; Child ; Child, Preschool ; Endothelial Growth Factors/*genetics/physiology/therapeutic use ; Female ; Genetic Variation ; Haplotypes ; Humans ; Intercellular Signaling Peptides and Proteins/*genetics/physiology/therapeutic use ; Ischemia/pathology ; Lymphokines/*genetics/physiology/therapeutic use ; Male ; Mice ; Mice, Knockout ; Mice, Transgenic ; Middle Aged ; Motor Neurons/drug effects/pathology ; Nerve Degeneration/genetics ; Paralysis/etiology ; Spinal Cord Ischemia/drug therapy/pathology ; Sweden ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is an incurable degenerative disorder of motoneurons. We recently reported that reduced expression of Vegfa causes ALS-like motoneuron degeneration in Vegfa(delta/delta) mice. In a meta-analysis of over 900 individuals from Sweden and over 1,000 individuals from Belgium and England, we now report that subjects homozygous with respect to the haplotypes -2,578A/-1,154A/-634G or -2,578A/-1,154G/-634G in the VEGF promoter/leader sequence had a 1.8 times greater risk of ALS (P = 0.00004). These 'at-risk' haplotypes lowered circulating VEGF levels in vivo and reduced VEGF gene transcription, IRES-mediated VEGF expression and translation of a novel large-VEGF isoform (L-VEGF) in vivo. Moreover, SOD1(G93A) mice crossbred with Vegfa(delta/delta) mice died earlier due to more severe motoneuron degeneration. Vegfa(delta/delta) mice were unusually susceptible to persistent paralysis after spinal cord ischemia, and treatment with Vegfa protected mice against ischemic motoneuron death. These findings indicate that VEGF is a modifier of motoneuron degeneration in human ALS and unveil a therapeutic potential of Vegfa for stressed motoneurons in mice.}, }
@article {pmid12215224, year = {2002}, author = {Swash, M}, title = {Ethical standards for authors, and for the Journal of Amyotrophic Lateral Sclerosis and other motor neuron diseases.}, journal = {Amyotrophic lateral sclerosis and other motor neuron disorders : official publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases}, volume = {3}, number = {2}, pages = {53}, doi = {10.1080/146608202760195995}, pmid = {12215224}, issn = {1466-0822}, mesh = {*Codes of Ethics ; Humans ; Periodicals as Topic/*standards ; }, }
@article {pmid11313167, year = {2001}, author = {, }, title = {Clinical investigation of medicinal products for treatment of amyotrophic lateral sclerosis (ALS).}, journal = {European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology}, volume = {11}, number = {2}, pages = {187-189}, doi = {10.1016/s0924-977x(01)00067-0}, pmid = {11313167}, issn = {0924-977X}, mesh = {Amyotrophic Lateral Sclerosis/diagnosis/*drug therapy ; Neuroprotective Agents/pharmacokinetics/*therapeutic use ; Research Design ; }, }
@article {pmid11278085, year = {2001}, author = {de Latorre, F and Nolan, J and Robertson, C and Chamberlain, D and Baskett, P and , }, title = {European Resuscitation Council Guidelines 2000 for Adult Advanced Life Support. A statement from the Advanced Life Support Working Group(1) and approved by the Executive Committee of the European Resuscitation Council.}, journal = {Resuscitation}, volume = {48}, number = {3}, pages = {211-221}, doi = {10.1016/s0300-9572(00)00379-8}, pmid = {11278085}, issn = {0300-9572}, mesh = {Adult ; Advanced Cardiac Life Support/*methods ; Airway Obstruction/therapy ; Algorithms ; Atrial Fibrillation/therapy ; Bradycardia/therapy ; Electric Countershock/methods ; Heart Arrest/therapy ; Humans ; Intubation, Intratracheal/methods ; Risk Assessment ; }, abstract = {The European Resuscitation Council (ERC) last issued guidelines for Basic Life Support (BLS) in 1998 [1]. These were based on the 1997 International Liaison Committee on Resuscitation (ILCOR) Advisory Statements [2]. In 1999 and 2000 representatives of ILCOR, at the invitation of the American Heart Association, met on a number of occasions in Dallas to agree a Consensus on Science upon which future guidelines would be based. Representatives from the ERC played a prominent role in the deliberations, which culminated in the publication of "Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care--A Consensus on Science" in August 2000 [3]. The consensus was evidence-based wherever possible. The ERC ALS Working Group has considered this document and has recommended some changes in the guidelines that will be suitable for European practice. These changes, together with a summary of the Sequence of Actions in ALS, are presented in this paper.}, }
@article {pmid11170123, year = {2001}, author = {Ahlbom, A}, title = {Neurodegenerative diseases, suicide and depressive symptoms in relation to EMF.}, journal = {Bioelectromagnetics}, volume = {Suppl 5}, number = {}, pages = {S132-43}, doi = {10.1002/1521-186x(2001)22:5+&lt;::aid-bem1029&gt;3.3.co;2-m}, pmid = {11170123}, issn = {0197-8462}, mesh = {Alzheimer Disease/epidemiology/etiology ; Amyotrophic Lateral Sclerosis/epidemiology/etiology ; Depression/epidemiology/*etiology ; Electromagnetic Fields/*adverse effects ; Humans ; Neurodegenerative Diseases/epidemiology/*etiology ; *Suicide ; }, abstract = {In 1979 the first study was published which indicated that environmental exposure to power frequency, electric and magnetic fields (EMF), might increase the risk of chronic disease. This was a study on cancer. However, this research area has gradually evolved and come also to include outcomes other than cancer. The purpose of this paper is to provide a better understanding of the literature on neurodegenerative diseases and on suicide and depressive symptoms in relation to EMF by using a meta-analysis technique. It is concluded that for amyotrophic lateral sclerosis, there are relatively strong data indicating that electric utility work may be associated with an increased risk. However, EMF exposure is only one of several possible explanations to this. For Alzheimer's disease the combined data on an association with EMF are weaker than that for ALS. For suicide an overall assessment yields the conclusion that the support for an association is weak. For depressive symptoms the assessment is more complex, but the overall conclusion is nevertheless that the evidence is relatively weak. For other diseases, such as Parkinson's, there is not enough information for an assessment.}, }
@article {pmid11129395, year = {2000}, author = {Mitchell, SL and Tetroe, JM}, title = {Survival after percutaneous endoscopic gastrostomy placement in older persons.}, journal = {The journals of gerontology. Series A, Biological sciences and medical sciences}, volume = {55}, number = {12}, pages = {M735-9}, doi = {10.1093/gerona/55.12.m735}, pmid = {11129395}, issn = {1079-5006}, mesh = {Aged ; Aging/*physiology ; Cohort Studies ; *Endoscopy, Gastrointestinal ; *Enteral Nutrition/instrumentation ; *Gastrostomy ; Humans ; Polyethylene Glycols ; Survival Analysis ; }, abstract = {BACKGROUND: The prolongation of life is an important consideration in the decision to initiate long-term tube feeding. This report critically synthesizes the evidence regarding the impact of percutaneous endoscopic gastrostomy (PEG) tube placement on survival in older persons.<br><br>METHODS: A systematic search was conducted using MEDLINE from January 1980 until January 1999. Articles reporting survival data in older persons (mean or median age >65 years) after PEG tube placement were identified. The number and age of subjects, length of follow-up, setting, and survival data were extracted from all eligible studies. Mortality data at 1, 2, 6, and 12 months after PEG placement were quantitatively synthesized. Clinical characteristics associated with decreased survival among subjects with PEG tubes were identified.<br><br>RESULTS: Five cohort studies compared survival in patients with and without feeding tubes in nursing homes, but none demonstrated a survival benefit. Another cohort study reported increased survival for tube-fed patients with amyotrophic lateral sclerosis. The pooled proportion of all subjects surviving after PEG placement was as follows: 1 month = 0.81 (95% confidence interval [CI], 0.74-0.88), 2 months = 0.70 (95% CI, 0.65-0.74), 6 months = 0.56 (95% CI, 0.20-0.92), and 12 months = 0.38 (95% CI, 0.26-0.49). Advanced age and malignancy were the factors most often reported to be associated with poorer survival among subjects with PEG tubes.<br><br>CONCLUSIONS: The impact of PEG placement on survival is not known because the level of evidence is limited. PEG tubes may prolong life in selected populations. However, the majority of older patients selected for PEG placement will not survive 1 year after the procedure. Certain factors may identify those patients more likely to derive a survival benefit from long-term tube feeding. This information may offer some guidance to decision makers for whom prolongation of life is an important factor in the tube-feeding decision.}, }
@article {pmid11038074, year = {2000}, author = {Liberman, M and Mulder, D and Sampalis, J}, title = {Advanced or basic life support for trauma: meta-analysis and critical review of the literature.}, journal = {The Journal of trauma}, volume = {49}, number = {4}, pages = {584-599}, doi = {10.1097/00005373-200010000-00003}, pmid = {11038074}, issn = {0022-5282}, mesh = {Emergency Medical Services/*methods ; Emergency Treatment/*methods ; Gravity Suits ; Humans ; Infusions, Intravenous ; Intubation, Intratracheal ; Multivariate Analysis ; Odds Ratio ; Survival Rate ; Time Factors ; Treatment Outcome ; Wounds and Injuries/mortality ; }, abstract = {BACKGROUND: The question of whether to use advanced life support (ALS) or basic life support (BLS) for trauma patients in the prehospital setting has been much debated and still lacks a clear answer. The purpose of this study was to conduct a comprehensive critical review of the literature regarding this controversy<br><br>METHODS: A total of 174 articles on prehospital ALS or BLS for trauma were reviewed. Fifteen of these studies were found to involve mortality statistics for both ALS- and BLS-treated patients. Odds ratios were calculated for survival in ALS versus BLS and summarized across studies on the basis of multivariate scoring systems that incorporated both design and methodological assessment. Overall odds ratios for all studies were calculated on the basis of both raw data from the papers, and weighted odds ratios were calculated from the scoring systems.<br><br>RESULTS: Six studies were scored as being methodologically average (5 favoring BLS and 1 favoring ALS), two were scored as good (1 favoring BLS and 1 favoring ALS), seven as excellent (6 favoring BLS and 1 favoring ALS). Ten studies had an average study design score (6 favoring BLS and 4 favoring ALS) and seven had a good study design score (6 favoring BLS and 1 favoring ALS). Weighted odds ratio for dying was 2.59 for patients receiving ALS compared with those receiving BLS. The crude odds ratio was 2.92.<br><br>CONCLUSION: The aggregated data in the literature have failed to demonstrate a benefit for on-site ALS provided to trauma patients and support the scoop and run approach.}, }
@article {pmid10417794, year = {1999}, author = {Miller, RG and Rosenberg, JA and Gelinas, DF and Mitsumoto, H and Newman, D and Sufit, R and Borasio, GD and Bradley, WG and Bromberg, MB and Brooks, BR and Kasarskis, EJ and Munsat, TL and Oppenheimer, EA}, title = {Practice parameter: The care of the patient with amyotrophic lateral sclerosis (An evidence-based review).}, journal = {Muscle &amp; nerve}, volume = {22}, number = {8}, pages = {1104-1118}, doi = {10.1002/(sici)1097-4598(199908)22:8&lt;1104::aid-mus15&gt;3.0.co;2-2}, pmid = {10417794}, issn = {0148-639X}, mesh = {*Amyotrophic Lateral Sclerosis ; Humans ; Quality of Life ; }, }
@article {pmid10227612, year = {1999}, author = {Miller, RG and Rosenberg, JA and Gelinas, DF and Mitsumoto, H and Newman, D and Sufit, R and Borasio, GD and Bradley, WG and Bromberg, MB and Brooks, BR and Kasarskis, EJ and Munsat, TL and Oppenheimer, EA}, title = {Practice parameter: the care of the patient with amyotrophic lateral sclerosis (an evidence-based review) [RETIRED]: report of the Quality Standards Subcommittee of the American Academy of Neurology: ALS Practice Parameters Task Force.}, journal = {Neurology}, volume = {52}, number = {7}, pages = {1311-1323}, doi = {10.1212/wnl.52.7.1311}, pmid = {10227612}, issn = {0028-3878}, mesh = {*Amyotrophic Lateral Sclerosis ; *Palliative Care ; Quality of Life ; }, }
@article {pmid9305318, year = {1997}, author = {}, title = {Practice advisory on the treatment of amyotrophic lateral sclerosis with riluzole: report of the Quality Standards Subcommittee of the American Academy of Neurology [RETIRED].}, journal = {Neurology}, volume = {49}, number = {3}, pages = {657-659}, doi = {10.1212/wnl.49.3.657}, pmid = {9305318}, issn = {0028-3878}, mesh = {Amyotrophic Lateral Sclerosis/*drug therapy ; Clinical Trials as Topic ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Excitatory Amino Acid Antagonists/administration &amp; dosage/*therapeutic use ; Humans ; Neurology ; Riluzole ; Societies, Medical ; Thiazoles/administration &amp; dosage/*therapeutic use ; Treatment Outcome ; }, }
@article {pmid9141155, year = {1997}, author = {Kloeck, W and Cummins, R and Chamberlain, D and Bossaert, L and Callanan, V and Carli, P and Christenson, J and Connolly, B and Ornato, J and Sanders, A and Steen, P}, title = {The Universal ALS algorithm. An advisory statement by the Advanced Life Support Working Group of the International Liaison Committee on Resuscitation.}, journal = {Resuscitation}, volume = {34}, number = {2}, pages = {109-111}, doi = {10.1016/s0300-9572(97)01100-3}, pmid = {9141155}, issn = {0300-9572}, mesh = {*Algorithms ; Humans ; *Life Support Care ; *Resuscitation ; }, }
@article {pmid8797493, year = {1996}, author = {}, title = {Assessment of plasmapheresis. Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.}, journal = {Neurology}, volume = {47}, number = {3}, pages = {840-843}, pmid = {8797493}, issn = {0028-3878}, mesh = {Humans ; Nervous System Diseases/*therapy ; *Plasmapheresis ; }, abstract = {Based on the review of the literature, therapeutic PP has a definite role in the treatment of patients with GBS, CIDP, polyneuropathies associated with MGUS, MG, and LEMS (table). PP may have a role in treating patients with Refsum's disease, acquired neuromyotonia, stiff-man syndrome, cryoglobulinemic polyneuropathy, CNS-SLE, ADEM, and MS, but these decisions should be made on a case-by-case basis. PP has no role in treating patients with ALS or paraneoplastic syndromes with circulating autoantibodies.}, }
@article {pmid8868814, year = {1996}, author = {Leslie, GD}, title = {A position statement on resuscitation by all levels of nurse. Confederation of Australian Critical Care Nurses Inc.}, journal = {Australian critical care : official journal of the Confederation of Australian Critical Care Nurses}, volume = {9}, number = {2}, pages = {48}, doi = {10.1016/s1036-7314(96)70349-1}, pmid = {8868814}, issn = {1036-7314}, mesh = {Australia ; *Critical Care ; Humans ; Life Support Care/*methods ; Resuscitation/education/*nursing ; Societies, Nursing ; }, abstract = {As part of its brief, the CACCN Inc. Advanced Life Support (ALS) Subcommittee has been reviewing and compiling a national policy for education in ALS for nurses. We believe this is an appropriate pursuit, since critical care nurses are at the forefront of practice in this area and also care for patients receiving life-saving interventions. One of the Subcommittee's concerns is the lack of a uniform approach to the issue of resuscitation across the nursing community, despite the broad applicability of such skills to many of the diverse settings in which nurses practice. The following is a position statement aimed at setting a precedent for both Basic and Advanced Life Support practice and education in the Australian nursing context. We have distributed the statement widely to stimulate debate and, eventually, a broader acceptance of this competency for nurses. We look forward to your comments.}, }
@article {pmid7644057, year = {1995}, author = {van Schaik, IN and Bossuyt, PM and Brand, A and Vermeulen, M}, title = {Diagnostic value of GM1 antibodies in motor neuron disorders and neuropathies: a meta-analysis.}, journal = {Neurology}, volume = {45}, number = {8}, pages = {1570-1577}, doi = {10.1212/wnl.45.8.1570}, pmid = {7644057}, issn = {0028-3878}, mesh = {Antibodies/*analysis ; G(M1) Ganglioside/*immunology ; Humans ; Immunoglobulin M/analysis ; Motor Neuron Disease/*diagnosis/*immunology ; Nervous System Diseases/*diagnosis/*immunology ; }, abstract = {We performed a meta-analysis on the diagnostic value of IgM anti-GM1 antibodies. The reported frequencies of IgM anti-GM1 antibodies ranged from 0 to 100% for patients with multifocal motor neuropathy (MMN), from 0 to 33% in the Guillain-Barré syndrome, from 0 to 65% in amyotrophic lateral sclerosis (ALS), from 0 to 77% in chronic inflammatory demyelinating neuropathy, and from 0 to 81% in lower motor neuron disease (LMND). However, using funnel graphs and a chi-square test we determined that the method of ELISA was the most important factor explaining these differences. After allowing for two factors--the use of detergent and the duration and temperature of serum incubation-studies became homogeneous in all but the LMND group of method A (no detergent, duration of serum incubation 5 hours) and the ALS group of method B (no detergent, duration of serum incubation at least 12 hours [overnight]). Since the anti-GM1 antibody assay serves to confirm clinical suspicion of MMN rather than to exclude the disease, specificity is more important than sensitivity. ELISA methods that do not use detergent and that incubate serum overnight resulted in a specificity of 90% and sensitivity of 38% in the comparison of MMN and LMND. With these values we calculated incremental ruling-in and ruling-out gain curves. Prior probabilities between 20 and 60% for having MMN changed to post-test probabilities between 50 and 85%, which is of clinical importance. In conclusion, ELISA is a useful diagnostic test to demonstrate IgM anti-GM1 antibodies provided the methods do not use detergent and do incubate serum overnight.}, }
@article {pmid7812703, year = {1994}, author = {Stephens, RJ and Girling, DJ and Machin, D}, title = {Treatment-related deaths in small cell lung cancer trials: can patients at risk be identified? Medical Research Council Lung Cancer Working Party.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {11}, number = {3-4}, pages = {259-274}, doi = {10.1016/0169-5002(94)90546-0}, pmid = {7812703}, issn = {0169-5002}, mesh = {Aged ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Carcinoma, Small Cell/*mortality/*therapy ; Clinical Trials, Phase II as Topic ; Combined Modality Therapy ; Humans ; Lung Neoplasms/*mortality/*therapy ; Middle Aged ; Prognosis ; Proportional Hazards Models ; Radiotherapy/adverse effects ; Randomized Controlled Trials as Topic/*adverse effects ; Risk Factors ; Surgical Procedures, Operative/adverse effects ; }, abstract = {OBJECTIVES: This paper investigates the problem of treatment-related deaths in small cell lung cancer (SCLC).<br><br>DESIGN: To observe and define increased hazard levels, and to identify factors relating to these excess deaths.<br><br>SETTING: The United Kingdom.<br><br>SUBJECTS: A total of 2196 patients entered into the series of six randomised clinical trials in SCLC conducted by the Medical Research Council (MRC) Lung Cancer Working Party (LCWP).<br><br>RESULTS: In this large series of patients an increased risk of death in the second week after commencing the first cycle of chemotherapy was observed, suggesting that of the 10% of patients who died within 3 weeks of starting chemotherapy, half may have been treatment-related. Much less additional risk was associated with subsequent cycles of chemotherapy, and no additional risk with either initial surgery or radiotherapy. Radford et al. [Eur J Cancer 1993; 29A: 81-86] suggested that the risk factors for death from sepsis were a Karnofsky Performance (KP) score of < or = 50 (translated as a WHO performance grade (PS) > or = 3), age > 50 years and three or more drugs in the chemotherapy regimen utilised. Starting with this model we found that our data suggest it can be refined by omitting age and including a white blood cell count > or = 10,000/mm3 (this variable was not tested by Radford), and changing the other categories to WHO PS > or = 2 (KP < or = 70), and four or more drugs. Within our data this revised model identified a high risk group of patients with an excess death rate of more than 15% in the second week after starting chemotherapy. Radford et als' suggestion that high risk patients be given half doses of drugs at the first cycle should be tested in a randomised clinical trial.}, }
@article {pmid1549146, year = {1992}, author = {}, title = {Guidelines in electrodiagnostic medicine. American Association of Electrodiagnostic Medicine.}, journal = {Muscle &amp; nerve}, volume = {15}, number = {2}, pages = {229-253}, doi = {10.1002/mus.880150218}, pmid = {1549146}, issn = {0148-639X}, mesh = {*Electrodiagnosis ; *Electromyography ; Ethics, Medical ; Humans ; Muscular Diseases/diagnosis ; Nervous System Diseases/diagnosis ; Neuromuscular Diseases/diagnosis ; Referral and Consultation ; *Societies, Medical ; United States ; }, abstract = {The American Association of Electrodiagnostic Medicine (AAEM) is committed to the development of sound and clinically relevant guidelines through review of literature, expert opinion and consensus. In 1979, with the assistance of its Professional Practice Committee and association leaders, the association published its initial guidelines, Guidelines in Electrodiagnostic Medicine, covering the practice of electrodiagnostic medicine. The committee is charged with ongoing revision of the document, as needed, and the current version includes standards of practice in clinical electromyography, risks in electrodiagnostic medicine, basic equipment requirements, and the role of paramedical support. In 1988, Educational Guidelines for Electrodiagnostic Training Programs (Appendix A) was prepared by the AAEM Training Program Committee and added to aid training program directors in establishing new training programs or in reviewing the current status of the educational aspects of existing programs. In 1986, the AAEM charged its Quality Assurance Committee with the responsibility for the development of guidelines pertinent to electrodiagnostic medical consultations. The impetus for the charge was the requests received from members of the AAEM and other interested parties for educational material on indications for and conduct of electrodiagnostic medical consultations. As a result of the committee's efforts, Suggested Guidelines for Electrodiagnostic Medical Consultations (Appendix D), was published in 1989 and additional sections added subsequently. The current document includes (1) general indications for an electrodiagnostic medical consultation for patients with suspected myopathies, neuromuscular junction disorders, polyneuropathies, mononeuropathies, plexopathies, radiculopathies, neuronopathies and central nervous system disorders, (2) specific indications for patients with suspected lumbosacral or cervical radiculopathies, (3) general principles of electrodiagnostic studies, including techniques and diagnostic categories, and (4) an overview of electrodiagnostic studies for patients with suspected carpal tunnel syndrome, idiopathic polyneuritis, amyotrophic lateral sclerosis and myasthenia gravis.}, }
@article {pmid20873123, year = {2010}, author = {Wegielnik, J and Dabrowski, S and Medrzycka-Dabrowska, W and Basiński, A and , }, title = {[Cardiopulmonary resuscitation in pregnancy--European Resuscitation Council guidelines].}, journal = {Ginekologia polska}, volume = {81}, number = {8}, pages = {606-612}, pmid = {20873123}, issn = {0017-0011}, mesh = {Adult ; Advanced Cardiac Life Support/standards ; Cardiopulmonary Resuscitation/education/*standards ; Emergency Medical Services/*standards ; Europe ; Female ; First Aid/*standards ; Heart Arrest/*prevention &amp; control ; Humans ; Poland ; Pregnancy ; Pregnancy Complications, Cardiovascular/*therapy ; Professional Competence ; Quality Assurance, Health Care/standards ; Young Adult ; }, abstract = {Cardio-pulmonary resuscitation is a life-saving technique that should be familiar to all people, even those without medical education. There are two basic life-saving levels: BLS (Basic Life Support) and ALS (Advanced Life Support). ALS a medical procedure that is restricted to medical practitioners. Cessation of circulation may happen to anyone. Cardiac arrest in case of pregnant women is a very specific state. The cause of life-threatening states during pregnancy can be connected with new infections, exacerbation of chronic diseases, as well as changes connected with the pregnancy itself. In those situations, due to physiological and anatomical changes which occur during pregnancy some modifications in the procedure of resuscitation are necessary}, }
@article {pmid20150676, year = {2010}, author = {Mahata, P}, title = {Exploratory consensus of hierarchical clusterings for melanoma and breast cancer.}, journal = {IEEE/ACM transactions on computational biology and bioinformatics}, volume = {7}, number = {1}, pages = {138-152}, doi = {10.1109/TCBB.2008.33}, pmid = {20150676}, issn = {1557-9964}, mesh = {*Algorithms ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*diagnosis/*metabolism ; Diagnosis, Computer-Assisted/*methods ; Gene Expression Profiling/methods ; Humans ; Melanoma/classification/*diagnosis/*metabolism ; Multigene Family ; Neoplasm Proteins/analysis ; }, abstract = {Finding subtypes of heterogeneous diseases is the biggest challenge in the area of biology. Often, clustering is used to provide a hypothesis for the subtypes of a heterogeneous disease. However, there are usually discrepancies between the clusterings produced by different algorithms. This work introduces a simple method which provides the most consistent clusters across three different clustering algorithms for a melanoma and a breast cancer data set. The method is validated by showing that the Silhouette, Dunne's and Davies-Bouldin's cluster validation indices are better for the proposed algorithm than those obtained by k-means and another consensus clustering algorithm. The hypotheses of the consensus clusters on both the data sets are corroborated by clear genetic markers and 100 percent classification accuracy. In Bittner et al.'s melanoma data set, a previously hypothesized primary cluster is recognized as the largest consensus cluster and a new partition of this cluster into two subclusters is proposed. In van't Veer et al.'s breast cancer data set, previously proposed "basal" and "luminal A" subtypes are clearly recognized as the two predominant clusters. Furthermore, a new hypothesis is provided about the existence of two subgroups within the "basal" subtype in this data set. The clusters of van't Veer's data set is also validated by high classification accuracy obtained in the data set of van de Vijver et al.}, }
@article {pmid19506136, year = {2009}, author = {Gordon, PH and Corcia, P and Lacomblez, L and Pochigaeva, K and Abitbol, JL and Cudkowicz, M and Leigh, PN and Meininger, V}, title = {Defining survival as an outcome measure in amyotrophic lateral sclerosis.}, journal = {Archives of neurology}, volume = {66}, number = {6}, pages = {758-761}, doi = {10.1001/archneurol.2009.1}, pmid = {19506136}, issn = {1538-3687}, mesh = {Amyotrophic Lateral Sclerosis/complications/drug therapy/*mortality ; Clinical Trials as Topic/*methods/standards/statistics &amp; numerical data ; Endpoint Determination/*methods ; Humans ; Kaplan-Meier Estimate ; Naphthalenes/administration &amp; dosage/adverse effects ; Outcome Assessment, Health Care/*methods ; Pentoxifylline/administration &amp; dosage/adverse effects ; Pyridines/administration &amp; dosage/adverse effects ; Respiration, Artificial/mortality/statistics &amp; numerical data ; Respiratory Paralysis/drug therapy/etiology/*mortality ; Tracheostomy/mortality/statistics &amp; numerical data ; Vasodilator Agents/administration &amp; dosage/adverse effects ; }, abstract = {OBJECTIVES: To examine how respiratory interventions affect survival as an outcome measure and to define survival rate for trials in amyotrophic lateral sclerosis.<br><br>DESIGN AND SETTING: We reviewed the data of 3 phase 3 clinical trials and examined differences in times to death, tracheostomy, and permanent assisted ventilation. We assessed the outcomes with chi(2) and Fisher exact tests for categorical variables and unpaired, 2-tailed t tests for continuous variables. We used Kaplan-Meier methods to estimate the differences in survival times between interventions. A power analysis generated sample size estimates for different end points.<br><br>PATIENTS: In all, 2077 patients in 2 phase 3 trials of xaliproden and 400 patients in a phase 3 trial of pentoxifylline.<br><br>MAIN OUTCOME MEASURES: Death or combined death, tracheostomy, or permanent assisted ventilation.<br><br>RESULTS: Of 745 deaths, 611 (82.0%) were owing to respiratory failure and 134 (18.0%) to other causes. The use of respiratory interventions across centers ranged from 0% to 6.6% (P = .001) of patients for tracheostomy and 11.1% to 23.1% (P = .05) of patients for noninvasive ventilation. Twelve of 55 patients (21.8%) undergoing tracheostomy had a vital capacity of 50% or more. Mean (SD) survival time was 457.9 (3.1) days using a combined end point and 467.2 (2.9) days with death alone as the outcome (P = .02). An estimated sample size to detect a 10% difference at 18 months between groups was 490 patients per arm for the combined end point and 410 patients for death alone.<br><br>CONCLUSIONS: Tracheostomy and permanent assisted ventilation are not equivalent to death in amyotrophic lateral sclerosis. The use of respiratory interventions differs between centers, leading to variability in combined outcome assessments. The time to the end point can differ significantly depending on its definition, and combining outcomes does not reduce the estimated sample size of a trial. The death rate alone is the least variable and most easily identifiable measure of survival rate in amyotrophic lateral sclerosis.}, }
@article {pmid19212735, year = {2009}, author = {Nolan, J and , }, title = {[Resuscitation techniques for adults (ALS). Section 4 of the Guidelines for Resuscitation 2005 of the European Resuscitation Council].}, journal = {Der Unfallchirurg}, volume = {112}, number = {2}, pages = {102-138}, doi = {10.1007/s00113-009-1583-4}, pmid = {19212735}, issn = {1433-044X}, mesh = {Adult ; Germany ; Humans ; Resuscitation/*standards ; }, }
@article {pmid18413368, year = {2009}, author = {Lambrechts, D and Poesen, K and Fernández-Santiago, R and Al-Chalabi, A and Del Bo, R and Van Vught, PW and Khan, S and Marklund, SL and Brockington, A and van Marion, I and Anneser, J and Shaw, C and Ludolph, AC and Leigh, NP and Comi, GP and Gasser, T and Shaw, PJ and Morrison, KE and Andersen, PM and Van den Berg, LH and Thijs, V and Siddique, T and Robberecht, W and Carmeliet, P}, title = {Meta-analysis of vascular endothelial growth factor variations in amyotrophic lateral sclerosis: increased susceptibility in male carriers of the -2578AA genotype.}, journal = {Journal of medical genetics}, volume = {46}, number = {12}, pages = {840-846}, doi = {10.1136/jmg.2008.058222}, pmid = {18413368}, issn = {1468-6244}, mesh = {Amyotrophic Lateral Sclerosis/*genetics/pathology ; Animals ; Disease Models, Animal ; Genetic Predisposition to Disease ; Heterozygote ; Humans ; Male ; Mice ; Motor Neurons/pathology ; Polymorphism, Single Nucleotide ; Sex Factors ; Vascular Endothelial Growth Factor A/*genetics ; }, abstract = {BACKGROUND: Targeted delivery of the angiogenic factor, vascular endothelial growth factor (VEGF), to motor neurons prolongs survival in rodent models of amyotrophic lateral sclerosis (ALS), while mice expressing reduced VEGF concentrations develop motor neuron degeneration reminiscent of ALS, raising the question whether VEGF contributes to the pathogenesis of ALS. An initial association study reported that VEGF haplotypes conferred increased susceptibility to ALS in humans, but later studies challenged this initial finding.<br><br>METHODS AND FINDINGS: A meta-analysis was undertaken to critically reappraise whether any of the three common VEGF gene variations (-2578C/A, -1154G/A and -634G/C) increase the risk of ALS. Over 7000 subjects from eight European and three American populations were included in the analysis. Pooled odds ratios were calculated using fixed-effects and random-effects models, and four potential sources of heterogeneity (location of disease onset, gender, age at disease onset and disease duration) were assessed. After correction, none of the genotypes or haplotypes was significantly associated with ALS. Subgroup analysis by gender revealed, however, that the -2578AA genotype, which lowers VEGF expression, increased the risk of ALS in males (OR = 1.46 males vs females; 95% CI = 1.19 to 1.80; p = 7.8 10E-5), even after correction for publication bias and multiple testing.<br><br>CONCLUSIONS: This meta-analysis does not support the original conclusion that VEGF haplotypes increase the risk of ALS in humans, but the significant association of the low-VEGF -2578AA genotype with increased susceptibility to ALS in males reappraises the link between reduced VEGF concentrations and ALS, as originally revealed by the fortuitous mouse genetic studies.}, }
@article {pmid18065789, year = {2008}, author = {Labriola, L and Crott, R and Jadoul, M}, title = {Preventing haemodialysis catheter-related bacteraemia with an antimicrobial lock solution: a meta-analysis of prospective randomized trials.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {23}, number = {5}, pages = {1666-1672}, doi = {10.1093/ndt/gfm847}, pmid = {18065789}, issn = {1460-2385}, mesh = {Anti-Bacterial Agents/*administration &amp; dosage ; Bacteremia/etiology/*prevention &amp; control ; Catheters, Indwelling/*adverse effects/*microbiology ; Gentamicins/administration &amp; dosage ; Humans ; Prospective Studies ; Randomized Controlled Trials as Topic ; Renal Dialysis/*adverse effects/*methods ; Risk Factors ; Risk Reduction Behavior ; }, abstract = {BACKGROUND: Catheter-related bacteraemia (CRB) is a major cause of morbidity and mortality in haemodialysis patients. Interdialytic locking of catheters with antimicrobial agents has recently been investigated for the prevention of CRB. We performed a meta-analysis of randomized controlled trials (RCT) to determine the efficacy of antimicrobial lock solutions (ALS) in the prevention of CRB in haemodialysis patients.<br><br>METHODS: We collected from Medline, Web of Science, the Cochrane Library and major nephrology journals, all relevant references (January 1990-March 2007). We selected RCT comparing an ALS to a standard heparin lock in CRB prevention. We extracted data concerning study quality, patient characteristics and CRB incidence. The relative risk (RR) of CRB was calculated as Ln (CRB incidence control/CRB incidence experimental) using both a fixed- and a random-effects model.<br><br>RESULTS: Eight studies were included, involving 829 patients, 882 catheters and 90 191 catheter-days. The use of an ALS significantly decreased the risk of CRB (RR 0.32; 95% CI 0.10-0.42). Borderline heterogeneity was observed in the fixed-effects model (Q = 14.42; P = 0.071). Despite the under-representation of small negative studies, the high number of additional trials necessary to reverse the final effect strengthens the confidence in the overall results. Subgroup analyses stratified by the presence of diabetes, duration of follow-up, biochemical markers, proportion of tunnelled cuffed catheters, intranasal mupirocin use and citrate use in the ALS did not show significant differences, except a higher efficacy of gentamicin-containing lock solutions (P = 0.003).<br><br>CONCLUSIONS: The use of ALS reduces by about a factor 3 the risk of CRB in haemodialysis patients. The achieved absolute incidence is similar to the best-published figures (presumably related to stricter hygienic measures). The limited follow-up of the studies does not exclude the onset of adverse events or bacterial resistance with longer use of ALS.}, }
@article {pmid17828789, year = {2007}, author = {Ellervik, C and Birgens, H and Tybjaerg-Hansen, A and Nordestgaard, BG}, title = {Hemochromatosis genotypes and risk of 31 disease endpoints: meta-analyses including 66,000 cases and 226,000 controls.}, journal = {Hepatology (Baltimore, Md.)}, volume = {46}, number = {4}, pages = {1071-1080}, doi = {10.1002/hep.21885}, pmid = {17828789}, issn = {0270-9139}, mesh = {Case-Control Studies ; Endpoint Determination ; Genetic Predisposition to Disease ; *Genotype ; Hemochromatosis/*genetics ; Hemochromatosis Protein ; Heterozygote ; Histocompatibility Antigens Class I/genetics ; Humans ; Liver Diseases/etiology/*genetics ; Liver Neoplasms/etiology/*genetics ; Membrane Proteins/genetics ; Mutation/genetics ; Odds Ratio ; Risk Factors ; }, abstract = {UNLABELLED: Hemochromatosis genotypes have been associated with liver disease, diabetes mellitus, heart disease, arthritis, porphyria cutanea tarda, stroke, neurodegenerative disorders, cancer, and venous disease. We performed meta-analyses including 202 studies with 66,263 cases and 226,515 controls to examine associations between hemochromatosis genotypes C282Y/C282Y, C282Y/H63D, C282Y/wild type, H63D/H63D, and H63D/wild type versus wild type/wild type and 9 overall endpoints and 22 endpoint subgroups. We also explored potential sources of heterogeneity. For liver disease, the odds ratio for C282Y/C282Y versus wild type/wild type was 3.9 (99% confidence interval: 1.9-8.1) overall, 11 (3.7-34) for hepatocellular carcinoma, 4.1 (1.2-14) for hepatitis C, and 10 (2.1-53) for nonalcoholic steatohepatitis. For porphyria cutanea tarda, the odds ratios were 48 (24-95) for C282Y/C282Y, 8.1 (3.9-17) for C282Y/H63D, 3.6 (1.8-7.3) for C282Y/wild type, 3.0 (1.6-5.6) for H63D/H63D, and 1.7 (1.0-3.1) for H63D/wild type versus wild type/wild type. Finally, for amyotrophic lateral sclerosis, the odds ratio was 3.9 (1.2-13) for H63D/H63D versus wild type/wild type. These findings were consistent across individual studies. The hemochromatosis genotypes were not associated with risk for diabetes mellitus, heart disease, arthritis, stroke, cancer, or venous disease in the overall analyses; however, the odds ratio for C282Y/C282Y versus wild type/wild type was 3.4 (1.1-11) for diabetes mellitus among North Europeans.<br><br>CONCLUSION: In aggregate, clinically ascertained cases who are homozygous for the C282Y mutation are associated with a 4-11-fold risk of liver disease, whereas all 5 hemochromatosis genotypes are associated with a 2-48-fold risk of porphyria cutanea tarda, and H63D/H63D is associated with a 4-fold risk of amyotrophic lateral sclerosis. These results, mainly from case-control studies, cannot necessarily be extrapolated to the general population.}, }
@article {pmid17653919, year = {2007}, author = {Ludolph, AC and Bendotti, C and Blaugrund, E and Hengerer, B and Löffler, JP and Martin, J and Meininger, V and Meyer, T and Moussaoui, S and Robberecht, W and Scott, S and Silani, V and Van Den Berg, LH and , }, title = {Guidelines for the preclinical in vivo evaluation of pharmacological active drugs for ALS/MND: report on the 142nd ENMC international workshop.}, journal = {Amyotrophic lateral sclerosis : official publication of the World Federation of Neurology Research Group on Motor Neuron Diseases}, volume = {8}, number = {4}, pages = {217-223}, doi = {10.1080/17482960701292837}, pmid = {17653919}, issn = {1748-2968}, mesh = {Amyotrophic Lateral Sclerosis/*drug therapy ; Animals ; *Disease Models, Animal ; Drug Evaluation, Preclinical/*methods ; Humans ; Mice ; Mice, Transgenic ; Superoxide Dismutase/genetics ; }, abstract = {A transgenic animal model for anterior horn cell loss was established in 1994. This model is based on the insertion of a high copy number of disease-causing human Cu/Zn SOD mutations into the intact mouse genome. It serves to establish hypotheses for the pathogenesis of anterior horn cell death, but also to test potential pharmacological approaches to therapy in human ALS. Today, more than 100 -- published and unpublished -- compounds have been tested in this animal model, a large part of them being reported as successful. However, it proved to be difficult to translate these therapeutic successes in the animal model into human trials. Also, a number of disease-modifying strategies were difficult to reproduce, even by the same group. On the other hand, the step from mice to men means a huge investment for the sponsors of clinical trials and the scientific community. Therefore, establishment of standard methods for drug testing in ALS models is mandatory. In this workshop, clinical and preclinical researchers established in the field of ALS/MND met in Holland in March 2006 in order to establish guidelines for the community for drug testing in mouse models.}, }
@article {pmid17060069, year = {2006}, author = {Liversidge, HM and Chaillet, N and Mörnstad, H and Nyström, M and Rowlings, K and Taylor, J and Willems, G}, title = {Timing of Demirjian's tooth formation stages.}, journal = {Annals of human biology}, volume = {33}, number = {4}, pages = {454-470}, doi = {10.1080/03014460600802387}, pmid = {17060069}, issn = {0301-4460}, mesh = {Adolescent ; Aging/*physiology ; Asia ; Australia ; Canada ; Child ; Child, Preschool ; Europe ; Female ; Humans ; Male ; Sex Characteristics ; Time Factors ; Tooth/anatomy &amp; histology/*growth &amp; development ; }, abstract = {BACKGROUND: Global differences in Demirjian et al.'s method of assessing dental maturity are thought to be due to population differences.<br><br>AIM: The aim of this study was to investigate the timing of individual tooth formation stages in children from eight countries.<br><br>RESEARCH DESIGN: This was a meta-analysis of previously published data from retrospective cross-sectional studies of dental maturity.<br><br>METHOD: Data of mandibular permanent developing teeth from panoramic radiographs (Demirjian's stages) were combined from Australia, Belgium, Canada, England, Finland, France, South Korea and Sweden (n = 9002, ages 2-16.99 years). Age-of-attainment was calculated using logistic regression for each group by sex and meta-analysis of the total. Overlapping 95% confidence intervals of the means was interpreted as no significant difference.<br><br>RESULTS: Mean ages for each group and total were significantly different in 65 out of 509 comparisons (p < 0.05). Some of these were of small sample size but there was no consistent pattern. Apex closure of the first molar was significantly later in children from Quebec and this might explain differences found in the dental maturity score.<br><br>CONCLUSIONS: These results suggest no major differences in the timing of tooth formation stages between these children. This fails to explain previous findings of differences using Demirjian's dental maturity method.}, }
@article {pmid1718581, year = {1991}, author = {Brooks, BR}, title = {The role of axonal transport in neurodegenerative disease spread: a meta-analysis of experimental and clinical poliomyelitis compares with amyotrophic lateral sclerosis.}, journal = {The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques}, volume = {18}, number = {3 Suppl}, pages = {435-438}, doi = {10.1017/s0317167100032625}, pmid = {1718581}, issn = {0317-1671}, mesh = {Amyotrophic Lateral Sclerosis/*physiopathology ; Axonal Transport/*physiology ; Follow-Up Studies ; Humans ; Meta-Analysis as Topic ; Poliomyelitis/*physiopathology ; Sex Factors ; Time Factors ; }, abstract = {ALS symptom spread results from local spread of the neuronal degeneration because contiguous areas are more quickly involved than non-contiguous areas. Local spread to contiguous areas of motor neuron dysfunction is faster at the brainstem, cervical and lumbar regions than spread to non-contiguous areas. The time for caudal-rostral symptomatic spread of ALS to involve a distant region is a function of the distance of that region from the site of onset. The time for spread to the bulbar region is shorter following arm onset than leg onset. Spread to non-contiguous areas is faster within the spinal cord than from the spinal cord to the bulbar region. These kinetics are consistent with axonal transport of the etiological agent in a manner similar to spread of poliovirus in poliomyelitis patients. Spread from the bulbar region to the spinal cord, on the other hand, occurs faster than symptom spread from the limb region to the bulbar region in limb onset patients. This rapid limb involvement following bulbar onset is more dramatic in males compared with females. Females with leg onset, on the other hand, show more rapid involvement of the opposite leg, either arm or bulbar structures than males. Gender effects may determine the course of ALS depending on the original site of onset.}, }
@article {pmid17128083, year = {2006}, author = {}, title = {[Proceedings of the Consensus Conference on Amyotrophic Lateral Sclerosis, 23-24 November 2005, Nice, France].}, journal = {Revue neurologique}, volume = {162 Spec No 2}, number = {}, pages = {4S11-391}, pmid = {17128083}, issn = {0035-3787}, mesh = {*Amyotrophic Lateral Sclerosis/therapy ; Humans ; }, }
@article {pmid41546910, year = {2026}, author = {Elyasi, L and Wężyk, M}, title = {Exosome-derived microRNAs from stem cells from human exfoliated deciduous teeth (SHED): Emerging therapeutics for neurodegenerative disorders.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {195}, number = {}, pages = {119001}, doi = {10.1016/j.biopha.2026.119001}, pmid = {41546910}, issn = {1950-6007}, abstract = {Neurodegenerative diseases (NDDs) cause progressive damage of brain structures, resulting in a loss of function and, eventually, the patient's death. Current therapeutic strategies are limited to late stages of the disease, culminating in palliative care, while tackling the underlying causes of neurodegeneration could halt or at least slow down the disease at an early stage. In this vein, stem cell transplantation therapies are emerging as a promising alternative, as such as cells can penetrate the central nervous system, engraft, differentiate, and secrete neurotrophic, neuro-regenerative, and neuroprotective factors. Stem cells derived from human exfoliated deciduous teeth (SHED) have demonstrated significant regenerative potential in various biological systems and pathological conditions, showing high proliferative capacity and multipotency to differentiate into neuronal cells both in vivo and in vitro, apparently functioning through exosome-derived microRNAs (exos-miRs). Here, we summarize recent reports on specific miRs from SHED's exosomes, which exert diverse regulatory functions counteracting oxidative stress, and provide immunomodulatory and neurotrophic benefits contributing to the treatment of neurodegeneration in NDDs. We discuss clinical and preclinical evidence supporting the potential of SHED cells in the treatment of NDDs, including Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), spinal cord injury, focal cerebral ischemia, and peripheral nerve damage. We also highlight that the use of SHED in NDDs treatment remains largely underexplored, opening a wide field for further research. We suggest deeper studies on the role of SHED-exos-miRs in NDDs, including their proneurotrophic activity, reduction of genotoxic neuronal stress, and disruption of proinflammatory signaling pathways.}, }
@article {pmid41538578, year = {2026}, author = {Khan, M and Saeed, U and Piracha, ZZ and Ozsahin, I and Shao-Chun, C}, title = {Innovative public-health strategies for neurodegenerative disease: leveraging diversified ultraviolet irradiation as a next-generation therapy.}, journal = {Brazilian journal of biology = Revista brasleira de biologia}, volume = {85}, number = {}, pages = {e297765}, doi = {10.1590/1519-6984.297765}, pmid = {41538578}, issn = {1678-4375}, mesh = {Humans ; *Neurodegenerative Diseases/radiotherapy/therapy ; *Ultraviolet Therapy/methods ; *Ultraviolet Rays ; *Public Health ; Oxidative Stress/radiation effects ; }, abstract = {Neurodegenerative diseases (NDs) such as Alzheimer's, Parkinson's, Huntington's disease, and amyotrophic lateral sclerosis are escalating worldwide, straining healthcare systems and leaving patients with therapies that are largely palliative. Emerging evidence positions diversified ultraviolet (UV) irradiation as a groundbreaking, non-invasive strategy to counter these disorders. Beyond its traditional use in sterilization, specific UV spectra, UV-B (280-320 nm), UV-C (200-280 nm), and far-UV (207-222 nm), are now recognized for modulating oxidative stress, restoring mitochondrial function, correcting apoptotic dysregulation, and enhancing DNA repair. Innovative approaches such as riboflavin-mediated phototherapy and photobiomodulation (PBM) show the capacity to disaggregate toxic protein aggregates like β-amyloid and α-synuclein, boost antioxidant defenses, stimulate neurotrophic factors, and quell neuroinflammation. Preclinical models and early clinical trials reveal preserved cognition, enhanced neurogenesis, and reduced disease biomarkers, suggesting real translational promise. From a public-health perspective, UV-based interventions offer a cost-effective, scalable option for aging populations and resource-limited settings, especially when integrated with community-level health technologies and remote delivery platforms. Continued investigation of optimal dosing, long-term safety, and mechanistic pathways will be pivotal to unlock the full therapeutic and population-wide impact of this novel modality.}, }
@article {pmid41534661, year = {2026}, author = {Costa, I and Barbosa, DJ and Remião, F and Sousa, ME and Silva, R}, title = {A dive into the untapped potential of marine compounds in counteracting neurodegeneration.}, journal = {Pharmacology &amp; therapeutics}, volume = {}, number = {}, pages = {108982}, doi = {10.1016/j.pharmthera.2026.108982}, pmid = {41534661}, issn = {1879-016X}, abstract = {Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis, are characterized by the progressive breakdown and eventual loss of synapses and neurons, primarily driven by the accumulation of pathologically altered proteins within the brain and spinal cord. These diseases have complex and multifactorial etiologies, involving a broad spectrum of pathophysiological mechanisms, many of which remain incompletely understood. Nonetheless, several key pathways are consistently implicated across these conditions, including oxidative stress, mitochondrial dysfunction, neuroinflammation, and apoptosis. Given their rising prevalence and the persistent lack of effective disease-modifying therapies, the development of novel therapeutic strategies capable of targeting multiple pathophysiological processes is of critical importance for delaying or halting disease progression. In this context, marine natural compounds have emerged as promising candidates for counteracting neurodegeneration, owing to their ability to modulate key pathophysiological hallmarks of distinct neurodegenerative diseases. Derived from a wide range of marine organisms - including algae, sponges, fungi, and cyanobacteria - these bioactive molecules possess unique chemical structures and exhibit a broad spectrum of neuroprotective effects. Many have demonstrated potent antioxidant, anti-apoptotic, and mitochondrial-stabilizing activities in preclinical models. This review highlights recent advances in the discovery and characterization of marine-derived compounds with therapeutic potential in neurodegenerative diseases, contextualizing their pathologic mechanisms.}, }
@article {pmid41532955, year = {2026}, author = {Bernal-Vicente, BN and Ponce, I and Ríos-Castro, E and Moreno-Castilla, P and Tovar-Y-Romo, LB}, title = {Unveiling the Proteomic Landscape of Extracellular Vesicles: Implications for Neurodegeneration and Neuroprotection.}, journal = {Journal of neurochemistry}, volume = {170}, number = {1}, pages = {e70350}, pmid = {41532955}, issn = {1471-4159}, support = {IN214723//Direcci&#xf3;n General de Asuntos del Personal Acad&#xe9;mico, Universidad Nacional Aut&#xf3;noma de M&#xe9;xico/ ; }, mesh = {Humans ; *Extracellular Vesicles/metabolism ; *Proteomics/methods ; Animals ; *Neurodegenerative Diseases/metabolism/pathology ; *Neuroprotection/physiology ; Biomarkers/metabolism ; }, abstract = {Extracellular vesicles (EVs) are instrumental mediators of intercellular communication and molecular exchange in neurodegenerative and neurovascular diseases. This review integrates recent advances in EV proteomics to elucidate their roles in Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), traumatic brain injury (TBI), and ischemic stroke. Across these conditions, EVs carry disease-relevant proteins that reflect and influence key pathological processes such as synaptic dysfunction, neuroinflammation, blood-brain barrier (BBB) disruption, and cell death. Proteomic profiling of brain- and biofluid-derived EVs has uncovered specific biomarkers and signaling pathways, ranging from tau and α-synuclein in AD and PD to mutant SOD1 in ALS and complement activation in stroke and TBI. Moreover, cell-type-specific EVs (e.g., from neurons, astrocytes, microglia, and stem cells) have been shown to exert either protective or deleterious effects, modulating apoptosis, axonal regeneration, and immune responses. Recent evidence highlights the translational potential of EVs as non-invasive biomarkers and therapeutic vectors across multiple disorders. By mapping shared and divergent proteomic signatures in EVs, we review the mechanistic relevance and clinical utility of EVs in neurodegeneration and CNS injury.}, }
@article {pmid37939113, year = {2024}, author = {Wang, Z and Liu, YL and Chen, Y and Siegel, L and Cappelleri, JC and Chu, H}, title = {Double-Negative Results Matter: A Reevaluation of Sensitivities for Detecting SARS-CoV-2 Infection Using Saliva Versus Nasopharyngeal Swabs.}, journal = {American journal of epidemiology}, volume = {193}, number = {3}, pages = {548-560}, pmid = {37939113}, issn = {1476-6256}, support = {R01 LM012982/LM/NLM NIH HHS/United States ; UL1 TR002494/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/diagnosis ; SARS-CoV-2 ; Negative Results ; Saliva ; Nasopharynx ; }, abstract = {In a recent systematic review, Bastos et al. (Ann Intern Med. 2021;174(4):501-510) compared the sensitivities of saliva sampling and nasopharyngeal swabs in the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by assuming a composite reference standard defined as positive if either test is positive and negative if both tests are negative (double negative). Even under a perfect specificity assumption, this approach ignores the double-negative results and risks overestimating the sensitivities due to residual misclassification. In this article, we first illustrate the impact of double-negative results in the estimation of the sensitivities in a single study, and then propose a 2-step latent class meta-analysis method for reevaluating both sensitivities using the same published data set as that used in Bastos et al. by properly including the observed double-negative results. We also conduct extensive simulation studies to compare the performance of the proposed method with Bastos et al.'s method for varied levels of prevalence and between-study heterogeneity. The results demonstrate that the sensitivities are overestimated noticeably using Bastos et al.'s method, and the proposed method provides a more accurate evaluation with nearly no bias and close-to-nominal coverage probability. In conclusion, double-negative results can significantly impact the estimated sensitivities when a gold standard is absent, and thus they should be properly incorporated.}, }
@article {pmid37431780, year = {2023}, author = {Potente, C and Chumbley, J and Xu, W and Levitt, B and Cole, SW and Ravi, S and Bodelet, JS and Gaydosh, L and Harris, KM and Shanahan, MJ}, title = {Socioeconomic Inequalities and Molecular Risk for Aging in Young Adulthood.}, journal = {American journal of epidemiology}, volume = {192}, number = {12}, pages = {1981-1990}, pmid = {37431780}, issn = {1476-6256}, support = {P01 HD031921/HD/NICHD NIH HHS/United States ; R01 AG043404/AG/NIA NIH HHS/United States ; P30 AG017265/AG/NIA NIH HHS/United States ; R01 AG033590/AG/NIA NIH HHS/United States ; P2C HD050924/HD/NICHD NIH HHS/United States ; R01 HD087061/HD/NICHD NIH HHS/United States ; }, mesh = {Adult ; Adolescent ; Humans ; Young Adult ; Longitudinal Studies ; *Social Class ; *Aging/genetics ; Smoking ; Income ; Socioeconomic Factors ; }, abstract = {Diverse manifestations of biological aging often reflect disparities in socioeconomic status (SES). In this paper, we examine associations between indicators of SES and an mRNA-based aging signature during young adulthood, before clinical indications of aging are common. We use data from wave V (2016-2018) of the National Longitudinal Study of Adolescent to Adult Health, a nationally representative study of adults aged 33-43 years, with transcriptomic data from a subset of 2,491 participants. Biological aging is measured using 1) a composite transcriptomic aging signature previously identified by Peters et al.'s out-of-sample meta-analysis (Nat Commun. 2015;6:8570) and 2) 9 subsets that represent functional pathways of coexpressed genes. SES refers to income, education, occupation, subjective social status, and a composite measure combining these 4 dimensions. We examine hypothesized mechanisms through which SES could affect aging: body mass index, smoking, health insurance status, difficulty paying bills, and psychosocial stress. We find that SES-especially the composite measure and income-is associated with transcriptomic aging and immune, mitochondrial, ribosomal, lysosomal, and proteomal pathways. Counterfactual mediational models suggest that the mediators partially account for these associations. The results thus reveal that numerous biological pathways associated with aging are already linked to SES in young adulthood.}, }
@article {pmid35652455, year = {2022}, author = {Fels, JA and Casalena, G and Konrad, C and Holmes, HE and Dellinger, RW and Manfredi, G}, title = {Gene expression profiles in sporadic ALS fibroblasts define disease subtypes and the metabolic effects of the investigational drug EH301.}, journal = {Human molecular genetics}, volume = {31}, number = {20}, pages = {3458-3477}, pmid = {35652455}, issn = {1460-2083}, support = {R35 NS122209/NS/NINDS NIH HHS/United States ; }, mesh = {*Amyotrophic Lateral Sclerosis/metabolism ; Antioxidants/metabolism ; Drugs, Investigational/metabolism/therapeutic use ; Fibroblasts/metabolism ; Humans ; Transcriptome/genetics ; }, abstract = {Metabolic alterations shared between the nervous system and skin fibroblasts have emerged in amyotrophic lateral sclerosis (ALS). Recently, we found that a subgroup of sporadic ALS (sALS) fibroblasts (sALS1) is characterized by metabolic profiles distinct from other sALS cases (sALS2) and controls, suggesting that metabolic therapies could be effective in sALS. The metabolic modulators nicotinamide riboside and pterostilbene (EH301) are under clinical development for the treatment of ALS. Here, we studied the transcriptome and metabolome of sALS cells to understand the molecular bases of sALS metabotypes and the impact of EH301. Metabolomics and transcriptomics were investigated at baseline and after EH301 treatment. Moreover, weighted gene coexpression network analysis (WGCNA) was used to investigate the association of the metabolic and clinical features. We found that the sALS1 transcriptome is distinct from sALS2 and that EH301 modifies gene expression differently in sALS1, sALS2 and the controls. Furthermore, EH301 had strong protective effects against metabolic stress, an effect linked to the antiinflammatory and antioxidant pathways. WGCNA revealed that the ALS functional rating scale and metabotypes are associated with gene modules enriched for the cell cycle, immunity, autophagy and metabolic genes, which are modified by EH301. The meta-analysis of publicly available transcriptomic data from induced motor neurons by Answer ALS confirmed the functional associations of genes correlated with disease traits. A subset of genes differentially expressed in sALS fibroblasts was used in a machine learning model to predict disease progression. In conclusion, multiomic analyses highlighted the differential metabolic and transcriptomic profiles in patient-derived fibroblast sALS, which translate into differential responses to the investigational drug EH301.}, }
@article {pmid35196023, year = {2022}, author = {Hop, PJ and Zwamborn, RAJ and Hannon, E and Shireby, GL and Nabais, MF and Walker, EM and van Rheenen, W and van Vugt, JJFA and Dekker, AM and Westeneng, HJ and Tazelaar, GHP and van Eijk, KR and Moisse, M and Baird, D and Al Khleifat, A and Iacoangeli, A and Ticozzi, N and Ratti, A and Cooper-Knock, J and Morrison, KE and Shaw, PJ and Basak, AN and Chiò, A and Calvo, A and Moglia, C and Canosa, A and Brunetti, M and Grassano, M and Gotkine, M and Lerner, Y and Zabari, M and Vourc'h, P and Corcia, P and Couratier, P and Mora Pardina, JS and Salas, T and Dion, P and Ross, JP and Henderson, RD and Mathers, S and McCombe, PA and Needham, M and Nicholson, G and Rowe, DB and Pamphlett, R and Mather, KA and Sachdev, PS and Furlong, S and Garton, FC and Henders, AK and Lin, T and Ngo, ST and Steyn, FJ and Wallace, L and Williams, KL and ,  and ,  and Neto, MM and Cauchi, RJ and Blair, IP and Kiernan, MC and Drory, V and Povedano, M and de Carvalho, M and Pinto, S and Weber, M and Rouleau, GA and Silani, V and Landers, JE and Shaw, CE and Andersen, PM and McRae, AF and van Es, MA and Pasterkamp, RJ and Wray, NR and McLaughlin, RL and Hardiman, O and Kenna, KP and Tsai, E and Runz, H and Al-Chalabi, A and van den Berg, LH and Van Damme, P and Mill, J and Veldink, JH}, title = {Genome-wide study of DNA methylation shows alterations in metabolic, inflammatory, and cholesterol pathways in ALS.}, journal = {Science translational medicine}, volume = {14}, number = {633}, pages = {eabj0264}, pmid = {35196023}, issn = {1946-6242}, support = {G0300329/MRC_/Medical Research Council/United Kingdom ; R56 NS073873/NS/NINDS NIH HHS/United States ; SHAW/APR18/864-791/MNDA_/Motor Neurone Disease Association/United Kingdom ; G0600974/MRC_/Medical Research Council/United Kingdom ; /DH_/Department of Health/United Kingdom ; G0500289/MRC_/Medical Research Council/United Kingdom ; MR/L501529/1/MRC_/Medical Research Council/United Kingdom ; G0900688/MRC_/Medical Research Council/United Kingdom ; MC_PC_17115/MRC_/Medical Research Council/United Kingdom ; SHAW/NOV14/985-797/MNDA_/Motor Neurone Disease Association/United Kingdom ; G0900635/MRC_/Medical Research Council/United Kingdom ; ALCHALABI-DOBSON/APR14/829-791/MNDA_/Motor Neurone Disease Association/United Kingdom ; R01 NS073873/NS/NINDS NIH HHS/United States ; MCLAUGHLIN/OCT15/957-799/MNDA_/Motor Neurone Disease Association/United Kingdom ; MR/L021803/1/MRC_/Medical Research Council/United Kingdom ; G1100695/MRC_/Medical Research Council/United Kingdom ; MR/R024804/1/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics ; Cholesterol ; DNA Methylation/genetics ; Epigenesis, Genetic ; Genome-Wide Association Study ; Humans ; *Neurodegenerative Diseases/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an estimated heritability between 40 and 50%. DNA methylation patterns can serve as proxies of (past) exposures and disease progression, as well as providing a potential mechanism that mediates genetic or environmental risk. Here, we present a blood-based epigenome-wide association study meta-analysis in 9706 samples passing stringent quality control (6763 patients, 2943 controls). We identified a total of 45 differentially methylated positions (DMPs) annotated to 42 genes, which are enriched for pathways and traits related to metabolism, cholesterol biosynthesis, and immunity. We then tested 39 DNA methylation-based proxies of putative ALS risk factors and found that high-density lipoprotein cholesterol, body mass index, white blood cell proportions, and alcohol intake were independently associated with ALS. Integration of these results with our latest genome-wide association study showed that cholesterol biosynthesis was potentially causally related to ALS. Last, DNA methylation at several DMPs and blood cell proportion estimates derived from DNA methylation data were associated with survival rate in patients, suggesting that they might represent indicators of underlying disease processes potentially amenable to therapeutic interventions.}, }
@article {pmid34873335, year = {2021}, author = {van Rheenen, W and van der Spek, RAA and Bakker, MK and van Vugt, JJFA and Hop, PJ and Zwamborn, RAJ and de Klein, N and Westra, HJ and Bakker, OB and Deelen, P and Shireby, G and Hannon, E and Moisse, M and Baird, D and Restuadi, R and Dolzhenko, E and Dekker, AM and Gawor, K and Westeneng, HJ and Tazelaar, GHP and van Eijk, KR and Kooyman, M and Byrne, RP and Doherty, M and Heverin, M and Al Khleifat, A and Iacoangeli, A and Shatunov, A and Ticozzi, N and Cooper-Knock, J and Smith, BN and Gromicho, M and Chandran, S and Pal, S and Morrison, KE and Shaw, PJ and Hardy, J and Orrell, RW and Sendtner, M and Meyer, T and Başak, N and van der Kooi, AJ and Ratti, A and Fogh, I and Gellera, C and Lauria, G and Corti, S and Cereda, C and Sproviero, D and D'Alfonso, S and Sorarù, G and Siciliano, G and Filosto, M and Padovani, A and Chiò, A and Calvo, A and Moglia, C and Brunetti, M and Canosa, A and Grassano, M and Beghi, E and Pupillo, E and Logroscino, G and Nefussy, B and Osmanovic, A and Nordin, A and Lerner, Y and Zabari, M and Gotkine, M and Baloh, RH and Bell, S and Vourc'h, P and Corcia, P and Couratier, P and Millecamps, S and Meininger, V and Salachas, F and Mora Pardina, JS and Assialioui, A and Rojas-García, R and Dion, PA and Ross, JP and Ludolph, AC and Weishaupt, JH and Brenner, D and Freischmidt, A and Bensimon, G and Brice, A and Durr, A and Payan, CAM and Saker-Delye, S and Wood, NW and Topp, S and Rademakers, R and Tittmann, L and Lieb, W and Franke, A and Ripke, S and Braun, A and Kraft, J and Whiteman, DC and Olsen, CM and Uitterlinden, AG and Hofman, A and Rietschel, M and Cichon, S and Nöthen, MM and Amouyel, P and ,  and ,  and ,  and ,  and Traynor, BJ and Singleton, AB and Mitne Neto, M and Cauchi, RJ and Ophoff, RA and Wiedau-Pazos, M and Lomen-Hoerth, C and van Deerlin, VM and Grosskreutz, J and Roediger, A and Gaur, N and Jörk, A and Barthel, T and Theele, E and Ilse, B and Stubendorff, B and Witte, OW and Steinbach, R and Hübner, CA and Graff, C and Brylev, L and Fominykh, V and Demeshonok, V and Ataulina, A and Rogelj, B and Koritnik, B and Zidar, J and Ravnik-Glavač, M and Glavač, D and Stević, Z and Drory, V and Povedano, M and Blair, IP and Kiernan, MC and Benyamin, B and Henderson, RD and Furlong, S and Mathers, S and McCombe, PA and Needham, M and Ngo, ST and Nicholson, GA and Pamphlett, R and Rowe, DB and Steyn, FJ and Williams, KL and Mather, KA and Sachdev, PS and Henders, AK and Wallace, L and de Carvalho, M and Pinto, S and Petri, S and Weber, M and Rouleau, GA and Silani, V and Curtis, CJ and Breen, G and Glass, JD and Brown, RH and Landers, JE and Shaw, CE and Andersen, PM and Groen, EJN and van Es, MA and Pasterkamp, RJ and Fan, D and Garton, FC and McRae, AF and Davey Smith, G and Gaunt, TR and Eberle, MA and Mill, J and McLaughlin, RL and Hardiman, O and Kenna, KP and Wray, NR and Tsai, E and Runz, H and Franke, L and Al-Chalabi, A and Van Damme, P and van den Berg, LH and Veldink, JH}, title = {Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology.}, journal = {Nature genetics}, volume = {53}, number = {12}, pages = {1636-1648}, pmid = {34873335}, issn = {1546-1718}, support = {MR/L501542/1/MRC_/Medical Research Council/United Kingdom ; R56 NS073873/NS/NINDS NIH HHS/United States ; MR/L501529/1/MRC_/Medical Research Council/United Kingdom ; G0701075/MRC_/Medical Research Council/United Kingdom ; G-1307/PUK_/Parkinson's UK/United Kingdom ; MC_UU_00011/1/MRC_/Medical Research Council/United Kingdom ; G0500289/MRC_/Medical Research Council/United Kingdom ; SMITH/APR16/847-791/MNDA_/Motor Neurone Disease Association/United Kingdom ; MR/J004758/1/MRC_/Medical Research Council/United Kingdom ; MC_PC_17115/MRC_/Medical Research Council/United Kingdom ; MC_UU_00011/4/MRC_/Medical Research Council/United Kingdom ; MR/R024804/1/MRC_/Medical Research Council/United Kingdom ; G0901254/MRC_/Medical Research Council/United Kingdom ; G0900635/MRC_/Medical Research Council/United Kingdom ; SHAW/APR15/970-797/MNDA_/Motor Neurone Disease Association/United Kingdom ; ALCHALABI-DOBSON/APR14/829-791/MNDA_/Motor Neurone Disease Association/United Kingdom ; MC_G1000733/MRC_/Medical Research Council/United Kingdom ; MR/K01417X/1/MRC_/Medical Research Council/United Kingdom ; G-0907/PUK_/Parkinson's UK/United Kingdom ; G0600974/MRC_/Medical Research Council/United Kingdom ; G1001253/MRC_/Medical Research Council/United Kingdom ; R01 NS073873/NS/NINDS NIH HHS/United States ; MR/L021803/1/MRC_/Medical Research Council/United Kingdom ; G1100695/MRC_/Medical Research Council/United Kingdom ; ALCHALABI-TALBOT/APR14/926-794/MNDA_/Motor Neurone Disease Association/United Kingdom ; G0900688/MRC_/Medical Research Council/United Kingdom ; MR/L023784/2/MRC_/Medical Research Council/United Kingdom ; MRF-060-0003-RG-SMITH/MRF_/MRF_/United Kingdom ; SHAW/NOV14/985-797/MNDA_/Motor Neurone Disease Association/United Kingdom ; }, mesh = {Amyotrophic Lateral Sclerosis/*genetics/metabolism ; Brain/metabolism ; Cholesterol/blood ; Disease Progression ; Female ; *Genome-Wide Association Study ; Glutamine/metabolism ; Humans ; Male ; Mendelian Randomization Analysis ; Microsatellite Repeats ; *Mutation ; Neurodegenerative Diseases/genetics ; Neurons/*metabolism ; Quantitative Trait Loci ; RNA-Seq ; Risk Factors ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons.}, }
@article {pmid34390790, year = {2022}, author = {Xiao, M and Chu, H and Cole, SR and Chen, Y and MacLehose, RF and Richardson, DB and Greenland, S}, title = {Controversy and Debate : Questionable utility of the relative risk in clinical research: Paper 4 :Odds Ratios are far from "portable" - A call to use realistic models for effect variation in meta-analysis.}, journal = {Journal of clinical epidemiology}, volume = {142}, number = {}, pages = {294-304}, pmid = {34390790}, issn = {1878-5921}, support = {R01 LM012607/LM/NLM NIH HHS/United States ; R01 LM012982/LM/NLM NIH HHS/United States ; R01 LM013049/LM/NLM NIH HHS/United States ; UL1 TR002494/TR/NCATS NIH HHS/United States ; }, mesh = {Bias ; Causality ; Humans ; *Odds Ratio ; Risk ; Systematic Reviews as Topic ; }, abstract = {OBJECTIVE: Recently Doi et al. argued that risk ratios should be replaced with odds ratios in clinical research. We disagreed, and empirically documented the lack of portability of odds ratios, while Doi et al. defended their position. In this response we highlight important errors in their position.<br><br>STUDY DESIGN AND SETTING: We counter Doi et&#xa0;al.'s arguments by further examining the correlations of odds ratios, and risk ratios, with baseline risks in 20,198 meta-analyses from the Cochrane Database of Systematic Reviews.<br><br>RESULTS: Doi et&#xa0;al.'s claim that odds ratios are portable is invalid because 1) their reasoning is circular: they assume a model under which the odds ratio is constant and show that under such a model the odds ratio is portable; 2) the method they advocate to convert odds ratios to risk ratios is biased; 3) their empirical example is readily-refuted by counter-examples of meta-analyses in which the risk ratio is portable but the odds ratio isn't; and 4) they fail to consider the causal determinants of meta-analytic inclusion criteria: Doi et&#xa0;al. mistakenly claim that variation in odds ratios with different baseline risks in meta-analyses is due to collider bias. Empirical comparison between the correlations of odds ratios, and risk ratios, with baseline risks show that the portability of odds ratios and risk ratios varies across settings.<br><br>CONCLUSION: The suggestion to replace risk ratios with odds ratios is based on circular reasoning and a confusion of mathematical and empirical results. It is especially misleading for meta-analyses and clinical guidance. Neither the odds ratio nor the risk ratio is universally portable. To address this lack of portability, we reinforce our suggestion to report variation in effect measures conditioning on modifying factors such as baseline risk; understanding such variation is essential to patient-centered practice.}, }
@article {pmid34384876, year = {2022}, author = {Xiao, M and Chen, Y and Cole, SR and MacLehose, RF and Richardson, DB and Chu, H}, title = {Controversy and Debate: Questionable utility of the relative risk in clinical research: Paper 2: Is the Odds Ratio "portable" in meta-analysis? Time to consider bivariate generalized linear mixed model.}, journal = {Journal of clinical epidemiology}, volume = {142}, number = {}, pages = {280-287}, pmid = {34384876}, issn = {1878-5921}, support = {R01 LM012982/LM/NLM NIH HHS/United States ; UL1 TR002494/TR/NCATS NIH HHS/United States ; R01 LM013049/LM/NLM NIH HHS/United States ; R01 LM012607/LM/NLM NIH HHS/United States ; }, mesh = {Humans ; Linear Models ; *Odds Ratio ; Risk ; Systematic Reviews as Topic ; }, abstract = {OBJECTIVES: A recent paper by Doi et al. advocated completely replacing the relative risk (RR) with the odds ratio (OR) as the effect measure in clinical trials and meta-analyses with binary outcomes. Besides some practical advantages of RR over OR, Doi et al.'s key assumption that the OR is "portable" in the meta-analysis, that is, study-specific ORs are likely not correlated with baseline risks, was not well justified.<br><br>STUDY DESIGNS AND SETTINGS: We summarized Spearman's rank correlation coefficient between study-specific ORs and baseline risks in 40,243 meta-analyses from the Cochrane Database of Systematic Reviews.<br><br>RESULTS: Study-specific ORs tend to be higher in studies with lower baseline risks of disease for most meta-analyses in Cochrane Database of Systematic Reviews. Using an actual meta-analysis example, we demonstrate that there is a strong negative correlation between OR (RR or RD) with the baseline risk and the conditional effects notably vary with baseline risks.<br><br>CONCLUSIONS: Replacing RR or RD with OR is currently unadvisable in clinical trials and meta-analyses. It is possible that no effect measure is "portable" in a meta-analysis. In addition to the overall (or marginal) effect, we suggest presenting the conditional effect based on the baseline risk using a bivariate generalized linear mixed model.}, }
@article {pmid33771206, year = {2021}, author = {Nabais, MF and Laws, SM and Lin, T and Vallerga, CL and Armstrong, NJ and Blair, IP and Kwok, JB and Mather, KA and Mellick, GD and Sachdev, PS and Wallace, L and Henders, AK and Zwamborn, RAJ and Hop, PJ and Lunnon, K and Pishva, E and Roubroeks, JAY and Soininen, H and Tsolaki, M and Mecocci, P and Lovestone, S and Kłoszewska, I and Vellas, B and ,  and ,  and Furlong, S and Garton, FC and Henderson, RD and Mathers, S and McCombe, PA and Needham, M and Ngo, ST and Nicholson, G and Pamphlett, R and Rowe, DB and Steyn, FJ and Williams, KL and Anderson, TJ and Bentley, SR and Dalrymple-Alford, J and Fowder, J and Gratten, J and Halliday, G and Hickie, IB and Kennedy, M and Lewis, SJG and Montgomery, GW and Pearson, J and Pitcher, TL and Silburn, P and Zhang, F and Visscher, PM and Yang, J and Stevenson, AJ and Hillary, RF and Marioni, RE and Harris, SE and Deary, IJ and Jones, AR and Shatunov, A and Iacoangeli, A and van Rheenen, W and van den Berg, LH and Shaw, PJ and Shaw, CE and Morrison, KE and Al-Chalabi, A and Veldink, JH and Hannon, E and Mill, J and Wray, NR and McRae, AF}, title = {Meta-analysis of genome-wide DNA methylation identifies shared associations across neurodegenerative disorders.}, journal = {Genome biology}, volume = {22}, number = {1}, pages = {90}, pmid = {33771206}, issn = {1474-760X}, support = {U24 AG021886/AG/NIA NIH HHS/United States ; U01 AG032984/AG/NIA NIH HHS/United States ; U01 AG024904/AG/NIA NIH HHS/United States ; 108890/Z/15/Z/WT_/Wellcome Trust/United Kingdom ; R01 AG033193/AG/NIA NIH HHS/United States ; 082604/2/07/Z/WT_/Wellcome Trust/United Kingdom ; TURNER/OCT15/972-797/MNDA_/Motor Neurone Disease Association/United Kingdom ; /DH_/Department of Health/United Kingdom ; U01 AG016976/AG/NIA NIH HHS/United States ; R01 HL105756/HL/NHLBI NIH HHS/United States ; 503480/MRC_/Medical Research Council/United Kingdom ; MR/R024804/1/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; }, mesh = {Alleles ; Biomarkers ; Blood Cells/metabolism ; Case-Control Studies ; *DNA Methylation ; Disease Susceptibility ; *Epigenesis, Genetic ; Gene Expression Profiling ; Genetic Loci ; Genetic Predisposition to Disease ; *Genome-Wide Association Study ; Humans ; Neurodegenerative Diseases/*etiology/metabolism ; }, abstract = {BACKGROUND: People with neurodegenerative disorders show diverse clinical syndromes, genetic heterogeneity, and distinct brain pathological changes, but studies report overlap between these features. DNA methylation (DNAm) provides a way to explore this overlap and heterogeneity as it is determined by the combined effects of genetic variation and the environment. In this study, we aim to identify shared blood DNAm differences between controls and people with Alzheimer's disease, amyotrophic lateral sclerosis, and Parkinson's disease.<br><br>RESULTS: We use a mixed-linear model method (MOMENT) that accounts for the effect of (un)known confounders, to test for the association of each DNAm site with each disorder. While only three probes are found to be genome-wide significant in each MOMENT association analysis of amyotrophic lateral sclerosis and Parkinson's disease (and none with Alzheimer's disease), a fixed-effects meta-analysis of the three disorders results in 12 genome-wide significant differentially methylated positions. Predicted immune cell-type proportions are disrupted across all neurodegenerative disorders. Protein inflammatory markers are correlated with profile sum-scores derived from disease-associated immune cell-type proportions in a healthy aging cohort. In contrast, they are not correlated with MOMENT DNAm-derived profile sum-scores, calculated using effect sizes of the 12 differentially methylated positions as weights.<br><br>CONCLUSIONS: We identify shared differentially methylated positions in whole blood between neurodegenerative disorders that point to shared pathogenic mechanisms. These shared differentially methylated positions may reflect causes or consequences of disease, but they are unlikely to reflect cell-type proportion differences.}, }
@article {pmid32668255, year = {2020}, author = {Wan, YW and Al-Ouran, R and Mangleburg, CG and Perumal, TM and Lee, TV and Allison, K and Swarup, V and Funk, CC and Gaiteri, C and Allen, M and Wang, M and Neuner, SM and Kaczorowski, CC and Philip, VM and Howell, GR and Martini-Stoica, H and Zheng, H and Mei, H and Zhong, X and Kim, JW and Dawson, VL and Dawson, TM and Pao, PC and Tsai, LH and Haure-Mirande, JV and Ehrlich, ME and Chakrabarty, P and Levites, Y and Wang, X and Dammer, EB and Srivastava, G and Mukherjee, S and Sieberts, SK and Omberg, L and Dang, KD and Eddy, JA and Snyder, P and Chae, Y and Amberkar, S and Wei, W and Hide, W and Preuss, C and Ergun, A and Ebert, PJ and Airey, DC and Mostafavi, S and Yu, L and Klein, HU and ,  and Carter, GW and Collier, DA and Golde, TE and Levey, AI and Bennett, DA and Estrada, K and Townsend, TM and Zhang, B and Schadt, E and De Jager, PL and Price, ND and Ertekin-Taner, N and Liu, Z and Shulman, JM and Mangravite, LM and Logsdon, BA}, title = {Meta-Analysis of the Alzheimer's Disease Human Brain Transcriptome and Functional Dissection in Mouse Models.}, journal = {Cell reports}, volume = {32}, number = {2}, pages = {107908}, pmid = {32668255}, issn = {2211-1247}, support = {U01 AG046152/AG/NIA NIH HHS/United States ; R01 AG053960/AG/NIA NIH HHS/United States ; R01 AG017917/AG/NIA NIH HHS/United States ; F31 AG050357/AG/NIA NIH HHS/United States ; RF1 AG051504/AG/NIA NIH HHS/United States ; U01 AG061357/AG/NIA NIH HHS/United States ; P30 AG010161/AG/NIA NIH HHS/United States ; P50 NS038377/NS/NINDS NIH HHS/United States ; R01 AG015473/AG/NIA NIH HHS/United States ; P01 AG017216/AG/NIA NIH HHS/United States ; R01 AG018023/AG/NIA NIH HHS/United States ; R01 AG057339/AG/NIA NIH HHS/United States ; RF1 AG057440/AG/NIA NIH HHS/United States ; P50 AG016574/AG/NIA NIH HHS/United States ; RF1 AG054014/AG/NIA NIH HHS/United States ; U01 AG032984/AG/NIA NIH HHS/United States ; R01 AG050631/AG/NIA NIH HHS/United States ; R01 AG030146/AG/NIA NIH HHS/United States ; U01 AG046170/AG/NIA NIH HHS/United States ; U24 AG061340/AG/NIA NIH HHS/United States ; R01 AG061796/AG/NIA NIH HHS/United States ; P50 AG025688/AG/NIA NIH HHS/United States ; R01 AG032990/AG/NIA NIH HHS/United States ; R01 NS080820/NS/NINDS NIH HHS/United States ; RF1 AG057443/AG/NIA NIH HHS/United States ; RF1 AG057473/AG/NIA NIH HHS/United States ; U01 AG046139/AG/NIA NIH HHS/United States ; P01 AG003949/AG/NIA NIH HHS/United States ; U24 NS072026/NS/NINDS NIH HHS/United States ; U01 AG046161/AG/NIA NIH HHS/United States ; P30 AG019610/AG/NIA NIH HHS/United States ; P50 AG025711/AG/NIA NIH HHS/United States ; U01 AG006786/AG/NIA NIH HHS/United States ; R01 AG036836/AG/NIA NIH HHS/United States ; R01 AG046174/AG/NIA NIH HHS/United States ; R01 AG015819/AG/NIA NIH HHS/United States ; R01 AG057914/AG/NIA NIH HHS/United States ; F31 AG067677/AG/NIA NIH HHS/United States ; }, mesh = {Alzheimer Disease/*genetics ; Animals ; Brain/*metabolism/*pathology ; Case-Control Studies ; Disease Models, Animal ; Female ; Gene Expression Profiling ; Gene Expression Regulation ; Gene Regulatory Networks ; Humans ; Male ; Mice ; Sex Characteristics ; Species Specificity ; Transcription, Genetic ; Transcriptome/*genetics ; }, abstract = {We present a consensus atlas of the human brain transcriptome in Alzheimer's disease (AD), based on meta-analysis of differential gene expression in 2,114 postmortem samples. We discover 30 brain coexpression modules from seven regions as the major source of AD transcriptional perturbations. We next examine overlap with 251 brain differentially expressed gene sets from mouse models of AD and other neurodegenerative disorders. Human-mouse overlaps highlight responses to amyloid versus tau pathology and reveal age- and sex-dependent expression signatures for disease progression. Human coexpression modules enriched for neuronal and/or microglial genes broadly overlap with mouse models of AD, Huntington's disease, amyotrophic lateral sclerosis, and aging. Other human coexpression modules, including those implicated in proteostasis, are not activated in AD models but rather following other, unexpected genetic manipulations. Our results comprise a cross-species resource, highlighting transcriptional networks altered by human brain pathophysiology and identifying correspondences with mouse models for AD preclinical studies.}, }
@article {pmid32594886, year = {2022}, author = {Duff, K and Hammers, DB}, title = {Practice effects in mild cognitive impairment: A validation of Calamia et al. (2012).}, journal = {The Clinical neuropsychologist}, volume = {36}, number = {3}, pages = {571-583}, pmid = {32594886}, issn = {1744-4144}, support = {R01 AG045163/AG/NIA NIH HHS/United States ; R01 AG055428/AG/NIA NIH HHS/United States ; }, mesh = {Aged ; *Cognitive Dysfunction/diagnosis/psychology ; Humans ; Neuropsychological Tests ; }, abstract = {OBJECTIVE: In a meta-analysis examining practice effects on repeated neuropsychological testing, Calamia et al. (2012) provided information to predict practice effects in healthy and clinical samples across a range of cognitive domains. However, these estimates have not been validated.<br><br>METHOD: This study used these prediction estimate calculations to predict follow-up scores across one year on a brief battery of neuropsychological tests in a sample of 93 older adults with amnestic mild cognitive impairment. The predicted follow-up scores were compared to observed follow-up scores.<br><br>RESULTS: Using Calamia et&#xa0;al. model's intercept, age, retest interval, clinical status, and specific cognitive tests, three of the seven observed follow-up scores in this cognitive battery were significantly lower than the Calamia et&#xa0;al. predicted follow-up scores. Differences between individual participants' observed and predicted follow-up scores were more striking. For example, on Delayed Recall of the Hopkins Verbal Learning Test - Revised, 40% of the sample had Calamia et&#xa0;al. predicted scores that were one or more standard deviations above their observed scores. These differences were most notable on tests that were not in Calamia et&#xa0;al.'s cognitive battery, suggesting the meta-analysis results may not generalize as well to other tests.<br><br>CONCLUSIONS: Although Calamia et&#xa0;al. provided a method for predicting practice effects and follow-up scores, these results raise caution when using them in MCI, especially on cognitive tests that were not in their meta-analysis.}, }
@article {pmid31315673, year = {2019}, author = {Iacoangeli, A and Al Khleifat, A and Jones, AR and Sproviero, W and Shatunov, A and Opie-Martin, S and ,  and Morrison, KE and Shaw, PJ and Shaw, CE and Fogh, I and Dobson, RJ and Newhouse, SJ and Al-Chalabi, A}, title = {C9orf72 intermediate expansions of 24-30 repeats are associated with ALS.}, journal = {Acta neuropathologica communications}, volume = {7}, number = {1}, pages = {115}, pmid = {31315673}, issn = {2051-5960}, support = {MC_PC_17214/MRC_/Medical Research Council/United Kingdom ; MR/L501529/1/MRC_/Medical Research Council/United Kingdom ; SHAW/APR18/864-791/MNDA_/Motor Neurone Disease Association/United Kingdom ; U01 AG024904/AG/NIA NIH HHS/United States ; G0600974/MRC_/Medical Research Council/United Kingdom ; AL-CHALABI/APR15/844-791/MNDA_/Motor Neurone Disease Association/United Kingdom ; G0500289/MRC_/Medical Research Council/United Kingdom ; G0900688/MRC_/Medical Research Council/United Kingdom ; ES/L008238/1//Economic and Social Research Council/International ; MC_PC_17115/MRC_/Medical Research Council/United Kingdom ; SHAW/NOV14/985-797/MNDA_/Motor Neurone Disease Association/United Kingdom ; G0900635/MRC_/Medical Research Council/United Kingdom ; ALCHALABI-DOBSON/APR14/829-791/MNDA_/Motor Neurone Disease Association/United Kingdom ; MR/L021803/1/MRC_/Medical Research Council/United Kingdom ; G1100695/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; MR/R024804/1/MRC_/Medical Research Council/United Kingdom ; 633413//Horizon 2020 Framework Programme/International ; }, mesh = {Aged ; Amyotrophic Lateral Sclerosis/diagnosis/epidemiology/*genetics ; C9orf72 Protein/*genetics ; DNA Repeat Expansion/*genetics ; Databases, Genetic/trends ; Female ; Humans ; Male ; Middle Aged ; White People/*genetics ; Whole Genome Sequencing/methods ; }, abstract = {The expansion of a hexanucleotide repeat GGGGCC in C9orf72 is the most common known cause of ALS accounting for ~ 40% familial cases and ~ 7% sporadic cases in the European population. In most people, the repeat length is 2, but in people with ALS, hundreds to thousands of repeats may be observed. A small proportion of people have an intermediate expansion, of the order of 20 to 30 repeats in size, and it remains unknown whether intermediate expansions confer risk of ALS in the same way that massive expansions do. We investigated the association of this intermediate repeat with ALS by performing a meta-analysis of four previously published studies and a new British/Alzheimer's Disease Neuroimaging Initiative dataset of 1295 cases and 613 controls. The final dataset comprised 5071 cases and 3747 controls. Our meta-analysis showed association between ALS and intermediate C9orf72 repeats of 24 to 30 repeats in size (random-effects model OR = 4.2, 95% CI = 1.23-14.35, p-value = 0.02). Furthermore, we showed a different frequency of the repeat between the northern and southern European populations (Fisher's exact test p-value = 5 × 10[- 3]). Our findings provide evidence for the association between intermediate repeats and ALS (p-value = 2 × 10[- 4]) with direct relevance for research and clinical practice by showing that an expansion of 24 or more repeats should be considered pathogenic.}, }
@article {pmid30620104, year = {2019}, author = {Pattee, GL and Plowman, EK and Focht Garand, KL and Costello, J and Brooks, BR and Berry, JD and Smith, RA and Atassi, N and Chapin, JL and Yunusova, Y and McIlduff, CE and Young, E and Macklin, EA and Locatelli, ER and Silani, V and Heitzman, D and Wymer, J and Goutman, SA and Gelinas, DF and Perry, B and Nalipinski, P and Stipancic, K and O'Brien, M and Sullivan, SL and Pioro, EP and Gargiulo, G and Green, JR and , }, title = {Provisional best practices guidelines for the evaluation of bulbar dysfunction in amyotrophic lateral sclerosis.}, journal = {Muscle &amp; nerve}, volume = {59}, number = {5}, pages = {531-536}, doi = {10.1002/mus.26408}, pmid = {30620104}, issn = {1097-4598}, support = {R01 DC013547/DC/NIDCD NIH HHS/United States ; }, mesh = {Amyotrophic Lateral Sclerosis/complications/*rehabilitation ; Communication Devices for People with Disabilities ; Deglutition Disorders/diagnosis/etiology/*rehabilitation ; Disease Management ; Humans ; Referral and Consultation ; Speech Disorders/diagnosis/etiology/*rehabilitation ; Speech Therapy ; }, abstract = {INTRODUCTION: Universally established comprehensive clinical bulbar scales objectively assessing disease progression in amyotrophic lateral sclerosis (ALS) are currently lacking. The goal of this working group project is to design a best practice set of provisional bulbar ALS guidelines, available for immediate implementation within all ALS clinics.<br><br>METHODS: ALS specialists across multiple related disciplines participated in a series of clinical bulbar symposia, intending to identify and summarize the currently accepted best practices for the assessment and management of bulbar dysfunction in ALS Results: Summary group recommendations for individual speech, Augmentative and Alternative Communication (AAC), and swallowing sections were achieved, focusing on the optimal proposed level of care within each domain.<br><br>DISCUSSION: We have identified specific clinical recommendations for each of the 3 domains of bulbar functioning, available for incorporation within all ALS clinics. Future directions will be to establish a formal set of bulbar guidelines through a methodological and evidence-based approach. Muscle Nerve 59:531-531, 2019.}, }
@article {pmid30594291, year = {2019}, author = {Yanagi, KS and Wu, Z and Amaya, J and Chapkis, N and Duffy, AM and Hajdarovic, KH and Held, A and Mathur, AD and Russo, K and Ryan, VH and Steinert, BL and Whitt, JP and Fallon, JR and Fawzi, NL and Lipscombe, D and Reenan, RA and Wharton, KA and Hart, AC}, title = {Meta-analysis of Genetic Modifiers Reveals Candidate Dysregulated Pathways in Amyotrophic Lateral Sclerosis.}, journal = {Neuroscience}, volume = {396}, number = {}, pages = {A3-A20}, pmid = {30594291}, issn = {1873-7544}, support = {T32 MH020068/MH/NIMH NIH HHS/United States ; R01 GM122083/GM/NIGMS NIH HHS/United States ; F31 NS110301/NS/NINDS NIH HHS/United States ; R01 GM118530/GM/NIGMS NIH HHS/United States ; T32 NS062443/NS/NINDS NIH HHS/United States ; P20 GM109035/GM/NIGMS NIH HHS/United States ; }, mesh = {Amyotrophic Lateral Sclerosis/*genetics ; Animals ; Computational Biology ; Genes, Modifier/*genetics ; Genetic Predisposition to Disease/genetics ; Humans ; Signal Transduction/*genetics ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease that has significant overlap with frontotemporal dementia (FTD). Mutations in specific genes have been identified that can cause and/or predispose patients to ALS. However, the clinical variability seen in ALS patients suggests that additional genes impact pathology, susceptibility, severity, and/or progression of the disease. To identify molecular pathways involved in ALS, we undertook a meta-analysis of published genetic modifiers both in patients and in model organisms, and undertook bioinformatic pathway analysis. From 72 published studies, we generated a list of 946 genes whose perturbation (1) impacted ALS in patient populations, (2) altered defects in laboratory models, or (3) modified defects caused by ALS gene ortholog loss of function. Herein, these are all called modifier genes. We found 727 modifier genes that encode proteins with human orthologs. Of these, 43 modifier genes were identified as modifiers of more than one ALS gene/model, consistent with the hypothesis that shared genes and pathways may underlie ALS. Further, we used a gene ontology-based bioinformatic analysis to identify pathways and associated genes that may be important in ALS. To our knowledge this is the first comprehensive survey of ALS modifier genes. This work suggests that shared molecular mechanisms may underlie pathology caused by different ALS disease genes. Surprisingly, few ALS modifier genes have been tested in more than one disease model. Understanding genes that modify ALS-associated defects will help to elucidate the molecular pathways that underlie ALS and provide additional targets for therapeutic intervention.}, }
@article {pmid29315334, year = {2018}, author = {Broce, I and Karch, CM and Wen, N and Fan, CC and Wang, Y and Tan, CH and Kouri, N and Ross, OA and Höglinger, GU and Muller, U and Hardy, J and ,  and Momeni, P and Hess, CP and Dillon, WP and Miller, ZA and Bonham, LW and Rabinovici, GD and Rosen, HJ and Schellenberg, GD and Franke, A and Karlsen, TH and Veldink, JH and Ferrari, R and Yokoyama, JS and Miller, BL and Andreassen, OA and Dale, AM and Desikan, RS and Sugrue, LP}, title = {Immune-related genetic enrichment in frontotemporal dementia: An analysis of genome-wide association studies.}, journal = {PLoS medicine}, volume = {15}, number = {1}, pages = {e1002487}, pmid = {29315334}, issn = {1549-1676}, support = {MC_UU_00024/1/MRC_/Medical Research Council/United Kingdom ; G0900652/MRC_/Medical Research Council/United Kingdom ; G0400074/MRC_/Medical Research Council/United Kingdom ; MC_UU_00024/9/MRC_/Medical Research Council/United Kingdom ; MC_UU_00005/12/MRC_/Medical Research Council/United Kingdom ; K01 AG049152/AG/NIA NIH HHS/United States ; G1100540/MRC_/Medical Research Council/United Kingdom ; MC_U123160657/MRC_/Medical Research Council/United Kingdom ; P01 AG017586/AG/NIA NIH HHS/United States ; MC_U123160651/MRC_/Medical Research Council/United Kingdom ; U24 DA041123/DA/NIDA NIH HHS/United States ; P01 AG003991/AG/NIA NIH HHS/United States ; P50 AG005681/AG/NIA NIH HHS/United States ; P01 AG026276/AG/NIA NIH HHS/United States ; MC_U105597119/MRC_/Medical Research Council/United Kingdom ; K01 AG046374/AG/NIA NIH HHS/United States ; G0502157/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Aged ; Frontotemporal Dementia/*genetics ; Genetic Predisposition to Disease/*genetics ; *Genome-Wide Association Study ; Humans ; Middle Aged ; *Polymorphism, Single Nucleotide ; }, abstract = {BACKGROUND: Converging evidence suggests that immune-mediated dysfunction plays an important role in the pathogenesis of frontotemporal dementia (FTD). Although genetic studies have shown that immune-associated loci are associated with increased FTD risk, a systematic investigation of genetic overlap between immune-mediated diseases and the spectrum of FTD-related disorders has not been performed.<br><br>METHODS AND FINDINGS: Using large genome-wide association studies (GWASs) (total n = 192,886 cases and controls) and recently developed tools to quantify genetic overlap/pleiotropy, we systematically identified single nucleotide polymorphisms (SNPs) jointly associated with FTD-related disorders-namely, FTD, corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), and amyotrophic lateral sclerosis (ALS)-and 1 or more immune-mediated diseases including Crohn disease, ulcerative colitis (UC), rheumatoid arthritis (RA), type 1 diabetes (T1D), celiac disease (CeD), and psoriasis. We found up to 270-fold genetic enrichment between FTD and RA, up to 160-fold genetic enrichment between FTD and UC, up to 180-fold genetic enrichment between FTD and T1D, and up to 175-fold genetic enrichment between FTD and CeD. In contrast, for CBD and PSP, only 1 of the 6 immune-mediated diseases produced genetic enrichment comparable to that seen for FTD, with up to 150-fold genetic enrichment between CBD and CeD and up to 180-fold enrichment between PSP and RA. Further, we found minimal enrichment between ALS and the immune-mediated diseases tested, with the highest levels of enrichment between ALS and RA (up to 20-fold). For FTD, at a conjunction false discovery rate < 0.05 and after excluding SNPs in linkage disequilibrium, we found that 8 of the 15 identified loci mapped to the human leukocyte antigen (HLA) region on Chromosome (Chr) 6. We also found novel candidate FTD susceptibility loci within LRRK2 (leucine rich repeat kinase 2), TBKBP1 (TBK1 binding protein 1), and PGBD5 (piggyBac transposable element derived 5). Functionally, we found that the expression of FTD-immune pleiotropic genes (particularly within the HLA region) is altered in postmortem brain tissue from patients with FTD and is enriched in microglia/macrophages compared to other central nervous system cell types. The main study limitation is that the results represent only clinically diagnosed individuals. Also, given the complex interconnectedness of the HLA region, we were not able to define the specific gene or genes on Chr 6 responsible for our pleiotropic signal.<br><br>CONCLUSIONS: We show immune-mediated genetic enrichment specifically in FTD, particularly within the HLA region. Our genetic results suggest that for a subset of patients, immune dysfunction may contribute to FTD risk. These findings have potential implications for clinical trials targeting immune dysfunction in patients with FTD.}, }
@article {pmid28017481, year = {2017}, author = {Sproviero, W and Shatunov, A and Stahl, D and Shoai, M and van Rheenen, W and Jones, AR and Al-Sarraj, S and Andersen, PM and Bonini, NM and Conforti, FL and Van Damme, P and Daoud, H and Del Mar Amador, M and Fogh, I and Forzan, M and Gaastra, B and Gellera, C and Gitler, AD and Hardy, J and Fratta, P and La Bella, V and Le Ber, I and Van Langenhove, T and Lattante, S and Lee, YC and Malaspina, A and Meininger, V and Millecamps, S and Orrell, R and Rademakers, R and Robberecht, W and Rouleau, G and Ross, OA and Salachas, F and Sidle, K and Smith, BN and Soong, BW and Sorarù, G and Stevanin, G and Kabashi, E and Troakes, C and van Broeckhoven, C and Veldink, JH and van den Berg, LH and Shaw, CE and Powell, JF and Al-Chalabi, A}, title = {ATXN2 trinucleotide repeat length correlates with risk of ALS.}, journal = {Neurobiology of aging}, volume = {51}, number = {}, pages = {178.e1-178.e9}, pmid = {28017481}, issn = {1558-1497}, support = {MC_G1000733/MRC_/Medical Research Council/United Kingdom ; MR/L501529/1/MRC_/Medical Research Council/United Kingdom ; G0600974/MRC_/Medical Research Council/United Kingdom ; MALASPINA/APR13/817-791/MNDA_/Motor Neurone Disease Association/United Kingdom ; G0900688/MRC_/Medical Research Council/United Kingdom ; JONES/OCT15/958-799/MNDA_/Motor Neurone Disease Association/United Kingdom ; G0300329/MRC_/Medical Research Council/United Kingdom ; G0900635/MRC_/Medical Research Council/United Kingdom ; ALCHALABI-DOBSON/APR14/829-791/MNDA_/Motor Neurone Disease Association/United Kingdom ; AL-CHALABI/APR15/844-791/MNDA_/Motor Neurone Disease Association/United Kingdom ; MR/M008606/1/MRC_/Medical Research Council/United Kingdom ; MR/L021803/1/MRC_/Medical Research Council/United Kingdom ; G1100695/MRC_/Medical Research Council/United Kingdom ; FRATTA/JAN15/946-795/MNDA_/Motor Neurone Disease Association/United Kingdom ; G0501573/MRC_/Medical Research Council/United Kingdom ; G0500289/MRC_/Medical Research Council/United Kingdom ; R35 NS097275/NS/NINDS NIH HHS/United States ; /WT_/Wellcome Trust/United Kingdom ; MRF-060-0003-RG-SMITH/MRF_/MRF_/United Kingdom ; SHAW/NOV14/985-797/MNDA_/Motor Neurone Disease Association/United Kingdom ; }, mesh = {Age of Onset ; Alleles ; Amyotrophic Lateral Sclerosis/*genetics ; Ataxin-2/*genetics ; Case-Control Studies ; Female ; *Genetic Association Studies ; Humans ; Male ; Risk ; Trinucleotide Repeat Expansion/*genetics ; Trinucleotide Repeats/*genetics ; }, abstract = {We investigated a CAG trinucleotide repeat expansion in the ATXN2 gene in amyotrophic lateral sclerosis (ALS). Two new case-control studies, a British dataset of 1474 ALS cases and 567 controls, and a Dutch dataset of 1328 ALS cases and 691 controls were analyzed. In addition, to increase power, we systematically searched PubMed for case-control studies published after 1 August 2010 that investigated the association between ATXN2 intermediate repeats and ALS. We conducted a meta-analysis of the new and existing studies for the relative risks of ATXN2 intermediate repeat alleles of between 24 and 34 CAG trinucleotide repeats and ALS. There was an overall increased risk of ALS for those carrying intermediate sized trinucleotide repeat alleles (odds ratio 3.06 [95% confidence interval 2.37-3.94]; p = 6 × 10[-18]), with an exponential relationship between repeat length and ALS risk for alleles of 29-32 repeats (R[2] = 0.91, p = 0.0002). No relationship was seen for repeat length and age of onset or survival. In contrast to trinucleotide repeat diseases, intermediate ATXN2 trinucleotide repeat expansion in ALS does not predict age of onset but does predict disease risk.}, }
@article {pmid26724605, year = {2016}, author = {Nichols, NL and Mitchell, GS}, title = {Quantitative assessment of integrated phrenic nerve activity.}, journal = {Respiratory physiology &amp; neurobiology}, volume = {226}, number = {}, pages = {81-86}, pmid = {26724605}, issn = {1878-1519}, support = {R00 HL119606/HL/NHLBI NIH HHS/United States ; R01 HL080209/HL/NHLBI NIH HHS/United States ; UL1 TR001427/TR/NCATS NIH HHS/United States ; P01 NS057778/NS/NINDS NIH HHS/United States ; K99 HL119606/HL/NHLBI NIH HHS/United States ; R01 HL069064/HL/NHLBI NIH HHS/United States ; }, mesh = {Amyotrophic Lateral Sclerosis/physiopathology ; Animals ; Chemoreceptor Cells/physiology ; Disease Models, Animal ; Humans ; In Vitro Techniques ; Male ; Microelectrodes ; Phrenic Nerve/*physiology/physiopathology ; Rats, Sprague-Dawley ; Rats, Transgenic ; Reflex/physiology ; Reproducibility of Results ; Respiration ; Species Specificity ; Superoxide Dismutase-1/genetics/metabolism ; }, abstract = {Integrated electrical activity in the phrenic nerve is commonly used to assess within-animal changes in phrenic motor output. Because of concerns regarding the consistency of nerve recordings, activity is most often expressed as a percent change from baseline values. However, absolute values of nerve activity are necessary to assess the impact of neural injury or disease on phrenic motor output. To date, no systematic evaluations of the repeatability/reliability have been made among animals when phrenic recordings are performed by an experienced investigator using standardized methods. We performed a meta-analysis of studies reporting integrated phrenic nerve activity in many rat groups by the same experienced investigator; comparisons were made during baseline and maximal chemoreceptor stimulation in 14 wild-type Harlan and 14 Taconic Sprague Dawley groups, and in 3 pre-symptomatic and 11 end-stage SOD1(G93A) Taconic rat groups (an ALS model). Meta-analysis results indicate: (1) consistent measurements of integrated phrenic activity in each sub-strain of wild-type rats; (2) with bilateral nerve recordings, left-to-right integrated phrenic activity ratios are ∼1.0; and (3) consistently reduced activity in end-stage SOD1(G93A) rats. Thus, with appropriate precautions, integrated phrenic nerve activity enables robust, quantitative comparisons among nerves or experimental groups, including differences caused by neuromuscular disease.}, }
@article {pmid25936935, year = {2015}, author = {Lill, CM and Rengmark, A and Pihlstrøm, L and Fogh, I and Shatunov, A and Sleiman, PM and Wang, LS and Liu, T and Lassen, CF and Meissner, E and Alexopoulos, P and Calvo, A and Chio, A and Dizdar, N and Faltraco, F and Forsgren, L and Kirchheiner, J and Kurz, A and Larsen, JP and Liebsch, M and Linder, J and Morrison, KE and Nissbrandt, H and Otto, M and Pahnke, J and Partch, A and Restagno, G and Rujescu, D and Schnack, C and Shaw, CE and Shaw, PJ and Tumani, H and Tysnes, OB and Valladares, O and Silani, V and van den Berg, LH and van Rheenen, W and Veldink, JH and Lindenberger, U and Steinhagen-Thiessen, E and ,  and Teipel, S and Perneczky, R and Hakonarson, H and Hampel, H and von Arnim, CAF and Olsen, JH and Van Deerlin, VM and Al-Chalabi, A and Toft, M and Ritz, B and Bertram, L}, title = {The role of TREM2 R47H as a risk factor for Alzheimer's disease, frontotemporal lobar degeneration, amyotrophic lateral sclerosis, and Parkinson's disease.}, journal = {Alzheimer's &amp; dementia : the journal of the Alzheimer's Association}, volume = {11}, number = {12}, pages = {1407-1416}, pmid = {25936935}, issn = {1552-5279}, support = {089701/WT_/Wellcome Trust/United Kingdom ; MC_G1000733/MRC_/Medical Research Council/United Kingdom ; MR/L021803/1/MRC_/Medical Research Council/United Kingdom ; G0500289/MRC_/Medical Research Council/United Kingdom ; P30 ES013508/ES/NIEHS NIH HHS/United States ; G0900688/MRC_/Medical Research Council/United Kingdom ; R01ES013717/ES/NIEHS NIH HHS/United States ; R01 ES013717/ES/NIEHS NIH HHS/United States ; MR/L501529/1/MRC_/Medical Research Council/United Kingdom ; P01 AG017586/AG/NIA NIH HHS/United States ; }, mesh = {Aged ; Alleles ; Alzheimer Disease/*genetics ; Amyotrophic Lateral Sclerosis/genetics ; Case-Control Studies ; Female ; Frontotemporal Lobar Degeneration/genetics ; *Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; Membrane Glycoproteins/*genetics ; Middle Aged ; Neurodegenerative Diseases/*genetics ; Parkinson Disease/genetics ; Quantitative Trait Loci ; Receptors, Immunologic/*genetics ; Risk Factors ; White People ; tau Proteins/cerebrospinal fluid ; }, abstract = {A rare variant in TREM2 (p.R47H, rs75932628) was recently reported to increase the risk of Alzheimer's disease (AD) and, subsequently, other neurodegenerative diseases, i.e. frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). Here we comprehensively assessed TREM2 rs75932628 for association with these diseases in a total of 19,940 previously untyped subjects of European descent. These data were combined with those from 28 published data sets by meta-analysis. Furthermore, we tested whether rs75932628 shows association with amyloid beta (Aβ42) and total-tau protein levels in the cerebrospinal fluid (CSF) of 828 individuals with AD or mild cognitive impairment. Our data show that rs75932628 is highly significantly associated with the risk of AD across 24,086 AD cases and 148,993 controls of European descent (odds ratio or OR = 2.71, P = 4.67 × 10(-25)). No consistent evidence for association was found between this marker and the risk of FTLD (OR = 2.24, P = .0113 across 2673 cases/9283 controls), PD (OR = 1.36, P = .0767 across 8311 cases/79,938 controls) and ALS (OR = 1.41, P = .198 across 5544 cases/7072 controls). Furthermore, carriers of the rs75932628 risk allele showed significantly increased levels of CSF-total-tau (P = .0110) but not Aβ42 suggesting that TREM2's role in AD may involve tau dysfunction.}, }
@article {pmid25285812, year = {2014}, author = {Neuenschwander, AG and Thai, KK and Figueroa, KP and Pulst, SM}, title = {Amyotrophic lateral sclerosis risk for spinocerebellar ataxia type 2 ATXN2 CAG repeat alleles: a meta-analysis.}, journal = {JAMA neurology}, volume = {71}, number = {12}, pages = {1529-1534}, pmid = {25285812}, issn = {2168-6157}, support = {R21NS081182/NS/NINDS NIH HHS/United States ; R01NS33123/NS/NINDS NIH HHS/United States ; R21NS079852/NS/NINDS NIH HHS/United States ; R37 NS033123/NS/NINDS NIH HHS/United States ; R01 NS033123/NS/NINDS NIH HHS/United States ; M01 RR000425/RR/NCRR NIH HHS/United States ; R21 NS079852/NS/NINDS NIH HHS/United States ; RC4 NS073009/NS/NINDS NIH HHS/United States ; RC4NS073009/NS/NINDS NIH HHS/United States ; R21 NS081182/NS/NINDS NIH HHS/United States ; R56 NS033123/NS/NINDS NIH HHS/United States ; }, mesh = {Amyotrophic Lateral Sclerosis/*genetics ; Ataxins ; Humans ; Nerve Tissue Proteins/*genetics ; Trinucleotide Repeat Expansion/*genetics ; }, abstract = {IMPORTANCE: Repeats of CAG in the ataxin 2 gene (ATXN2) in the long-normal range (sometimes referred to as intermediate) have been identified as modifiers of amyotrophic lateral sclerosis (ALS) risk. Prior studies have used thresholding considering various cutoffs for ATXN2 repeat length.<br><br>OBJECTIVE: To calculate association between ATXN2 CAG repeat alleles and increased risk of ALS across multiple ethnic groups.<br><br>DATA SOURCES: The MEDLINE database was searched for studies published by December 29, 2013, reporting ATXN2 CAG repeat length in patients with ALS and controls.<br><br>STUDY SELECTION: Studies were included if they reported original data on relative risks or odds ratios (ORs) from ALS and control populations for individual ATXN2 alleles. Review articles that reported no new data were not included in the analysis.<br><br>DATA EXTRACTION AND SYNTHESIS: Analysis of allele distribution was performed to ensure that all studies followed identical allele sizing. The ORs, 95% confidence intervals, and population attributable risk percentages were calculated according to standard procedures.<br><br>MAIN OUTCOMES AND MEASURES: Occurrence of ALS associated with ATXN2 repeat alleles, expressed as ORs.<br><br>RESULTS: Nine studies were analyzed, including 7505 controls and 6151 sporadic ALS cases. The ALS and control cohorts were recruited from different geographical and ethnic regions including the United States, French Canada/Canada, Belgium and the Netherlands, Germany, Italy, mainland China, Turkey, and Flanders-Belgium. The ATXN2 CAG repeat lengths ranged from 13 to 39 in patients with ALS and from 13 to 34 in controls. The ORs were less than 1.00 for alleles with 25 to 28 repeats. The OR was 1.55 for 30 repeats, but this elevation was not statistically significant (95% CI, 0.88-2.73). The ORs were 2.70 (95% CI, 1.47-4.93) for 31 CAG repeats, 11.09 (95% CI, 4.16-29.57) for 32 repeats, and 5.76 (95% CI, 1.79-18.57) for 33 repeats.<br><br>CONCLUSIONS AND RELEVANCE: In contrast to prior studies with smaller numbers, risk for ALS associated with long-normal alleles is complex. Alleles with 27 and 28 repeats lower ALS risk slightly. The risk for ALS increases beginning with 29 repeats and reaches a maximum at 32 and 33 repeats. Of note, alleles with repeats of these lengths are known to be predisposed to meiotic expansion to full-penetrance mutant alleles. In patients with ALS, alleles with 31 to 33 repeats may have undergone preferential expansion in motor neurons during mitosis or DNA repair. Our meta-analysis provides a framework for counseling individuals with long-normal ATXN2 repeats.}, }
@article {pmid25233373, year = {2014}, author = {Simpson, CL and Wojciechowski, R and Oexle, K and Murgia, F and Portas, L and Li, X and Verhoeven, VJ and Vitart, V and Schache, M and Hosseini, SM and Hysi, PG and Raffel, LJ and Cotch, MF and Chew, E and Klein, BE and Klein, R and Wong, TY and van Duijn, CM and Mitchell, P and Saw, SM and Fossarello, M and Wang, JJ and ,  and Polašek, O and Campbell, H and Rudan, I and Oostra, BA and Uitterlinden, AG and Hofman, A and Rivadeneira, F and Amin, N and Karssen, LC and Vingerling, JR and Döring, A and Bettecken, T and Bencic, G and Gieger, C and Wichmann, HE and Wilson, JF and Venturini, C and Fleck, B and Cumberland, PM and Rahi, JS and Hammond, CJ and Hayward, C and Wright, AF and Paterson, AD and Baird, PN and Klaver, CC and Rotter, JI and Pirastu, M and Meitinger, T and Bailey-Wilson, JE and Stambolian, D}, title = {Genome-wide meta-analysis of myopia and hyperopia provides evidence for replication of 11 loci.}, journal = {PloS one}, volume = {9}, number = {9}, pages = {e107110}, pmid = {25233373}, issn = {1932-6203}, support = {N01 HC095168/HL/NHLBI NIH HHS/United States ; ZIA EY000403/ImNIH/Intramural NIH HHS/United States ; R01 DK077510/DK/NIDDK NIH HHS/United States ; N01-DK-6-2204/DK/NIDDK NIH HHS/United States ; HHSN268200782096C/HG/NHGRI NIH HHS/United States ; N01 HC-95159/HC/NHLBI NIH HHS/United States ; ZIAEY000403//PHS HHS/United States ; N01 HC095166/HL/NHLBI NIH HHS/United States ; MC_U127584475/MRC_/Medical Research Council/United Kingdom ; R01 EY016379/EY/NEI NIH HHS/United States ; N02-HL-6-4278/HL/NHLBI NIH HHS/United States ; UL1 RR033176/RR/NCRR NIH HHS/United States ; CZB/4/710/CSO_/Chief Scientist Office/United Kingdom ; CZB/4/438/CSO_/Chief Scientist Office/United Kingdom ; U01 DK094176/DK/NIDDK NIH HHS/United States ; N01-HC-95162/HC/NHLBI NIH HHS/United States ; UL1RR033176/RR/NCRR NIH HHS/United States ; UL1TR000124/TR/NCATS NIH HHS/United States ; N01 HC095161/HL/NHLBI NIH HHS/United States ; N01 HC095169/HL/NHLBI NIH HHS/United States ; Z99 EY999999/ImNIH/Intramural NIH HHS/United States ; RR-024156/RR/NCRR NIH HHS/United States ; N01-HC-95163/HC/NHLBI NIH HHS/United States ; N01-HC-95168/HC/NHLBI NIH HHS/United States ; Z01 EY000403/ImNIH/Intramural NIH HHS/United States ; UL1 RR024156/RR/NCRR NIH HHS/United States ; N01 HC095167/HL/NHLBI NIH HHS/United States ; R01-DK-077510/DK/NIDDK NIH HHS/United States ; 085475/B/08/Z/WT_/Wellcome Trust/United Kingdom ; K08 EY022943/EY/NEI NIH HHS/United States ; N01-HC-95165/HC/NHLBI NIH HHS/United States ; UL1 TR000114/TR/NCATS NIH HHS/United States ; UL1 TR000124/TR/NCATS NIH HHS/United States ; N01-HC-95169/HC/NHLBI NIH HHS/United States ; R01 EY020483/EY/NEI NIH HHS/United States ; R01EY020483/EY/NEI NIH HHS/United States ; N01-HC-95164/HC/NHLBI NIH HHS/United States ; N01-HC-95160/HC/NHLBI NIH HHS/United States ; MC_PC_U127561128/MRC_/Medical Research Council/United Kingdom ; N01 HC095163/HL/NHLBI NIH HHS/United States ; UL1 TR000142/TR/NCATS NIH HHS/United States ; N01-HC-95161/HC/NHLBI NIH HHS/United States ; /WT_/Wellcome Trust/United Kingdom ; N01 HC095162/HL/NHLBI NIH HHS/United States ; N01-HC-95166/HC/NHLBI NIH HHS/United States ; 085475/08/Z/WT_/Wellcome Trust/United Kingdom ; SRF/01/010/DH_/Department of Health/United Kingdom ; N01 HC095165/HL/NHLBI NIH HHS/United States ; N01 HC095164/HL/NHLBI NIH HHS/United States ; N01 HC095159/HC/NHLBI NIH HHS/United States ; N01-HC-95167/HC/NHLBI NIH HHS/United States ; R01EY016379/EY/NEI NIH HHS/United States ; N01 HC095160/HL/NHLBI NIH HHS/United States ; }, mesh = {Adult ; Age of Onset ; Aged ; Aged, 80 and over ; Alleles ; Eye/*physiopathology ; Female ; Genetic Association Studies ; Genetic Markers/genetics ; Genetic Predisposition to Disease ; Humans ; Hyperopia/*genetics ; Linkage Disequilibrium ; Male ; Middle Aged ; Myopia/*genetics ; Phenotype ; Polymorphism, Single Nucleotide ; White People/genetics ; }, abstract = {Refractive error (RE) is a complex, multifactorial disorder characterized by a mismatch between the optical power of the eye and its axial length that causes object images to be focused off the retina. The two major subtypes of RE are myopia (nearsightedness) and hyperopia (farsightedness), which represent opposite ends of the distribution of the quantitative measure of spherical refraction. We performed a fixed effects meta-analysis of genome-wide association results of myopia and hyperopia from 9 studies of European-derived populations: AREDS, KORA, FES, OGP-Talana, MESA, RSI, RSII, RSIII and ERF. One genome-wide significant region was observed for myopia, corresponding to a previously identified myopia locus on 8q12 (p = 1.25×10(-8)), which has been reported by Kiefer et al. as significantly associated with myopia age at onset and Verhoeven et al. as significantly associated to mean spherical-equivalent (MSE) refractive error. We observed two genome-wide significant associations with hyperopia. These regions overlapped with loci on 15q14 (minimum p value = 9.11×10(-11)) and 8q12 (minimum p value 1.82×10(-11)) previously reported for MSE and myopia age at onset. We also used an intermarker linkage- disequilibrium-based method for calculating the effective number of tests in targeted regional replication analyses. We analyzed myopia (which represents the closest phenotype in our data to the one used by Kiefer et al.) and showed replication of 10 additional loci associated with myopia previously reported by Kiefer et al. This is the first replication of these loci using myopia as the trait under analysis. "Replication-level" association was also seen between hyperopia and 12 of Kiefer et al.'s published loci. For the loci that show evidence of association to both myopia and hyperopia, the estimated effect of the risk alleles were in opposite directions for the two traits. This suggests that these loci are important contributors to variation of refractive error across the distribution.}, }
@article {pmid25187168, year = {2014}, author = {Li, MD and Burns, TC and Morgan, AA and Khatri, P}, title = {Integrated multi-cohort transcriptional meta-analysis of neurodegenerative diseases.}, journal = {Acta neuropathologica communications}, volume = {2}, number = {}, pages = {93}, pmid = {25187168}, issn = {2051-5960}, support = {U19 AI057229/AI/NIAID NIH HHS/United States ; U19 AI109662/AI/NIAID NIH HHS/United States ; 1U19AI109662/AI/NIAID NIH HHS/United States ; }, mesh = {Central Nervous System/*metabolism ; Cohort Studies ; Female ; Gene Expression Profiling ; *Gene Expression Regulation ; Humans ; Male ; Neurodegenerative Diseases/*pathology ; Oligonucleotide Array Sequence Analysis ; Transcription Factors/genetics/*metabolism ; }, abstract = {INTRODUCTION: Neurodegenerative diseases share common pathologic features including neuroinflammation, mitochondrial dysfunction and protein aggregation, suggesting common underlying mechanisms of neurodegeneration. We undertook a meta-analysis of public gene expression data for neurodegenerative diseases to identify a common transcriptional signature of neurodegeneration.<br><br>RESULTS: Using 1,270 post-mortem central nervous system tissue samples from 13 patient cohorts covering four neurodegenerative diseases, we identified 243 differentially expressed genes, which were similarly dysregulated in 15 additional patient cohorts of 205 samples including seven neurodegenerative diseases. This gene signature correlated with histologic disease severity. Metallothioneins featured prominently among differentially expressed genes, and functional pathway analysis identified specific convergent themes of dysregulation. MetaCore network analyses revealed various novel candidate hub genes (e.g. STAU2). Genes associated with M1-polarized macrophages and reactive astrocytes were strongly enriched in the meta-analysis data. Evaluation of genes enriched in neurons revealed 70 down-regulated genes, over half not previously associated with neurodegeneration. Comparison with aging brain data (3 patient cohorts, 221 samples) revealed 53 of these to be unique to neurodegenerative disease, many of which are strong candidates to be important in neuropathogenesis (e.g. NDN, NAP1L2). ENCODE ChIP-seq analysis predicted common upstream transcriptional regulators not associated with normal aging (REST, RBBP5, SIN3A, SP2, YY1, ZNF143, IKZF1). Finally, we removed genes common to neurodegeneration from disease-specific gene signatures, revealing uniquely robust immune response and JAK-STAT signaling in amyotrophic lateral sclerosis.<br><br>CONCLUSIONS: Our results implicate pervasive bioenergetic deficits, M1-type microglial activation and gliosis as unifying themes of neurodegeneration, and identify numerous novel genes associated with neurodegenerative processes.}, }
@article {pmid25023276, year = {2014}, author = {Fitzgerald, KC and O'Reilly, &#xc9;J and Falcone, GJ and McCullough, ML and Park, Y and Kolonel, LN and Ascherio, A}, title = {Dietary ω-3 polyunsaturated fatty acid intake and risk for amyotrophic lateral sclerosis.}, journal = {JAMA neurology}, volume = {71}, number = {9}, pages = {1102-1110}, pmid = {25023276}, issn = {2168-6157}, support = {P01 CA055075/CA/NCI NIH HHS/United States ; P01 CA087969/CA/NCI NIH HHS/United States ; R01 NS045893/NS/NINDS NIH HHS/United States ; P01 CA87969/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Amyotrophic Lateral Sclerosis/*prevention &amp; control ; Dietary Supplements/*statistics &amp; numerical data ; Energy Intake ; Fatty Acids, Omega-3/*pharmacology ; Female ; Humans ; Longitudinal Studies ; Male ; Middle Aged ; Proportional Hazards Models ; Risk ; }, abstract = {IMPORTANCE: Amyotrophic lateral sclerosis (ALS) is a severe progressive disease that cannot be prevented or cured. Diet-derived long-chain polyunsaturated fatty acids (PUFAs) are incorporated in brain lipids and modulate oxidative and inflammatory processes and could thus affect ALS risk and progression.<br><br>OBJECTIVE: To examine the association between &#x3c9;-6 and &#x3c9;-3 PUFA consumption and ALS risk.<br><br>Longitudinal analyses based on 1,002,082 participants (479,114 women and 522,968 men) in 5 prospective cohorts: the National Institutes of Health-AARP Diet and Health Study, the Cancer Prevention Study II Nutrition Cohort, the Health Professionals Follow-up Study, the Multiethnic Cohort Study, and the Nurses' Health Study. Diet was assessed via food frequency questionnaire developed or modified for each cohort. Participants were categorized into cohort-specific quintiles of intake of energy-adjusted dietary variables.<br><br>MAIN OUTCOMES AND MEASURES: Cohort-specific multivariable-adjusted risk ratios (RRs) of ALS incidence or death estimated by Cox proportional hazards regression and pooled using random-effects methods.<br><br>RESULTS: A total of 995 ALS cases were documented during the follow-up. A greater &#x3c9;-3 PUFA intake was associated with a reduced risk for ALS. The pooled, multivariable-adjusted RR for the highest to the lowest quintile was 0.66 (95% CI, 0.53-0.81; P <&#x2009;.001 for trend). Consumption of both &#x3b1;-linolenic acid (RR, 0.73; 95% CI, 0.59-0.89; P =&#x2009;.003 for trend) and marine &#x3c9;-3 PUFAs (RR, 0.84; 95% CI, 0.65-1.08; P =&#x2009;.03 for trend) contributed to this inverse association. Intakes of &#x3c9;-6 PUFA were not associated with ALS risk.<br><br>CONCLUSIONS AND RELEVANCE: Consumption of foods high in &#x3c9;-3 PUFAs may help prevent or delay the onset of ALS.}, }
@article {pmid25023141, year = {2014}, author = {Keller, MF and Ferrucci, L and Singleton, AB and Tienari, PJ and Laaksovirta, H and Restagno, G and Chiò, A and Traynor, BJ and Nalls, MA}, title = {Genome-wide analysis of the heritability of amyotrophic lateral sclerosis.}, journal = {JAMA neurology}, volume = {71}, number = {9}, pages = {1123-1134}, pmid = {25023141}, issn = {2168-6157}, support = {Z01 AG000949/ImNIH/Intramural NIH HHS/United States ; R01 ES013244/ES/NIEHS NIH HHS/United States ; /MRC_/Medical Research Council/United Kingdom ; ZIA AG000933/ImNIH/Intramural NIH HHS/United States ; ES013244/ES/NIEHS NIH HHS/United States ; Z01AG000949-02/AG/NIA NIH HHS/United States ; }, mesh = {Amyotrophic Lateral Sclerosis/*genetics ; Case-Control Studies ; Cohort Studies ; Female ; Genetic Predisposition to Disease/genetics ; *Genome-Wide Association Study ; Genotype ; Humans ; Male ; Phenotype ; Polymorphism, Single Nucleotide/genetics ; }, abstract = {IMPORTANCE: Considerable advances have been made in our understanding of the genetics underlying amyotrophic lateral sclerosis (ALS). Nevertheless, for the majority of patients who receive a diagnosis of ALS, the role played by genetics is unclear. Further elucidation of the genetic architecture of this disease will help clarify the role of genetic variation in ALS populations.<br><br>OBJECTIVE: To estimate the relative importance of genetic factors in a complex disease such as ALS by accurately quantifying heritability using genome-wide data derived from genome-wide association studies.<br><br>We applied the genome-wide complex trait analysis algorithm to 3 genome-wide association study data sets that were generated from ALS case-control cohorts of European ancestry to estimate the heritability of ALS. Cumulatively, these data sets contained genotype data from 1223 cases and 1591 controls that had been previously generated and are publically available on the National Center for Biotechnology Information database of genotypes and phenotypes website (http://www.ncbi.nlm.nih.gov/gap). The cohorts genotyped as part of these genome-wide association study efforts include the InCHIANTI (aging in the Chianti area) Study, the Piemonte and Valle d'Aosta Register for Amyotrophic Lateral Sclerosis, the National Institute of Neurological Disorders and Stroke Repository, and an ALS specialty clinic in Helsinki, Finland.<br><br>MAIN OUTCOMES AND MEASURES: A linear mixed model was used to account for all known single-nucleotide polymorphisms simultaneously and to quantify the phenotypic variance present in ostensibly outbred individuals. Variance measures were used to estimate heritability.<br><br>RESULTS: With our meta-analysis, which is based on genome-wide genotyping data, we estimated the overall heritability of ALS to be approximately 21.0% (95% CI, 17.1-24.9) (SE = 2.0%), indicating that additional genetic variation influencing risk of ALS loci remains to be identified. Furthermore, we identified 17 regions of the genome that display significantly high heritability estimates. Eleven of these regions represent novel candidate regions for ALS risk.<br><br>CONCLUSIONS AND RELEVANCE: We found the heritability of ALS to be significantly higher than previously reported. We also identified multiple, novel genomic regions that we hypothesize may contain causative risk variants that influence susceptibility to ALS.}, }
@article {pmid24931836, year = {2014}, author = {Diekstra, FP and Van Deerlin, VM and van Swieten, JC and Al-Chalabi, A and Ludolph, AC and Weishaupt, JH and Hardiman, O and Landers, JE and Brown, RH and van Es, MA and Pasterkamp, RJ and Koppers, M and Andersen, PM and Estrada, K and Rivadeneira, F and Hofman, A and Uitterlinden, AG and van Damme, P and Melki, J and Meininger, V and Shatunov, A and Shaw, CE and Leigh, PN and Shaw, PJ and Morrison, KE and Fogh, I and Chiò, A and Traynor, BJ and Czell, D and Weber, M and Heutink, P and de Bakker, PI and Silani, V and Robberecht, W and van den Berg, LH and Veldink, JH}, title = {C9orf72 and UNC13A are shared risk loci for amyotrophic lateral sclerosis and frontotemporal dementia: a genome-wide meta-analysis.}, journal = {Annals of neurology}, volume = {76}, number = {1}, pages = {120-133}, pmid = {24931836}, issn = {1531-8249}, support = {089701/WT_/Wellcome Trust/United Kingdom ; G0900635/MRC_/Medical Research Council/United Kingdom ; MC_G1000733/MRC_/Medical Research Council/United Kingdom ; G0600974/MRC_/Medical Research Council/United Kingdom ; G0500289/MRC_/Medical Research Council/United Kingdom ; G0900688/MRC_/Medical Research Council/United Kingdom ; R01 NS050557/NS/NINDS NIH HHS/United States ; ZIA AG000933/ImNIH/Intramural NIH HHS/United States ; MR/L501529/1/MRC_/Medical Research Council/United Kingdom ; P01 AG017586/AG/NIA NIH HHS/United States ; R01 NS073873/NS/NINDS NIH HHS/United States ; G1100695/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Amyotrophic Lateral Sclerosis/*genetics ; C9orf72 Protein ; Chromosomes, Human, Pair 19/genetics ; Chromosomes, Human, Pair 9/genetics ; DNA Repeat Expansion/genetics ; Frontotemporal Dementia/*genetics ; Genome-Wide Association Study/*methods/trends ; Humans ; Mutation ; Nerve Tissue Proteins/*genetics ; Polymorphism, Single Nucleotide/genetics ; Proteins/*genetics ; }, abstract = {OBJECTIVE: Substantial clinical, pathological, and genetic overlap exists between amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). TDP-43 inclusions have been found in both ALS and FTD cases (FTD-TDP). Recently, a repeat expansion in C9orf72 was identified as the causal variant in a proportion of ALS and FTD cases. We sought to identify additional evidence for a common genetic basis for the spectrum of ALS-FTD.<br><br>METHODS: We used published genome-wide association studies data for 4,377 ALS patients and 13,017 controls, and 435 pathology-proven FTD-TDP cases and 1,414 controls for genotype imputation. Data were analyzed in a joint meta-analysis, by replicating topmost associated hits of one disease in the other, and by using a conservative rank products analysis, allocating equal weight to ALS and FTD-TDP sample sizes.<br><br>RESULTS: Meta-analysis identified 19 genome-wide significant single nucleotide polymorphisms (SNPs) in C9orf72 on chromosome 9p21.2 (lowest p = 2.6 &#xd7; 10(-12)) and 1 SNP in UNC13A on chromosome 19p13.11 (p = 1.0 &#xd7; 10(-11)) as shared susceptibility loci for ALS and FTD-TDP. Conditioning on the 9p21.2 genotype increased statistical significance at UNC13A. A third signal, on chromosome 8q24.13 at the SPG8 locus coding for strumpellin (p = 3.91 &#xd7; 10(-7)) was replicated in an independent cohort of 4,056 ALS patients and 3,958 controls (p = 0.026; combined analysis p = 1.01 &#xd7; 10(-7)).<br><br>INTERPRETATION: We identified common genetic variants in C9orf72, but in addition in UNC13A that are shared between ALS and FTD. UNC13A provides a novel link between ALS and FTD-TDP, and identifies changes in neurotransmitter release and synaptic function as a converging mechanism in the pathogenesis of ALS and FTD-TDP.}, }
@article {pmid24256812, year = {2014}, author = {Fogh, I and Ratti, A and Gellera, C and Lin, K and Tiloca, C and Moskvina, V and Corrado, L and Sorarù, G and Cereda, C and Corti, S and Gentilini, D and Calini, D and Castellotti, B and Mazzini, L and Querin, G and Gagliardi, S and Del Bo, R and Conforti, FL and Siciliano, G and Inghilleri, M and Saccà, F and Bongioanni, P and Penco, S and Corbo, M and Sorbi, S and Filosto, M and Ferlini, A and Di Blasio, AM and Signorini, S and Shatunov, A and Jones, A and Shaw, PJ and Morrison, KE and Farmer, AE and Van Damme, P and Robberecht, W and Chiò, A and Traynor, BJ and Sendtner, M and Melki, J and Meininger, V and Hardiman, O and Andersen, PM and Leigh, NP and Glass, JD and Overste, D and Diekstra, FP and Veldink, JH and van Es, MA and Shaw, CE and Weale, ME and Lewis, CM and Williams, J and Brown, RH and Landers, JE and Ticozzi, N and Ceroni, M and Pegoraro, E and Comi, GP and D'Alfonso, S and van den Berg, LH and Taroni, F and Al-Chalabi, A and Powell, J and Silani, V and , }, title = {A genome-wide association meta-analysis identifies a novel locus at 17q11.2 associated with sporadic amyotrophic lateral sclerosis.}, journal = {Human molecular genetics}, volume = {23}, number = {8}, pages = {2220-2231}, pmid = {24256812}, issn = {1460-2083}, support = {MR/K013041/1/MRC_/Medical Research Council/United Kingdom ; 089701/WT_/Wellcome Trust/United Kingdom ; G0900635/MRC_/Medical Research Council/United Kingdom ; MR/L501529/1/MRC_/Medical Research Council/United Kingdom ; RC2 NS070342/NS/NINDS NIH HHS/United States ; MR/J006742/1/MRC_/Medical Research Council/United Kingdom ; G0902227/MRC_/Medical Research Council/United Kingdom ; G0900688/MRC_/Medical Research Council/United Kingdom ; R01 NS050557/NS/NINDS NIH HHS/United States ; MR/L010305/1/MRC_/Medical Research Council/United Kingdom ; 1R01NS073873/NS/NINDS NIH HHS/United States ; G0701420/MRC_/Medical Research Council/United Kingdom ; MC_G1000733/MRC_/Medical Research Council/United Kingdom ; MR/K01417X/1/MRC_/Medical Research Council/United Kingdom ; R01 NS073873/NS/NINDS NIH HHS/United States ; MR/L501517/1/MRC_/Medical Research Council/United Kingdom ; G1100695/MRC_/Medical Research Council/United Kingdom ; G0501573/MRC_/Medical Research Council/United Kingdom ; G0500289/MRC_/Medical Research Council/United Kingdom ; G0600974/MRC_/Medical Research Council/United Kingdom ; 070122/A/02/Z/WT_/Wellcome Trust/United Kingdom ; RC2-NS070-342/NS/NINDS NIH HHS/United States ; GTB12001/TI_/Telethon/Italy ; }, mesh = {Amyotrophic Lateral Sclerosis/*genetics ; Case-Control Studies ; Chromosomes, Human, Pair 17/*genetics ; *Genome-Wide Association Study ; Humans ; Prognosis ; }, abstract = {Identification of mutations at familial loci for amyotrophic lateral sclerosis (ALS) has provided novel insights into the aetiology of this rapidly progressing fatal neurodegenerative disease. However, genome-wide association studies (GWAS) of the more common (∼90%) sporadic form have been less successful with the exception of the replicated locus at 9p21.2. To identify new loci associated with disease susceptibility, we have established the largest association study in ALS to date and undertaken a GWAS meta-analytical study combining 3959 newly genotyped Italian individuals (1982 cases and 1977 controls) collected by SLAGEN (Italian Consortium for the Genetics of ALS) together with samples from Netherlands, USA, UK, Sweden, Belgium, France, Ireland and Italy collected by ALSGEN (the International Consortium on Amyotrophic Lateral Sclerosis Genetics). We analysed a total of 13 225 individuals, 6100 cases and 7125 controls for almost 7 million single-nucleotide polymorphisms (SNPs). We identified a novel locus with genome-wide significance at 17q11.2 (rs34517613 with P = 1.11 × 10(-8); OR 0.82) that was validated when combined with genotype data from a replication cohort (P = 8.62 × 10(-9); OR 0.833) of 4656 individuals. Furthermore, we confirmed the previously reported association at 9p21.2 (rs3849943 with P = 7.69 × 10(-9); OR 1.16). Finally, we estimated the contribution of common variation to heritability of sporadic ALS as ∼12% using a linear mixed model accounting for all SNPs. Our results provide an insight into the genetic structure of sporadic ALS, confirming that common variation contributes to risk and that sufficiently powered studies can identify novel susceptibility loci.}, }
@article {pmid24234648, year = {2014}, author = {Goris, A and van Setten, J and Diekstra, F and Ripke, S and Patsopoulos, NA and Sawcer, SJ and ,  and van Es, M and ,  and Andersen, PM and Melki, J and Meininger, V and Hardiman, O and Landers, JE and Brown, RH and Shatunov, A and Leigh, N and Al-Chalabi, A and Shaw, CE and Traynor, BJ and Chiò, A and Restagno, G and Mora, G and Ophoff, RA and Oksenberg, JR and Van Damme, P and Compston, A and Robberecht, W and Dubois, B and van den Berg, LH and De Jager, PL and Veldink, JH and de Bakker, PI}, title = {No evidence for shared genetic basis of common variants in multiple sclerosis and amyotrophic lateral sclerosis.}, journal = {Human molecular genetics}, volume = {23}, number = {7}, pages = {1916-1922}, pmid = {24234648}, issn = {1460-2083}, support = {G0900635/MRC_/Medical Research Council/United Kingdom ; Z01 AG000949/ImNIH/Intramural NIH HHS/United States ; MC_G1000733/MRC_/Medical Research Council/United Kingdom ; R01 NS049477/NS/NINDS NIH HHS/United States ; G0600974/MRC_/Medical Research Council/United Kingdom ; R01 NS050557/NS/NINDS NIH HHS/United States ; 089701/WT_/Wellcome Trust/United Kingdom ; NS050557/NS/NINDS NIH HHS/United States ; R01 NS073873/NS/NINDS NIH HHS/United States ; G1100695/MRC_/Medical Research Council/United Kingdom ; G0501573/MRC_/Medical Research Council/United Kingdom ; G0500289/MRC_/Medical Research Council/United Kingdom ; G0900688/MRC_/Medical Research Council/United Kingdom ; Z01-AG000949-02/AG/NIA NIH HHS/United States ; }, mesh = {Amyotrophic Lateral Sclerosis/*epidemiology/*genetics ; Comorbidity ; Genetic Predisposition to Disease ; Humans ; Multiple Sclerosis/*epidemiology/*genetics ; Polymorphism, Single Nucleotide ; }, abstract = {Genome-wide association studies have been successful in identifying common variants that influence the susceptibility to complex diseases. From these studies, it has emerged that there is substantial overlap in susceptibility loci between diseases. In line with those findings, we hypothesized that shared genetic pathways may exist between multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). While both diseases may have inflammatory and neurodegenerative features, epidemiological studies have indicated an increased co-occurrence within individuals and families. To this purpose, we combined genome-wide data from 4088 MS patients, 3762 ALS patients and 12 030 healthy control individuals in whom 5 440 446 single-nucleotide polymorphisms (SNPs) were successfully genotyped or imputed. We tested these SNPs for the excess association shared between MS and ALS and also explored whether polygenic models of SNPs below genome-wide significance could explain some of the observed trait variance between diseases. Genome-wide association meta-analysis of SNPs as well as polygenic analyses fails to provide evidence in favor of an overlap in genetic susceptibility between MS and ALS. Hence, our findings do not support a shared genetic background of common risk variants in MS and ALS.}, }
@article {pmid24092916, year = {2015}, author = {Scammacca, NK and Roberts, G and Vaughn, S and Stuebing, KK}, title = {A Meta-Analysis of Interventions for Struggling Readers in Grades 4-12: 1980-2011.}, journal = {Journal of learning disabilities}, volume = {48}, number = {4}, pages = {369-390}, pmid = {24092916}, issn = {1538-4780}, support = {P50 HD052117/HD/NICHD NIH HHS/United States ; }, mesh = {Adolescent ; Child ; Dyslexia/*rehabilitation ; Education, Special/*statistics &amp; numerical data ; Humans ; Outcome Assessment, Health Care/*statistics &amp; numerical data ; }, abstract = {This meta-analysis synthesizes the literature on interventions for struggling readers in Grades 4 through 12 published between 1980 and 2011. It updates Scammacca et al.'s analysis of studies published between 1980 and 2004. The combined corpus of 82 study-wise effect sizes was meta-analyzed to determine (a) the overall effectiveness of reading interventions studied over the past 30 years, (b) how the magnitude of the effect varies based on student, intervention, and research design characteristics, and (c) what differences in effectiveness exist between more recent interventions and older ones. The analysis yielded a mean effect of 0.49, considerably smaller than the 0.95 mean effect reported in 2007. The mean effect for standardized measures was 0.21, also much smaller than the 0.42 mean effect reported in 2007. The mean effects for reading comprehension measures were similarly diminished. Results indicated that the mean effects for the 1980-2004 and 2005-2011 groups of studies were different to a statistically significant degree. The decline in effect sizes over time is attributed at least in part to increased use of standardized measures, more rigorous and complex research designs, differences in participant characteristics, and improvements in the school's "business-as-usual" instruction that often serves as the comparison condition in intervention studies.}, }
@article {pmid23362045, year = {2013}, author = {Fitzgerald, KC and O'Reilly, &#xc9;J and Fondell, E and Falcone, GJ and McCullough, ML and Park, Y and Kolonel, LN and Ascherio, A}, title = {Intakes of vitamin C and carotenoids and risk of amyotrophic lateral sclerosis: pooled results from 5 cohort studies.}, journal = {Annals of neurology}, volume = {73}, number = {2}, pages = {236-245}, pmid = {23362045}, issn = {1531-8249}, support = {P01 CA087969/CA/NCI NIH HHS/United States ; P01 CA055075/CA/NCI NIH HHS/United States ; R37 CA54281/CA/NCI NIH HHS/United States ; P01 CA87969/CA/NCI NIH HHS/United States ; R01 NS045893/NS/NINDS NIH HHS/United States ; R37 CA054281/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Amyotrophic Lateral Sclerosis/*epidemiology/*metabolism ; Antioxidants/*administration &amp; dosage ; Ascorbic Acid/*administration &amp; dosage ; Carotenoids/*administration &amp; dosage ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Oxidative Stress/drug effects ; Proportional Hazards Models ; Prospective Studies ; Risk Factors ; }, abstract = {OBJECTIVE: Prior research has suggested the possible role of oxidative stress in the pathogenesis of amyotrophic lateral sclerosis (ALS). Prospective data examining dietary antioxidants such carotenoids and vitamin C are limited.<br><br>METHODS: Risk of ALS associated with carotenoid and vitamin C intake was investigated in 5 prospective cohorts: the National Institutes of Health-Association of American Retired Persons Diet and Health Study, the Cancer Prevention Study II Nutrition Cohort, the Multiethnic Cohort, the Health Professionals Follow-up Study (HPFS), and the Nurses Health Study (NHS). ALS deaths were documented using the National Death Index, and confirmed nonfatal ALS cases were included from HPFS and NHS. A total of 1,153 ALS deaths occurred among 1,100,910 participants (562,942 men; 537,968 women). Participants were categorized into cohort-specific quintiles of intake for dietary variables. We applied Cox proportional hazards regression to calculate cohort-specific risk ratios (RRs), and pooled results using random-effects methods.<br><br>RESULTS: A greater total major carotenoids intake was associated with a reduced risk of ALS (pooled, multivariate-adjusted RR for the highest to the lowest quintile = 0.75, 95% confidence interval [CI] = 0.61-0.91, p for trend = 0.004). Individually, higher dietary intakes of &#x3b2;-carotene and lutein were inversely associated with ALS risk. The pooled multivariate RRs comparing the highest to the lowest quintile for &#x3b2;-carotene and lutein were 0.85 (95% CI = 0.64-1.13, p for trend = 0.03) and 0.79 (95% CI = 0.64-0.96, p for trend = 0.01), respectively. Lycopene, &#x3b2;-cryptoxanthin, and vitamin C were not associated with reduced risk of ALS.<br><br>INTERPRETATION: Consumption of foods high in carotenoids may help prevent or delay onset of ALS.}, }
@article {pmid23253611, year = {2012}, author = {Teng, YD and Benn, SC and Kalkanis, SN and Shefner, JM and Onario, RC and Cheng, B and Lachyankar, MB and Marconi, M and Li, J and Yu, D and Han, I and Maragakis, NJ and Lládo, J and Erkmen, K and Redmond, DE and Sidman, RL and Przedborski, S and Rothstein, JD and Brown, RH and Snyder, EY}, title = {Multimodal actions of neural stem cells in a mouse model of ALS: a meta-analysis.}, journal = {Science translational medicine}, volume = {4}, number = {165}, pages = {165ra164}, doi = {10.1126/scitranslmed.3004579}, pmid = {23253611}, issn = {1946-6242}, support = {1RC1NS068391-01/NS/NINDS NIH HHS/United States ; 1RC2NS070342-01/NS/NINDS NIH HHS/United States ; R01-NS34247/NS/NINDS NIH HHS/United States ; R01NS050557-05/NS/NINDS NIH HHS/United States ; R21NS053935/NS/NINDS NIH HHS/United States ; U01NS05225-03/NS/NINDS NIH HHS/United States ; }, mesh = {Amyotrophic Lateral Sclerosis/*pathology ; Animals ; Cell Differentiation ; Disease Models, Animal ; Mice ; Mice, Transgenic ; Neural Stem Cells/*cytology ; Superoxide Dismutase/genetics ; Superoxide Dismutase-1 ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a lethal disease characterized by the unremitting degeneration of motor neurons. Multiple processes involving motor neurons and other cell types have been implicated in its pathogenesis. Neural stem cells (NSCs) perform multiple actions within the nervous system to fulfill their functions of organogenesis and homeostasis. We test the hypothesis that transplanted, undifferentiated multipotent migratory NSCs may help to ameliorate an array of pathological mechanisms in the SOD1(G93A) transgenic mouse model of ALS. On the basis of a meta-analysis of 11 independent studies performed by a consortium of ALS investigators, we propose that transplanted NSCs (both mouse and human) can slow both the onset and the progression of clinical signs and prolong survival in ALS mice, particularly if regions sustaining vital functions such as respiration are rendered chimeric. The beneficial effects of transplanted NSCs seem to be mediated by a number of actions including their ability to produce trophic factors, preserve neuromuscular function, and reduce astrogliosis and inflammation. We conclude that the widespread, pleiotropic, modulatory actions exerted by transplanted NSCs may represent an accessible therapeutic application of stem cells for treating ALS and other untreatable degenerative diseases.}, }
@article {pmid22749050, year = {2012}, author = {Foerster, BR and Dwamena, BA and Petrou, M and Carlos, RC and Callaghan, BC and Pomper, MG}, title = {Diagnostic accuracy using diffusion tensor imaging in the diagnosis of ALS: a meta-analysis.}, journal = {Academic radiology}, volume = {19}, number = {9}, pages = {1075-1086}, pmid = {22749050}, issn = {1878-4046}, support = {P30 CA006973/CA/NCI NIH HHS/United States ; }, mesh = {Amyotrophic Lateral Sclerosis/*diagnosis/pathology ; Anisotropy ; Diffusion Tensor Imaging/*methods ; Humans ; Monte Carlo Method ; ROC Curve ; Sensitivity and Specificity ; }, abstract = {RATIONALE AND OBJECTIVES: A number of studies have reported decreases in fractional anistropy (FA) in amyotrophic lateral sclerosis using diffusion tensor imaging (DTI). The purpose of this study was to perform a meta-analysis in order to estimate the diagnostic test accuracy measures of DTI for the diagnosis of amyotrophic lateral sclerosis (ALS).<br><br>MATERIALS AND METHODS: We searched MEDLINE (1966-April 2011), EMBASE (1999-April 2011), CINAHL (1999-April 2011), and Cochrane (2005-April 2011) databases to identify studies that measured FA in ALS subjects. Human, single-center studies using a DTI region of interest (ROI) or tractography techniques were used to compare FA values along the brain corticospinal tracts between ALS subjects and healthy controls. There were no language restrictions. Independent extraction of articles by 2 authors using predefined data fields including study quality indicators. We identified 30 case-control studies that used region of interest or tractography DTI techniques. We applied binormal receiver operative characteristic (ROC) curve analysis to assign specificity and sensitivity for each study. We applied the bivariate mixed-effects regression model using the Markov Chain Monte Carlo Simulation to calculate summary estimates for the sensitivity and specificity. We used the metan module in Stata, version 11.0, to calculate the area under the ROC curve, diagnostic odds ratio and the test effectiveness summary estimates.<br><br>RESULTS: The pooled sensitivity was 0.65 (95% CI 0.61-0.69); the pooled specificity, 0.67 (95% CI 0.63-0.72); the pooled diagnostic odds ratio, 1.88 (95% CI 1.46-2.30); the pooled test effectiveness, 1.04 (95% CI 0.81-1.27); and the pooled area under the ROC curve, 0.76 (95% CI 0.71-0.81). Subanalyses comparing magnetic resonance imaging (MRI) field strength (1.5T vs. 3.0T) and brain location (corticospinal tract average vs. internal capsule) revealed no significant differences in the test accuracy measures. Reference standard used for the diagnosis of ALS was the El Escorial criteria. There was at least moderate heterogeneity between the studies. True study quality is uncertain.<br><br>CONCLUSION: The discriminatory capability of DTI to make a diagnosis of ALS is only modest. There were no significant differences in the diagnostic test accuracy summary estimates with respect to MRI field strength or brain location.}, }
@article {pmid22082213, year = {2012}, author = {Slattery, TJ and Staub, A and Rayner, K}, title = {Saccade launch site as a predictor of fixation durations in reading: comments on Hand, Miellet, O'Donnell, and Sereno (2010).}, journal = {Journal of experimental psychology. Human perception and performance}, volume = {38}, number = {1}, pages = {251-261}, doi = {10.1037/a0025980}, pmid = {22082213}, issn = {1939-1277}, support = {HD 26765/HD/NICHD NIH HHS/United States ; }, mesh = {Analysis of Variance ; *Data Interpretation, Statistical ; Fixation, Ocular/*physiology ; Humans ; Linear Models ; Psycholinguistics/*methods ; *Reading ; Saccades/*physiology ; Time Factors ; }, abstract = {An important question in research on eye movements in reading is whether word frequency and word predictability have additive or interactive effects on fixation durations. A fair number of studies have reported only additive effects of the frequency and predictability of a target word on reading times on that word, failing to show significant interactions. Recently, however, Hand, Miellet, O'Donnell, and Sereno (see record 2010-19099-001) reported interactive effects in a study that included the distance of the prior fixation from the target word (launch site). They reported that when the saccade into the target word was launched from very near to the word (within 3 characters), the predictability effect was larger for low frequency words, but when the saccade was launched from a medium distance (4-6 characters from the word) the predictability effect was larger for high frequency words. Hand et al. argued for the importance of including launch site in analyses of target word fixation durations. Here we describe several problems with Hand et al.'s use of analyses of variance in which launch site is divided into distinct ordinal levels. We describe a more appropriate way to analyze such data-linear mixed-effect models-and we use this method to show that launch site does not modulate the interaction between frequency and predictability in two other data sets.}, }
@article {pmid19321847, year = {2009}, author = {Wills, AM and Cronin, S and Slowik, A and Kasperaviciute, D and Van Es, MA and Morahan, JM and Valdmanis, PN and Meininger, V and Melki, J and Shaw, CE and Rouleau, GA and Fisher, EM and Shaw, PJ and Morrison, KE and Pamphlett, R and Van den Berg, LH and Figlewicz, DA and Andersen, PM and Al-Chalabi, A and Hardiman, O and Purcell, S and Landers, JE and Brown, RH}, title = {A large-scale international meta-analysis of paraoxonase gene polymorphisms in sporadic ALS.}, journal = {Neurology}, volume = {73}, number = {1}, pages = {16-24}, pmid = {19321847}, issn = {1526-632X}, support = {089701/WT_/Wellcome Trust/United Kingdom ; G0600974/MRC_/Medical Research Council/United Kingdom ; G0500289/MRC_/Medical Research Council/United Kingdom ; R01 ES013482-01/ES/NIEHS NIH HHS/United States ; G0900688/MRC_/Medical Research Council/United Kingdom ; G0400149/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Amyotrophic Lateral Sclerosis/*genetics ; Aryldialkylphosphatase/*genetics ; Bias ; Chromosome Mapping/methods ; DNA Mutational Analysis/methods/statistics &amp; numerical data ; Data Interpretation, Statistical ; Genetic Markers/genetics ; Genetic Predisposition to Disease/*genetics ; Genetic Testing/methods/statistics &amp; numerical data ; Genome-Wide Association Study/methods/statistics &amp; numerical data ; Genotype ; Humans ; Odds Ratio ; Polymorphism, Single Nucleotide/*genetics ; Reproducibility of Results ; }, abstract = {BACKGROUND: Six candidate gene studies report a genetic association of DNA variants within the paraoxonase locus with sporadic amyotrophic lateral sclerosis (ALS). However, several other large studies, including five genome-wide association studies, have not duplicated this finding.<br><br>METHODS: We conducted a meta-analysis of 10 published studies and one unpublished study of the paraoxonase locus, encompassing 4,037 ALS cases and 4,609 controls, including genome-wide association data from 2,018 ALS cases and 2,425 controls.<br><br>RESULTS: The combined fixed effects odds ratio (OR) for rs662 (PON1 Q192R) was 1.09 (95% confidence interval [CI], 1.02-1.16, p = 0.01); the genotypic OR for RR homozygotes at Q192R was 1.25 (95% CI, 1.07-1.45, p = 0.0004); the combined OR for rs854560 (PON1 L55M) was 0.97 (95% CI, 0.86-1.10, p = 0.62); the OR for rs10487132 (PON2) was 1.08 (95% CI, 0.92-1.27, p = 0.35). Although the rs662 polymorphism reached a nominal level of significance, no polymorphism was significant after multiple testing correction. In the subanalysis of samples with genome-wide data from which population outliers were removed, rs662 had an OR of 1.06 (95% CI, 0.97-1.16, p = 0.22).<br><br>CONCLUSIONS: In contrast to previous positive smaller studies, our genetic meta-analysis showed no significant association of amyotrophic lateral sclerosis (ALS) with the PON locus. This is the largest meta-analysis of a candidate gene in ALS to date and the first ALS meta-analysis to include data from whole genome association studies. The findings reinforce the need for much larger and more collaborative investigations of the genetic determinants of ALS.}, }
@article {pmid18234791, year = {2008}, author = {Worobey, M}, title = {Phylogenetic evidence against evolutionary stasis and natural abiotic reservoirs of influenza A virus.}, journal = {Journal of virology}, volume = {82}, number = {7}, pages = {3769-3774}, pmid = {18234791}, issn = {1098-5514}, support = {R21 AI065371/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Disease Reservoirs/*virology ; Humans ; Influenza A virus/*genetics ; Phylogeny ; RNA, Viral/*genetics ; Sequence Analysis, DNA ; Siberia ; Water Microbiology ; }, abstract = {Zhang et al. (G. Zhang, D. Shoham, D. Gilichinsky, S. Davydov, J. D. Castello, and S. O. Rogers, J. Virol. 80:12229-12235, 2006) have claimed to have recovered influenza A virus RNA from Siberian lake ice, postulating that ice might represent an important abiotic reservoir for the persistence and reemergence of this medically important pathogen. A rigorous phylogenetic analysis of these influenza A virus hemagglutinin gene sequences, however, indicates that they originated from a laboratory reference strain derived from the earliest human influenza A virus isolate, WS/33. Contrary to Zhang et al.'s assertions that the Siberian "ice viruses" are most closely related either to avian influenza virus or to human influenza virus strains from Asia from the 1960s (Zhang et al., J. Virol. 81:2538 [erratum], 2007), they are clearly contaminants from the WS/33 positive control used in their laboratory. There is thus no credible evidence that environmental ice acts as a biologically relevant reservoir for influenza viruses. Several additional cases with findings that seem at odds with the biology of influenza virus, including modern-looking avian influenza virus RNA sequences from an archival goose specimen collected in 1917 (T. G. Fanning, R. D. Slemons, A. H. Reid, T. A. Janczewski, J. Dean, and J. K. Taubenberger, J. Virol. 76:7860-7862, 2002), can also be explained by laboratory contamination or other experimental errors. Many putative examples of evolutionary stasis in influenza A virus appear to be due to laboratory artifacts.}, }
@article {pmid17908587, year = {2007}, author = {Cong, X and Cox, DD and Cantor, SB}, title = {Bayesian meta-analysis of Papanicolaou smear accuracy.}, journal = {Gynecologic oncology}, volume = {107}, number = {1 Suppl 1}, pages = {S133-7}, pmid = {17908587}, issn = {0090-8258}, support = {P01 CA082710/CA/NCI NIH HHS/United States ; CA82710/CA/NCI NIH HHS/United States ; }, mesh = {Bayes Theorem ; Female ; Humans ; *Papanicolaou Test ; Sensitivity and Specificity ; Uterine Cervical Neoplasms/diagnosis/*pathology ; Vaginal Smears/*standards ; }, abstract = {OBJECTIVE: To perform a Bayesian analysis of data from a previous meta-analysis of Papanicolaou (Pap) smear accuracy (Fahey et al. Am J Epidemiol 1995; 141:680-689) and compare the results.<br><br>METHODS: We considered two Bayesian models for the same data set used in the Fahey et al. study. Model I was a beta-binomial model which considered the number of true positives and false negatives as independent binomial random variables with probability parameters beta (sensitivity) and alpha (one minus specificity), respectively. We assumed that beta and alpha are independent, each following a beta distribution with exponential priors. Model II considered sensitivity and specificity jointly through a bivariate normal distribution on the logits of the sensitivity and specificity. We performed sensitivity analysis to examine the effect of prior selection on the parameter estimates.<br><br>RESULTS: We compared the estimates of average sensitivity and specificity from the Bayesian models with those from Fahey et al.'s summary receiver operating characteristics (SROC) approach. Model I produced results similar to those of the SROC approach. Model II produced point estimates higher than those of the SROC approach, although the credible intervals overlapped and were wider. Sensitivity analysis showed that the Bayesian models are somewhat sensitive to the variance of the prior distribution, but their point estimates are more robust than those of the SROC approach.<br><br>CONCLUSIONS: The Bayesian approach has advantages over the SROC approach in that it accounts for between-study variation and allows for estimating the sensitivity and specificity for a particular trial, taking into consideration the results of other trials, i.e., "borrowing strength" from other trials.}, }
@article {pmid17641152, year = {2007}, author = {Chen, H and Richard, M and Sandler, DP and Umbach, DM and Kamel, F}, title = {Head injury and amyotrophic lateral sclerosis.}, journal = {American journal of epidemiology}, volume = {166}, number = {7}, pages = {810-816}, pmid = {17641152}, issn = {0002-9262}, support = {Z01 ES049005/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Amyotrophic Lateral Sclerosis/*epidemiology/etiology ; Case-Control Studies ; Confidence Intervals ; Craniocerebral Trauma/complications/*epidemiology ; Female ; Humans ; Life Style ; Male ; Middle Aged ; New England/epidemiology ; Odds Ratio ; Risk Assessment ; Risk Factors ; Soccer/*injuries ; }, abstract = {Recent data showed that soccer players in Italy had an unusually high risk of amyotrophic lateral sclerosis (ALS) and that repeated head trauma might have contributed to this increase. The authors examined whether head injury was related to ALS risk in a case-control study of 109 New England ALS cases diagnosed in 1993-1996 and 255 matched controls. They also conducted a meta-analysis of the published literature. Overall, ever having experienced a head injury was nonsignificantly associated with a higher ALS risk. When compared with persons without a head injury, a statistically significant ALS risk elevation was found for participants with more than one head injury (odds ratio (OR) = 3.1, 95 percent confidence interval (CI): 1.2, 8.1) and patients who had had a head injury during the past 10 years (OR = 3.2, 95 percent CI: 1.0, 10.2). For participants who had had multiple head injuries with the latest occurring in the past 10 years, risk was elevated more than 11-fold. The meta-analysis also indicated a moderately elevated risk of ALS among persons with previous head injuries (OR = 1.7, 95 percent CI: 1.3, 2.2). In this study population, physical injuries to other body parts, including the trunk, arms, or legs, were not related to ALS risk. These data support the notion that head injury may increase the risk of ALS.}, }
@article {pmid17261678, year = {2007}, author = {Hirtz, D and Thurman, DJ and Gwinn-Hardy, K and Mohamed, M and Chaudhuri, AR and Zalutsky, R}, title = {How common are the "common" neurologic disorders?.}, journal = {Neurology}, volume = {68}, number = {5}, pages = {326-337}, doi = {10.1212/01.wnl.0000252807.38124.a3}, pmid = {17261678}, issn = {1526-632X}, mesh = {Bias ; Data Interpretation, Statistical ; Developed Countries/statistics &amp; numerical data ; Humans ; Incidence ; Nervous System Diseases/*epidemiology ; Prevalence ; *Proportional Hazards Models ; Reproducibility of Results ; Risk Assessment/*methods ; Risk Factors ; Sample Size ; United States/epidemiology ; }, abstract = {OBJECTIVE: To estimate the current incidence and prevalence in the United States of 12 neurologic disorders.<br><br>METHODS: We summarize the strongest evidence available, using data from the United States or from other developed countries when US data were insufficient.<br><br>RESULTS: For some disorders, prevalence is a better descriptor of impact; for others, incidence is preferable. Per 1,000 children, estimated prevalence was 5.8 for autism spectrum disorder and 2.4 for cerebral palsy; for Tourette syndrome, the data were insufficient. In the general population, per 1,000, the 1-year prevalence for migraine was 121, 7.1 for epilepsy, and 0.9 for multiple sclerosis. Among the elderly, the prevalence of Alzheimer disease was 67 and that of Parkinson disease was 9.5. For diseases best described by annual incidence per 100,000, the rate for stroke was 183, 101 for major traumatic brain injury, 4.5 for spinal cord injury, and 1.6 for ALS.<br><br>CONCLUSIONS: Using the best available data, our survey of a limited number of disorders shows that the burden of neurologic illness affects many millions of people in the United States.}, }
@article {pmid8644956, year = {1996}, author = {Nichol, G and Detsky, AS and Stiell, IG and O'Rourke, K and Wells, G and Laupacis, A}, title = {Effectiveness of emergency medical services for victims of out-of-hospital cardiac arrest: a metaanalysis.}, journal = {Annals of emergency medicine}, volume = {27}, number = {6}, pages = {700-710}, doi = {10.1016/s0196-0644(96)70187-7}, pmid = {8644956}, issn = {0196-0644}, support = {U01 HL077885/HL/NHLBI NIH HHS/United States ; }, mesh = {Cardiopulmonary Resuscitation ; *Emergency Medical Services/organization &amp; administration/standards ; Heart Arrest/mortality/*therapy ; Humans ; Life Support Care ; Reaction Time ; Survival Analysis ; }, abstract = {STUDY OBJECTIVE: To determine the relative effectiveness of differences in response time interval, proportion of bystander CPR, and type and tier of emergency medical services (EMS) system on survival after out of hospital cardiac arrest.<br><br>METHODS: We performed a comprehensive literature search, excluding EMS systems other than those of interest (systems of interest were those comprising one tier with providers of basic life support [BLS] or advanced life support [ALS] and those comprising two tiers with providers of BLS or BLS-defibrillation followed by ALS), patient population of fewer than 100 cardiac arrests, studies in which we could not determine the total number of arrests of presumed cardiac origin, and studies lacking data on survival to hospital discharge. Metaanalysis using generalized linear model with dispersion estimation for random effects was then performed.<br><br>RESULTS: Increased survival to hospital discharge was significantly associated with tier (P < .01), response time interval (P < .01), and bystander CPR (P = .04). A significant interaction was detected between response time interval and bystander CPR (P = .02). For the studies analyzed, survival was 5.2% in a one-tier EMS system or 10.5% in a two-tier EMS system. A 1-minute decrease in mean response time interval was associated with absolute increases in survival rates of .4% and .7% in a one-tier and two-tier EMS systems, respectively.<br><br>CONCLUSION: Increased survival to hospital discharge may be associated with decreased response time interval and with the use of a two-tier EMS system as opposed to a one-tier system. The data available for this analysis were suboptimal. Policymakers need more methodologically rigorous research to have more reliable and valid estimates of the effectiveness of different EMS systems.}, }
@article {pmid41530593, year = {2026}, author = {Muneer, MA and Tariq, I and Zulfiqar, E and Saaki, SS and Gupta, I and Bokhari, SMNA and Verma, A and Mehta, R and Sah, R and Ahmed, SI}, title = {Efficacy and safety of dextromethorphan/quinidine in treating pseudobulbar affect in neurological disorders: A systematic review and dose-classified network meta-analysis.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {47}, number = {1}, pages = {159}, pmid = {41530593}, issn = {1590-3478}, mesh = {Humans ; *Dextromethorphan/administration &amp; dosage/adverse effects/pharmacology/therapeutic use ; *Quinidine/administration &amp; dosage/adverse effects/pharmacology/therapeutic use ; *Pseudobulbar Palsy/drug therapy ; Network Meta-Analysis as Topic ; Drug Combinations ; *Nervous System Diseases/drug therapy/complications ; Randomized Controlled Trials as Topic ; }, abstract = {BACKGROUND: Pseudobulbar affect (PBA) is a disabling neuropsychiatric condition characterized by sudden, involuntary episodes of crying or laughing incongruent with mood. It occurs in several neurological disorders, including amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), stroke, and traumatic brain injury (TBI). Dextromethorphan/quinidine (DM/Q) is the only Food and Drug Administration (FDA)-approved therapy for PBA, but optimal dosing and safety profiles remain uncertain.<br><br>OBJECTIVE: To evaluate the efficacy and safety of different DM/Q dosing regimens for treating PBA through a systematic review and network meta-analysis.<br><br>METHODS: A comprehensive search of PubMed, Embase, Cochrane Library, and ClinicalTrials.gov was conducted through March 2025. Randomized controlled trials reporting outcomes on the Center for Neurologic Study-Lability Scale (CNS-LS), Visual Analog Scale-Quality of Life (VAS-QOL), Visual Analog Scale-Quality of Recovery (VAS-QOR), and adverse events were included. Analyses were performed using R (netmeta package), and bias was assessed with the Cochrane RoB 2.0 tool.<br><br>RESULTS: Five randomized controlled trials comprising 605 participants were analyzed. DM/Q 20/10&#xa0;mg and 30/10&#xa0;mg significantly improved CNS-LS scores (mean difference [MD] -&#x2009;2.52 and -&#x2009;2.45, respectively), while DM/Q 30/30&#xa0;mg produced greater gains in VAS-QOL (MD 17.20) and VAS-QOR (MD 14.90). Dizziness was the only statistically significant, dose-related adverse event.<br><br>CONCLUSION: DM/Q combination therapy provides effective symptom control for PBA, with favorable tolerability. Both 20/10&#xa0;mg and 30/10&#xa0;mg doses improve emotional lability, while 30/30&#xa0;mg yields additional quality-of-life benefits. Further studies should assess long-term safety and disorder-specific dosing optimization.}, }
@article {pmid41527739, year = {2026}, author = {Le, J and Hu, X and Jiang, Y and Wang, Q and Ma, Q and Cui, W}, title = {Insights into phosphoproteomic studies and prospects of phosphoproteins as biomarkers for brain disorders.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {}, number = {}, pages = {13872877251411546}, doi = {10.1177/13872877251411546}, pmid = {41527739}, issn = {1875-8908}, abstract = {The dysregulation of phosphorylation networks plays a critical role in the pathogenesis of a wide spectrum of brain disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, traumatic brain injury, ischemic stroke, drug abuse, major depressive disorder, and schizophrenia. Notably, phosphorylated isoforms of microtubule-associated protein tau and neurofilament heavy polypeptide are already utilized in clinical diagnostics, highlighting the promise of protein phosphorylation signatures as biomarkers for prediction, diagnosis, prognosis, and treatment monitoring. Recent advances in deep phosphoproteomic technologies now facilitate the comprehensive mapping of phosphorylation alterations across diverse biological samples and disease stages. This review summarizes current phosphoproteomic studies aimed at identifying biomarkers for brain disorders and elaborates on the promising application of phosphorylated proteins in this context.}, }
@article {pmid41422050, year = {2025}, author = {Valletta, M and Briel, N and Yuksekel, I and Barboure, M and Coward, A and De Houwer, JFH and Fawad, A and González-Mayoral, A and Iaccarino, G and Martínez-Dubarbie, F and Moukaled, S and Andreasson, U and Gobom, J and Brinkmalm, A and Tijms, B and Zetterberg, H and Blennow, K and Suárez-Calvet, M and Schöll, M and Paterson, RW and Montoliu-Gaya, L and Sogorb-Esteve, A}, title = {Fluid biomarkers for neurodegenerative diseases: a comprehensive update.}, journal = {Alzheimer's research &amp; therapy}, volume = {18}, number = {1}, pages = {12}, pmid = {41422050}, issn = {1758-9193}, abstract = {UNLABELLED: Fluid biomarkers are revolutionizing the diagnosis and management of neurodegenerative diseases by enabling earlier diagnosis and disease monitoring. In particular, blood-based biomarkers have emerged as a minimally invasive and scalable alternative to cerebrospinal fluid analysis. Recent advances in blood-based tau biomarkers have shown high diagnostic accuracy for Alzheimer’s disease (AD). Other neurodegenerative diseases—such as synucleinopathies, frontotemporal lobar degeneration, limbic-predominant age-related TDP-43 encephalopathy (LATE), and amyotrophic lateral sclerosis—pose substantial challenges due to their heterogeneous clinical presentations and the current absence of robust biomarkers for hallmark pathologies. Nonetheless, promising candidate markers are emerging for improved disease characterization and staging. Technological innovations, including single-molecule arrays (Simoa), advanced mass spectrometry workflows and nucleic acid linked immune-sandwich assay (NULISA) have markedly enhanced the sensitivity and precision of biomarker quantification from low-concentration biological matrices. More recently, the development of fully automated platforms shows great promise for routine measurement of blood-based biomarkers in clinical settings. Despite this progress key challenges remain, including the need for improved assay reproducibility, standardization, and the optimization of clinical workflows. In this review, we provide a comprehensive update on recent progress in fluid biomarker research across AD and major neurodegenerative diseases, highlight technological advances in detection methods, and discuss current challenges and opportunities for clinical translation.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13195-025-01919-z.}, }
@article {pmid41380476, year = {2026}, author = {Gu, Y and Chen, Y and Tang, X and Guo, J and Hu, J and Yang, W and Li, J and Chen, X and Fan, D and Chen, GB and He, J and Ren, Y and Dong, Y and Sato, C and Chen, Y and Zinman, L and Rogaeva, E and Zhang, M}, title = {Multi-omics analyses identify potential epigenetic loci associated with survival in amyotrophic lateral sclerosis across diverse populations.}, journal = {EBioMedicine}, volume = {123}, number = {}, pages = {106071}, pmid = {41380476}, issn = {2352-3964}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/mortality ; DNA Methylation ; *Epigenesis, Genetic ; Polymorphism, Single Nucleotide ; Male ; Female ; Middle Aged ; CpG Islands ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; *Genetic Loci ; Aged ; Genotype ; Epigenomics/methods ; Whole Genome Sequencing ; Multiomics ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a severe motor neuron disease, with highly diverse survival time. However, genetic and epigenetic factors influencing ALS survival across diverse populations remain unclear.<br><br>METHODS: We performed whole-genome sequencing (WGS) and DNA methylome array in blood DNA of patients with ALS. For survival analysis, we used Cox proportional hazards model for genetic variants, DNA methylation (DNAm) of CpG sites or CpG-SNPs in Chinese and Canadian cohorts, followed by meta-analysis. We performed pathway enrichment analysis for candidate genes inferred from DNAm events associated with survival. In paired genome and methylome data, we analysed the effect of the candidate CpG-SNP genotypes on DNAm status.<br><br>FINDINGS: Genome-wide cross-population meta-analysis of common variants in 511 patients with ALS showed a suggestive association of CAV1/CAV2 rs117002347 genotypes with survival. Epigenome-wide cross-population meta-analysis in 459 patients revealed that ALS survival was significantly linked to DNAm of 88 CpGs on 40 genes, and highlighted the AMPK and cytoskeleton pathways. Epigenome-wide cross-population meta-analysis of CpG-SNPs in 459 patients identified 8 loci on 4 genes, including BAG6 (cg27014438/rs28732154), which was further validated in another 204 patients with ALS. Moreover, analysis of paired genome/epigenome data (n = 454) indicated that BAG6 rs28732154 genotypes may modulate cg27014438 methylation, which is also a cis-eQTM of BAG6 expression in blood.<br><br>INTERPRETATION: Our study identified BAG6 cg27014438 methylation as a potential epigenetic modifier of ALS survival. BAG6 cg27014438 methylation is modulated by rs28732154 genotypes, and linked to BAG6 expression. Our findings extended our understanding of epigenetic modifiers in ALS survival.<br><br>FUNDING: This work was supported by the National Natural Science Foundation of China (82071430, 82371878) (MZ), Shanghai Municipal Natural Science Foundation General Program (22ZR1466400) (MZ), the Fundamental Research Funds for the Central Universities (MZ), the G. Harry Sheppard Memorial Research Fund, and Canadian Consortium on Neurodegeneration in Aging (ER).}, }
@article {pmid41028808, year = {2025}, author = {Rawat, A and Khurana, S and Verma, S and Dhawan, U and Gourie-Devi, M and Ganguly, NK and Taneja, V}, title = {Insights from meta-analysis and experimental validation identify exosomal miR-146a-5p as a potential biomarker for sporadic amyotrophic lateral sclerosis.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {33846}, pmid = {41028808}, issn = {2045-2322}, support = {2020-2641/CMB/ADHOC-BMS//Indian Council of Medical Research/ ; 3/1/2/151/Neuro/2021-NCD-I//Indian Council of Medical Research/ ; 420804-07627//Research Development Program, Sir Ganga Ram Hospital/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics/diagnosis/blood/mortality ; Humans ; *MicroRNAs/genetics/blood/metabolism ; Biomarkers/blood/metabolism ; *Exosomes/genetics/metabolism ; Male ; Female ; Gene Expression Profiling ; Middle Aged ; }, abstract = {MicroRNAs (miRNAs) have emerged as key regulators in the pathogenesis of amyotrophic lateral sclerosis (ALS). Despite growing evidence that miRNAs exhibit altered expression profiles in ALS, their utility as a biomarker remains limited. To address this, we conducted a meta-analysis using the Robust Rank Aggregation package, incorporating 20 differential miRNA profiling studies. Among these, miR-146a-5p emerged as the most dysregulated and significant miRNA in ALS (P = 0.0000142, P-adj = 0.0096), particularly in extracellular vesicle-derived studies. To evaluate its diagnostic accuracy, we validated miR-146a-5p expression in serum-derived exosomes and observed a significant increase in sporadic ALS (sALS) patients (n = 22) as compared to healthy controls (n = 18). Moreover, higher levels of miR-146a-5p were strongly associated with longer survival (≥ 5 years) (P = 0.0135), with a positive correlation between miR-146a-5p expression and survival duration (P = 0.0313) in sALS patients. Further, gene set enrichment analysis of miR-146a-5p target genes highlighted critical involvement of the Immune system and NF-kappa B signaling pathways in ALS pathophysiology. These findings highlight miR-146a-5p as a potential biomarker for ALS.}, }
@article {pmid40180646, year = {2025}, author = {Temiz, K and Gul, A and Gov, E}, title = {5-Repurposed Drug Candidates Identified in Motor Neurons and Muscle Tissues with Amyotrophic Lateral Sclerosis by Network Biology and Machine Learning Based on Gene Expression.}, journal = {Neuromolecular medicine}, volume = {27}, number = {1}, pages = {24}, pmid = {40180646}, issn = {1559-1174}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/genetics ; Humans ; *Machine Learning ; *Motor Neurons/metabolism/drug effects ; *Drug Repositioning/methods ; Transcriptome ; Gene Expression Profiling ; *Muscle, Skeletal/metabolism ; Gene Regulatory Networks ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that leads to motor neuron degeneration, muscle weakness, and respiratory failure. Despite ongoing research, effective treatments for ALS are limited. This study aimed to apply network biology and machine learning (ML) techniques to identify novel repurposed drug candidates for ALS. In this study, we conducted a meta-analysis using 4 transcriptome data in ALS patients (including motor neuron and muscle tissue) and healthy controls. Through this analysis, we uncovered common shared differentially expressed genes (DEGs) separately for motor neurons and muscle tissue. Using common DEGs as proxies, we identified two distinct clusters of highly clustered differential co-expressed cluster genes: the 'Muscle Tissue Cluster' for muscle tissue and the 'Motor Neuron Cluster' for motor neurons. We then evaluated the performance of the nodes of these two modules to distinguish between diseased and healthy states with ML algorithms: KNN, SVM, and Random Forest. Furthermore, we performed drug repurposing analysis and text-mining analyses, employing the nodes of clusters as drug targets to identify novel drug candidates for ALS. The potential impact of the drug candidates on the expression of cluster genes was predicted using linear regression, SVR, Random Forest, Gradient Boosting, and neural network algorithms. As a result, we identified five novel drug candidates for the treatment of ALS: Nilotinib, Trovafloxacin, Apratoxin A, Carboplatin, and Clinafloxacin. These findings highlight the potential of drug repurposing in ALS treatment and suggest that further validation through experimental studies could lead to new therapeutic avenues.}, }
@article {pmid33814477, year = {2021}, author = {Su, CL and Tam, KW and Fang, TP and Chiang, LL and Chen, HC}, title = {Effects of pulmonary rehabilitation program on amyotrophic lateral sclerosis: A meta-analysis of randomized controlled trials.}, journal = {NeuroRehabilitation}, volume = {48}, number = {3}, pages = {255-265}, doi = {10.3233/NRE-210052}, pmid = {33814477}, issn = {1878-6448}, mesh = {Amyotrophic Lateral Sclerosis/*rehabilitation ; Humans ; Muscle Weakness ; Randomized Controlled Trials as Topic ; Resistance Training/*methods ; *Respiration ; }, abstract = {BACKGROUND: Patients with amyotrophic lateral sclerosis (ALS) develop respiratory failure and progressive muscle weakness. The effects of pulmonary rehabilitation on the lung function of patients with ALS are unclear.<br><br>OBJECTIVE: Through this meta-analysis of randomized controlled trials (RCTs), we evaluated the effects of pulmonary rehabilitation, such as type of treatment, on patients with ALS and compared the effectiveness of this treatment.<br><br>METHODS: PubMed, EMBASE, Web of Science, and Cochrane databases were searched until December 2020. The methodological quality of each study was assessed using the updated Cochrane Risk of Bias tool (RoB 2.0). Data were analyzed using Review Manager version 5.4 (Cochrane Collaboration, Oxford, England), and the meta-analysis was performed in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines.<br><br>RESULTS: Of 2168 articles, 10 trials were reviewed; among these trials, two focused on respiratory training and eight on physical exercise, three of which involved a combination of aerobic and resistance training. Our meta-analysis demonstrated no difference in the ALSFRS-R score and % FVC among patients with ALS.<br><br>CONCLUSIONS: Respiratory training or physical exercise did not significantly affect the ALSFRS-R score and % FVC of patients with ALS. At 12 months after intervention, the ALSFRS-R score in the physical exercise group was higher than that in the usual care group. Further clinical trials are warranted to develop approaches for improving the lung function of patients with ALS.}, }
@article {pmid21925771, year = {2012}, author = {Mok, K and Traynor, BJ and Schymick, J and Tienari, PJ and Laaksovirta, H and Peuralinna, T and Myllykangas, L and Chiò, A and Shatunov, A and Boeve, BF and Boxer, AL and DeJesus-Hernandez, M and Mackenzie, IR and Waite, A and Williams, N and Morris, HR and Simón-Sánchez, J and van Swieten, JC and Heutink, P and Restagno, G and Mora, G and Morrison, KE and Shaw, PJ and Rollinson, PS and Al-Chalabi, A and Rademakers, R and Pickering-Brown, S and Orrell, RW and Nalls, MA and Hardy, J}, title = {Chromosome 9 ALS and FTD locus is probably derived from a single founder.}, journal = {Neurobiology of aging}, volume = {33}, number = {1}, pages = {209.e3-8}, pmid = {21925771}, issn = {1558-1497}, support = {R01 AG26251/AG/NIA NIH HHS/United States ; 089701/WT_/Wellcome Trust/United Kingdom ; G0701075/MRC_/Medical Research Council/United Kingdom ; R01 AG038791/AG/NIA NIH HHS/United States ; R01AG031278/AG/NIA NIH HHS/United States ; MC_G1000735/MRC_/Medical Research Council/United Kingdom ; 089698/WT_/Wellcome Trust/United Kingdom ; G0701441/MRC_/Medical Research Council/United Kingdom ; R01AG038791/AG/NIA NIH HHS/United States ; R01 AG026251/AG/NIA NIH HHS/United States ; ZIA AG000933/ImNIH/Intramural NIH HHS/United States ; G0700943/MRC_/Medical Research Council/United Kingdom ; Z01 AG000949/ImNIH/Intramural NIH HHS/United States ; R01 AG031278/AG/NIA NIH HHS/United States ; }, mesh = {Amyotrophic Lateral Sclerosis/*genetics ; Chromosomes, Human, Pair 9/*genetics ; Finland ; Frontotemporal Dementia/*genetics ; Genetic Linkage ; *Genome-Wide Association Study ; Haplotypes ; Humans ; *Polymorphism, Single Nucleotide ; }, abstract = {We and others have recently reported an association between amyotrophic lateral sclerosis (ALS) and single nucleotide polymorphisms on chromosome 9p21 in several populations. Here we show that the associated haplotype is the same in all populations and that several families previously shown to have genetic linkage to this region also share this haplotype. The most parsimonious explanation of these data are that there is a single founder for this form of disease.}, }
@article {pmid41525888, year = {2026}, author = {Tessitore, S and Torazza, C and Bonifacino, T and Bacchetti, F and Roselli, F and Raiteri, L and Milanese, M and Bonanno, G}, title = {Focus on the excitatory and inhibitory neurotransmission imbalance in amyotrophic lateral sclerosis: a harmful disease player or a potential therapeutic opportunity?.}, journal = {Neurobiology of disease}, volume = {}, number = {}, pages = {107272}, doi = {10.1016/j.nbd.2026.107272}, pmid = {41525888}, issn = {1095-953X}, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease affecting both upper and lower motor neurons. Evidence indicates that ALS is a "multifactorial" and "multicellular" disease; however, the causes of ALS remain elusive, as the mechanisms underlying the disease have not yet been completely clarified. One major proposed mechanism, first described in 1990, is the glutamate excitotoxicity theory. This theory suggests that excessive glutamatergic neurotransmission, combined with impaired glutamate clearance, significantly contributes to motor neuron degeneration. Aberrant glutamate neurotransmission may lead to precocious motor neuron hyperexcitability in the brain cortex and spinal cord, which can be later followed by hypoexcitability phases. Accumulating evidence suggests that impairment in inhibitory neurotransmission is relevant for excitation/inhibition imbalance, leading to excitotoxicity, a critical feature of ALS. Gamma-aminobutyric acid (GABA) and glycine are the primary inhibitory neurotransmitters that modulate neuronal excitability, including that of motor neurons. In ALS, dysfunction of inhibitory processes and loss of cortical and spinal inhibitory interneurons are observed. Renshaw cells, which mediate recurrent inhibition in the spinal cord, seem particularly vulnerable. The interactions among neurotransmitters, including glutamate, GABA, and glycine, play pivotal roles in regulating the excitation/inhibition balance. Auto- or hetero-receptor-mediated interactions are crucial, but auto- or hetero-transporter-mediated neurotransmission control, as well as other molecular mechanisms that regulate neuronal interplay, are also relevant, as they can be altered in pathological conditions such as ALS. To facilitate the search for new effective therapies for ALS, attention toward the impairment of inhibitory neurotransmission is essential to determine the role of excitation/inhibition imbalance on excitotoxicity. Different pharmacological agents are being used to treat other pathologies in which the excitation/inhibition ratio is impaired. Among these, we highlighted the potential of novel glycine and GABA receptor ligands and transporter inhibitors, as stand-alone interventions or in combination with other treatments. The present review aims to elucidate the complex interplay between excitatory and inhibitory neurotransmission in ALS, exploring the potential to target this imbalance for therapeutic purposes.}, }
@article {pmid41525811, year = {2026}, author = {Pradhan, LK and Das, SK}, title = {Zebrafish neural regeneration: mechanistic insights into human nervous system repair.}, journal = {Neuroscience}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.neuroscience.2026.01.009}, pmid = {41525811}, issn = {1873-7544}, abstract = {The zebrafish (Danio rerio) is a powerful vertebrate model for studying neurodegenerative diseases and regenerative medicine due to its genetic similarity to humans and its unique ability to regenerate the central nervous system (CNS). This review synthesizes key findings on zebrafish neural regeneration across the retina, spinal cord, and brain, emphasizing translational relevance. Zebrafish effectively model disorders such as Alzheimer's, Parkinson's, amyotrophic lateral sclerosis, stroke, epilepsy, autism spectrum disorders, and CNS injuries. Unlike mammals, they restore damaged axons and recover function through a permissive extracellular matrix, transient inflammation, and glial plasticity. In the retina, Müller glia reprograms after injury to generate progenitors that replace lost neurons, regulated by Wnt/β-catenin, Shh, EGF, Hippo/YAP, and ROCK signaling. In the spinal cord, ependymo-radial glia forms a laminin- and fibronectin-rich "glial bridge," guided by FGF and CTGF signaling, supporting axon regrowth. In the brain, GFAP- and Olig2-positive radial glia drive neurogenesis within ventricular niches, integrating new neurons while maintaining circuit integrity. Regeneration involves transient Notch suppression, context-specific Wnt and FGF activation, and immune modulation without fibrosis. Advances in single-cell RNA sequencing, CRISPR-Cas9, lineage tracing, and multi-omics have identified injury-induced progenitor states, regulators (ascl1a, lin28, sox2, stat3), and epigenetic programs enabling regeneration. Emerging research on bioelectric signaling, microbiota-brain interactions, and lipid mediators further expands systemic understanding. Overall, zebrafish provide a unified model for decoding vertebrate CNS regeneration and guiding therapeutic strategies to restore neural repair in humans.}, }
@article {pmid41524979, year = {2026}, author = {Sun, Y and Huang, C and Pan, Y and He, X and Zhang, H}, title = {Muscle Fibrosis in Amyotrophic Lateral Sclerosis: Molecular Mechanisms, Diagnostic Advances, and Therapeutic Strategies.}, journal = {Molecular neurobiology}, volume = {63}, number = {1}, pages = {357}, pmid = {41524979}, issn = {1559-1182}, support = {2021KY727//Health Commission of Zhejiang Province, Medical and health project/ ; A20210510//Hangzhou Municipal Health Commission, Medical and health science project/ ; }, mesh = {Animals ; Humans ; *Amyotrophic Lateral Sclerosis/therapy/pathology/diagnosis/metabolism/complications ; Fibrosis ; *Muscle, Skeletal/pathology/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder primarily characterized by the degeneration of motor neurons. However, the pathological process of ALS extends beyond the central nervous system, with dynamic changes in skeletal muscle playing a crucial role in the progression of the disease. Recent research has shown that muscle fibrosis, marked by the abnormal accumulation of extracellular matrix (ECM), leads to reduced muscle elasticity, compromised contractile function, and impaired regeneration of neuromuscular junctions (NMJs). This condition represents not only the final stage of muscle atrophy in ALS but also a significant factor accelerating disease progression through "neuromuscular interactions." We conducted a systematic review of the molecular mechanisms of muscle fibrosis in ALS. This included examining the dysregulation of transforming growth factor-β (TGF-β), connective tissue growth factor (CTGF/CCN2), and the Wnt/β-catenin signaling pathways. We also considered key cellular contributors, such as fibro-adipogenic precursor cells and macrophages. The review also covers the use of non-invasive imaging techniques, such as MRI and muscle ultrasound, for early detection and monitoring. We also evaluate potential therapeutic approaches, ranging from anti-fibrotic drugs and gene therapy to physical interventions. In summary, muscle fibrosis is a promising therapeutic target that could complement strategies focused on motor neurons, ultimately improving functional outcomes in patients with amyotrophic lateral sclerosis.}, }
@article {pmid41518742, year = {2026}, author = {Milella, G and Carlone, S and Luisi, F and Velucci, V and Defazio, G}, title = {Facial-onset SOD1 amyotrophic lateral sclerosis: A case report and systematic review.}, journal = {Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia}, volume = {145}, number = {}, pages = {111856}, doi = {10.1016/j.jocn.2026.111856}, pmid = {41518742}, issn = {1532-2653}, abstract = {BACKGROUND: Facial-onset weakness is an exceptionally rare presentation of SOD1-associated amyotrophic lateral sclerosis (ALS), and its natural history, anatomical spread, and prognostic implications remain unclear.<br><br>METHODS: We report a woman carrying a heterozygous SOD1 A5T variant who presented with isolated, rapidly progressive bilateral facial palsy, and we performed a PRISMA-compliant systematic review of MEDLINE, Scopus, and Web of Science to identify genetically confirmed SOD1-positive ALS with facial-onset weakness. Case-level demographic, genetic, clinical, neurophysiological, and outcome data were extracted and synthesised descriptively.<br><br>RESULTS: Eleven patients were included (7 men, 4 women; mean age at onset 52.3&#xa0;years). Seven SOD1 variants were represented, predominantly associated with short survival (e.g. A5V, C7G, A5T). Facial weakness was initially confined to the lower face in 5/11 patients, while 6/11 had combined upper and lower facial involvement. Disease spread followed a stereotyped pattern: early contralateral facial recruitment (mean 3.6&#xa0;months), rapid bulbar involvement (4.2&#xa0;months), and later extension to the upper limbs (9.2&#xa0;months), frequently with side-concordance between facial and arm involvement. Lower motor neuron (LMN) signs predominated in the early phases of the disease. Survival was short (median 16&#xa0;months), lower than reported for unselected SOD1-ALS cohorts with the same genotypes. Three patients received tofersen, with heterogeneous outcomes.<br><br>CONCLUSIONS: Facial-onset SOD1 ALS defines a distinctive phenotype characterised by LMN-predominant facial palsy in early phases, near-neighbour spread, and an aggressive course exceeding genotype-based expectations. Prompt recognition and genetic testing in progressive facial palsy unresponsive to immunotherapy are essential to ensure access to gene-targeted treatments.}, }
@article {pmid41518572, year = {2026}, author = {Zhang, Z and Zhang, M and Cao, Z and Zhao, H and Li, X and Luo, P}, title = {Fibrillarin: bridging ribosome biogenesis and apoptosis in cellular stress and disease.}, journal = {Apoptosis : an international journal on programmed cell death}, volume = {31}, number = {1}, pages = {11}, pmid = {41518572}, issn = {1573-675X}, support = {82171363//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Apoptosis/genetics ; *Ribosomes/metabolism/genetics ; *Neoplasms/genetics/metabolism/pathology ; *Stress, Physiological ; Animals ; Tumor Suppressor Protein p53/metabolism/genetics ; *Neurodegenerative Diseases/genetics/metabolism/pathology ; Cell Nucleolus/metabolism ; Signal Transduction ; Chromosomal Proteins, Non-Histone ; }, abstract = {Nucleolar stress has emerged as a critical regulatory mechanism linking ribosome biogenesis defects to apoptotic cell death in various pathological conditions. Fibrillarin (FBL), the catalytic component of box C/D small nucleolar ribonucleoproteins, participates in multiple forms of programmed cell death through both p53-dependent and p53-independent pathways across diverse disease contexts including cancer and neurodegeneration. In malignancies including breast cancer, colorectal cancer, and hepatocellular carcinoma, FBL overexpression promotes apoptosis resistance, whereas in Alzheimer's disease and ALS/FTD, FBL dysfunction contributes to pathological neuronal death. Dysregulation of FBL can lead to excessive apoptosis or apoptosis resistance depending on cellular context and disease state. Various cellular stressors trigger aberrant FBL function, disrupting rRNA processing and ribosome assembly, which then activates nucleolar stress responses that culminate in cell death through ribosomal protein-MDM2-p53 axis activation or selective translational control of survival factors in a context-dependent manner. Therefore, targeting FBL-mediated apoptotic pathways is considered an important avenue for the treatment of various cancers and neurodegenerative diseases. In this review, we summarize the major and recent findings focusing on the mechanisms of FBL-regulated apoptosis in disease pathogenesis and provide a systematic overview of current therapeutic strategies targeting nucleolar stress pathways, including RNA polymerase I inhibitors and precision medicine approaches based on p53 status, which may provide important therapeutic targets that merit further investigation.}, }
@article {pmid41517697, year = {2026}, author = {Wang, Z and Yao, L and Tu, M}, title = {Evaluating the causal connections between sleep duration and disease prevalence: A comprehensive systematic review and meta-analysis of Mendelian randomization studies.}, journal = {Medicine}, volume = {105}, number = {2}, pages = {e45225}, doi = {10.1097/MD.0000000000045225}, pmid = {41517697}, issn = {1536-5964}, mesh = {Humans ; Mendelian Randomization Analysis ; *Sleep/genetics/physiology ; Prevalence ; Genetic Predisposition to Disease ; Sleep Duration ; }, abstract = {BACKGROUND: The causal link between sleep duration and diverse health conditions remains unconfirmed. This meta-analysis aimed to clarify these relationships by synthesizing Mendelian randomization (MR) study evidence.<br><br>METHODS: PubMed was systematically searched up to February 15, 2024, for MR studies exploring genetic predispositions to sleep duration/insomnia (short/long/overall sleep duration, insomnia) and associations with circulatory, digestive, neurodegenerative, metabolic diseases, and cancers. Eligible effect estimates were meta-analyzed.<br><br>RESULTS: Fifty-one MR studies were included. Genetic variations in sleep traits were strongly linked to elevated risk of 12 cardiovascular diseases, obesity-related metrics (Type 2 diabetes, fasting glucose/insulin, HbA1c), neurological disorders (Alzheimer, amyotrophic lateral sclerosis, Parkinson disease), mental health conditions (attention-deficit/hyperactivity disorder, autism, bipolar disorder, major depressive disorder, schizophrenia), inflammatory bowel disease, and lung cancer.<br><br>CONCLUSION: Genetic evidence confirms causal associations between sleep characteristics and multiple diseases, emphasizing sleep's key role in health promotion and supporting personalized sleep management to reduce disease risk.}, }
@article {pmid41517538, year = {2025}, author = {Dziadkowiak, E and Marschollek, K and Kwaśniak-Nowakowska, A and Zimny, A and Rałowska-Gmoch, W and Boroń, M and Koszewicz, M}, title = {Establishing Diagnostic and Differential Diagnostic Criteria for Amyotrophic Lateral Sclerosis.}, journal = {Journal of clinical medicine}, volume = {15}, number = {1}, pages = {}, pmid = {41517538}, issn = {2077-0383}, abstract = {Motor neuron disease (MND) represents a broad and heterogeneous group of disorders involving the upper or lower motor neurons, represented mainly by amyotrophic lateral sclerosis (ALS), primary lateral sclerosis (PLS), progressive muscular atrophy (PMA) and progressive bulbar palsy (PBP). Primary motor neuronopathies are characterized by progressive degenerative loss of anterior horn cell motoneurons (lower motor neurons) or loss of giant pyramidal Betz cells (upper motor neurons). Rare atypical variants of MND-ALS include flail arm syndrome (FA), flail leg syndrome (FL), facial-onset sensory and motor neuronopathy (FOSMN), finger extension weakness and downbeat nystagmus motor neuron disease (FEWDON-MND) and long-standing and juvenile MND-ALS. In this article, we present a review of diagnostic criteria and the differential diagnosis for MND, focusing on ALS.}, }
@article {pmid41512846, year = {2026}, author = {Zou, C and Li, P and Li, B and Sparwasser, T and Yuan, J}, title = {Next steps in regulatory T cells: Biology and clinical application.}, journal = {Cell}, volume = {189}, number = {1}, pages = {6-22}, doi = {10.1016/j.cell.2025.11.035}, pmid = {41512846}, issn = {1097-4172}, mesh = {Humans ; *T-Lymphocytes, Regulatory/immunology/cytology ; Animals ; Interleukin-2/therapeutic use ; Graft vs Host Disease/immunology/prevention &amp; control/therapy ; Immune Tolerance ; Amyotrophic Lateral Sclerosis/therapy/immunology ; }, abstract = {Recent advances in regulatory T cell (Treg) biology and clinical application of Treg-based treatments show promise as a new generation of transforming therapeutics for immune-related disorders, positioning Tregs as a "living drug" to rebuild immune tolerance and repair damaged tissues simultaneously. This perspective summarizes the key knowledge on Treg biology and highlights the recent important discoveries in the development of clinical applications based on Treg biology, from low-dose interleukin-2 therapy showing promising results in trials for ALS and adoptive Treg transfer demonstrating efficacy in preventing GVHD to early pilot studies of CAR Tregs. Drawing on these advances, we provide perspectives on key research priorities and translational challenges and set forth a roadmap that integrates basic and clinical insights into developing next-generation therapies focusing on precision tolerance strategies.}, }
@article {pmid41511321, year = {2025}, author = {Borgheai, SB and Achorn, BE and Zisk, AH and Hosni, SM and Richter, KEG and Menniti, FS and Shahriari, Y}, title = {A Comprehensive Overview of Neurophysiological Correlates of Cognitive Impairment in Amyotrophic Lateral Sclerosis.}, journal = {Cells}, volume = {15}, number = {1}, pages = {}, pmid = {41511321}, issn = {2073-4409}, support = {NSF-1913492//U.S. National Science Foundation/ ; NSF-2006012//U.S. National Science Foundation/ ; P20GM103430//Institutional Development Award (IDeA) Network for Biomedical Research Excellence/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/complications/genetics ; *Cognitive Dysfunction/physiopathology ; Brain/physiopathology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that leads to the gradual loss of motor control, typically resulting in paralysis and death within 3 to 5 years of diagnosis. ALS shares neuropathological and genetic associations with fronto-temporal dementia (FTD), a neurodegenerative condition primarily impacting cognitive functions. These two conditions are increasingly viewed as manifestations of a single molecular disease process that affects distinct brain systems, impacting motor neuronal pathways in ALS and fronto-cortical functions in FTD. However, this simple dichotomy belies the complexity of these conditions. In particular, patients with primary motor ALS can also experience significant cognitive deficits. Investigating the pathobiological and neurophysiological underpinnings of these impairments is essential for a comprehensive understanding of ALS and may open avenues for targeted therapies to alleviate these debilitating symptoms. Moreover, the biophysical correlates of cognitive deficits in ALS may serve as sensitive biomarkers for evaluating potential therapeutics. In this narrative review, we begin with an overview of the clinical features and genetics of ALS, followed by a review of the associated cognitive deficits that are adjunctive to motor decline. We then highlight neuroimaging studies from our laboratory and the broader literature, using EEG and other modalities that are beginning to uncover systems-level brain disruptions potentially underlying cognitive impairment in motor-dominant ALS.}, }
@article {pmid41504939, year = {2026}, author = {Evola, V and Parmar, MS}, title = {Targeting neuroinflammation in neurodegenerative disorders: the emerging potential of semaglutide.}, journal = {Inflammation research : official journal of the European Histamine Research Society ... [et al.]}, volume = {75}, number = {1}, pages = {13}, pmid = {41504939}, issn = {1420-908X}, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/immunology ; *Glucagon-Like Peptides/therapeutic use/pharmacology ; Animals ; *Neuroprotective Agents/therapeutic use ; *Neuroinflammatory Diseases/drug therapy ; *Anti-Inflammatory Agents/therapeutic use ; Glucagon-Like Peptide-1 Receptor Agonists ; Glucagon-Like Peptide 1 ; }, abstract = {BACKGROUND: Chronic neuroinflammation is increasingly recognized not as a secondary effect but as a primary driver of neurodegenerative disease progression. In conditions such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Huntington's disease (HD), and Lewy body dementia (LBD), dysregulated glial activity, marked by sustained microglial and astrocytic activation, initiates a cascade of cytokine release, oxidative stress, and impaired neuronal support. This review synthesizes recent advances in understanding these shared inflammatory processes, emphasizing how glia-centric pathology shapes disease-specific trajectories and therapeutic responses.<br><br>FINDINGS: Within this framework, we evaluate the therapeutic potential of semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA) with emerging neuroprotective properties. Preclinical studies suggest that semaglutide can suppress pro-inflammatory signaling, mitigate oxidative injury, and enhance key anti-inflammatory and neuroprotective pathways that restore trophic support and cellular resilience. We also examine real-world evidence and emerging human clinical trial data, which recently demonstrated that semaglutide rapidly modulates AD pathology by significantly reducing cerebrospinal fluid (CSF) levels of p-tau, t-tau, and neurogranin, and promoting a less inflammatory CD8[+]T-cell signature. In addition to reduction in neuroinflammation marker, YKL-40. While subsequent large-scale Phase 3 trials in early AD did not meet primary cognitive endpoints (CDR-SB) despite favorable biomarker modulation.<br><br>CONCLUSION: Positioning semaglutide as a therapeutic option targeting neuroinflammation-mediated neuropathology, this review underscores its potential for repurposing as a disease-modifying therapy across diverse neurodegenerative disorders and highlights the urgent need for targeted trials in MS, ALS, FTD, HD, and LBD-conditions that remain without effective immunomodulatory treatments despite clear inflammatory origins. However, while direct CSF measurements confirm limited but measurable BBB penetration, the clinical translation of its effects remains a key challenge.}, }
@article {pmid41504202, year = {2025}, author = {Wu, JY and Ye, S and Yin, TL and Zhang, S and Zheng, DF and Fu, JY and Ma, GW and Fan, DS}, title = {Amyotrophic Lateral Sclerosis With Concurrent LHON-associated m.14484T&gt;C Mutation: A Case Report and Literature Review.}, journal = {Revista de neurologia}, volume = {80}, number = {11}, pages = {44110}, pmid = {41504202}, issn = {1576-6578}, support = {81873784//National Natural Sciences Foundation of China/ ; 82071426//National Natural Sciences Foundation of China/ ; BYSYDL2019002//Clinical Cohort Construction Program of Peking University Third Hospital/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Male ; *Mutation ; Adult ; Female ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease that mostly presents as sporadic cases. Currently, no mitochondrial-related gene mutations have been identified as the cause of ALS. Mitochondrial gene mutations cause rare hereditary diseases, and the symptoms of pure muscle weakness and muscle atrophy are rarely observed.<br><br>CASE REPORT: We report the case of a young patient clinically diagnosed with ALS concurrently associated with a pathogenic mutation in the mitochondrially encoded nicotinamide adenine dinucleotide: ubiquinone oxidoreductase core subunit 6 (MT-ND6) gene. However, the pathogenic relationship between the MT-ND6 gene and ALS has not been confirmed.<br><br>CONCLUSION: We provide a case report and a literature review aimed at increasing the understanding of the connection between the two. It is essential to consider the potential modifying role of mitochondrial pathogenic genes in ALS.}, }
@article {pmid41504056, year = {2025}, author = {Lymperopoulos, A and M'Sadoques, AJ and Stoicovy, RA and Altsman, VL}, title = {Why Is Epinephrine Preferred for Cardiac Arrest? The Answer May Lie in β2-Adrenergic Receptor Activation.}, journal = {Frontiers in bioscience (Landmark edition)}, volume = {30}, number = {12}, pages = {47927}, doi = {10.31083/FBL47927}, pmid = {41504056}, issn = {2768-6698}, support = {R01 #HL155718-01//National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI) grant/ ; #333609-2025//American Foundation for Pharmaceutical Education (AFPE) Gateway to Research Scholarship/ ; }, mesh = {*Epinephrine/therapeutic use/pharmacology ; Humans ; *Heart Arrest/drug therapy ; *Receptors, Adrenergic, beta-2/metabolism ; *Vasoconstrictor Agents/therapeutic use/pharmacology ; Cardiopulmonary Resuscitation/methods ; Animals ; }, abstract = {Epinephrine (Epi, adrenaline) is routinely used during cardiopulmonary resuscitation (CPR) for cardiac arrest and is a first line treatment according to the international advanced life support (ALS) guidelines, which recommend 1 mg Epi be administered every 3-5 minutes during CPR. However, specific pharmacological factors that may distinguish Epi from other vasopressor agents used during CPR are unclear. This opinion article argues that one such factor, perhaps even the most important, is the activation of the β2-adrenergic receptor (AR) subtype, which only Epi, among all vasopressor hormones, can induce. β2AR activation equips Epi with more robust capabilities for pulse generation in the pacemaker cells (sinoatrial node) for the heart and of restoring contractile function in ischemic/hypoxic cardiomyocytes via sodium/potassium pump activation, compared to all other vasopressor hormones, including the closely related catecholamine norepinephrine (NE, noradrenaline). These additional actions of Epi via the β2AR, which are probably not shared by NE or other vasopressor agents, may make it particularly useful in situations where simple blood pressure elevation is insufficient, such as cardiac arrest.}, }
@article {pmid41503832, year = {2026}, author = {Tuli, S and Patel, P and Shethji, A and Gau, D}, title = {Mitochondria and the Actin Cytoskeleton in Neurodegeneration.}, journal = {Cytoskeleton (Hoboken, N.J.)}, volume = {}, number = {}, pages = {}, doi = {10.1002/cm.70095}, pmid = {41503832}, issn = {1949-3592}, support = {CA267180/NH/NIH HHS/United States ; TL1 TR001858/NH/NIH HHS/United States ; }, abstract = {Mitochondrial dysfunction and cytoskeletal disorganization are widely recognized hallmarks of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). Although these disorders differ in clinical presentation and etiology, accumulating evidence points to a shared cellular vulnerability at the intersection of mitochondrial dynamics and actin cytoskeletal regulation. In this review, we examine the emerging role of actin-mitochondria crosstalk as a convergent mechanism in neurodegeneration. We discuss how disruptions in actin filament remodeling, mitochondrial fission and fusion, organelle transport, and mitophagy contribute to neuronal dysfunction and loss across these diseases. Particular attention is given to disease-specific pathways, including cofilin-actin rod formation in AD, α-synuclein-driven actin disruption in PD, mutant huntingtin's effects on mitochondrial fragmentation in HD, and profilin-1-associated mitochondrial defects in ALS. By synthesizing findings from diverse models, we highlight how perturbations in the cytoskeleton-mitochondria interface may act as an upstream trigger and amplifier of neurodegenerative cascades. We also outline key knowledge gaps and propose future directions for research, with an emphasis on targeting actin-mitochondrial interactions as a potential therapeutic strategy across multiple neurodegenerative conditions.}, }
@article {pmid41499987, year = {2026}, author = {Poulidou, V and Tseriotis, VS and Bombaci, A and Vucic, S and Pavey, N and Papagiannopoulos, S and Kimiskidis, VK and Arnaoutoglou, M}, title = {The split elbow sign in amyotrophic lateral sclerosis: A systematic review and meta-analysis.}, journal = {Neurophysiologie clinique = Clinical neurophysiology}, volume = {56}, number = {2}, pages = {103134}, doi = {10.1016/j.neucli.2025.103134}, pmid = {41499987}, issn = {1769-7131}, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) patients can exhibit split phenomena, with preferential weakness of specific muscle groups. The aim of this review is to investigate the split elbow (SE) phenomenon (different weakness/wasting pattern between biceps and triceps) as a potential clinical and neurophysiological feature in ALS.<br><br>METHODS: Our study was reported according to the PRISMA statement and registered in PROSPERO (CRD42024528359). MEDLINE, SCOPUS, Web of Science, and grey literature sources were searched using the terms "split elbow" and "amyotrophic lateral sclerosis" up to April 2025. English-written peer-reviewed, randomized, non-randomized, observational, diagnostic accuracy, and case-control studies were included. Study quality was assessed using Joanna Briggs Institute critical appraisal tool. Regarding muscle strength, we pooled the standardized mean difference of normalized Medical Research Council (MRC) scores using random effects. We used a bivariate random-effects model to evaluate SE index (SEICMAP, compound muscle action potential of biceps/triceps) in distinguishing ALS from controls.<br><br>RESULTS: Seven studies with 1941 ALS patients (61.8 % male) met inclusion criteria. Pooled standardized mean difference (triceps - biceps MRC scores) was -0.17 [95 % CI, -1.03 to 0.69], p = 0.63, indicating no significant difference in muscle strength between elbow flexion and extension. Between-study heterogeneity was high (I[2] = 97.1 % [95.5 %; 98.2 %], p < 0.0001). The SEICMAP demonstrated only moderate accuracy in distinguishing ALS from controls (pooled sensitivity, specificity, and AUC of 0.789 [0.655-0.880], 0.580 [0.487-0.668], and 0.661, respectively).<br><br>CONCLUSIONS: Current evidence does not support a consistent SE pattern in ALS. Methodological variability and small sample sizes limit the generalizability of available findings, indicating that the SE is unlikely to provide meaningful diagnostic utility in routine clinical practice.}, }
@article {pmid41498587, year = {2026}, author = {Maskell, KG and Cook, AL and King, AE and Dickson, TC and Blizzard, CA}, title = {Modeling amyotrophic lateral sclerosis (ALS) in vitro: from mechanistic studies to translatable drug discovery.}, journal = {Lab on a chip}, volume = {}, number = {}, pages = {}, doi = {10.1039/d5lc00577a}, pmid = {41498587}, issn = {1473-0189}, abstract = {Amyotrophic lateral sclerosis is a rapidly progressing, fatal neurodegenerative disease that causes selective degeneration of the corticomotor system. Currently, ALS remains incurable, and the available treatment options offer little in the way of extending life or improving quality of life. This is due, at least in part, to a lack of representative disease models. In vitro modeling offers rapid, experimentally accessible platforms for mechanistic discovery research and drug screening, but modeling the complexity of ALS - a multicellular, multisystem disease - in a dish, is not without its challenges. Here, we review the current landscape of in vitro pre-clinical ALS research, with emphasis on the development of compartmentalised culture and the promise this holds for translatable modeling of ALS.}, }
@article {pmid41498352, year = {2026}, author = {Hewitt-Dean, J and Tebbutt, J and Hobson, E}, title = {The impact of motor neurone disease on oral health: a scoping review.}, journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration}, volume = {}, number = {}, pages = {1-7}, doi = {10.1080/21678421.2025.2603312}, pmid = {41498352}, issn = {2167-9223}, abstract = {OBJECTIVE: To identify current evidence on oral health-related quality of life in people with Motor Neurone Disease (MND), as well as identify barriers to oral health and care, and establish priorities for future research.<br><br>METHODS: A scoping review was conducted. Electronic databases and grey literature sources were searched from 2000 to 2024. Articles discussing oral health in adults with MND were included. Findings were supplemented by stakeholder consultation with people with MND, caregivers, clinicians, and researchers.<br><br>RESULTS: Fourteen articles met inclusion criteria, comprising eight cross-sectional studies, one prospective quality improvement project, one single center observational and four review articles. Five key themes emerged: dental status and oral hygiene activities, orofacial function, secretion management, service delivery and Oral health-related quality of life (OHRQoL). Studies indicated that MND negatively impacts oral health through impaired ability to perform oral hygiene and altered orofacial functioning. Only one study examined oral health-related quality of life. Stakeholder consultation highlighted additional concerns including challenges with service access, the impact of MND on oral health, and difficulties maintaining oral hygiene due to physical limitations.<br><br>CONCLUSIONS: Oral health remains an under-researched area in MND care despite its potential impact on quality of life and overall wellbeing. Future research priorities should include investigating relationships between oral health and MND outcomes, improving service delivery models, and increasing dental professional awareness. Active involvement of people with MND in research design and implementation is essential for developing effective interventions.}, }
@article {pmid41498289, year = {2025}, author = {Ram, J and Glickman, MH}, title = {The many faces of p97/Cdc48 in mitochondrial homeostasis.}, journal = {Essays in biochemistry}, volume = {69}, number = {5}, pages = {}, doi = {10.1042/EBC20253045}, pmid = {41498289}, issn = {1744-1358}, mesh = {Humans ; *Valosin Containing Protein/metabolism/genetics ; *Mitochondria/metabolism ; *Homeostasis ; Animals ; *Adenosine Triphosphatases/metabolism/genetics ; Nuclear Proteins ; }, abstract = {Through its various roles in protein quality control, membrane dynamics, and cellular survival pathways, the AAA+ ATPase p97/valosin-containing protein emerges as a significant regulator of mitochondrial homeosta sis. This review comprehensively examines the multifaceted functions of p97 in mitochondrial biology, spanning from mitochondria-associated degradation to newly discovered functions in organellar cross-talk and disease pathogenesis. Underlying its cellular importance, p97 mutations are found in amyotrophic lateral sclerosis and frontotemporal dementia. To elucidate its mechanistic contribution to these processes, we provide a detailed table (Table 1) listing all known mitochondrial Cdc48/p97 substrates and associ ated proteins, categorized by their respective pathways. Recruitment to most of these substrates occurs by specialized adaptors, including Doa1/phospholipase A-2-activating protein, UBXD8, and UBXN1. p97 orchestrates the extraction and proteasomal degradation of outer mitochondrial membrane proteins, which are essential for maintaining mitochondrial integrity. For example, by controlling the turnover of fusion factors MFN1/2 and fission machinery, p97 regulates mitochondrial dynamics. p97 also governs apoptotic signaling through the regulated degradation of anti-apoptotic factors, such as myeloid cell leukemia-1 and VDAC, thereby modulating mitochondrial permeability. In mitophagy, p97 enables the clearance of damaged organelles by extracting ubiquitinated substrates and recruiting autophagy machinery. Beyond proteolysis, p97 facilitates recycling of endoplasmic reticulum-mitochondria contact sites through regulation of UBXD8-dependent lipid metabolism. Recent discoveries have revealed p97's involvement in pathogen host interactions and circular RNA-mediated regulation, thereby expanding our understanding of its cellular functions. The emerging picture positions p97 as an integrative hub co-ordinating mitochondrial protein homeostasis, organellar dynamics, and cell fate decisions, with therapeutic potential for metabolic and neurodegenerative disorders.}, }
@article {pmid41498281, year = {2026}, author = {Santamaria, MP and Mathias-Santamaria, IF and Tavelli, L and Barootchi, S and Prato, GPP}, title = {An updated evidence-based recommendation for the treatment of gingival recession associated with non-carious cervical lesions.}, journal = {Journal of periodontology}, volume = {}, number = {}, pages = {}, doi = {10.1002/jper.70049}, pmid = {41498281}, issn = {1943-3670}, abstract = {BACKGROUND: Approximately 50% of the gingival recessions (GRs) are associated with non-carious cervical lesions (NCCLs), forming what are known as combined defects (CDs), which often require specific treatment protocols that differ from those used for GRs on teeth with an intact and sound surface. This narrative review aims to evaluate the current and relevant literature on the treatment of CDs and update the latest decision-making process with the new literature.<br><br>METHODS: Medline/PubMed, Embase, BIREME, and Google Scholar databases were searched. The NCCL portion of the CDs was classified according to Pini-Prato et&#xa0;al.'s classification (2010). The GR portion of the CDs was classified according to Cairo et&#xa0;al.'s classification (2011) and gingival phenotype. Based on these, a decision tree, supported by the current literature, was proposed.<br><br>RESULTS: Several approaches associating different surgical techniques/graft materials with different NCCL restoration protocols and materials are available. When A-, A+, and B- NCCL are present, only a surgical procedure for root coverage is needed based on GR characteristics. When either B+ or V-shaped NCCL is present, a composite restorative protocol and a root coverage procedure should be considered.<br><br>CONCLUSIONS: CDs are characterized by the coexistence of gingival recession and a non-carious cervical lesion. This updated decision-making process incorporated current literature, including new evidence on soft tissue grafts, which can guide clinicians in the treatment of CDs.<br><br>PLAIN LANGUAGE SUMMARY: Gum recession often occurs alongside defects in the tooth that are not caused by cavities. These two conditions can appear on the same tooth in about half of the cases. When that happens, treatment becomes more complex and requires careful planning. Choosing the best approach depends on the shape and severity of the tooth defect. This recommendation helps dentists and patients understand how to manage these combined problems. Most cases fall into mild categories (A-, A+, and B-; i.e., shallow tooth defects) and can be treated with standard procedures for gum recession alone. However, about 25% of cases have a more advanced defect (B+; i.e., deep tooth defects), which requires both a tooth restoration and gum surgery. The way gum recession is treated also depends on how thick the gum tissue is. If the tissue is thin, using the patient's own tissue for a graft usually gives the best results. If the tissue is already thick, a graft may not be necessary. In moderate cases, a graft using either patient tissue or commercial materials can improve long-term success. This recommendation summarizes the latest research and provides practical guidance to improve treatment outcomes for both patients and clinicians.}, }
@article {pmid41496184, year = {2026}, author = {Portaro, S and Latella, D and Manuli, A and Calderone, A and Calabrò, RS}, title = {Bridging the gap in sexuality and neuromuscular disorders: a scoping review of an overlooked but crucial topic.}, journal = {Sexual medicine reviews}, volume = {14}, number = {1}, pages = {}, doi = {10.1093/sxmrev/qeaf076}, pmid = {41496184}, issn = {2050-0521}, support = {//Current Research Funds 2024-2025/ ; //Ministry of Health, Italy/ ; }, mesh = {Humans ; *Neuromuscular Diseases/psychology ; *Quality of Life/psychology ; *Sexuality/psychology ; *Sexual Dysfunction, Physiological/psychology ; Social Stigma ; Female ; *Sexual Health ; }, abstract = {INTRODUCTION: Neuromuscular disorders (NMDs) comprise a group of conditions affecting the muscles and/or the nerves controlling them, resulting in progressive muscle weakness. Beyond the physical limitations, NMDs can significantly impact quality of life (QoL), including sexuality. Sexuality, as defined by the World Health Organization, encompasses physical, psychological, and social dimensions. However, research exploring the multifaceted impact of NMDs on sexual well-being remains limited, despite the potential influence of physical impairments, psychological distress, and social stigma.<br><br>OBJECTIVES: This scoping review aims to synthesize the existing literature on sexuality in individuals with NMDs, identifying the interplay of physical, psychological, and social factors affecting sexual QoL, highlighting research gaps, and informing future research and clinical practice.<br><br>METHODS: A scoping review was conducted using PubMed, Web of Science, Cochrane Library, Embase, and Scopus databases (up to May 15, 2025) to identify studies examining sexuality in individuals with NMDs. Studies addressing physical, psychological, and social factors influencing sexual health in NMD patients were included. Data were extracted using a standardized form and synthesized narratively. The review was registered on Open OSF (DOI https://doi.org/10.17605/OSF.IO/RP9U2).<br><br>RESULTS: Fourteen studies with various conditions such as Duchenne muscular dystrophy, amyotrophic lateral sclerosis (ALS), myotonic dystrophy type 1, myasthenia gravis, and Charcot-Marie-Tooth&#x2002;disease were included, from interviews to surveys. One key theme that emerged was the extent to which&#x2002;personal narratives reveal the emotional weight of stigma, the struggle with body image, and how intimacy is peripheral in medical institutions. In surveys, many said their sexual activity had declined, particularly among people with progressive diseases like ALS and myotonic dystrophy. Many of these studies also pointed to how sexual health was directly associated with QoL, a good reminder that it's an important aspect of well-being that we need to pay more attention to in care and support.<br><br>CONCLUSION: This scoping review highlights a significant gap in research regarding sexuality in individuals with NMDs. The limited number of studies identified underscores the need for further research to understand the complex interplay of physical, psychosocial, and social factors affecting sexual well-being in this population.}, }
@article {pmid41493706, year = {2026}, author = {Hashemi, M and Shafiei Asheghabadi, P and Moassesfar, M and Mashhadikhan, S and Nasirzade, S and Vasheghani Farahani, A and Mehdizadeh, S and Minaei, S and Rahmani, M and Jamshidian, F and Farahani, N and Reiter, RJ and Taheriazam, A and Hasani Sadi, F and Hushmandi, K and Alimohammadi, M and Rahimzadeh, P and Entezari, M}, title = {MicroRNAs and Long Non-Coding RNAs Affect the Mechanisms Involved in Age-Related Neurodegeneration in a Manner Depending on RNA-Binding Proteins.}, journal = {Molecular neurobiology}, volume = {63}, number = {1}, pages = {343}, pmid = {41493706}, issn = {1559-1182}, mesh = {Humans ; *RNA, Long Noncoding/metabolism/genetics ; *MicroRNAs/genetics/metabolism ; Animals ; *RNA-Binding Proteins/metabolism/genetics ; *Aging/genetics/pathology/metabolism ; *Neurodegenerative Diseases/genetics/metabolism/pathology ; }, abstract = {Neurodegenerative diseases (NDs), including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD), are marked by progressive neuronal loss and aberrant protein aggregation, presenting substantial global healthcare challenges. Recent research has illuminated the pivotal roles of RNA-binding proteins (RBPs) and non-coding RNAs (ncRNAs), notably microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), in the molecular pathogenesis of age-related neurodegeneration. RBPs orchestrate RNA metabolism and engage extensively with miRNAs and lncRNAs to modulate gene expression at the post-transcriptional level. Dysregulation of these interactions precipitates pathological phenomena such as protein misfolding, stress granule formation, and disrupted RNA processing, thereby exacerbating neuronal dysfunction and death. Specific miRNAs have been implicated in regulating key neurodegenerative biomarkers, including tau and amyloid-β in AD, motor neuron maintenance in ALS, and survival pathways in HD. Elucidating the intricate interplay between RBPs and ncRNAs holds significant promise for the development of therapeutic strategies aimed at ameliorating RNA-mediated mechanisms in neurodegenerative disorders.}, }
@article {pmid41488323, year = {2025}, author = {Lotlikar, MS and Zellmer, JC and Bhattacharyya, R}, title = {Sigma receptors and mitochondria-associated ER membranes are converging therapeutic targets for Alzheimer's disease.}, journal = {Frontiers in neuroscience}, volume = {19}, number = {}, pages = {1733659}, pmid = {41488323}, issn = {1662-4548}, abstract = {Alzheimer's disease (AD) begins decades before clinical symptoms emerge. The "amyloid hypothesis" suggests that amyloid-β (Aβ) deposition initiates a cascade of tau hyperphosphorylation, neuroinflammation, and neuronal loss leading to cognitive decline. The recent success of anti-Aβ therapies such as Leqembi in prodromal or mild cognitive impaired patients underscores the importance of early intervention and Aβ clearance. However, safety and cost limitations highlight the need for alternative therapeutic strategies. Small-molecule modulators of Sigma-1 and Sigma-2 receptors (σ1R and σ2R) have emerged as promising candidates for AD treatment. σ1R agonists exhibit neuroprotective and anti-amnestic effects under pathological conditions without affecting normal cognition. Beyond AD, σ1R is implicated in several neurodegenerative diseases including ALS (amyotrophic lateral sclerosis), Parkinson's, and Huntington's diseases, stroke, and epilepsy. σ1R plays a key role at mitochondria-associated ER membranes (MAMs)-specialized lipid raft-like domains that form functional membrane contact sites between the endoplasmic reticulum (ER) and mitochondria. β-secretase (BACE1), γ-secretase, and their substrates APP and palmitoylated APP (palAPP) localize in the MAMs, promoting amyloidogenic Aβ production. MAMs serve as dynamic hubs for inter-organelle communication, calcium signaling, and lipid metabolism. The "MAM hypothesis" proposes that MAM dysregulation drives early AD pathology and persists throughout disease progression, contributing to neurofibrillary tangle formation, calcium imbalance, and neuroinflammation. This review aims to summarize the current understanding of σ1R-mediated regulation of MAMs and its neuroprotective mechanisms, highlighting potential therapeutic opportunities for targeting σ1R in AD and other neurodegenerative disorders.}, }
@article {pmid41481411, year = {2026}, author = {Ortholand, J and Gensollen, N and Durrleman, S and Du Montcel, ST}, title = {Joint model with latent disease age: Overcoming the need for reference time.}, journal = {Statistical methods in medical research}, volume = {}, number = {}, pages = {9622802251399917}, doi = {10.1177/09622802251399917}, pmid = {41481411}, issn = {1477-0334}, abstract = {Heterogeneity of the progression of neurodegenerative diseases is one of the main challenges faced in developing therapies. Thanks to the increasing number of clinical databases, progression models have allowed a better understanding of this heterogeneity. Joint models have proven their effectiveness by combining longitudinal and survival data. Nevertheless, they require a reference time, which is ill-defined for neurodegenerative diseases, where biological underlying processes start before the first symptoms. In this work, we propose a joint non-linear mixed-effect model with a latent disease age, to overcome this need for a precise reference time. We used a longitudinal model with a latent disease age as a longitudinal sub-model. We associated it with a survival sub-model that estimates a Weibull distribution from the latent disease age. We validated our model on simulated data and benchmarked it with a state-of-the-art joint model on data from patients with Amyotrophic Lateral Sclerosis (ALS). Finally, we showed how the model could be used to describe ALS heterogeneity. Our model got significantly better results than the state-of-the-art joint model for absolute bias on ALS functional rating scale revised score (4.21(SD 4.41) versus 4.24(SD 4.14)(p-value=1.4×10-17)), and mean-cumulative-AUC for right-censored events on death (0.67(0.07) versus 0.61(0.09)(p-value=1.7×10-03)). To conclude, we propose a new model better suited in the context of unreliable reference time.}, }
@article {pmid41480618, year = {2025}, author = {Hu, G and Gogzheyan, C and Panja, S and Sil, S and Gendelman, HE}, title = {Extracellular vesicle-based therapies for neurodegenerative diseases.}, journal = {NeuroImmune pharmacology and therapeutics}, volume = {4}, number = {4}, pages = {377-390}, pmid = {41480618}, issn = {2750-6665}, abstract = {Extracellular vesicles (EVs) are mediators of neurodegeneration and emerging therapeutic tools for central nervous system disorders. On the one hand, they help spread beta amyloid, tau, α-synuclein, TDP-43, and mutant SOD1, contributing to the signs and symptoms of Alzheimer's, Parkinson's, Amyotrophic lateral sclerosis, and Huntington's Diseases. By activating glial cells, they promote chronic neuroinflammation through carrying cytokines, inflammasomes, and chemokines. On the other hand, EVs' ability to transport neuroregulatory products and cross the blood-brain barrier makes them ideal vehicles for drug delivery. Their function can be surface-modified to deliver targeted therapies, including anti-inflammatory and neuroprotective regulatory RNAs, proteins, and lipids, as well as factors that help maintain neural homeostasis. Notably, we suggest that colostrum-derived EVs, enriched with growth factors and immune-regulatory microRNAs, offer a natural, scalable, and biocompatible source for neuroprotective treatment. Although EVs can act as "Janus-faced" entities - serving both as disease initiators and versatile therapeutic vehicles - controlling their activity can enable immune-based therapeutics for neurodegenerative diseases.}, }
@article {pmid41479097, year = {2026}, author = {Stamatelopoulos, D and Papakonstantinou, E and Bacopoulou, F and Vlachakis, D}, title = {Polyphenols from Olive Oil: A Promising Therapeutic Approach for Neurodegenerative Diseases.}, journal = {Advances in experimental medicine and biology}, volume = {1490}, number = {}, pages = {343-349}, pmid = {41479097}, issn = {0065-2598}, mesh = {*Olive Oil/chemistry/therapeutic use ; Humans ; *Polyphenols/therapeutic use/pharmacology ; *Neurodegenerative Diseases/drug therapy/metabolism/pathology ; *Neuroprotective Agents/therapeutic use ; Animals ; Oxidative Stress/drug effects ; Antioxidants/therapeutic use ; Diet, Mediterranean ; Anti-Inflammatory Agents/therapeutic use ; }, abstract = {Neurodegenerative diseases such as Alzheimer's, Parkinson's, ALS, and Huntington's disease pose a growing global health challenge due to their prevalence in aging populations and their devastating impact on cognitive and motor functions. Current treatments focus on symptom management, with no options available to reverse neuronal damage. Emerging evidence highlights the potential role of extra virgin olive oil (EVOO) polyphenols in neuroprotection, particularly in the context of the Mediterranean diet, which is associated with lower rates of neurodegenerative disorders. EVOO's rich polyphenolic compounds, including hydroxytyrosol, oleuropein, tyrosol, and oleocanthal, exhibit potent antioxidant, anti-inflammatory, and neuroprotective properties. These bioactive molecules have shown potential in modulating disease-specific pathways, such as reducing oxidative stress, inhibiting abnormal protein aggregation, and regulating neuroinflammation. This paper explores the therapeutic potential of olive oil polyphenols for neurodegenerative diseases, detailing their mechanisms of action across different conditions. Our findings suggest that incorporating EVOO into dietary and medical interventions could serve as a promising strategy for mitigating neurodegenerative disease progression and enhancing cognitive health.}, }
@article {pmid40990470, year = {2026}, author = {Siu, MC and Selinopoulou, M and Abarca Salazar, S and Sturgeon, JP and Huynh, J and Basu Roy, R}, title = {Diagnostic Performance of Host-based Gene Expression Diagnostics in Children With Extrapulmonary Tuberculosis: A Systematic Review.}, journal = {The Pediatric infectious disease journal}, volume = {45}, number = {2}, pages = {140-146}, doi = {10.1097/INF.0000000000004998}, pmid = {40990470}, issn = {1532-0987}, mesh = {Humans ; Child ; *Tuberculosis/diagnosis/genetics ; Child, Preschool ; Adolescent ; Sensitivity and Specificity ; Infant ; Mycobacterium tuberculosis/genetics ; *Gene Expression Profiling ; Infant, Newborn ; Tuberculosis, Extrapulmonary ; }, abstract = {BACKGROUND: Diagnosing extrapulmonary tuberculosis (EPTB) in children is challenging due to nonspecific presentations and poor diagnostic yield from conventional microbiologic tests. Host gene expression signatures offer a non-sputum-based diagnostic alternative. This systematic review evaluates their diagnostic performance in pediatric EPTB.<br><br>METHODS: We systematically reviewed host-based gene expression diagnostics for pediatric EPTB. PubMed, Embase and Cochrane Library (January 1965-May 2025) were searched for studies in children (0-18 years) with EPTB. Exclusions were adult-only studies, mixed data on pulmonary TB and EPTB without disaggregation, pulmonary TB-only studies, reviews and abstracts. Two reviewers screened data, resolving disagreements by discussion.<br><br>RESULTS: Of 830 records, 2 studies met the inclusion criteria: Pan et al. (2017) and Olbrich et al. (2024), both in low and middle-income countries, enrolling a total of 891 children under 15 years. Olbrich et al.'s 3-gene MTB-HR prototype showed 59.8% sensitivity against a strict culture-confirmed reference standard and 50.0% in isolated EPTB with a low risk of bias. Using a microbiologic, clinical and radiologic composite standard, Pan et al.'s miRNA-29a assay achieved 67.2% sensitivity, 88.5% specificity in peripheral blood mononuclear cells; 81.1% sensitivity, 90.0% specificity in cerebrospinal fluid; 84.4% sensitivity, 95.4% specificity in combined peripheral blood mononuclear cell/cerebrospinal fluid with a high risk of bias.<br><br>CONCLUSIONS: Evidence for host gene expression diagnostics in pediatric EPTB is limited by few studies, small sample sizes, bias and lack of disaggregated data, with accuracy falling short of the World Health Organization targets.}, }
@article {pmid40631493, year = {2026}, author = {Li, W and Gillies, RM and Sun, H and Khan, A}, title = {Career indecision among medical students: A scoping review of contributing sources, associated factors, and support strategies.}, journal = {Medical teacher}, volume = {48}, number = {1}, pages = {42-60}, doi = {10.1080/0142159X.2025.2520927}, pmid = {40631493}, issn = {1466-187X}, mesh = {Humans ; *Students, Medical/psychology ; *Career Choice ; *Decision Making ; Self Efficacy ; Adaptation, Psychological ; }, abstract = {BACKGROUND: While career indecision is well-studied in vocational psychology, its application in medical education remains limited. This scoping review examined sources of indecision, associated factors, and strategies to support medical students' career decision-making.<br><br>METHODS: A systematic search of PubMed, Scopus, CINAHL, and ERIC identified relevant studies published from January 2014 to December 2024. Two reviewers independently screened articles and data were charted. Eligible articles were synthesised using directed qualitative content analysis with inductive expansion, guided by Kulcs&#xe1;r et al.'s career decision-making taxonomy.<br><br>RESULTS: Ninety-three studies were included. Most studies focused on the career aspect of specialty selection. Career decision-making difficulties were categorised into Readiness (dysfunctional beliefs, career decision-making self-efficacy, willingness, general indecisiveness), Lack of Information (about self, about world of work, about how to make career decisions) and Use of Information (unreliable information, internal conflicts, external conflicts). Personal coping strategies and institutional support recommendations were identified. Influencing factors included demographics, personal traits, educational experiences, attitudes, and macro-level disruptions.<br><br>CONCLUSIONS: This review maps medical students' career decision-making difficulties to a structured framework and outlines support strategies and influencing factors. Findings underscore the value of integrating career psychology into medical education and addressing structural barriers to better support students' career development.}, }
@article {pmid39871563, year = {2025}, author = {Guo, J and Liu, XY and Yang, SS and Li, Q and Duan, Y and Zhu, SS and Zhou, K and Yan, YZ and Zeng, P}, title = {Roles of C/EBPβ/AEP in Neurodegenerative Diseases.}, journal = {Current topics in medicinal chemistry}, volume = {25}, number = {20}, pages = {2440-2452}, pmid = {39871563}, issn = {1873-4294}, support = {82301506//National Natural Science Foundation of China/ ; 220XQD090//Research Foundation of Scientific Research Program of University of South China/ ; 2023JJ40560//Provincial Natural Science Foundation of Hunan/ ; S202410555234, S202410555259, S202410555262//Science and Technology Innovation Project for College Students/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/drug therapy/pathology ; *CCAAT-Enhancer-Binding Protein-beta/metabolism/antagonists &amp; inhibitors/chemistry ; Animals ; Small Molecule Libraries/chemistry/pharmacology ; }, abstract = {In recent years, an increasing number of studies have shown that increased activation of aspartic endopeptidases (AEPs) is a common symptom in neurodegenerative diseases (NDDs). AEP cleaves amyloid precursor protein (APP), tau (microtubule-associated protein tau), α- synuclein (α-syn), SET (a 39-KDa phosphoprotein widely expressed in various tissues and localizes predominantly in the nucleus), and TAR DNA-binding protein 43 (TDP-43), and promotes their aggregation, contributing to Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease, multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD) pathogenesis. Abundant evidence supports the notion that CCAAT/enhancer-binding protein β (C/EBPβ)/AEP may play an important role in NDDs. Developing its small molecule inhibitors is a promising treatment of NDDs. However, current research suggests that the pathophysiological mechanism of the C/EBPβ/AEP pathway is very complex in NDDs. This review summarizes the structure of C/EBPβ and AEP, their major physiological functions, potential pathogenesis, their small molecule inhibitors, and how C/EBPβ/AEP offers a novel pathway for the treatment of NDDs.}, }
@article {pmid41477139, year = {2025}, author = {Syamal, M}, title = {Treatment of Neurogenic Voice Disorders.}, journal = {World journal of otorhinolaryngology - head and neck surgery}, volume = {11}, number = {4}, pages = {541-547}, pmid = {41477139}, issn = {2589-1081}, abstract = {This overview serves as a foundational resource for clinicians caring for neurologically complex patients presenting with voice complaints. Neurogenic voice disorders are diverse in their clinical presentations and therapeutic approaches. A thorough medical history, including family history, detailed laryngeal examination, voice assessments, and neuroimaging, are imperative, as well as a multidisciplinary, collaborative approach with neurologists, speech language pathologists, and patient caregivers. Disorders such as amyotrophic lateral sclerosis (ALS), cerebrovascular accidents (strokes), Huntington's disease, myasthenia gravis (MG), Parkinson's disease (PD), and voice tremor should be understood by otolaryngologists. Each condition presents unique challenges and requires tailored treatment strategies ranging from supportive therapies and pharmacological interventions to surgery. Voice management techniques, including the use of botulinum toxin for hyperkinetic disorders and deep brain stimulation for refractory cases, are highlighted as promising interventions.}, }
@article {pmid41476438, year = {2025}, author = {Oza, R}, title = {Physical Activity as an Intervention for Frailty Syndrome: A Narrative Review.}, journal = {Cureus}, volume = {17}, number = {12}, pages = {e100293}, pmid = {41476438}, issn = {2168-8184}, abstract = {Frailty is a geriatric syndrome characterised by a decline in functional reserves as the body ages, resulting in increased disability, comorbidity, and mortality. With trends towards ageing populations, frailty syndrome becomes more clinically relevant, highlighting the importance of appropriately preventing and managing the characteristics of frailty syndrome. Risk factor modification is recommended to delay or prevent the onset of frailty, including physical activity alongside other modifiable behaviours such as diet. Ageing is associated with chronic low-grade inflammation, resulting in reduced muscle protein synthesis and increased resistance to insulin, which both contribute to sarcopenia. Sarcopenia underpins key characteristics of frailty, including weakness and slow speed. Physical activity stimulates anabolic pathways and improves insulin resistance, reducing sarcopenia. Moreover, aerobic exercise is responsible for increasing the VO2 peak, whilst resistance exercise improves muscle strength, both of which are known to decrease in frail elders. This narrative review primarily explored the effectiveness of physical activity in reducing the risk of the onset of frailty syndrome through a narrative review of the relevant literature concerning this subject. A secondary focus of this narrative review is to compare the success of alternative interventions for preventing frailty, relative to physical activity. Physical activity interventions have been shown to improve components of frailty scoring and selected biological markers of frailty, with evidence suggesting physical activity is an effective single-domain intervention for frailty; however, multidomain approaches may result in a greater overall improvement in frailty prevention. Further research is required to identify the types of exercise that modify specific aspects of Fried et al.'s frailty criteria (FFC), as well as what interventions can be used alongside physical activity, to holistically treat all characteristics of frailty syndrome.}, }
@article {pmid37827930, year = {2023}, author = {Cassereau, J and Bernard, E and Genestet, S and Chebbah, M and Le Clanche, S and Verschueren, A and Couratier, P}, title = {Management of amyotrophic lateral sclerosis in clinical practice: Results of the expert consensus using the Delphi methodology.}, journal = {Revue neurologique}, volume = {179}, number = {10}, pages = {1134-1144}, doi = {10.1016/j.neurol.2023.07.011}, pmid = {37827930}, issn = {0035-3787}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/therapy ; Riluzole/therapeutic use ; Motor Neurons ; Diagnosis, Differential ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a rare disease characterized by a progressive and irreversible degeneration of upper and lower motor neurons leading to death. In France, limited data exist describing the criteria used in clinical practice for diagnosis and follow-up, and how novel therapies may fit in. The objective of this Delphi panel was to obtain an overview of current French practices in ALS diagnosis, management, and follow-up by determining the scales and criteria used in clinical practice outside of clinical trials, as well as the place of a future treatment like AMX0035, acting on endoplasmic reticulum (ER) stress and mitochondrial dysfunction, in the current therapeutic strategies. A questionnaire was administered to 24 ALS healthcare providers practicing in ALS centers in France. Two rounds of remote voting were organized, before proposition of final consensus statements. Consensus was considered reached when at least 66% of the voters agreed. Consensus were obtained to define the new Gold Coast criteria as the ones used in clinical practice to establish the diagnosis of ALS, thus replacing the revised El Escorial criteria, considered too complex and now mainly used to characterize the patient populations to be included in clinical trials. The clinical factors considered to establish ALS diagnosis are mainly the demonstration of progression of the motor deficit and elimination of differential diagnoses. The ALSFRS-R scale is used in daily clinical practice to assess patient's functional impairment in terms of number of points lost, with the bulbar, respiratory, and fine motor subscores being the most important to evaluate independently. A critical medical need was identified regarding the provision of new therapeutic alternatives in ALS. The panel members would support the earliest management of patients. In this landscape, based on data from a very encouraging phase II (Centaur trial), AMX0035 represents a new tool of choice in current treatment strategies for all patients for whom experts are confident in the diagnosis of ALS, in combination with riluzole. These results will need to be confirmed by the ongoing phase III trial (Phoenix trial).}, }
@article {pmid41471389, year = {2025}, author = {Gershoni Emek, N and Tan, AM and Geva, M and Fekete, A and Abate, C and Hayden, MR}, title = {Pridopidine, a Potent and Selective Therapeutic Sigma-1 Receptor (S1R) Agonist for Treating Neurodegenerative Diseases.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {18}, number = {12}, pages = {}, pmid = {41471389}, issn = {1424-8247}, abstract = {Pridopidine is a highly selective sigma-1 receptor (S1R) agonist in clinical development for Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS). The S1R is a ubiquitous chaperone protein enriched in the central nervous system and regulates multiple pathways critical for neuronal cell function and survival, including cellular stress responses, mitochondrial function, calcium signaling, protein folding, and autophagy. S1R has a crucial role in the ER mitochondria-associated membrane (MAM), whose dysfunction is implicated in several neurodegenerative diseases. By activating the S1R, pridopidine corrects multiple cellular pathways necessary to the cell's ability to respond to stress, which are disrupted in neurodegenerative diseases. Pridopidine restores MAM integrity; rescues Ca[2+] homeostasis and autophagy; mitigates ER stress, mitochondrial dysfunction, and oxidative damage; and enhances brain-derived neurotrophic factor (BDNF) axonal transport and secretion, synaptic plasticity, and dendritic spine density. Pridopidine demonstrates neuroprotective effects in in vivo models of neurodegenerative diseases (NDDs). Importantly, pridopidine demonstrates the biphasic dose response characteristic of S1R agonists. In clinical trials in HD and ALS, pridopidine has shown benefits across multiple endpoints. Pridopidine's mechanism of action, modulating core cellular survival pathways, positions it as a promising candidate for disease modification for different nervous system disorders. Its broad therapeutic potential includes neurodevelopmental disorders, and rare diseases including Wolfram syndrome, Rett syndrome, and Vanishing White Matter Disease. Here, we review the experimental data demonstrating pridopidine's S1R-mediated neuroprotective effects. These findings underscore the therapeutic relevance of S1R activation and support further investigation of pridopidine for the treatment of different neurodegenerative diseases including ALS and HD.}, }
@article {pmid41468784, year = {2025}, author = {Palanivel, V and Salkar, A and Shenoy, A and Eva, TA and Perera, R and Chitranshi, N and Gupta, V and You, Y and Mirzaei, M and Graham, SL and Gupta, V and Basavarajappa, D}, title = {Neuropeptide Y at the crossroads of neurodegeneration: Mechanistic insights and emerging therapeutic strategies.}, journal = {Neuropeptides}, volume = {115}, number = {}, pages = {102583}, doi = {10.1016/j.npep.2025.102583}, pmid = {41468784}, issn = {1532-2785}, abstract = {Neuropeptide Y (NPY), a widely distributed and highly conserved neuropeptide, plays a central role in the regulation of diverse physiological processes, including stress responses, energy homeostasis, vascular tone, and immune modulation, via activation of its receptor subtypes. Beyond its physiological roles, the dysregulation of NPY expression has been documented in several neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, Machado-Joseph disease, and retinal disorders such as diabetic retinopathy and glaucoma. These alterations in NPY levels and receptor activity highlight its potential not only as a biomarker for disease progression but also as a promising therapeutic target. Previous evidence revealed that NPY exerts neuroprotection by alleviating excitotoxicity, oxidative stress, mitochondrial dysfunction, and neuroinflammation while concurrently facilitating neurogenesis, synaptic plasticity, and cellular resilience. NPY activates receptor-mediated intracellular signaling cascades like PI3K/Akt, MAPK/ERK, and p38K, that control cellular survival, proteostasis, and inflammation and thereby influence disease trajectories. Understanding NPY operation with these mechanisms can unveil new avenues for targeted therapy. Current insights into the complex roles of NPY in neurodegeneration are discussed in this review, and their implications in diagnostic and treatment strategies are addressed.}, }
@article {pmid41465514, year = {2025}, author = {Riku, Y and Brion, JP and Ando, K and Uchihara, T and Iwasaki, Y}, title = {The Determinant of Tau Spreading in Alzheimer's Disease: Dependent on Senile Plaque, Neural Circuits, or Spatial Proximity?.}, journal = {International journal of molecular sciences}, volume = {26}, number = {24}, pages = {}, pmid = {41465514}, issn = {1422-0067}, support = {JPMH23FC1008//MHLW Research on rare and intractable diseases Program/ ; 23K06935, 25K22597, and 25K10781//JSPS-KAKENHI/ ; }, mesh = {Humans ; *Alzheimer Disease/metabolism/pathology ; *tau Proteins/metabolism ; *Plaque, Amyloid/metabolism/pathology ; Animals ; Neurofibrillary Tangles/metabolism/pathology ; Amyloid beta-Peptides/metabolism ; Brain/metabolism/pathology ; }, abstract = {Alzheimer's disease (AD) is neuropathologically characterized by tau-immunopositive neurofibrillary tangles (NFTs) and amyloid-β (Aβ)-immunopositive senile plaques. According to the widely accepted amyloid cascade hypothesis, Aβ pathology represents the upstream event in AD pathophysiology and induces tau aggregation. However, numerous studies have suggested that tau aggregates correlate more closely with neuronal loss and regional brain atrophy than with Aβ depositions. Tau aggregation in AD demonstrates a hierarchical spreading pattern beginning in the transentorhinal cortex, but the mechanisms underlying this spreading manner of lesions remain to be elucidated. This review aims to address current controversies regarding tau pathology in AD from the perspectives of both the 'amyloid cascade' and 'tauopathy' hypotheses. From the 'amyloid cascade' viewpoint, Aβ deposition prominently involves distal axon and axon terminals, and in some regions, there are anatomical correspondences between axonal Aβ pathology and cytoplasmic tau aggregations (e.g., a close relationship between senile plaques in the molecular layer of the hippocampal dentate gyrus and NFTs in the transentorhinal cortex). Nevertheless, this model cannot explain the whole body of hierarchical spreading of tau aggregation because notable spaciotemporal discrepancies also exist in many regions. From the 'tauopathy' perspective, the distribution of tau aggregates in AD involves key nodes within the memory circuits. Also, experimental studies have suggested that patient-derived tau exhibits seeding and neuron-to-neuron propagation properties. Interestingly, tau aggregation in AD appears to spread laterally in a proximity-dependent, cortico-cortical fashion rather than along long-range memory circuits. This contrasts with the system-selective, poly-nodal degenerations seen in four-repeat tauopathies, amyotrophic lateral sclerosis, or spinocerebellar degenerations. Moreover, the proportions of three-repeat and four-repeat isoforms shift during the maturation of NFTs in AD. Overall, spreading patterns of tau-pathology in AD cannot be fully explained by Aβ pathology and also differ from the system degeneration seen in other tauopathies.}, }
@article {pmid41065069, year = {2026}, author = {Shan, Y and Jing, W and Zhang, H and Liu, Y and Wei, S and Wu, F and Pan, W}, title = {Amyotrophic lateral sclerosis rehabilitation management and non-pharmacological symptomatic treatment: A review.}, journal = {International journal of clinical pharmacology and therapeutics}, volume = {64}, number = {1}, pages = {38-46}, doi = {10.5414/CP204744}, pmid = {41065069}, issn = {0946-1965}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/rehabilitation/physiopathology/diagnosis/psychology/therapy ; Quality of Life ; Treatment Outcome ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that lacks effective treatment options for the prevention of progression. Relieving swallowing difficulties, reducing breathing difficulties, and alleviating muscle spasms are essential to improving the quality of life in patients with ALS. Many symptoms can be treated clinically with medication; however, the evidence level of related research is relatively low. Rehabilitation management can aid in improving various functional impairments and enhancing quality of life. This review introduces and describes the relevant evaluations of rehabilitation and nonpharmacological symptomatic treatment methods for functional disorders from the perspectives of motor and nonmotor symptoms. This review may promote the popularization of ALS rehabilitation management and provide an additional reference for ALS treatment.}, }
@article {pmid41465278, year = {2025}, author = {Marzetti, E and Di Lorenzo, R and Calvani, R and Coelho-Júnior, HJ and Landi, F and Pesce, V and Picca, A}, title = {Linking Cell Architecture to Mitochondrial Signaling in Neurodegeneration: The Role of Intermediate Filaments.}, journal = {International journal of molecular sciences}, volume = {26}, number = {24}, pages = {}, pmid = {41465278}, issn = {1422-0067}, support = {D1.2024//Universit&#xe0; Cattolica del Sacro Cuore/ ; D1.2025//Universit&#xe0; Cattolica del Sacro Cuore/ ; Ricerca Corrente 2025//Italian Ministry of Health/ ; DM 1557 11.10.2022//European Commission/ ; 2022YNENP3//Italian Ministry of University and Research/ ; }, mesh = {Humans ; *Mitochondria/metabolism/pathology ; Animals ; *Neurodegenerative Diseases/metabolism/pathology ; *Intermediate Filaments/metabolism/pathology ; *Signal Transduction ; Neurons/metabolism/pathology ; }, abstract = {Mitochondrial dysfunction is a pivotal contributor to neurodegeneration. Neurons heavily rely on mitochondrial oxidative metabolism and therefore need highly efficient quality control mechanisms, including proteostasis, mitochondrial biogenesis, fusion-fission dynamics, and mitophagy, to sustain bioenergetics and synaptic function. With aging, deterioration of mitochondrial quality control pathways leads to impaired oxidative phosphorylation, excessive reactive oxygen species generation, calcium imbalance, and defective clearance of damaged organelles, ultimately compromising neuronal viability. Pathological protein aggregates, such as α-synuclein in Parkinson's disease, β-amyloid and tau in Alzheimer's disease, and misfolded superoxide dismutase 1 and transactive response DNA-binding protein 43 in amyotrophic lateral sclerosis, further aggravate mitochondrial stress, establishing self-perpetuating cycles of neurotoxicity. Such mitochondrial defects underscore mitochondria as a convergent pathogenic hub and a promising therapeutic target for neuroprotection. Intermediate filaments (IFs), traditionally viewed as passive structural elements, have recently gained attention for their roles in cytoplasmic organization, mitochondrial positioning, and energy regulation. Emerging evidence indicates that IF-mitochondria interactions critically influence organelle morphology and function in neurons. This review highlights the multifaceted involvement of mitochondrial dysfunction and IF dynamics in neurodegeneration, emphasizing their potential as targets for novel therapeutic strategies.}, }
@article {pmid41464650, year = {2025}, author = {Sonaglioni, A and Nicolosi, GL and Lombardo, M and Baravelli, M and Muti, P}, title = {Comparative Meta-Analysis of Left Ventricular Mechanics in Takotsubo Syndrome and Anterior STEMI Due to Left Anterior Descending Artery Occlusion.}, journal = {Journal of clinical medicine}, volume = {14}, number = {24}, pages = {}, pmid = {41464650}, issn = {2077-0383}, support = {N/A//Ministero della Salute/ ; }, abstract = {Background: Takotsubo syndrome (TTS) often mimics anterior ST-elevation myocardial infarction (STEMI) caused by left anterior descending (LAD) occlusion, yet the two entities differ fundamentally in pathophysiology and mechanical behavior. Two-dimensional speckle-tracking echocardiography (2D-STE) enables detailed assessment of left ventricular (LV) deformation beyond conventional ejection fraction (LVEF). This meta-analysis compared global and regional LV strain patterns in TTS versus LAD-related anterior STEMI during the acute phase. Methods: A systematic search of PubMed, Embase, and Scopus through October 2025 identified observational case-control studies directly comparing TTS and angiographically confirmed anterior STEMI, with LV mechanics assessed by 2D-STE. Random-effects models were used to pool standardized mean differences (SMDs) for LVEF; global longitudinal strain (GLS); apical, mid-ventricular, and basal longitudinal strain (ALS, MLS, BLS); and global radial strain (GRS). Heterogeneity (I[2]), publication bias (funnel plots, Egger's test), meta-regression, and leave-one-out sensitivity analyses were performed. Results: Six studies comprising 221 TTS and 290 anterior STEMI patients met the inclusion criteria. TTS patients were older, predominantly female, and had fewer metabolic risk factors, while LV size was comparable. LVEF was significantly lower in TTS (SMD -1.149; 95% CI -2.20 to -0.10; p = 0.032), with stable findings across sensitivity analyses and no evidence of publication bias. GLS, ALS, MLS, and BLS showed only a non-significant trend toward greater impairment in TTS, and these comparisons were limited by marked inter-study heterogeneity. In contrast, GRS was significantly and consistently more reduced in TTS (SMD -1.284; 95% CI -1.59 to -0.98; p < 0.001), indicating more profound global radial dysfunction. Meta-regression showed no significant influence of demographic factors or vendor-specific software on LVEF or GLS differences. Conclusions: Compared with LAD-related anterior STEMI, TTS is associated with more severely depressed LVEF and markedly impaired radial strain, while longitudinal strain differences remain inconclusive and suggest only a potential trend toward greater dysfunction, reflecting the limited and heterogeneous evidence. These findings are consistent with diffuse, stress-induced myocardial stunning in TTS and suggest that 2D-STE may aid differentiation between stress cardiomyopathy and ischemic infarction in the acute setting, although longitudinal strain parameters should be interpreted cautiously and regarded as hypothesis-generating.}, }
@article {pmid41464612, year = {2025}, author = {Klumb, S and Haley, L and Hathaway, C and Irby, J and Cheng, J and Rumley, J}, title = {Degenerative Cervical Myelopathy Diagnosis and Its Differentiation from Neurological Mimics, MS and ALS: A Literature Review.}, journal = {Journal of clinical medicine}, volume = {14}, number = {24}, pages = {}, doi = {10.3390/jcm14248711}, pmid = {41464612}, issn = {2077-0383}, abstract = {Multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and degenerative cervical myelopathy (DCM) share features that may confound diagnosis. DCM is caused by degenerative changes in the cervical spine leading to spinal cord compression and injury, resulting in significant disability. Misdiagnosis of DCM for a similar neurological condition can lead to further spinal cord damage from delayed surgical treatment. Here we review the diagnostic criteria, clinical signs and symptoms, and imaging typical for DCM, and two of its clinical mimics, MS and ALS. Shared motor symptoms of all three conditions can make diagnosis difficult, especially early in disease course. Noteworthy differences include neck and shoulder pain in DCM, visual disturbances in MS, and bulbar symptoms and the absence of sensory deficits in ALS. In DCM and MS, MRI is used to support the diagnosis, with specific findings on MRI that differentiate DCM versus MS. In ALS, MRI is used to rule out differential diagnoses. Applying the diagnostic criteria for MS and ALS, as well as understanding the typical presentation and MRI findings of DCM, is crucial. Through discussion of these conditions, this review aims to help limit misdiagnosis rates, allowing for early management, which can improve long-term patient outcomes.}, }
@article {pmid41463333, year = {2025}, author = {Tendero-Lopez, D and Dominguez, M and Aguilar-Aragon, M}, title = {Modelling Neural Disorders with the D. melanogaster Larval Peripheral and Adult Dopaminergic Systems.}, journal = {Biomolecules}, volume = {15}, number = {12}, pages = {}, doi = {10.3390/biom15121677}, pmid = {41463333}, issn = {2218-273X}, mesh = {Animals ; *Drosophila melanogaster/metabolism ; Larva/metabolism ; *Disease Models, Animal ; Humans ; *Dopamine/metabolism ; *Dopaminergic Neurons/metabolism/pathology ; *Nervous System Diseases/metabolism ; Parkinson Disease/metabolism ; }, abstract = {The increasing prevalence of neurological disorders highlights the need for disease animal models to elucidate the underlying biomolecular and cellular mechanisms of disease and to facilitate studies aimed at developing effective treatments. The fruit fly Drosophila melanogaster, at both larval and adult stages, can serve as an effective model for different human-relevant neurological diseases. Larvae are particularly suited for studying peripheral nervous system disorders, such as Charcot-Marie-Tooth and amyotrophic lateral sclerosis, while adults enable investigations of higher-order cognitive functions and age-related conditions, including Parkinson's disease and depression-like behaviours. Combining larval and adult models offers a complementary framework to dissect the biomolecular pathways of neurological disorders and accelerate preclinical research.}, }
@article {pmid41462890, year = {2025}, author = {Fajkić, A and Belančić, A and Lam, YW and Rački, V and Pilipović, K and Janković, T and Mežnarić, S and Mršić-Pelčić, J and Vitezić, D}, title = {Novel Translational Concept: Axon-to-Muscle Exosomal Signaling as an Emerging Therapeutic Target in Spinal Muscular Atrophy.}, journal = {Biomedicines}, volume = {13}, number = {12}, pages = {}, doi = {10.3390/biomedicines13122876}, pmid = {41462890}, issn = {2227-9059}, abstract = {Spinal muscular atrophy (SMA) has transitioned from a uniformly fatal disease to a treatable condition, yet incomplete neuromuscular recovery underscores the limits of current SMN-restorative therapies. Emerging data implicate disrupted axon-to-muscle exosomal signaling as an important, overlooked driver of residual dysfunction. Exosomes, nanovesicles mediating bidirectional neuronal-muscular communication, carry synaptic organizers, trophic factors, and microRNAs essential for neuromuscular junction integrity. SMN deficiency alters exosomal biogenesis and cargo, leading to loss of agrin-MuSK signaling, impaired β-actin transport, and muscle atrophy. Comparative insights from amyotrophic lateral sclerosis and muscular dystrophy reveal that stem-cell-derived or engineered exosomes restore synaptic stability, enhance regeneration, and cross biological barriers safely. Thus, we speculate herein on a translational model integrating exosome-based therapies with existing genetic interventions to achieve durable, systems-level recovery in SMA. Exosomal profiling may further yield minimally invasive biomarkers for disease monitoring and treatment optimization, establishing vesicle-mediated communication as a novel therapeutic axis in neuromuscular medicine.}, }
@article {pmid41459056, year = {2025}, author = {Auclair-Ouellet, N and Kassem, O and Bronner, S and Oula, ML and Binda, S}, title = {Leveraging microbiome-based interventions to improve the management of neurodegenerative diseases: evidence for effects along the microbiota-gut-brain axis.}, journal = {Frontiers in nutrition}, volume = {12}, number = {}, pages = {1699884}, pmid = {41459056}, issn = {2296-861X}, abstract = {The microbiota-gut-brain axis (MGBA) has recently emerged as a useful model for the understanding of the onset and progression of neurodegenerative diseases (NDDs). Microbiome-based interventions using biotic supplements (probiotics, prebiotics, synbiotics, postbiotics) can modulate the MGBA and constitute relevant solutions to help reduce the risk of neurological changes associated with NDDs and manage symptoms. This narrative review provides a summary of the functioning of the MGBA and of its interactions with disease processes involved in the onset and progression of NDDs. Microbiome-based interventions and their mechanisms of action are reviewed, and important considerations for the design of interventions are discussed. Next, preclinical and clinical studies on the potential of microbiome-based interventions in Alzheimer's disease (AD), Parkinson's disease (PD), Multiple Sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS), and Huntington's disease (HD) are reviewed. Evidence related to biomarkers of pathology (e.g., beta-amyloid or alpha-synuclein protein depositions), neuroinflammation, and metabolic activity is summarized, along with emerging evidence for the improvement of clinical symptoms and disease trajectories. Overall, preclinical studies show that microbiome-based supplements have significant positive effects on mechanisms and pathways involved in the pathophysiology of NDDs. Clinical studies show that these interventions provide important benefits both in terms of biomarkers and clinical symptoms. However, evidence is limited in some key clinical areas, such as mental wellbeing in AD and cognition in PD, and for the management of clinical symptoms in ALS and HD overall. Gaps in knowledge and open questions as well as perspectives for future research are discussed.}, }
@article {pmid41458376, year = {2025}, author = {Qian, G and Ding, L and Tan, C and Wang, L and Long, C}, title = {Mucosal immune response modulated by secreted and membrane-bound hydrolases of Candida albicans in vulvovaginal candidiasis.}, journal = {Frontiers in fungal biology}, volume = {6}, number = {}, pages = {1692795}, pmid = {41458376}, issn = {2673-6128}, abstract = {Vulvovaginal candidiasis (VVC) affects the physical and mental health of millions of women worldwide. The leading cause of VVC, Candida albicans, can induce a strong mucosal inflammatory reaction during the VVC infection, where secreted and membrane-bound adhesion and hydrolases seem to be the key virulent factors to promote the mucosal antifungal immunity and immunopathology. Several hydrolases, such as Saps, Als, candidalysin, lipases, and phospholipases, have been identified in vaginal secretions isolated from VVC patients; however, the immune impacts of some hydrolases have not been well documented. In this review, we focus on the literature that addresses the immunopathogenic roles of the Als adhesin family or proteinase, such as Sap and candidalysin, in VVC. Our goal is to expand our knowledge of VVC pathogenesis in order to provide new strategies for VVC treatment.}, }
@article {pmid41456636, year = {2025}, author = {Koppali, SR and Vadia, N and Varma, P and Mishra, S and Joshi, N and Bansal, P and Al-Hasnaawei, S and Chauhan, AS and Jain, H and Nathiya, D and Devi, A and Jayasingh Chellammal, HS and Gupta, P and Wal, P and Koppula, S}, title = {Neurodevelopmental origins of neurodegeneration: a lifespan perspective on brain vulnerability.}, journal = {Brain research}, volume = {}, number = {}, pages = {150134}, doi = {10.1016/j.brainres.2025.150134}, pmid = {41456636}, issn = {1872-6240}, abstract = {Neurodegenerative disorders-including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis-are increasingly understood to have origins in early neurodevelopmental disturbances. This review examines how genetic, epigenetic, and environmental factors impact brain development during critical periods, predisposing individuals to neurodegeneration later in life. Prenatal and early-life exposures such as maternal stress, malnutrition, infection, and environmental toxins can alter key developmental processes, leading to long-term vulnerability. Mechanistic pathways linking early-life disruptions to neurodegenerative outcomes include persistent mitochondrial dysfunction, chronic neuroinflammation, increased oxidative stress, and aberrant synaptic pruning, all of which contribute to progressive neuronal damage and dysfunction. The gut-brain axis is also discussed as a key intermediary, where early microbiota dysbiosis alters neuroimmune signaling and inflammatory responses, modulating susceptibility to age-related neurological disorders. In this context, the review highlights emerging molecular and imaging biomarkers capable of detecting subtle neurodevelopmental deviations that may precede clinical symptoms by decades. The paper emphasizes the need for early-life interventions, including maternal nutritional optimization, management of prenatal stress, and microbiome-targeted strategies, as potential tools to reduce long-term neurological risk. Furthermore, it proposes the integration of precision medicine approaches aimed at individualized risk assessment and therapeutic targeting of developmental pathways. Adopting a lifespan perspective, this review argues for a paradigm shift from reactive to preventive strategies in neurology. Understanding the developmental roots of neurodegeneration opens new avenues for research and intervention, enabling resilience and reducing disease burden through early diagnostics and tailored therapeutics across the lifespan.}, }
@article {pmid41455134, year = {2025}, author = {Du, O and Wu, YJ and Li, MY and Du, JR}, title = {The role of HMGB1 in central nervous system (CNS) diseases: mechanisms and therapeutic perspectives.}, journal = {Cytokine}, volume = {198}, number = {}, pages = {157099}, doi = {10.1016/j.cyto.2025.157099}, pmid = {41455134}, issn = {1096-0023}, abstract = {Central nervous system (CNS) diseases represent a major global health burden and are among the leading causes of disability and mortality worldwide. The pathological mechanisms underlying CNS disorders are complex and multifactorial, involving processes such as neuroinflammation, oxidative stress, neuronal damage, and synaptic dysfunction. High-mobility group box 1 (HMGB1), a member of the high-mobility group box (HMGB) protein family, is predominantly localized in the nucleus under physiological conditions, where it contributes to DNA repair, transcriptional regulation, and other cellular functions. However, in various CNS pathologies-including stroke, traumatic brain injury (TBI), Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), glioblastoma (GBM), epilepsy, depression, multiple sclerosis (MS), and schizophrenia-HMGB1 is released or secreted into the extracellular space. There, it plays a key role in regulating neuroinflammation, cell death, cell migration, and tissue damage and repair, thereby contributing to disease pathogenesis and progression. HMGB1 not only functions as a critical regulator in the progression of CNS diseases but also serves as a biomarker for predicting poor clinical outcomes. Moreover, a growing body of evidence indicates that therapeutic strategies targeting HMGB1 can significantly alleviate pathological damage in various CNS disorders, highlighting its potential as a promising therapeutic target. This review comprehensively summarizes the structure, post-translational modifications, release mechanisms, and receptor systems of HMGB1, along with its roles and mechanisms in CNS diseases. It also discusses the potential of HMGB1 as a biomarker and examines emerging HMGB1-targeted therapeutic strategies, aiming to provide a theoretical foundation for the treatment and drug development of CNS disorders.}, }
@article {pmid41454317, year = {2025}, author = {Abdi, M and Sooudi, OK and Milota, M}, title = {Professional identity formation for underrepresented groups in medicine: challenges and interventions for Dutch medical schools: a systematic scoping review.}, journal = {BMC medical education}, volume = {25}, number = {1}, pages = {1715}, pmid = {41454317}, issn = {1472-6920}, mesh = {Humans ; Netherlands ; *Schools, Medical/organization &amp; administration ; *Students, Medical/psychology ; *Social Identification ; *Minority Groups/psychology/education ; Cultural Diversity ; *Ethnicity ; }, abstract = {BACKGROUND: The concept of intersectionality is important when considering the professional identity formation (PIF) of students who are racially and ethnically underrepresented in medicine (URiM), as they must navigate race and ethnicity within the medical landscape. Despite a growing body of studies that shed light on the challenges that URiM students face in their PIF, there remains a notable lack of practical interventions for medical schools to address these challenges. Our objective is to highlight the challenges faced by URiM students and identify interventions in the literature that would be most suitable for Dutch medical schools to address them.<br><br>METHODS: This study builds upon Teo et al.'s (2022) scoping review. We examined articles from January 1, 2000, to December 31, 2021, and conducted an extended search from January 1, 2022, to November 30, 2023. Our focus was on articles exploring the intersectionality of PIF, perspectives of minoritized groups, and diversity, equity, and inclusion (DEI) within the context of PIF in medical education. We used the Systematic Evidence-Based Approach (SEBA) guided systematic scoping review, encompassing four stages: Systematic Approach, Structured Summary and Synthesis, Jigsaw Perspective, and Literature Analysis.<br><br>RESULTS: A total of 692 abstracts were reviewed, 36 full-text articles were evaluated, and 22 articles were included. URiM students encounter multiple challenges in their PIF journeys such as a lack of role models and representation, experiences of microaggressions, and pressure to assimilate into the majority culture. The proposed interventions for medical schools included diversifying recruitment practices to create more role models, developing curricula to address these challenges, and establishing a supportive network for URiM students.<br><br>CONCLUSIONS: Our study highlights the pressing need for Dutch medical schools to address the challenges faced by URiM students in PIF. The identified interventions offer actionable strategies to cultivate a more supportive and equitable learning environment. The implementation of these interventions has the potential to enhance URiM students' educational experiences, reduce disparities, and promote diversity within the medical profession. These findings underscore the importance of ongoing efforts to prioritize inclusivity and equity in medical education.}, }
@article {pmid41438688, year = {2026}, author = {Su, T and Li, Z and Yang, Y and Dai, Y and Li, Y and Zhao, H}, title = {In vitro 3D models of neuron-astrocyte interactions.}, journal = {Biochemistry and biophysics reports}, volume = {45}, number = {}, pages = {102400}, pmid = {41438688}, issn = {2405-5808}, abstract = {The pathological processes of neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, and Amyotrophic Lateral Sclerosis) also include relationships between neuron and glia cells. Conventional two-dimensional (2D) cell cultures have limitations to mimic the microenvironment of cells inside living organisms because of flaws in intercellular relationships investigated using 2D cell cultures. Recent advances have introduced three-dimensional (3D) cell cultures that have the capability to create 3D cellular architecture to mimic advanced platforms for scientific inquiries into neurodegenerative diseases, simulating microenvironments inside living organisms.This review provides a brief overview of the development of in vitro 3D cell culture models of astrocytes and attempts to highlight the role of astrocytes in crucial pathophysiologic events occurring in 3D cultures. Studies have shown the use of in vitro 3D cultures to better represent the dual functions of astrocytes in neurodegenerative disorders. Looking ahead to the future, novel advances in microfluidics and multi-omics analysis promise to further improve 3D cultures and push forward new insights into neurological dysfunction to spark innovative advances for treatment strategies.}, }
@article {pmid41438236, year = {2025}, author = {Li, T and Gao, Y and Zhou, J and Chen, Y and Zhang, S and Gong, X and Liu, Y}, title = {Advancements in the application of brain-computer interfaces based on different paradigms in amyotrophic lateral sclerosis.}, journal = {Frontiers in neuroscience}, volume = {19}, number = {}, pages = {1658315}, pmid = {41438236}, issn = {1662-4548}, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurological condition that leads to the gradual loss of movement and communicative abilities, significantly diminishing the quality of life for affected individuals. Recent advancements in neuroscience and engineering have propelled the swift evolution of brain-computer interfaces (BCIs), which are now extensively utilised in medical rehabilitation, military applications, assistive technologies, and various other domains. As a communication medium facilitating direct interaction between the brain and the external world independent of the peripheral nervous system, BCI provides ALS patients with an innovative method for communication and control, offering unparalleled prospects for improving their quality of life. Recent collaborative endeavours among several specialists have markedly enhanced the precision and velocity of diverse BCI paradigms, signifying a breakthrough in BCI applications for ALS. Nonetheless, obstacles and constraints remain. This study methodically extracted pertinent literature from the Web of Science and PubMed databases in accordance with PRISMA guidelines. Following stringent inclusion and exclusion criteria, 23 studies were identified. This data allows us to summarise the application results and current limitations of several BCI paradigms in motor control and communication, while delineating prospects in multimodal fusion and adaptive calibration. This review presents evidence-based references for the effective translation and application of BCI technology in ALS rehabilitation.}, }
@article {pmid41431371, year = {2025}, author = {Dobbertin, T and Schirmer, L}, title = {Spatially Resolved Profiling of Compartmentalized Muscle and Brain Inflammation.}, journal = {European journal of immunology}, volume = {55}, number = {12}, pages = {e70119}, pmid = {41431371}, issn = {1521-4141}, support = {P1180016//Gemeinn&#xfc;tzige Hertie-Stiftung/ ; GRK2727(InCheck)//Deutsche Forschungsgemeinschaft/ ; FOR2690(SCHI1330/7-2)//Deutsche Forschungsgemeinschaft/ ; SPP2395(SCHI1330/10-1)//Deutsche Forschungsgemeinschaft/ ; FOR5705(SCHI1330/13-1)//Deutsche Forschungsgemeinschaft/ ; SCHI1330/2-1//Deutsche Forschungsgemeinschaft/ ; SCHI1330/4-1//Deutsche Forschungsgemeinschaft/ ; SCHI1330/11-1//Deutsche Forschungsgemeinschaft/ ; 950584//H2020 European Research Council/ ; }, mesh = {Humans ; Animals ; *Muscle, Skeletal/immunology/pathology/metabolism ; Proteomics/methods ; *Brain/immunology/pathology ; Inflammation/immunology ; *Neuroinflammatory Diseases/immunology ; *Encephalitis/immunology ; Transcriptome ; }, abstract = {Spatial omics technologies enable high-resolution mapping of transcriptomic, proteomic, and metabolic profiles within intact tissues, revealing how immune, stromal, and parenchymal cells interact in situ during inflammation. Chronic inflammation in skeletal muscle and the central nervous system is spatially organized within defined niches that shape disease progression and therapeutic response. In skeletal muscle, spatial analyses have uncovered fiber-type-specific vulnerability, regenerative trajectories, and immune-stromal crosstalk in disorders such as Duchenne muscular dystrophy and inclusion body myositis. In the central nervous system, these approaches have revealed compartmentalized neuroinflammation in multiple sclerosis, innate immune activation in amyotrophic lateral sclerosis, and immune evasion in glioma. Integration with single-cell gene expression enables inference of cell-cell communication networks and identification of spatial gradients of immune activation and tissue remodeling. Despite major advances, clinical translation remains limited by small cohorts, methodological variability, and insufficient functional validation. As spatial profiling becomes more accessible, standardized, and scalable, it promises to stratify inflammatory disease states, identify tissue-resident immune programs, and guide mechanism-based therapies. Hence, spatial omics provide an unprecedented opportunity to resolve the cellular architecture of inflammation, revealing not only where immune activity occurs, but how it is orchestrated within complex tissue microenvironments.}, }
@article {pmid41428942, year = {2025}, author = {Sannes, A and Rognli, EW and Hanssen-Bauer, K and Torp, NC and Storfossen, SK and Høstaker, MN and Aalberg, M}, title = {Barriers to and Facilitators of Implementation of Internet-Delivered Therapist-Guided Therapy in Child and Adolescent Mental Health Services: Systematic Review and Bayesian Meta-Analysis.}, journal = {Journal of medical Internet research}, volume = {27}, number = {}, pages = {e83543}, pmid = {41428942}, issn = {1438-8871}, mesh = {Adolescent ; Child ; Humans ; *Adolescent Health Services ; Bayes Theorem ; *Child Health Services ; *Internet ; *Mental Health Services ; *Psychotherapy/methods ; }, abstract = {BACKGROUND: Internet-delivered therapist-guided therapy (e-therapy) represents a promising approach for enhancing accessibility, treatment fidelity, and scalability within child and adolescent mental health services (CAMHS).<br><br>OBJECTIVE: This systematic review aimed to (1) identify and synthesize determinants of implementation, specifically barriers to and facilitators of e-therapy in CAMHS structured according to the Consolidated Framework of Implementation Research (CFIR); and (2) provide pooled benchmark estimates of key implementation outcomes for fidelity, cost-effectiveness, and acceptability.<br><br>METHODS: A PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses)-compliant systematic review was performed across PsycINFO, MEDLINE, Web of Science, CINAHL, Embase, Cochrane, and ProQuest Dissertations &amp; Thesis on June 6, 2025-to identify peer-reviewed studies assessing implementation outcomes or determinants of e-therapy in the context of outpatient CAMHS (ages 8-18 years). Barriers and facilitators were synthesized qualitatively with thematic analysis applying CFIR. A parallel quantitative synthesis of Proctor et al's taxonomy of implementation outcomes was performed using Bayesian multilevel random-effects meta-analyses to estimate pooled effect sizes and 95% credible intervals (CIs). By combining quantitative benchmarks of implementation success with qualitative insights into contextual determinants, the review provides an integrated understanding of what drives effective e-therapy implementation in CAMHS. Study quality was assessed using the CASP (Critical Appraisal Skills Programme) checklist, Cochrane Risk of Bias tool, and Risk Of Bias In Non-randomized Studies-of Interventions tool. Small study effects were evaluated using funnel plots, sensitivity analyses, and the Egger test.<br><br>RESULTS: From 50,026 screened reports, 50 studies published between 2007 and 2025 were included: 18 randomized controlled trials, 17 cohort, and 15 qualitative or mixed methods studies. Most studies originated from Western Europe (n=34), Northern America (n=11), and Oceania (n=5), targeting anxiety (n=24) and depression (n=9), through cognitive behavioral therapy-based programs (n=47), with parallel parent content (n=31). Therapist guidance was primarily asynchronous (n=43). Among the 39 studies reporting determinants, common barriers and facilitators were identified across intervention, organization, therapist, and patient domains, structured via CFIR. Pooled implementation outcomes showed modest dropout rates (~20%, CI 14%-27%), high module completion (~68%, CI 60%-75%), low therapist time (24 min per wk per patient, 95% CI 19-28), and high patient satisfaction (24/32 on Client Satisfaction Questionnaire-8, 95% CI 22-27; and 76% satisfaction rate, 95% CI 62%-87%), suggesting e-therapy is resource efficient and acceptable if implemented successfully.<br><br>CONCLUSIONS: This review provided the first integrated synthesis of pooled benchmarks for implementation outcomes of e-therapy in CAMHS and modifiable determinants to inform future service planning and scale-up. These findings highlighted service-level enablers, such as leadership anchoring, targeted use, technical stability, structured patient flow, and therapist training, that organizations could prioritize to strengthen sustainable e-therapy implementation in CAMHS.}, }
@article {pmid41426554, year = {2025}, author = {Liang, L and Zhang, Y and Zhang, X and Guo, X and Yan, Y}, title = {Historical evolution, research hotspots and emerging trends of pediatric hand, foot, and mouth disease: a bibliometric worldview since the 21st century.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1722750}, pmid = {41426554}, issn = {2296-858X}, abstract = {BACKGROUND: Hand, foot, and mouth disease (HFMD) poses a significant challenge to global public health. Primarily caused by enterovirus and coxsackievirus infections, the disease has a particularly pronounced impact in the Asia-Pacific region. However, systematic analysis and discussion regarding the developmental trajectory, core research entities, current status, key research directions, and future prospects of pediatric HFMD research remain lacking.<br><br>METHODS: This study collected and analyzed papers and reviews on pediatric HFMD published between January 1, 2000, and February 1, 2025, from the Web of Science Core Collection and PubMed. Key research indicators were analyzed through bibliometric visualization, using tools including Excel, CiteSpace, VOSviewer, and BibliomeTools (an R-based tool in R-Studio).<br><br>RESULTS: Since the start of the 21 st century, academic publications in pediatric HFMD have steadily increased, with a cumulative total of 2,034 papers published by February 1, 2025. Global research distribution exhibits uneven patterns, with China emerging as core contributors. Specifically, Lin, Tzou-Yien from China, has published the largest number of papers, while Chang, Luan-Yin is the co-cited author with the highest citation rate. Solomon T et al.'s "Virology," Epidemiology, Pathogenesis, and Control of Enterovirus 71" being the most cited study in the field. Research on pediatric HFMD is closely integrated with disciplines such as virology and epidemiology, forming core research themes around "HFMD," "enterovirus 71," and "enteroviruses." Recent research has focused on the pathogenesis, epidemiology, novel therapeutic discoveries and vaccine development for pediatric HFMD. Looking ahead, it is essential to delve deeper into the molecular mechanisms underlying the interaction between the human HFMD virus and its host, and to develop multivalent vaccines targeting multiple serotypes.<br><br>CONCLUSION: This study employs bibliometric methods to visualize research in the field of pediatric hand, foot, and mouth disease, revealing trends and frontiers in this area. It will provide valuable reference for scholars seeking key research questions and potential collaborators.}, }
@article {pmid41420832, year = {2025}, author = {Wang, X and Wei, M and Qiao, Y}, title = {Modulation of Liquid-to-Solid Phase Transition in Coacervates for Neurodegenerative Disease Treatments.}, journal = {Chembiochem : a European journal of chemical biology}, volume = {}, number = {}, pages = {e202500795}, doi = {10.1002/cbic.202500795}, pmid = {41420832}, issn = {1439-7633}, support = {2023YFC2507000//National Key R&amp;D Program of China/ ; 22272183//National Natural Science Foundation of China/ ; T2425001//National Natural Science Foundation of China/ ; }, abstract = {Coacervates formed through liquid-liquid phase separation represent a fundamental model for protocell and serve as a membraneless organelle in living cells, modulating various biological processes. During aging or under stress, protein misfolding and oligomerization trigger aberrant liquid-to-solid phase transition (LSPT), a process driven by multivalent interactions. These phase transitions disrupt cellular equilibrium, leading to neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. The regulatory strategies is summarize to enhance molecular interactions in coacervate LSPT into three categories, including physical stimulation, molecular modulation, and sequence regulation. This review aims to establish a conceptual framework for modulating coacervate LSPT and further explores potential clinical treatments for neurodegenerative diseases.}, }
@article {pmid41419286, year = {2025}, author = {Phillips, G and Sharma, D and O'Reilly, G and Romero, L and Cameron, P}, title = {Developing emergency care systems in low-income and middle-income countries: a scoping review to examine the role of leadership and governance.}, journal = {BMJ open}, volume = {15}, number = {12}, pages = {e102624}, pmid = {41419286}, issn = {2044-6055}, mesh = {Humans ; *Developing Countries ; *Leadership ; *Emergency Medical Services/organization &amp; administration ; }, abstract = {BACKGROUND: More knowledge and resources are required to strengthen 'leadership and governance' (L+G) as a central building block to further develop emergency care (EC) systems in low-income and middle-income countries (LMICs).<br><br>OBJECTIVES: This scoping review aimed to examine and map the impact of individual, collective or institutional L+G on the development of EC systems (prehospital and facility-based) in LMICs.<br><br>ELIGIBILITY CRITERIA: English language publications from January 2005 to April 2024 that linked any L+G action with the development and capacity of everyday EC in LMICs, specifically excluding disaster responses.<br><br>SOURCES OF EVIDENCE: Medline (Ovid), Embase (Ovid), CINAHL, Web of Science (Clarivate), Central (Cochrane Central Register of Controlled Trials), Global Health (Ovid) and select grey literature.<br><br>CHARTING METHODS: Data from all eligible papers were jointly extracted using a piloted tool developed from the literature and WHO's EC Systems Framework. L+G descriptors included level (from clinical to national) and components (informed by Siddiqi et al's LMIC health system 'good governance' framework and a synthesis of EC policy documents). Impact of L+G on EC systems and key lessons were extracted from each publication.<br><br>RESULTS: From an initial 9713 items, 129 papers were included for final analysis and divided by EC component: prehospital (n=35), facility-based (n=53) and 'whole of EC system' (n=41). Qualitative and descriptive papers were most common, and 72 out of a possible 131 LMICs were represented. Findings were heterogeneous across all building blocks of EC systems and for different components of leadership and/or governance. Cross-cutting L+G themes were identified that demonstrated consistent impact across all EC systems development: government recognition, vision and human rights framing; coalition-building for effective partnerships and trained, empowered EC clinicians demonstrating emotionally intelligent, transformational leadership.<br><br>CONCLUSIONS: Applying new models such as Theories of Change and Social Network Analysis concepts may assist to illuminate how effective L+G is attained, what are the essential components and how these influence EC systems for better patient-centred outcomes. Further understanding the role of L+G for EC systems has utility for future EC clinician leadership training and policy-maker awareness, to strengthen resilience of overall health systems against likely future shocks.}, }
@article {pmid41417080, year = {2025}, author = {Zafar, U and Abdullah, M and Butt, TN and Uddin, MMZ and Masood, MH and Chu, LC and Zaheer, A}, title = {A bibliometric analysis of the 100 most cited radiology papers on pancreatic diseases (1990-Present).}, journal = {Abdominal radiology (New York)}, volume = {}, number = {}, pages = {}, pmid = {41417080}, issn = {2366-0058}, abstract = {PURPOSE: To map the intellectual evolution of pancreatic radiology through a comprehensive bibliometric analysis of the 100 most-cited articles, identifying influential contributors and publications, geographical and institutional patterns, and delineating the thematic and technological trends shaping research from 1990 to the present.<br><br>METHODS: A systematic search of the Scopus database, conducted on May 11, 2025, identified the top 1,000 most-cited pancreatic radiology records between 1990 and 2025. Two reviewers independently screened articles for a primary focus on pancreatic imaging within core radiology journals. The final 100 articles were analyzed using the Bibliometrix R package to evaluate publication trends, contributor influence, and collaborative networks. The conceptual structure and thematic evolution of the field were mapped using VOSviewer (version 1.6.20).<br><br>RESULTS: The median citation count was 223 (IQR: 190.2-264.5). A significant temporal bias was evident: the most-cited article was Balthazar et al.'s 1990 study on CT in pancreatitis (1,424 citations), while a 2015 deep learning paper achieved the highest citation velocity (58.5 citations/year). Analysis of research topics revealed a strong oncologic focus, with pancreatic neoplasms accounting for 51% of all articles. CT was the predominant imaging modality (55%), followed by MRI (24%). The research ecosystem was concentrated, with the United States contributing 46 articles and Radiology publishing 44 of the top 100 papers. Leading institutions included Johns Hopkins University and the Mayo Clinic. Co-authorship network analysis identified Megibow AJ as the researcher with the highest network centrality, highlighting the importance of collaborative hubs.<br><br>CONCLUSION: This bibliometric analysis charts the field's evolution from foundational CT/MRI applications to the current AI frontier. Our findings serve as a guide to the characteristics of high-impact research, highlighting a consistent focus on oncology, driven by key authors and US institutions. While historical benchmarks focused on morphological assessment, citation metrics confirm computational methods as the principal driver of future innovation.}, }
@article {pmid41417044, year = {2025}, author = {Rott, N and Reinsch, L and Dirks, B and Böttiger, BW}, title = {[The new European Resuscitation Council (ERC) guidelines 2025-Overview of the most important changes; the first 3-5 min are decisive].}, journal = {Die Anaesthesiologie}, volume = {}, number = {}, pages = {}, pmid = {41417044}, issn = {2731-6866}, abstract = {In October 2025 the new resuscitation guidelines of the European Resuscitation Council (ERC) were published. In the chapter on advanced life support (ALS) for adults the update emphasizes topics such as efficient ventilation with adequate chest compressions, early defibrillation, identification and treatment of reversible causes as rapidly as possible and the administration of epinephrine in cases of non-defibrillatable cardiac arrest. The aim of the guidelines is to sustainably improve survival rates after cardiac arrest through structured and evidence-based care systems.}, }
@article {pmid41385186, year = {2025}, author = {Mitsiadou, D and Xirodimas, DP and Polanowska, J}, title = {NEDD8, stress granules, and amyotrophic lateral sclerosis: unveiling the therapeutic potential of the NEDP1 protease.}, journal = {Essays in biochemistry}, volume = {69}, number = {5}, pages = {}, doi = {10.1042/EBC20253036}, pmid = {41385186}, issn = {1744-1358}, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/drug therapy ; Humans ; Animals ; *Stress Granules/metabolism ; *NEDD8 Protein/metabolism ; }, abstract = {Protein quality control (PQC) systems are crucial for maintaining cellular proteostasis, particularly under stress that promotes misfolded protein accumulation. A central component of this response is the assembly of stress granules (SGs), cytoplasmic condensates of RNA and proteins that temporarily stall translation. Aberrant SG dynamics, often linked to mutations in SG proteins, contribute to neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), where persistent protein aggregates are hallmarks. This review examines the emerging role of the ubiquitin-like modifier NEDD8 and its deconjugating enzyme NEDP1 in regulating SG homeostasis. Recent studies identify NEDP1 as a critical factor controlling SG clearance. Inhibition of NEDP1 enhances SG turnover, prevents pathological solidification, and promotes the disassembly of toxic aggregates through hyper-NEDDylation of PARP1, a DNA repair enzyme that also governs SG dynamics. Unlike broad-spectrum PARP1 inhibitors, which can impair DNA repair and cause cytotoxicity, NEDP1 inhibition offers a stress-specific approach that preserves normal cellular functions. Encouragingly, NEDP1 inhibition effectively causes aggregate elimination in ALS patient-derived fibroblasts and restores motility in Caenorhabditis elegans disease models. Altogether, these findings highlight NEDP1 as a key regulator of SG regulation and a promising therapeutic target for ALS and related neurodegenerative disorders.}, }
@article {pmid41415845, year = {2025}, author = {Harsa, HS and González Domenech, CM and Prvulović, M and Agirbasli, Z and Bagherzadehsurbagh, E and Simeunović, V and Naziri, E and Adesemoye, E and Yigit Cinar, A and Mukherjee, A and Laranjo, M and Vidović, B and Alves, E and Vukojević, A and Özmen Toğay, S and Düven, G and Saar, H and Salminen, S and Matalas, A and Paveljšek, D and Schneider, E and Liwinski, T and Chassard, C and Vergères, G and Bär, C and Praćer, S}, title = {The effects of Lactobacillus and/or Bifidobacterium in fermented foods on cognitive health: a systematic review.}, journal = {Frontiers in nutrition}, volume = {12}, number = {}, pages = {1682419}, pmid = {41415845}, issn = {2296-861X}, abstract = {BACKGROUND: Psychobiotics are microorganisms that modulate brain function via the gut-brain axis and are increasingly studied for their cognitive benefits. Lactobacillus and Bifidobacterium species, widely present in fermented foods, are considered safe and may influence cognition by modulating neuroinflammation, neurotransmitters, and gut barrier integrity. This systematic review examined the effects of foods fermented with these species on cognitive performance in healthy adults and individuals with mild cognitive impairment.<br><br>METHODS: We conducted the systematic review following EFSA guidelines, Cochrane methodology, and a PROSPERO protocol, using CADIMA for study selection and data extraction. PubMed, Scopus, and Cochrane Library were searched (1 January 1970-31 August 2023) for human intervention and observational studies assessing cognitive outcomes after ingestion of foods fermented with Lactobacillus or Bifidobacterium. Eligible populations included healthy adults and individuals with mild cognitive impairment; studies involving disease were excluded. Screening, data extraction, and bias assessment followed Muka et al.'s 24-step guide using ROBINS and Cochrane/CADIMA frameworks. Evidence was synthesized narratively, while a non-systematic component examined food characteristics, potential mechanisms, and factors affecting bioavailability of bioactive constituents.<br><br>RESULTS: We included 21 studies (8 interventional, 13 observational). The majority of studies reported benefits, particularly in episodic memory, executive functions, and global cognition, but evidence was limited by inadequate controls, small sample sizes, short interventions, inconsistent domain assessment, and incomplete food characterization. Observational studies had larger populations and longer follow-ups but were limited by exposure assessment and depth of cognitive testing.<br><br>CONCLUSION: Consumption of foods fermented with Lactobacillus and/or Bifidobacterium species may offer promising cognitive benefits. However, following EFSA's guidance on the substantiation of health claims, the current evidence is "neither convincing nor sufficient" to establish a causal relationship. Well-designed studies with thorough product characterization are needed to substantiate effects and support potential health claims.<br><br>This study was registered at the Open Science Framework (10.17605/OSF.IO/Z6GRW).}, }
@article {pmid41411702, year = {2025}, author = {Lebkuecher, AL and Coslett, HB and Buxbaum, LJ}, title = {The cognitive neuropsychology of action semantics: A review.}, journal = {Cortex; a journal devoted to the study of the nervous system and behavior}, volume = {194}, number = {}, pages = {159-190}, doi = {10.1016/j.cortex.2025.11.008}, pmid = {41411702}, issn = {1973-8102}, abstract = {The conceptual knowledge that mediates our ability to use familiar objects, understand viewed actions, and engage in communication about actions is often termed "action semantics". The underlying format, cognitive organization, and neural substrates of these representations are matters of active scientific investigation. This review synthesizes the large and diverse literature on action semantics in individuals with neurological disorders characterized by prominent motor deficits (e.g., Parkinson's disease and Amyotrophic lateral sclerosis), as well as those for whom motor deficits are often less prominent (e.g., Alzheimer's disease, Frontotemporal Dementia, stroke). Research in these two groups of disorders is strikingly "siloed" and offers many contradictory findings with respect to whether action semantic representations are abstract (i.e., "disembodied") or grounded in sensory and motor features that reflect the way knowledge was acquired. Findings across these populations also disagree as to whether action semantic representations are organized somatotopically or with a semantic feature-based architecture, and mediated by anterior motor-related or relatively posterior sensory-related brain regions. Many of these disparate findings can be reconciled with consideration of a multidimensional, multimodal representational architecture mediated by a distributed left-lateralized network of brain regions. We provide suggestions for specific methodological approaches for research with neurological populations that may further our understanding of the format, organization, and neural substrates of action semantics.}, }
@article {pmid41408263, year = {2025}, author = {Doughty, J and Booth, J and Smith, M and Saini, K and Paisi, M and Rodriguez, A and Levine, A and Bedos, C and Muirhead, V and Martins de Barros, C and Freeborn, C}, title = {Unmasking oral health stigma: a qualitative scoping review.}, journal = {BMC oral health}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12903-025-07329-9}, pmid = {41408263}, issn = {1472-6831}, abstract = {INTRODUCTION: Health-related stigma can limit access to care, impair adherence to treatment, and negatively impact mental health and quality-of-life. Oral health stigma, defined as stigma arising from oral conditions that diverge from sociocultural norms, operates through labelling, stereotyping, othering, and exclusion. Oral health stigma can lead to shame, diminished self-confidence, and avoidance of dental care, creating a self-perpetuating cycle of poor oral health and reinforcing internalised and anticipated stigma. While previous research has explored the social implications of oral appearance, little is known about the broader concept of oral health stigma or strategies to mitigate it.<br><br>METHODS: This scoping review adopted Levac et al.'s six-stage framework. The review utilised data from qualitative studies to explore lived experiences of oral health stigma and consider ways to mitigate it. Patient and public involvement (PPI) informed the development of the research question, search strategy, and interpretation of findings.<br><br>RESULTS: Seventy-two qualitative studies were included, comprising 2,455 participants. Themes included stigma associated with physical appearance and attractiveness, judgement, labelling, and stereotyping. Consequences included low self-esteem, social exclusion, impacts to care seeking behaviours, and efforts to conceal oral appearance. Participants highlighted the transformative value of dental care and described coping strategies to build resilience. Other proposed solutions included fostering social connection and implementing trauma-informed, non-judgemental dental care.<br><br>CONCLUSION: Oral health stigma has significant social and psychological consequences and impacts on care-seeking behaviours. Addressing it requires targeted interventions at multiple levels, including individual, community, professionals and wider system / policy.}, }
@article {pmid41407165, year = {2025}, author = {Ghosh, N and Ghosh, J and Ghosh, S and Sinha, K and Sil, PC}, title = {Nutraceutical interventions for neuroprotection: a comprehensive review.}, journal = {Biochemical pharmacology}, volume = {245}, number = {}, pages = {117637}, doi = {10.1016/j.bcp.2025.117637}, pmid = {41407165}, issn = {1873-2968}, abstract = {Nutraceuticals, bioactive compounds derived from food sources, are emerging as promising agents for neuroprotection, particularly through their modulation of gut health. Unlike conventional single-molecule therapeutics that often target isolated pathways, nutraceuticals offer a multi-targeted approach by influencing the gut-brain axis, a bidirectional communication network linking the gut microbiota and the central nervous system. Key nutraceuticals such as probiotics, prebiotics, polyphenols, omega-3 fatty acids, and vitamins have been shown to beneficially alter microbiota composition, reduce intestinal inflammation, and strengthen gut barrier integrity. These changes can significantly influence brain function by modulating neurotransmitter activity and systemic immune responses. This review compares the holistic action of nutraceuticals with the more focused effects of single-molecules, particularly in the context of neurodegenerative diseases like Alzheimer's, Parkinson's, Huntington's Disease and Motor Neuron Diseases like amyotrophic lateral sclerosis. It discusses how nutraceuticals may mitigate key pathological features of these conditions-including neuroinflammation, oxidative stress, and mitochondrial dysfunction, through gut-mediated pathways. Despite their potential, challenges remain regarding the standardization of formulations, bioavailability, dosage optimization, and long-term safety. Further clinical research is needed to validate the efficacy of nutraceuticals as complementary or alternative strategies to traditional neuroprotective agents.}, }
@article {pmid41402228, year = {2025}, author = {Vovard, B and Faure-de Baets, J and Codron, P and Allain, P and Cassereau, J}, title = {Assessment of social cognition impairments in patients with amyotrophic lateral sclerosis: How can it be improved? A systematic review.}, journal = {Revue neurologique}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.neurol.2025.11.003}, pmid = {41402228}, issn = {0035-3787}, abstract = {OBJECTIVES: The aim of this review was to evaluate the current evidence on which part of social cognition is impaired in amyotrophic lateral sclerosis (ALS) patients among emotion recognition, affective empathy and Theory of Mind (ToM) and to suggest improvements in social cognition testing protocols.<br><br>METHODS: A systematic review was conducted according to PRISMA guidelines. We included controlled cross-sectional or longitudinal studies published in English before September 1, 2024, that assessed social cognition in non-demented ALS patients. Searches were performed in Medline, Embase, Web of Science, and PsycINFO using specific MeSH terms. Studies using social cognition tests as a primary or secondary outcome were included.<br><br>RESULTS: Thirty-four studies were analyzed. Impairments in emotion recognition -&#xa0;especially for negative emotions&#xa0;- were frequently reported, even in cognitively preserved ALS patients. Results for cognitive ToM were mixed and may be confounded by executive dysfunction or test limitations. In contrast, affective ToM deficits were more consistently identified. However, no included study directly assessed affective empathy. Tests used in the reviewed studies were often overly specific and lacked ecological validity, which may explain inconsistent results across domains and weak correlations with imaging or executive function.<br><br>CONCLUSION: Social cognition is increasingly recognized as a key non-motor domain affected in ALS. However, current assessment tools may lack the sensitivity and ecological validity needed to capture real-life deficits. The implementation of dynamic, multimodal assessments such as real-life social interaction tests or tests like the Movie Assessment for Social Cognition (MASC) could improve detection and guide clinical interventions but remain to be validated for ALS patients.}, }
@article {pmid40473505, year = {2026}, author = {Song, W and Huang, Q and Jiang, Z}, title = {Clinical efficacy of athletic taping-assisted physiotherapy for plantar fasciitis: A systematic evaluation and meta-analysis.}, journal = {Foot and ankle surgery : official journal of the European Society of Foot and Ankle Surgeons}, volume = {32}, number = {1}, pages = {11-25}, doi = {10.1016/j.fas.2025.05.013}, pmid = {40473505}, issn = {1460-9584}, mesh = {Humans ; *Fasciitis, Plantar/therapy ; *Athletic Tape ; Randomized Controlled Trials as Topic ; Pain Measurement ; Treatment Outcome ; *Physical Therapy Modalities ; }, abstract = {BACKGROUND: Plantar fasciitis is a common sports injury with long-term chronic pain in the heel as the main symptom, and athletic taping has achieved certain therapeutic effects to improve it, but the clinical efficacy of the problem is still controversial, which was evaluated by Meta-analysis to evaluate the clinical efficacy of the athletic taping technique on patients with plantar fasciitis.<br><br>METHODS: The Cochrane Library, Embase, PubMed, Web of Science, CNKI, Wanfang, and Vip databases were searched by computer for randomized controlled trial on the clinical efficacy of exercise taping in patients with PF from the time of construction to 1 September 2024, and the PRISMA 2020 checklist was strictly followed. Quality was assessed using the cochrane 2.0 randomized controlled trials scale by two independent reviewers. Endings were meta-analysis using RevMan 5.4.1 analysis software to analyse the data.<br><br>RESULTS: Eleven randomized controlled trial with a total of 395 patients were included. On VAS scores, KT effectively reduced VAS pain scores (MD=-0.79,95&#x202f;% CI -1.10,-0.48, P&#x202f;<&#x202f;0.00001); on AOFAS scores, KT improved AOFAS function scores (MD=6.58, 95&#x202f;% CI 5.03,8.13, P&#x202f;<&#x202f;0.00001) and the results remained consistent across intervention durations; on plantar fascia thickness measurements, KT significantly reduced plantar fascia thickness (MD=-0.33, 95&#x202f;% CI -0.56,-0.10, P&#x202f;=&#x202f;0.005); on BBS scores, KT significantly improved BBS scores [MD=&#x202f;4.75, 95&#x202f;% CI (3.17, 6.32), P&#x202f;<&#x202f;0.00001]; on FFI-FPS scores, KT effectively improved FFI-FPS scores [MD =&#x202f;-2.59, 95&#x202f;% CI (-3.50, -1.69), P&#x202f;<&#x202f;0.00001]; on FFI-FDS scores, there was a significant improvement on FFI-FDS scores; on FFI-ALS scores, KT had a significant improvement on the FFI-ALS score had a significant effect [MD=&#x202f;-11.03, 95&#x202f;% CI (-14.79, -7.27), P&#x202f;<&#x202f;0.00001]; and on VAS scores after follow-up, the pain relief effect was sustained (MD=-1.03, 95&#x202f;% CI -1.21, -0.85, P&#x202f;<&#x202f;0.00001).<br><br>CONCLUSION: Based on the available evidence, preliminary analyses suggest that KT combined with conventional rehabilitation may have some advantages in improving pain, ankle-hindfoot function, and plantar fascia thickness in patients with plantar fasciitis, and some of the efficacy is short-term sustained. However, due to the heterogeneity and sample size of the included studies, the above conclusions need to be further validated by more high-quality studies.}, }
@article {pmid41399798, year = {2025}, author = {Ghosh, S and Debnath, I and Bhunia, S and Nandi, S and Ashique, S and Nayak, A and Mallick, S and Basak, S}, title = {Decoding natural products for neuroprotection: Pathway networks and structural insights for drug development.}, journal = {Chinese herbal medicines}, volume = {17}, number = {4}, pages = {643-672}, pmid = {41399798}, issn = {2589-3610}, abstract = {Neurodegenerative diseases (NDs), including Alzheimer's, Parkinson's, Huntington's, and amyotrophic lateral sclerosis, are progressive disorders marked by neuronal dysfunction and death, driven by pathological mechanisms such as oxidative stress, mitochondrial dysfunction, neuroinflammation, apoptosis, and protein misfolding. Despite scientific advances, current treatments remain largely palliative, underscoring the need for multitargeted therapeutic strategies. This narrative review synthesizes preclinical and clinical evidence to explore the neuroprotective potential of natural products, with a focus on their ability to modulate key molecular pathways implicated in NDs. A comprehensive literature search across Scopus, ScienceDirect, PubMed, MDPI, and Web of Science identified relevant studies. Bioactive compounds such as curcumin, resveratrol, ginsenosides, quercetin, and marine-derived molecules like fucoxanthin and phlorotannin demonstrated antioxidant, anti-inflammatory, anti-amyloidogenic, and mitochondrial-protective effects by modulating pathways including PI3K/Akt, NF-κB, and Nrf2/ARE, thereby mitigating neuronal damage and promoting cell survival. Natural products from diverse sources, including honey, ginseng, marine macroalgae, and cyanobacteria, exhibited broad-spectrum neuroprotective properties, with advances in nano-formulations improving bioavailability and brain penetration. Furthermore, emerging approaches such as gene-drug interaction studies and scaffold-based drug design offer promising avenues for enhancing clinical translation. While natural products provide a holistic, multitargeted approach to combat NDs, challenges related to bioavailability and therapeutic translation persist, necessitating future research that integrates advanced drug delivery systems, precision medicine, and synthetic modifications to develop innovative and effective treatment paradigms.}, }
@article {pmid41395267, year = {2025}, author = {Roy, T and Al-Chalabi, A and Iacoangeli, A and Al Khleifat, A}, title = {Biomarkers in ALS trials: from discovery to clinical utility.}, journal = {Frontiers in neuroscience}, volume = {19}, number = {}, pages = {1636303}, pmid = {41395267}, issn = {1662-4548}, abstract = {INTRODUCTION: Motor neuron disease (MND), also known as amyotrophic lateral sclerosis (ALS), is a progressive neurodegenerative disorder characterized by motor neuron degeneration, leading to muscle weakness, paralysis, and eventual respiratory failure. Despite advances in understanding its pathology, effective therapies remain limited, underscoring the need for reliable biomarkers to aid early diagnosis, monitor disease progression, and optimize clinical trials. This systematic review explores the role of biomarkers in ALS, focusing on their application in clinical trials to accelerate therapeutic development and enhance patient care.<br><br>METHODS: A comprehensive search of PubMed, EMBASE, MedLine, and Google Scholar identified 93 studies investigating various biomarkers, including neurofilament light chain (NFL), inflammatory markers, genetic markers like SOD1 and C9orf72, and imaging modalities.<br><br>RESULTS: NFL emerged as a robust biomarker, strongly correlating with disease progression and therapeutic response, and was frequently used in trials like RESCUE-ALS and CENTAUR. Genetic biomarkers, such as C9orf72 and SOD1 mutations, provided insights into ALS mechanisms and informed targeted therapeutic approaches. Emerging biomarkers, such as retroviral elements, show potential but require further validation. Included studies span key trials such as Lighthouse-II, MIROCALS, and MND-SMART.<br><br>DISCUSSION: This systematic review evaluates which biomarkers are currently validated for monitoring disease progression and therapeutic response in ALS clinical trials, including protein, genetic, inflammatory, metabolic, and imaging markers. It also highlights the critical role of biomarkers in advancing MND clinical trials by enabling adaptive trial designs, patient stratification, and the use of surrogate endpoints, thereby reducing trial duration and improving efficiency. The review also highlights the translational gap between biomarker discovery and clinical application, emphasizing their potential to optimize trial design and patient stratification. While biomarkers like NFL have transformed trial methodologies, challenges such as disease specificity and inter-patient heterogeneity persist. Future efforts should focus on multimodal biomarker approaches to achieve comprehensive disease assessment and advance personalized therapeutic strategies, ultimately improving outcomes for patients with MND.}, }
@article {pmid41386298, year = {2025}, author = {Ealy, A and Serapiglia, AM and Panicker, N}, title = {Sterile Innate Immune Mechanisms in Neurodegenerative diseases.}, journal = {The Journal of biological chemistry}, volume = {}, number = {}, pages = {111039}, doi = {10.1016/j.jbc.2025.111039}, pmid = {41386298}, issn = {1083-351X}, abstract = {Neurodegenerative diseases are characterized by the dysfunction and death of susceptible neuronal populations. Increasing evidence has demonstrated that sustained neuroinflammation and activation of innate immune complexes underlie neurodegeneration, worsening disease progression and outcomes. Sterile inflammation (which occurs in the absence of infection) can be triggered by neurodegenerative disease-associated misfolded proteins. These studies highlight the need to decipher the complexities of innate immune signaling mechanisms and their contribution to neuropathology. In this review, we focus on major neurodegenerative diseases that have a well-documented neuroinflammatory component: Alzheimer's Disease (AD), Parkinson's Disease (PD), Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (MS) and Frontotemporal Dementia (FTD). In the context of these diseases, we discuss recent advances in innate-immune mechanisms that have been demonstrated to partake in disease progression and neurodegeneration. These include evolutionarily conserved innate-immune signaling complexes whose uncontrolled activation amplifies neurodegeneration, damaging lipid droplets that accumulate within myeloid cells and prevent their ability to clear toxic protein aggregates, as well as genome-wide studies implicated genes/proteins. The individual and/or concerted actions of these pathways could be leveraged to rationally target the pathogenesis or progression of neurodegenerative diseases.}, }
@article {pmid33557659, year = {2021}, author = {Lyng, J and Adelgais, K and Alter, R and Beal, J and Chung, B and Gross, T and Minkler, M and Moore, B and Stebbins, T and Vance, S and Williams, K and Yee, A}, title = {Recommended Essential Equipment for Basic Life Support and Advanced Life Support Ground Ambulances 2020: A Joint Position Statement.}, journal = {Prehospital emergency care}, volume = {25}, number = {3}, pages = {451-459}, doi = {10.1080/10903127.2021.1886382}, pmid = {33557659}, issn = {1545-0066}, mesh = {Allied Health Personnel ; Ambulances ; Certification ; *Emergency Medical Services ; *Emergency Medical Technicians ; Humans ; }, abstract = {In continued support of establishing and maintaining a foundation for standards of care, our organizations remain committed to periodic review and revision of this position statement. This latest revision was created based on a structured review of the National Model EMS Clinical Guidelines Version 2.2 in order to identify the equipment items necessary to deliver the care defined by those guidelines. In addition, in order to ensure congruity with national definitions of provider scope of practice, the list is differentiated into BLS and ALS levels of service utilizing the National Scope of Practice-defined levels of Emergency Medical Responder (EMR) and Emergency Medical Technician (EMT) as BLS, and Advanced EMT (AEMT) and Paramedic as ALS. Equipment items listed within each category were cross-checked against recommended scopes of practice for each level in order to ensure they were appropriately dichotomized to BLS or ALS levels of care. Some items may be considered optional at the local level as determined by agency-defined scope of practice and applicable clinical guidelines. In addition to the items included in this position statement our organizations agree that all EMS service programs should carry equipment and supplies in quantities as determined by the medical director and appropriate to the agency's level of care and available certified EMS personnel and as established in the agency's approved protocols.}, }
@article {pmid41384353, year = {2025}, author = {Yu, H and Zhang, X and Liu, Z and Zhang, L}, title = {Explaining Isoform Selectivity of c-Jun N-Terminal Kinase 3 (JNK3) Inhibitors through Its Development and Structural Insights.}, journal = {Journal of medicinal chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jmedchem.5c01488}, pmid = {41384353}, issn = {1520-4804}, abstract = {c-Jun N-terminal kinase 3 (JNK3), a member of the mitogen-activated protein kinase (MAPK) family, is selectively enriched in the brain. It plays a significant role in the pathogenesis of neurodegenerative disorders, glaucoma, amyotrophic lateral sclerosis, and cancer, which makes it a promising drug target. However, the advancement of JNK3 inhibitors has been challenged by limited isoform selectivity. This article explains the pathway regulated by JNK3 and the unique functions of JNK3. A detailed structural analysis of JNK3 complexes with ligands is presented to uncover the molecular basis of binding interactions. The inhibitors are systematically classified according to their chemical scaffolds, and the reason for their isoform selectivity was discussed, providing a structural rationale for the evolution of JNK3 inhibitor design. The perspective concludes with an exploration of the challenges in the discovery of selective JNK3 inhibitors and proposes innovative strategies to surmount these obstacles.}, }
@article {pmid41379273, year = {2025}, author = {Zhang, R and Gao, B and Li, R and Zhou, R}, title = {Meta-analysis of the effects of dance- and movement-based kinesthetic games on cognitive function in older adults with cognitive impairment (CI) under different intervention periods.}, journal = {Aging clinical and experimental research}, volume = {37}, number = {1}, pages = {343}, pmid = {41379273}, issn = {1720-8319}, support = {24YJC890031//he&#xa0;Ministry of Education 's Youth&#xa0;Fund&#xa0;Project&#xa0;for&#xa0;Humanities&#xa0;and&#xa0;Social&#xa0;Sciences/ ; 22PJC094//Shanghai Pujiang Program/ ; }, mesh = {Humans ; *Cognitive Dysfunction/therapy/psychology ; Aged ; *Cognition/physiology ; *Video Games ; *Dancing ; *Dance Therapy/methods ; Male ; Randomized Controlled Trials as Topic ; *Exercise Therapy/methods ; Female ; }, abstract = {OBJECTIVE: To evaluate the effects of different types and durations of exergame interventions on cognition in elderly individuals with cognitive impairment (CI) through a meta-analysis.<br><br>METHODS: A computerized search was conducted in databases including Cochrane Library, PubMed, Web of Science, Embase, and CNKI from database inception to September 2025. Quality assessment and data extraction were performed on the included studies. Results measures included the MoCA , MMSE, etc. The study designs were randomized controlled trials or qua-si-experimental studies. The Cochrane Handbook's risk of bias tool was used for quality assessment, and Rev Man 5.0 software was employed to conduct meta-analyses on the ef-fects of dance-based and movement-based exergames on cognitive function in elderly CI patients.<br><br>RESULTS: A total of 13 studies involving 433 CI patients were included. Analysis of the 13 studies showed that dance-based exergaming was significantly superior to exercise-based exergaming in cognitive ability (SMD = 0.73, P < 0.01); interventions lasting &#x2265;8 weeks were more effective than those lasting <8 weeks (SMD = 1.01, P = 0.02).<br><br>CONCLUSION: Dance-based exergames significantly improve cognition in elderly individu-als with CI, with better effects observed in long-term interventions. However, more high-quality studies are needed to verify these findings and to supplement analyses on ex-ercise dose effects.}, }
@article {pmid41375912, year = {2025}, author = {Sancho, J and Ferrer, S and Signes-Costa, J}, title = {Noninvasive Ventilation Effectiveness in Amyotrophic Lateral Sclerosis.}, journal = {Journal of clinical medicine}, volume = {14}, number = {23}, pages = {}, pmid = {41375912}, issn = {2077-0383}, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects motor neurons; respiratory problems are the leading cause of death and hospital admissions and are secondary to progressive weakness of the respiratory muscles and upper airway. Noninvasive ventilation (NIV) can increase survival, alleviate symptoms, reduce hospital admissions, and improve the quality of life of these patients. The key factor in respiratory management of patients with ALS is achieving effective NIV; ineffective NIV has a negative impact on survival, with a reduction of up to 50% compared to patients with an effective technique. The most common cause of ineffective NIV is air leaks; other causes include upper airway obstruction events, residual hypoventilation, hyperventilation, and upper airway obstruction secondary to an oronasal mask. Regular monitoring of the effectiveness of NIV is essential given its impact on survival; the key tools that detect the main problems are the presence of hypoventilation symptoms, arterial blood gases, nocturnal oximetry and capnography, and built-in ventilator software. Different measures have been proposed to address the ineffectiveness of NIV, such as fitting the mask to reduce air leaks, increasing ventilatory support for residual hypoventilation, decreasing ventilatory support for hyperventilation, or a trial with a nasal mask to address oronasal interface effects. In the case of obstruction, the most common measure is to increase positive expiratory pressure during NIV. These measures enable NIV to be effective in 58% of cases, achieving a survival rate similar to that of patients who have effective NIV from the outset.}, }
@article {pmid41205880, year = {2026}, author = {Cho, H and Lee, B and Son, C and Choi, J and Eom, S and Park, J}, title = {ERLIN1: A central regulator of protein quality control, lipid homeostasis, and cellular signaling at the endoplasmic reticulum.}, journal = {Cellular signalling}, volume = {138}, number = {}, pages = {112224}, doi = {10.1016/j.cellsig.2025.112224}, pmid = {41205880}, issn = {1873-3913}, mesh = {Humans ; *Endoplasmic Reticulum/metabolism ; *Membrane Proteins/metabolism/genetics ; Homeostasis ; *Signal Transduction ; Animals ; *Lipid Metabolism ; Endoplasmic Reticulum-Associated Degradation ; Cholesterol/metabolism ; Nerve Tissue Proteins ; }, abstract = {Endoplasmic reticulum lipid raft-associated protein 1 (ERLIN1) is an endoplasmic reticulum (ER)-resident stomatin/prohibitin/flotillin/HflK/C (SPFH) family protein that assembles into oligomeric complexes within detergent-resistant membrane domains. ERLIN1 regulates multiple cellular functions, including protein quality control, calcium signaling, and lipid metabolism. Together with ERLIN2, it forms ER-associated degradation (ERAD) nanodomains through interactions with RING finger protein 170 (RNF170) and transmembrane and ubiquitin-like domain-containing 1 (TMUB1). These specialized domains facilitate the degradation of inositol 1,4,5-trisphosphate receptor type 1 (IP3R) via the ERAD pathway. ERLIN1 also controls cholesterol metabolism by inhibiting sterol regulatory element-binding protein (SREBP) activation and promoting 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) degradation. In addition, it blocks cholesterol esterification, thereby enhancing cholesterol transport to the Golgi apparatus. ERLIN1 further regulates cell fate by promoting autophagy and suppressing apoptosis; in complex with ERLIN2, it interacts with activating molecule in Beclin 1-regulated autophagy protein 1 (AMBRA1) at mitochondria-associated membranes to initiate autophagy and binds phosphatidylinositol 3-phosphate to stabilize autophagy signaling. Its overexpression enhances tumor progression, whereas silencing triggers apoptosis in colorectal cancer. Mutations in ERLIN1 are linked to neurodegenerative diseases such as hereditary spastic paraplegia type 62 and atypical amyotrophic lateral sclerosis. The ERLIN1/2 complex also influences immune responses and viral replication through cholesterol regulation. Collectively, these diverse and integrated functions highlight the potential of ERLIN1 as a therapeutic target in cancer, metabolic, neurodegenerative, and infectious diseases.}, }
@article {pmid41375893, year = {2025}, author = {Gratzer, A and Gdynia, N and Sasse, N and Beese, R and Winterholler, C and Bauer, Y and Schröter, C and Gdynia, HJ}, title = {Rehabilitation in Amyotrophic Lateral Sclerosis: Recommendations for Clinical Practice and Further Research.}, journal = {Journal of clinical medicine}, volume = {14}, number = {23}, pages = {}, pmid = {41375893}, issn = {2077-0383}, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative condition characterized by the degeneration of upper and lower motor neurons. This degeneration leads to a gradual muscle weakness, dysarthria, dysphagia, respiratory insufficiency, and, in some patients, alterations in cognitive and behavioral performance. Regardless of advancements made in pharmacological and gene-targeted interventions, a definitive curative treatment remains elusive. Consequently, rehabilitation plays a pivotal role in preserving autonomy, participation, and overall quality of life. This review outlines the current evidence and clinical approaches related to multidisciplinary rehabilitation in ALS. It covers physical and occupational therapy, respiratory, speech and language, psychological, and palliative care domains. Evidence supports moderate tailored exercise programs, early respiratory therapy, and structured management of mobility deficits, spasticity, pain, dysphagia, and communication impairments as key elements of symptomatic treatment. Psychological and social support, which includes the involvement of caregivers and relatives, enhances emotional well-being and coping resilience. Even with progressive development of gene-targeted and disease-modifying therapies, rehabilitation will stay relevant for maintaining long-term motor function. This review highlights the need for standardized, evidence-based rehabilitation protocols and intensified neurorehabilitation research to strengthen clinical outcomes and quality of life as key therapeutic goals in ALS management.}, }
@article {pmid41373784, year = {2025}, author = {Basavarajappa, BS and Subbanna, S}, title = {From Synaptic Plasticity to Neurotoxicity: Endocannabinoid Influence on Addiction and Neurodegeneration.}, journal = {International journal of molecular sciences}, volume = {26}, number = {23}, pages = {}, pmid = {41373784}, issn = {1422-0067}, mesh = {Humans ; *Endocannabinoids/metabolism ; *Neuronal Plasticity ; Animals ; *Neurodegenerative Diseases/metabolism ; *Substance-Related Disorders/metabolism ; Receptors, Cannabinoid/metabolism ; }, abstract = {The endocannabinoid system (eCBS) is a versatile neuromodulatory network that orchestrates synaptic plasticity, reward processing, and neuronal homeostasis. Increasing evidence implicates eCBS dysregulation in both addiction and neurodegenerative (ND) disorders, suggesting overlapping molecular and cellular mechanisms underlying these conditions. This review synthesizes recent advances in understanding how eCBS components-cannabinoid receptors (CB1 and CB2), endogenous ligands (anandamide and 2-arachidonoylglycerol), and their metabolic enzymes-modulate dopaminergic and glutamatergic signaling within reward and reinforcement circuits. Chronic exposure to drugs of abuse, including alcohol, opioids, cocaine, and methamphetamine, perturbs eCBS homeostasis, promoting oxidative stress, neuroinflammation, excitotoxicity, mitochondrial dysfunction, and protein aggregation-pathological features common to Alzheimer's, Parkinson's, Huntington's, and amyotrophic lateral sclerosis. These overlapping mechanisms disrupt neuronal integrity and contribute to progressive neurotoxicity, highlighting shared pathogenic pathways between addiction and neurodegeneration. Despite these advances, critical gaps remain in delineating how substance-induced eCBS alterations precipitate neurodegenerative cascades. Addressing these gaps will be essential for harnessing the eCBS as a therapeutic target to mitigate addiction-driven neurotoxicity and age-related cognitive decline.}, }
@article {pmid41373533, year = {2025}, author = {Apolloni, S and Tortoriello, S and Milani, M and Rossi, S}, title = {Extracellular Matrix Remodeling in Motor Neuron Diseases.}, journal = {International journal of molecular sciences}, volume = {26}, number = {23}, pages = {}, doi = {10.3390/ijms262311376}, pmid = {41373533}, issn = {1422-0067}, support = {GR-2021-12375436//Ministero della Salute/ ; PNRR project "Rome Technopole - Innovation Ecosystem"//European Union/ ; }, mesh = {Humans ; *Extracellular Matrix/metabolism/pathology ; *Motor Neuron Disease/metabolism/pathology ; Animals ; Amyotrophic Lateral Sclerosis/metabolism/pathology ; Motor Neurons/metabolism/pathology ; }, abstract = {The extracellular matrix (ECM) constitutes a dynamic scaffold composed of both cellular and non-cellular elements that not only ensure tissue integrity but also regulate signaling events crucial for development and homeostasis. While its dysregulation has long been investigated in cancer, fibrosis, and autoimmunity, increasing evidence implicates ECM remodeling in neurodegenerative diseases, including motor neuron diseases (MNDs). Amyotrophic lateral sclerosis and spinal muscular atrophy, the most studied MNDs, both exhibit profound ECM alterations that influence synaptic connectivity, glial reactivity, and neuroinflammation. This review outlines recent data on ECM dynamics in MNDs, highlighting shared and disease-specific mechanisms, their potential as biomarkers, and therapeutic opportunities targeting the ECM environment to preserve neuronal function and slow disease progression.}, }
@article {pmid41373461, year = {2025}, author = {Butcher, EL and Arthur, S}, title = {Emerging Roles of Bile Acids in Neuroinflammation.}, journal = {International journal of molecular sciences}, volume = {26}, number = {23}, pages = {}, doi = {10.3390/ijms262311301}, pmid = {41373461}, issn = {1422-0067}, mesh = {Humans ; *Bile Acids and Salts/metabolism ; *Neuroinflammatory Diseases/metabolism/pathology ; Animals ; Gastrointestinal Microbiome ; Signal Transduction ; Biomarkers/metabolism ; Blood-Brain Barrier/metabolism ; Inflammation/metabolism ; Central Nervous System/metabolism ; }, abstract = {Bile acids, once considered mere digestive detergents, have emerged as multifaceted signaling molecules with systemic influence extending far beyond the gastrointestinal tract. Recent discoveries reveal their capacity to modulate immune responses, cross the blood-brain barrier, and interact with central nervous system (CNS) cells through their receptors. Neuroinflammation, a key driver of neurodegenerative and neuroimmune disorders, is increasingly linked to bile acid signaling pathways that regulate glial activation, cytokine production, and neuronal survival. This review compiles the current evidence connecting bile acids to CNS inflammation, highlighting mechanistic insights, disease-specific alterations, and the gut-microbiome-bile acid-brain axis. It also explores the therapeutic potential of bile acid derivatives and receptor modulators, as well as their emerging role as biomarkers in conditions such as Alzheimer's disease, multiple sclerosis, and hepatic encephalopathy. Despite promising advances, critical gaps remain, including the need for bile receptor mapping in human CNS cells, standardized CNS bile acid profiling, and longitudinal metabolomic studies. Bridging these gaps may unlock new strategies for targeting neuroinflammation through bile acid-immune crosstalk.}, }
@article {pmid41366852, year = {2025}, author = {Barahona-López, C and Plans-Beriso, E and Diez-Echave, P and Hernández, O and de Larrea, NF and Craciun, O and García-Ovejero, E and Petrova, D and Fernández-Martínez, NF and Arruabarrena-Blanco, E and Babb-de-Villiers, C and Turner, H and Jimenez, RC and Erady, C and Wilson, H and Fernández-Navarro, P and García-Esquinas, EG and Kuhn, I and Sánchez, P and Rodríguez-Artalejo, F and Sánchez, MJ and Moreno, V and Blackburn, L and Pollán, M and Kroese, M and Perez-Gomez, B}, title = {Personalized prevention of neurodegenerative diseases: scoping review and evidence gap map.}, journal = {Alzheimer's &amp; dementia : the journal of the Alzheimer's Association}, volume = {21}, number = {12}, pages = {e70980}, pmid = {41366852}, issn = {1552-5279}, support = {101057721//Horizon Europe / H2020 Health/ ; 10040946//UKRI/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/prevention &amp; control/genetics ; Biomarkers ; *Precision Medicine/methods ; Evidence Gaps ; }, abstract = {Neurodegenerative diseases represent a major public health challenge due to their high prevalence and poor prognosis. Identifying biomarkers to stratify individuals by their risk of developing these diseases may help to define new personalized prevention interventions. The objective of this study was to conduct a scoping review of biomarkers for primary and secondary personalized prevention of neurodegenerative diseases. The search targeted biomarkers in adults or high-risk subpopulations in clinical or public health settings for Alzheimer's disease, vascular dementia, Lewy body disease, frontotemporal dementia, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis. Ultimately, 286 papers were included in the review and the interactive gap map. There is a strong focus on Alzheimer's disease, and most papers included -omics-based biomarkers and/or used artificial intelligence. Genetics/genomics are at the forefront of current scientific research, although there is a notable gap in studying gene-environment interactions, and studies in clinical settings are still scarce. HIGHLIGHTS: Research indicates a strong focus on Alzheimer´s disease and limited research in other diseases. Genetics and genomics are at the forefront of current scientific research. We found biomarkers for predicting progression in mild cognitive decline. There is a notable gap in studying gene-environment interactions. Studies investigating biomarkers in a clinical context are still scarce.}, }
@article {pmid41366746, year = {2025}, author = {Huang, J and Liu, Y and Li, M and He, R and Tang, Z and Lei, Y and Zha, Y and Wei, J}, title = {Safety and efficacy of botulinum toxin injection for sialorrhea in amyotrophic lateral sclerosis: a systematic review and meta-analysis.}, journal = {BMC neurology}, volume = {25}, number = {1}, pages = {496}, pmid = {41366746}, issn = {1471-2377}, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease, with 80% of ALS patients experiencing bulbar weakness at some stage of the disease. ALS patients with bulbar weakness often suffer from troublesome sialorrhea. Botulinum toxin injection, as a neuromuscular blocker, has been widely used in the treatment of sialorrhea. This paper evaluates the safety and efficacy of botulinum toxin injections for the treatment of sialorrhea in ALS patients through a systematic review and meta-analysis.<br><br>METHODS: A systematic review and meta-analysis was conducted by searching eight databases, including PubMed, EMBASE, and CNKI, up to April 13, 2025. Eligible randomized controlled trials and quasi-experimental studies were analyzed using Review Manager 5.4 and Stata software.<br><br>RESULTS: Thirteen studies (2 RCTs, 11 quasi-experimental studies) with 130 ALS patients were included. Botulinum toxin significantly reduced sialorrhea and improved quality of life (Z&#x2009;=&#x2009;10.98, p&#x2009;<&#x2009;0.00001; RD&#x2009;=&#x2009;0.82, 95% CI: 0.67&#x2013;0.97). The treatment effect was independent of toxin type (p&#x2009;=&#x2009;0.48), injection site (p&#x2009;=&#x2009;0.17), and ultrasound guidance use (p&#x2009;=&#x2009;0.44).<br><br>CONCLUSION: Botulinum toxin appears to be a safe and effective option for managing sialorrhea in ALS patients, regardless of injection technique. However, given that most included studies were observational, further validation through high-quality RCTs is warranted.<br><br>TRIAL REGISTRATION: This meta-analysis has been registered with Prospero, and the registration number is CRD420251029441. The registration period is April 9, 2025.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12883-025-04515-8.}, }
@article {pmid41356579, year = {2025}, author = {Seyam, MK and Shaik, RA and Miraj, M and Alzahrani, NS and Shaik, AR and Ajmera, P and Kalra, S and Miraj, SA and Shawky, GM and Nurani, KM and A, P}, title = {Effect of mobile phone applications on medication adherence among patients with coronary artery diseases: A scoping review.}, journal = {World journal of cardiology}, volume = {17}, number = {11}, pages = {114140}, pmid = {41356579}, issn = {1949-8462}, abstract = {Patients with cardiovascular disease rely on medication to achieve favorable long-term clinical results. Poor adherence has been linked to a relative increase in mortality of 50%-80% as well as higher health care costs. This scoping review thus aimed to explore the evidence of the effects of mobile health care apps on medication adherence in patients with cardiovascular diseases. A comprehensive data search and extraction was done in line with the updated Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews checklist. A total of 10 studies were included for the review. The mean pooled improvement in adherence was found to be 18% and the most effective tool was the digital therapeutics app discussed in Li et al's study. Smartphones and apps enhance coronary artery disease management by promoting medication compliance. Challenges include data security and smartphone usage among the elderly. Tailored apps or voice assistants offer potential solutions.}, }
@article {pmid41354564, year = {2025}, author = {Mouhi, S and Pio, T and Andersen, J}, title = {Revisiting oligodendrocytes in amyotrophic lateral sclerosis using human multicellular stem cell models.}, journal = {Trends in cell biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tcb.2025.11.003}, pmid = {41354564}, issn = {1879-3088}, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron degeneration, muscle wasting, and eventual paralysis. The clinical and genetic complexity along with rapid disease progression has hindered efforts to model the disease and develop effective treatments. Rodent models and human tissue studies point to dysfunction in oligodendrocyte lineage cells early in disease, although the underlying mechanisms remain unclear. Advances in stem cell research have introduced novel platforms to investigate cells in the oligodendrocyte lineage and their interactions with neurons and other glial cells in complex human genetic backgrounds. This Review summarizes the literature implicating oligodendrocyte lineage cells in ALS and discusses both the potential and limitations of in vitro-derived cultures to shed light on their vulnerabilities and cellular interactions.}, }
@article {pmid41352634, year = {2025}, author = {Geleta, LA and Doyle, C and Garton, FC and Fowler, M and Carr, JM and Akkari, PA and McRae, AF and Rogers, ML and Madakkatel, I and Benyamin, B}, title = {The roles of human endogenous retrovirus in neurodegenerative diseases: A systematic review.}, journal = {Brain, behavior, and immunity}, volume = {132}, number = {}, pages = {106201}, doi = {10.1016/j.bbi.2025.106201}, pmid = {41352634}, issn = {1090-2139}, abstract = {BACKGROUND: Human endogenous retroviruses (HERVs) constitute ∼8 % of the human genome, far exceeding the 2 % occupied by protein-coding genes. Although most HERV sequences are inactive, some HERV elements can be reactivated under certain conditions and may contribute to neurodegenerative diseases (NDDs). However, the findings vary across different HERV families, disease models, and detection methods. Here, we systematically review and synthesize the available evidence on the role of HERVs in human NDDs and reconcile inconsistencies in the literature.<br><br>METHODS: We systematically searched MEDLINE, EMBASE, Cochrane Library, PsycINFO, Scopus, Web of Science, CINAHL, and Emcare to identify relevant studies. Two independent reviewers screened studies, assessed quality, and extracted data. Qualitative synthesis was conducted for all included NDDs, specifically Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Parkinson's disease (PD), and due to data availability, meta-analysis was used to assess the impact of HERVs antibodies on ALS only.<br><br>RESULTS: Twenty-six studies (N ranges: 6-485) met the inclusion criteria, with majority focusing on HERV-K and ALS. Across studies, the association between HERV expression and NDDs was inconsistent, particularly for ALS, PD, and FTD, whereas investigations in AD showed a more consistent upregulation of specific HERVs. Studies relying on polymerase chain reaction (PCR) (typically smaller) showed inconsistent associations (21 studies), while RNA sequencing studies reported consistent associations (9 studies). A preliminary meta-analysis revealed a fivefold increase [OR: 5.83; 95&#xa0;% CI: 4.14, 8.18] in ALS risk among participants with positive HERV antibodies.<br><br>CONCLUSIONS: The inconsistencies in HERV involvement across NDDs highlight the need for further studies employing standardized methodologies. RNAseq findings on the association of HERVs expression and NDDs support the need for large-scale RNA sequencing studies (rather than small, PCR studies) and careful tissue selection to clarify HERVs' role in NDDs. The association of HERV-K antibodies with ALS risk and prognosis suggests a significant role in disease, which could help detect biomarkers and used as a target for treatment.}, }
@article {pmid40925732, year = {2025}, author = {, }, title = {[Expert consensus on the diagnosis and treatment of sleep-disordered breathing related to neuromuscular diseases].}, journal = {Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases}, volume = {48}, number = {9}, pages = {815-830}, doi = {10.3760/cma.j.cn112147-20250614-00332}, pmid = {40925732}, issn = {1001-0939}, support = {82270107//National Natural Science Fundation of China/ ; }, mesh = {Humans ; *Neuromuscular Diseases/complications ; *Sleep Apnea Syndromes/diagnosis/therapy/etiology ; Consensus ; Noninvasive Ventilation ; Sleep Apnea, Obstructive/diagnosis/therapy ; China ; }, abstract = {Neuromuscular diseases are often accompanied by various types of sleep-related breathing disorders, which can exacerbate the underlying condition and are associated with a poor prognosis. Early identification is essential, and interventions such as non-invasive ventilation, oxygen therapy, and respiratory rehabilitation should be initiated promptly to mitigate disease progression and improve outcomes. Nevertheless, the rates of missed and misdiagnosed cases remain common in clinical practice. Currently, there are no standardized guidelines for the diagnosis and treatment of sleep-disordered breathing related to neuromuscular diseases in China. Therefore, based on the latest domestic and international research progress, and combined with domestic clinical diagnosis and treatment experience, the Sleep Disorder Group of Chinese Thoracic Society has brought together multidisciplinary experts to develop this expert consensus. This consensus provides a comprehensive overview of the epidemiology, clinical manifestations, diagnostic approaches, assessment strategies, and treatment of sleep-disordered breathing related to neuromuscular diseases. It formulates evidence-based recommendations to guide clinical practice, with the aim of providing standardized recommendations for their diagnosis and management.Statement 1: The neuromuscular disorders that are most frequently associated with sleep-disordered breathing include: myasthenia gravis (1A), amyotrophic lateral sclerosis (2B), post-polio syndrome (2B), myotonic dystrophy (2B), peripheral neuropathies (2C), and metabolic myopathies, among other neuromuscular conditions.Statement 2: Patients with neuromuscular disorders frequently develop multiple types of sleep-disordered breathing concurrently or sequentially, with obstructive sleep apnea (OSA) being the most prevalent manifestation. Distinct clinical manifestations of OSA are observed across different neuromuscular disease subtypes (1A).Statement 3: Neuromuscular disorders predispose to central sleep apnea (CSA), with clinical manifestations varying significantly across disease subtypes, stages of progression, and severity levels (1A).Recommendation 1: In patients with neuromuscular disorders exhibiting progressive hypercapnia or worsening hypoxemia, clinicians should investigate potential comorbid nocturnal alveolar hypoventilation and/or sleep-associated hypoxemia (1A).Recommendation 2: When sleep-disordered breathing is suspected, patients with neuromuscular disorders should be evaluated for symptoms of sleep-disordered breathing. Meanwhile, sleep monitoring, non-invasive CO2 monitoring, and related examinations should be actively performed according to the actual situation (1A). A polysomnography should be performed when there is a high clinical suspicion of sleep-disordered breathing but a negative result on a portable sleep monitor (1A).Recommendation 3: (1) Noninvasive positive pressure ventilation (NPPV) titration under polysomnography is the standard method to determine the effective treatment parameters for neuromuscular diseases with sleep-disordered breathing (1A). (2) Positive airway pressure titration in OSA patients with neuromuscular diseases should follow American Academy of Sleep Medicine (AASM) guidelines (1A). (3) For neuromuscular disorders with CSA or Cheyne-Stokes respiration, bi-level positive airway pressure (BPAP) with ST pattern is recommended (1A); When BPAP is not tolerated or accompanied by severe Cheyne-Stokes respiratory and heart failure in patients, adaptive support ventilation (ASV) should be used (2B). (4) Patients with neuromuscular disease and sleep-related alveolar hypoventilation should be treated with BPAP or variable assurance pressure support (VAPS) (1A). (5) BPAP with alternate frequency is preferred for neuromuscular disorders with "pseudo-central events" (1A).Recommendation 4: Oxygen therapy alone is not recommended for neuromuscular disease patients combined with sleep-disordered breathing (2D). Oxygen therapy with monitoring of CO2 level is recommended when non-invasive ventilation therapy cannot effectively correct hypoxemia (2C). Diaphragmatic pacing should not be routinely used in amyotrophic lateral sclerosis patients with respiratory failure (2B). Transvenous phrenic nerve stimulation is not currently applied to CSA caused by neuromuscular disorders (2D). Respiratory rehabilitation may improve respiratory muscle strength in a subset of patients with neuromuscular disorders (2B). Protiline can be used for REM-associated alveolar hypoventilation, and daytime sleepiness could be addressed with methylphenidate and modafinil (2C).Recommendation 5: Neuromuscular disease combined with sleep-disordered breathing is a chronic disease requiring patient-centered, individualized education and long-term follow-up management (1A).}, }
@article {pmid41351663, year = {2025}, author = {Amirian, R and Merati, A and Babamohamadi, M and Mirahmadi, Y and Esfahani, ML and Rahmani, S and Izadi, Z and Rezazadeh, D}, title = {Navigating the Autophagy Maze: ATG and Their Impact on Neurodegenerative Diseases.}, journal = {Molecular neurobiology}, volume = {63}, number = {1}, pages = {260}, pmid = {41351663}, issn = {1559-1182}, mesh = {*Autophagy/genetics/physiology ; Humans ; *Neurodegenerative Diseases/genetics/metabolism/pathology ; Animals ; *Autophagy-Related Proteins/metabolism/genetics ; Signal Transduction ; }, abstract = {Autophagy, a tightly regulated process essential for maintaining cellular homeostasis, plays a critical role in the pathogenesis and progression of neurodegenerative diseases (NDs). These disorders-marked by diverse mechanisms and clinical heterogeneity-pose significant challenges in developing effective therapies. Central to the autophagic machinery are autophagy-related genes (ATGs), whose functions and variants are increasingly recognized as pivotal in modulating disease-specific pathways. This review explores the intricate roles of ATGs in NDs, emphasizing the need for a comprehensive understanding of molecular signaling networks, protein-protein interactions, and regulatory checkpoints that may serve as therapeutic targets. We highlight recent advancements in disease modeling, autophagy assays, and biomarker identification that facilitate the translation of ATG-related discoveries into clinical practice. Furthermore, we underscore the importance of interdisciplinary collaboration across academia, industry, clinical medicine, and regulatory bodies to harness the therapeutic potential of autophagy. This article aims to serve as a detailed roadmap for understanding the role of ATGs in NDs and to illuminate promising avenues for future research and therapeutic development.}, }
@article {pmid41349278, year = {2025}, author = {García-Parra, B and Guiu, JM and Povedano, M and Modamio, P}, title = {Real-world evidence supporting orphan drugs approvals for rare neuromuscular disorders in the European Union and the United States: Review of public assessment reports (2015-2025).}, journal = {Current opinion in pharmacology}, volume = {86}, number = {}, pages = {102586}, doi = {10.1016/j.coph.2025.102586}, pmid = {41349278}, issn = {1471-4973}, abstract = {Real-world data (RWD) and real-world evidence (RWE) are becoming essential complements to conventional clinical trials for drug assessment, particularly for rare neuromuscular disorders where small patient populations heighten outcome uncertainty. Robust RWE could reduce that uncertainty and inform regulatory decisions on orphan drugs (ODs). To review how the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) have incorporated RWE into OD approvals for neuromuscular diseases from January 2015 to January 2025. We reviewed all publicly available EMA European Public Assessment Reports and FDA review packages for ODs targeting neuromuscular indications. Each document was screened for mention of RWD sources and by the regulatory weight assigned to the resulting RWE. We identified 14 OD approvals by the EMA and 13 by the FDA, with greater use of RWE by the FDA. Indications comprised spinal muscular atrophy (3/3 EMA/FDA), amyotrophic lateral sclerosis (1/3), amyloid neuropathies (2/2), Friedreich ataxia (1/1), Lambert-Eaton syndrome (1/1), myasthenia gravis (2/2), myotonic disorders (1/0), and Duchenne muscular dystrophy (2/1). Among 18 evaluable dossiers, clinical outcome assessments (COA) were reported as follows: patient-reported outcomes - 39.1%, clinician-reported outcomes - 34.7%, observer-reported outcomes - 13.1 %, and performance outcomes - 13.1%. Only tofersen incorporated all COA types. The use of RWE for the evaluation of ODs is increasing for both the FDA and the EMA, more so for the former than for the latter. Harmonized methodological standards and transparent reporting frameworks are urgently needed to generate quality evidence that benefits stakeholders.}, }
@article {pmid41345582, year = {2025}, author = {Ebrahimian, A and Moradi, A and Athari, SZ and Farajdokht, F}, title = {Restless legs syndrome as a comorbidity in amyotrophic lateral sclerosis: a systematic review and meta-analysis.}, journal = {BMC neurology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12883-025-04543-4}, pmid = {41345582}, issn = {1471-2377}, support = {74962//Student Research Committee, Tabriz University of Medical Sciences/ ; }, abstract = {BACKGROUND: Restless Legs Syndrome (RLS), characterized by an urge to move the legs, is linked to neurodegenerative diseases. Emerging evidence suggests a higher RLS prevalence in Amyotrophic Lateral Sclerosis (ALS), impacting quality of life. However, there is lack of comprehensive review addressing its prevalence and associated risk factors. This meta-analysis estimates RLS prevalence in ALS patients compared to healthy controls.<br><br>METHODS: We searched PubMed, Embase, Web of Science, and Scopus for studies assessing RLS in ALS patients versus controls, adhering to PRISMA guidelines. Two reviewers independently extracted data and assessed bias using Joanna Briggs Institute (JBI) checklist. Meta-analysis used Comprehensive Meta-Analysis software with a random-effects model due to heterogeneity. The certainty of evidence was appraised using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework.<br><br>RESULTS: Out of 291 studies, eight studies (792 ALS, 716 controls) were included. The pooled RLS prevalence in ALS was 17% (95% CI: 14.0%-21.1%; I&#xb2;: 56.5%; p-value&#x2009;<&#x2009;0.001). The fixed effect meta-analysis of four studies indicated that the difference of RLS prevalence was statically significant between patients with ALS and healthy controls (OR: 5.65; CI: 2.86-11.13; P-value&#x2009;<&#x2009;0.001; I&#xb2;: 28.7.).<br><br>CONCLUSION: RLS is significantly more prevalent in ALS patients, potentially worsening sleep and quality of life, mental health, and social well-being. Therefore, it is essential to draw clinicians' attention to RLS in ALS patients due to its potential impact on overall health.}, }
@article {pmid41345047, year = {2025}, author = {Bahbah, EI}, title = {Tetramethylpyrazine nitrone: a multifaceted neuroprotective agent in neurodegenerative disorders.}, journal = {Neurodegenerative disease management}, volume = {}, number = {}, pages = {1-15}, doi = {10.1080/17582024.2025.2598227}, pmid = {41345047}, issn = {1758-2032}, abstract = {Neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) share key pathological features, including oxidative stress, mitochondrial dysfunction, and impaired protein homeostasis, yet remain without effective disease-modifying therapies. Tetramethylpyrazine nitrone (TBN), a synthetic derivative of tetramethylpyrazine bearing a free radical-scavenging nitrone moiety, has emerged as a promising multi-target neuroprotective agent. This review synthesizes preclinical and clinical data supporting TBN's therapeutic potential in AD, PD, and ALS. In AD models, TBN reduces amyloid-β accumulation and tau hyperphosphorylation, enhances autophagic clearance, preserves synaptic integrity, and improves cognitive performance. In PD models, TBN confers dopaminergic neuroprotection, restores motor function, and promotes α-synuclein degradation, effects mediated largely through activation of the PGC-1α/Nrf2 pathway and augmentation of the ubiquitin-proteasome system (UPS). In ALS models, TBN mitigates motor neuron loss, improves motor performance, and extends survival, likely via the PGC-1α/Nrf2/HO-1 axis and enhanced autophagic activity. Phase I studies have established TBN's favorable oral and intravenous pharmacokinetics, effective blood - brain barrier penetration, and overall safety and tolerability in healthy volunteers. Owing to its multi-pathway mechanism, principally engaging antioxidant/mitochondrial pathways and proteostasis (autophagy/UPS), TBN represents a compelling candidate for continued clinical development, either as monotherapy or in combination with disease-specific interventions.}, }
@article {pmid41175990, year = {2025}, author = {Konopka, A}, title = {Perspectives on the utilization of cell-free DNA in amyotrophic lateral sclerosis (ALS) diagnostics and prognostics - insight from cancer research.}, journal = {Neurobiology of disease}, volume = {217}, number = {}, pages = {107167}, doi = {10.1016/j.nbd.2025.107167}, pmid = {41175990}, issn = {1095-953X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics/blood ; *Cell-Free Nucleic Acids/blood ; Prognosis ; Biomarkers/blood ; }, abstract = {Amyotrophic lateral sclerosis (ALS) remains a devastating neurodegenerative disease with limited diagnostic and prognostic tools. In recent years, cell-free DNA (cfDNA) has emerged as a promising non-invasive biomarker in various clinical settings, particularly in oncology. Despite its potential, the application of cfDNA in ALS is still in its early stages, and several critical gaps must be addressed. This discussion article reviews the current knowledge about cfDNA in ALS and explores its potential applications for disease diagnosis, monitoring, and prognosis. Drawing on the advances made in cancer research, it also examines the challenges that ALS research may face in cfDNA utilization, highlighting lessons learned from oncology. Taken together, these insights point to the urgent need for a comprehensive understanding of cfDNA characteristics specific to ALS. Given the current lack of reliable diagnostic and prognostic biomarkers in ALS, further investigation into cfDNA represents a valuable and necessary scientific endeavor with the potential to transform patient care and disease management.}, }
@article {pmid41341655, year = {2025}, author = {Almalki, S and Salama, M and Taylor, MJ and Ahmed, Z and Tuxworth, RI}, title = {C9orf72-related amyotrophic lateral sclerosis-frontotemporal dementia and links to the DNA damage response: a systematic review.}, journal = {Frontiers in molecular neuroscience}, volume = {18}, number = {}, pages = {1671906}, pmid = {41341655}, issn = {1662-5099}, abstract = {The G4C2 repeat expansion in C9orf72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). While healthy individuals have fewer than 30 repeats, affected patients may carry hundreds to thousands. This expansion accounts for approximately 40% of familial ALS and 25% of familial FTD cases, and between 5 and 10% cases of sporadic ALS and FTD. Three overlapping pathological mechanisms have been proposed for the C9orf72 expansion: loss of function due to protein deficiency, gain of function through RNA foci, and the production of toxic dipeptide repeat proteins (DPRs) via repeat-associated non-ATG (RAN) translation. This systematic review investigates the role of DNA damage in C9orf72-related ALS-FTD. Analysis of twelve peer-reviewed studies showed that C9orf72 repeat expansions and DPRs compromise genome stability across four experimental models: human cell lines, induced pluripotent stem cell-derived neurons, rodent neurons, and postmortem tissue. We identified four mechanisms underlying DNA damage accumulation: disruption of the ATM pathway, impairment of DNA repair efficiency, formation of R-loops, and mitochondrial dysfunction with oxidative stress. In addition, several consequences of DNA damage were identified, including misrepair-mediated repeat expansion and activation of STING pathway. These findings highlight the key role of DNA damage in C9orf72-related pathology. Consistent with this, targeting DNA damage response factors extended lifespan and improved motor function in mouse models. This review highlights the contribution of DNA damage to C9orf72 pathology and suggest new therapeutic avenues, including personalized approaches based on genetic background.}, }
@article {pmid41341510, year = {2025}, author = {Yang, J and Yang, F and Chen, G and Liu, M and Yuan, S and Zhang, TE}, title = {Receptor-mediated mitophagy: a new target of neurodegenerative diseases.}, journal = {Frontiers in neurology}, volume = {16}, number = {}, pages = {1665315}, pmid = {41341510}, issn = {1664-2295}, abstract = {Neurodegenerative diseases are a category of neurological conditions with high prevalence that pose major treatment challenges. Common pathologies involve protein accumulation and mitochondrial damage. Mitophagy maintains cellular homeostasis by removing defective mitochondria, which are associated with the pathogenesis of neurodegenerative diseases. Although the ubiquitin-dependent mitophagy mediated by the PINK1-Parkin pathway has been extensively studied, growing evidence indicates that receptor-mediated mitophagy plays a crucial compensatory role in neurons, particularly when the PINK1-Parkin pathway is impaired. This review focuses on the emerging field of receptor-mediated mitophagy, systematically elaborating its role as a key homeostatic mechanism operating independently of the canonical PINK1/Parkin pathway. It provides a focused analysis of the specific functions and activation mechanisms of key receptors-including BNIP3, NIX, FUNDC1, and AMBRA1-in models of Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Furthermore, this review explores the clinical potential of targeting these specific receptors for precise intervention, aiming to provide a new theoretical foundation and direction for developing therapeutic strategies against neurodegenerative diseases.}, }
@article {pmid41330444, year = {2025}, author = {Rosso, F and Magdalena, R and Torazza, C and Bacchetti, F and Milanese, M and Poletti, A and Bonanno, G and Cristofani, R and Bonifacino, T}, title = {Non-cell autonomous autophagy in amyotrophic lateral sclerosis: A new promising target?.}, journal = {Neurobiology of disease}, volume = {218}, number = {}, pages = {107203}, doi = {10.1016/j.nbd.2025.107203}, pmid = {41330444}, issn = {1095-953X}, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative non-cell-autonomous disease with no cure, thus research is intensely focused on identifying pharmacological targets. Several studies aimed to clarify the pathogenic mechanisms and involvement in various cell types. A crucial factor in ALS is autophagy, which plays a key role in degrading intracellular protein aggregates. The connection between ALS and autophagy is reinforced by the fact that several genes mutated in ALS are linked to fundamental aspects of autophagy. The blockage of the autophagic flux was observed in ALS motor neurons, where it occurs earlier than in glia. However, the inconsistent effects of autophagy modulators in preclinical and clinical studies indicate the need for a deeper understanding of the role of autophagy in other cell types, such as astrocytes, microglia, and oligodendrocytes. Astrocytes and microglia are significantly impacted by autophagy dysregulation, contributing to neurodegeneration in both mouse and human-derived models. Autophagy is overactivated early in the disease, even before symptoms appear. This overactivation is influenced by the timing and specific tissue involved. It can alter cells' immunophenotype, favouring proinflammatory responses and affecting the cellular environment and autophagy in the surrounding cells. In contrast, oligodendrocytes show mild autophagic alterations. Additionally, sex hormones may affect proper autophagy function and ALS progression. The lack of information on how sex influences autophagy in glia highlights the need for more nuanced investigation into this mechanism. Future research should focus on these aspects, paving the way for personalised pharmacological approaches that consider the roles of cell types, time of intervention, and sex.}, }
@article {pmid41328916, year = {2025}, author = {Ahsan, A and Kar, O and Akter, K and Ta, HDK and Shen, CJ and Datta, K and Chatterjee, B and Huang, CC and Majumder, P}, title = {Regulatory Functions of TDP-43 and FMRP in Non-Neuronal Diseases: Are Co-Targeted mRNAs the Keys?.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {39}, number = {23}, pages = {e71292}, doi = {10.1096/fj.202502281R}, pmid = {41328916}, issn = {1530-6860}, support = {110-2320-B-038-090-MY3//National Science and Technology Council (NSTC)/ ; }, mesh = {Humans ; *Fragile X Mental Retardation Protein/metabolism/genetics ; *DNA-Binding Proteins/metabolism/genetics ; *RNA, Messenger/genetics/metabolism ; Animals ; *Neurodegenerative Diseases/metabolism/genetics ; Amyotrophic Lateral Sclerosis/genetics/metabolism ; Fragile X Syndrome/genetics/metabolism ; }, abstract = {RNA binding proteins (RBPs) act as the central nodal point in shaping the cellular transcriptome through their involvement in various aspects of RNA metabolism including stability, splicing, polyadenylation, modifications, translation and transport. Dysregulation in the function of various RBPs can be associated with different human pathophysiological conditions. Owing to their ability to regulate various RNA metabolism-associated processes, the same RBPs can functionally be involved in human pathologies with distinct underlying pathophysiological mechanisms. Two such important RBPs, namely TDP-43 and FMRP, have long been implicated respectively, in neurodegenerative diseases like amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) etc. and in neurodevelopmental diseases like fragile-X syndrome (FXS). However, numerous recent reports indicate that these ubiquitously expressed proteins can regulate important cellular functions and signaling cascades, misregulation which results in different disease phenotypes. In this review, the association of TDP-43 and FMRP with different non-neuronal disease mechanisms has been discussed. Furthermore, to anticipate yet-to-be-explored non-neuronal disease mechanisms involving mismanagement in co-regulation of spatial and temporal transport/translation processes of TDP-43 and FMRP targeted RNAs, as observed in neuronal diseases for example, autism, RNA target databases of these two proteins are compared followed by GO and KEGG analysis. The lists of RNAs co-targeted by TDP-43 and FMRP are presumably involved in different non-neuronal diseases and disease-associated mechanistic pathways and will open up new phases of research to establish new disease mechanism(s). Different disease mechanisms and their interconnections expectantly will also lead to the discovery of new drug targets.}, }
@article {pmid41126461, year = {2025}, author = {Ayton, S and Moreau, C and Devos, D and Bush, AI}, title = {Iron on trial: recasting the role of iron in neurodegeneration.}, journal = {Brain : a journal of neurology}, volume = {148}, number = {12}, pages = {4241-4247}, doi = {10.1093/brain/awaf398}, pmid = {41126461}, issn = {1460-2156}, support = {//National Health &amp; Medical Research Council of Australia/ ; //Florey Institute of Neuroscience/ ; }, mesh = {Humans ; *Iron/metabolism ; *Neurodegenerative Diseases/metabolism/drug therapy ; *Brain/metabolism ; Iron Chelating Agents/therapeutic use ; Animals ; Oxidative Stress/physiology ; }, abstract = {Iron is critical for numerous neurophysiological functions, while its dysregulation is potentially hazardous for neurodegeneration through oxidative stress and ferroptosis. For decades, elevated brain iron levels observed in neurodegenerative diseases such as Alzheimer's, Parkinson's and amyotrophic lateral sclerosis was presumed to drive disease progression; a hypothesis that propelled clinical trials of strong iron chelators like deferiprone. Results from these trials, however, have challenged this paradigm, with deferiprone markedly worsening outcomes in patients with Alzheimer's disease and, in certain contexts, patients with Parkinson's disease. These findings underscore the vital role of iron for brain health and suggest functional compensatory mechanisms that could become deleterious at the extremes of iron distribution (both low and high levels). Here, we outline an evolving understanding of iron's role in neurodegeneration, and we explore pathways for therapeutic development strategies that mitigate potential iron-mediated damage, while preserving its essential functions in the brain.}, }
@article {pmid41328354, year = {2026}, author = {Huang, Q and Wang, S and Liu, Z and Rao, L and Cheng, K and Mao, X}, title = {Engineering exosomes for targeted neurodegenerative therapy: innovations in biogenesis, drug loading, and clinical translation.}, journal = {Theranostics}, volume = {16}, number = {1}, pages = {545-579}, pmid = {41328354}, issn = {1838-7640}, mesh = {Humans ; *Exosomes/metabolism ; *Neurodegenerative Diseases/drug therapy/therapy ; Animals ; *Drug Delivery Systems/methods ; Blood-Brain Barrier/metabolism ; Bioengineering/methods ; Translational Research, Biomedical ; }, abstract = {Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD) and multiple sclerosis (MS), are characterized by progressive neuronal dysfunction and limited therapeutic options, largely due to the restrictive nature of the blood-brain barrier (BBB). Exosomes, naturally occurring extracellular vesicles (EVs), have gained attention as innovative drug delivery vehicles owing to their intrinsic ability to cross the BBB, minimal immunogenicity, high biocompatibility, and capability to carry diverse therapeutic cargos such as proteins, nucleic acids, and small molecules. Furthermore, exosomes can be bioengineered to enhance drug-loading efficiency and targeting specificity, positioning them as a versatile and effective platform for treating NDDs. In this review, we summarize recent advances in exosome biogenesis, secretion, and engineering, with an emphasis on innovative strategies for exosome isolation, drug loading, and surface modification. We further explore their roles in modulating neuroinflammation, promoting neural regeneration, and enabling precise therapeutic delivery. Critical challenges associated with large-scale production, quality control, and regulatory compliance under Good Manufacturing Practices (GMP) are also discussed. Collectively, these developments underscore the transformative potential of engineered exosomes in advancing precision therapies for neurodegenerative disorders and offer strategic insights into their clinical translation.}, }
@article {pmid41327675, year = {2025}, author = {Kiristioglu, MO and Akova, B and Sogutlu Sari, E and Baykara, M}, title = {Anterior segment optical coherence tomography in corneal diseases: A bibliometric analysis and visualization research of global research trends (1994-2024).}, journal = {Medicine}, volume = {104}, number = {48}, pages = {e45679}, doi = {10.1097/MD.0000000000045679}, pmid = {41327675}, issn = {1536-5964}, mesh = {*Tomography, Optical Coherence/methods/trends ; *Bibliometrics ; Humans ; *Corneal Diseases/diagnostic imaging ; *Biomedical Research/trends ; *Anterior Eye Segment/diagnostic imaging ; }, abstract = {PURPOSE: This study provides a bibliometric analysis of global research on anterior segment optical coherence tomography (AS-OCT) in corneal diseases, mapping key research trajectories, collaborations, and emerging trends.<br><br>METHODS: A systematic search in the Web of Science Core Collection on January 1, 2025, retrieved 3634 records (1994-2024). After excluding non-English publications, non-ophthalmology studies, and non-corneal research, 2079 publications were analyzed using VOSviewer and CiteSpace for citation networks, coauthorship trends, and keyword co-occurrence.<br><br>RESULTS: AS-OCT research has grown significantly (Mann-Kendall &#x3c4;&#x2005;=&#x2005;0.929, P&#x2005;<&#x2005;.001). The United States led in publications (639 papers, 19,594 citations), followed by China (333 papers, 4502 citations). The University of California was the most productive institution. The first AS-OCT study, published in the Archives of Ophthalmology (1994) by Izatt JA et al, marked the field's inception. The most cited article was Huang et al's 1991 Science paper on optical coherence tomography. Recent trends highlight the integration of artificial intelligence, deep learning, and optical coherence elastography in AS-OCT applications. The top 3 contributing journals were Cornea, Journal of Refractive Surgery, and Journal of Cataract and Refractive Surgery. Coauthorship analysis identified Jodhbir S. Mehta and David Huang as central figures in AS-OCT research collaborations.<br><br>CONCLUSION: AS-OCT research has expanded significantly, enhancing diagnostics, surgical planning, and disease monitoring. Artificial intelligence-driven analytics and optical coherence elastography are promising future directions. This bibliometric analysis guides advancing AS-OCT research and clinical applications.}, }
@article {pmid41327179, year = {2025}, author = {Eshak, D and Arumugam, M}, title = {Nanomaterials: an overview of current trends and future prospects in neurological disorder treatment.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {1366}, pmid = {41327179}, issn = {1479-5876}, mesh = {Humans ; *Nervous System Diseases/therapy/drug therapy ; *Nanostructures/therapeutic use/chemistry ; Animals ; Blood-Brain Barrier ; }, abstract = {The World Health Organization (WHO) has identified neurological disorders (NDs) as one of the major health concerns worldwide, resulting in high mortality rates. NDs are conditions affecting the central and peripheral nervous systems, including the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, neuromuscular junctions, and muscles. These neurological diseases include Alzheimer's disease, Parkinson's disease, glioma/brain cancer, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, neuroinfections, ischemic stroke, trauma, hypoxia/anoxia, and depression. Unfortunately, these disorders remain difficult to treat due to the limited ability of conventional drugs to cross the blood-brain barrier (BBB) and achieve significant pharmacological effects in the brain. There is an urgent need to develop methods that can enhance drug efficacy and bypass the BBB. The application of various nanomaterials represents a promising approach to address these neurological disorders. Drugs incorporated with nanomaterials help improve therapeutic outcomes, reduce toxicity, provide better stability, enable targeted delivery, and enhance drug loading capacity. Numerous types and morphologies of inorganic and organic nanomaterials are increasingly employed for treating NDs, including quantum dots, dendrimers, metal nanoparticles, polymeric nanoparticles, liposomes, carbon nanotubes, metal oxide nanoparticles, and micelles. Their exceptional properties such as sensitivity, selectivity, and potential to bypass the BBB make them suitable for both diagnosis and treatment of NDs. In this review article, we briefly summarize the etiology and pathophysiology of various NDs along with current literature highlighting the use of nanomaterials for treating neurological disorders.}, }
@article {pmid41320876, year = {2025}, author = {Tang, YB and Zhang, J and Liu, Q}, title = {tRNA-derived small noncoding RNAs: Roles in brain aging and neurodegenerative disorders.}, journal = {Zoological research}, volume = {46}, number = {6}, pages = {1575-1587}, doi = {10.24272/j.issn.2095-8137.2025.349}, pmid = {41320876}, issn = {2095-8137}, mesh = {*Aging/physiology ; *Neurodegenerative Diseases/genetics/metabolism ; Animals ; *Brain/physiology/metabolism ; *RNA, Transfer/metabolism/genetics ; *RNA, Small Untranslated/metabolism/genetics ; Humans ; }, abstract = {Transfer ribonucleic acid-derived small ribonucleic acids (tsRNAs) are an emerging class of regulatory noncoding RNAs produced through the precise cleavage of mature or precursor tRNAs (pre-tRNAs). Once considered degradation byproducts, tsRNAs are now recognized as key modulators of gene expression, epigenetic regulation, and cellular stress responses. In recent years, growing evidence has implicated tsRNAs in the aging process of the brain and in the pathogenesis of age-related neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). These small RNAs are involved in modulating synaptic function, neuronal survival, and neuroinflammation, and their expression profiles are dynamically altered in response to aging and disease-associated stressors. This review summarizes the biogenesis, classification, and molecular and cellular mechanisms of tsRNAs, with an emphasis on their subcellular locations and associated biological functions. We further explore their roles in brain aging and age-related neurodegenerative diseases and the emerging potential of tsRNAs as biomarkers and therapeutic targets for age-related neurological disorders while highlighting current challenges and future directions in this rapidly advancing field.}, }
@article {pmid41109516, year = {2026}, author = {Pandya, K and Kumar, D}, title = {CRISPR/cas genome editing for neurodegenerative diseases: Mechanisms, therapeutic advances, and clinical prospects.}, journal = {Ageing research reviews}, volume = {113}, number = {}, pages = {102922}, doi = {10.1016/j.arr.2025.102922}, pmid = {41109516}, issn = {1872-9649}, mesh = {Humans ; *Gene Editing/methods/trends ; *Neurodegenerative Diseases/genetics/therapy ; *CRISPR-Cas Systems/genetics ; Animals ; *Genetic Therapy/methods/trends ; }, abstract = {Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS), Spinocerebral Ataxia (SCA), and Huntington's disease (HD) are major global health challenges. Current treatments are only symptomatic and do not address the underlying pathogenic genetic mechanisms. The development of the CRISPR/Cas genome editing technologies, has increased possibilities for targeted repair of pathological mutations. CRISPR/Cas9, Cas12, and Cas13 systems enable targeted editing and transcriptome modulation in various preclinical models. CRISPR/Cas9 disruption of mutant APP, Tau, and LRRK2 genes, reducing toxic protein aggregration in AD models has restored normal genetic function. While correction of CAG nucleotide repeats in HD, and reduction of alpha-synuclein expression in PD. RNA targeting systems like Cas13 offers additional therapeutics potential by selectively degrading disease assciated transcript without altering genomic DNA. Advancements in engineered Cas variants with enhanced specificity, such as SpCas9-HF1, base editors and prime editors, with innovative delivery strategies including adeno-associated virus (AAVs) and nanoparticle-based systems, have improved genome editing. However, challenges remain, including off-target effects, mosaicism, and delivery across the BBB, and long-term safety. Ethical consideration focuses on somatic versus germline editing, equitable access, and regulatory oversight. While somatic editing shows acceptance in treating neurological disorders. Germline interventions face strict regulations due to potential multigeneration impacts. Collectively, these technologies are the vanguard of precision molecular medicine, advancing from symptom management towards potentially curative gene therapies for neurological disorders.}, }
@article {pmid41319477, year = {2025}, author = {Benussi, A and Vucic, S}, title = {Emergent technologies and applications of TMS and TMS-EEG in clinical neurophysiology for early and differential diagnosis: IFCN handbook chapter.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {182}, number = {}, pages = {2111459}, doi = {10.1016/j.clinph.2025.2111459}, pmid = {41319477}, issn = {1872-8952}, abstract = {This chapter examines how emerging neurophysiological technologies are transforming the early and differential diagnosis of neurological disorders. While imaging and fluid biomarkers have greatly advanced the field, they remain limited by cost, invasiveness, and their inability to directly capture dynamic brain activity. Neurophysiological techniques, particularly transcranial magnetic stimulation (TMS) and TMS combined with EEG, offer a unique, non-invasive means of probing cortical excitability, connectivity, and plasticity with millisecond precision. Recent technological and analytical breakthroughs are moving these approaches from research laboratories into clinical practice. By detecting subtle network dysfunctions that precede structural degeneration, they open the possibility of identifying disease in its prodromal or even presymptomatic stages, when interventions may be most effective. This chapter outlines the principles of advanced TMS paradigms and TMS-EEG and explores their application across a range of conditions, including amyotrophic lateral sclerosis, dementias, and movement disorders. It also highlights how integrating neurophysiological measures with blood-based biomarkers and computational tools, such as machine learning, can enhance diagnostic accuracy and guide individualized treatment strategies. Together, these innovations establish neurophysiology as a cornerstone of precision neurology, linking mechanistic insights to clinical decision-making and enabling earlier diagnosis, improved patient stratification, and more targeted therapeutic interventions.}, }
@article {pmid41314748, year = {2025}, author = {Quadri, SN and Tiwari, S and Siddiqi, B and Fatima, S and Khan, MA and Abdin, MZ}, title = {Advanced neuroimaging in precision neurology: Tools, trends, and translational impact.}, journal = {Progress in brain research}, volume = {297}, number = {}, pages = {221-246}, doi = {10.1016/bs.pbr.2025.08.005}, pmid = {41314748}, issn = {1875-7855}, mesh = {Humans ; *Neuroimaging/methods/trends ; *Neurodegenerative Diseases/diagnostic imaging ; *Precision Medicine/methods/trends ; Translational Research, Biomedical ; *Neurology/methods/trends ; Artificial Intelligence ; Machine Learning ; }, abstract = {Advances in neuroimaging are revolutionizing the landscape of precision neurology by enabling high-resolution, multimodal visualization of brain structure, function, and pathology. As traditional, symptom-based frameworks fall short in capturing the biological complexity of neurodegenerative diseases, imaging modalities such as structural MRI, diffusion tensor imaging, functional MRI, PET, and hybrid PET/MRI have emerged as essential tools for early diagnosis, patient stratification, and therapeutic monitoring. These technologies not only reveal hallmark features like hippocampal atrophy and disrupted neural networks but also uncover molecular signatures such as amyloid and tau deposition, synaptic density, and neuroinflammation. Integration with artificial intelligence (AI) and machine learning (ML) further enhances diagnostic precision by decoding subtle imaging patterns, facilitating subtype classification, and predicting disease progression. Despite transformative progress, disparities in access and implementation remain a critical challenge, particularly in low- and middle-income countries. This chapter provides a comprehensive overview of neuroimaging modalities, their diagnostic and prognostic relevance across major neurodegenerative conditions including Alzheimer's disease, Parkinson's disease, ALS, and frontotemporal dementia and the evolving role of hybrid platforms and AI integration in shaping the future of individualized neurological care.}, }
@article {pmid41314746, year = {2025}, author = {Ceballos, MWG and Sy, FFA and Akbar, A and Taofiq, A}, title = {Multi-omics integration in disease research.}, journal = {Progress in brain research}, volume = {297}, number = {}, pages = {155-189}, doi = {10.1016/bs.pbr.2025.08.012}, pmid = {41314746}, issn = {1875-7855}, mesh = {Humans ; *Neurodegenerative Diseases/genetics/metabolism ; *Proteomics/methods ; *Genomics/methods ; *Metabolomics/methods ; Animals ; Multiomics ; }, abstract = {Neurodegenerative diseases, marked by complex molecular mechanisms and diverse clinical features, challenge conventional research approaches. This chapter emphasizes the value of multi-omics integration in understanding the biology of Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS). Genomic studies reveal risk variants such as APOE ε4 in Alzheimer's and rare mutations in familial forms. Transcriptomics highlights gene expression changes, including synaptic dysfunction in early Parkinson's and alternative splicing errors in TARDBP-related ALS. Proteomics identifies key protein aggregates like amyloid beta and alpha-synuclein, along with modifications such as hyperphosphorylated tau that correlate with cognitive decline. Metabolomics uncovers metabolic alterations, including mitochondrial dysfunction in Parkinson's and lipid peroxidation in ALS, which contribute to disease progression. By combining these layers with high-throughput tools like single-cell sequencing, spatial transcriptomics, and mass spectrometry, researchers can reconstruct molecular networks linking genetic risk, gene regulation, protein dysfunction, and metabolic imbalance. This approach enables patient stratification into molecular subtypes, such as neuroinflammatory clusters defined by microglial gene signatures and cytokine expression. Biomarkers from blood and cerebrospinal fluid allow for minimally invasive disease monitoring. Despite challenges such as data heterogeneity and limited standardization, multi-omics approaches support biomarker discovery and therapeutic development. Integrating these datasets with neuroimaging and digital tools enhances diagnostic precision and guides targeted interventions, such as antisense therapies for SOD1-linked ALS. Multi-omics integration is thus a critical foundation for advancing personalized strategies in neurodegenerative disease research.}, }
@article {pmid41070448, year = {2025}, author = {ElDabour, MA}, title = {Circumferential clues: strain patterns and arrhythmia risk in pulmonary regurgitation.}, journal = {Cardiology in the young}, volume = {35}, number = {11}, pages = {2332-2333}, doi = {10.1017/S1047951125110032}, pmid = {41070448}, issn = {1467-1107}, mesh = {Humans ; *Pulmonary Valve Insufficiency/physiopathology/complications/surgery ; *Tetralogy of Fallot/surgery/complications/physiopathology ; *Arrhythmias, Cardiac/etiology/physiopathology ; *Heart Ventricles/physiopathology/diagnostic imaging ; Risk Factors ; }, abstract = {Slim et al.'s paper provided an insight into the differences between repaired tetralogy of Fallot and isolated pulmonary regurgitation in their strain. Repaired tetralogy of Fallot had higher right ventricular circumferential strain, while isolated pulmonary regurgitation relied on longitudinal strain more. This allowed the authors to infer that repaired tetralogy of Fallot can withstand more chronic regurgitation before valve replacement is necessary. We highlighted new findings relevant to this paper. Arrhythmia in repaired tetralogy of Fallot is associated with a reduced global circumferential strain of the right ventricle. Specifically, a value of below -14% was associated with a 6.3 times increase in the risk for an arrhythmic event. We believe this would be beneficial for patients when considered for valve replacements, suggesting modification of current valve replacement guidelines to include strain thresholds alongside current volumetric thresholds. However, the data for isolated pulmonary regurgitation remains scarce. Further investigation is needed to provide clearer timelines for valve replacement. We emphasised the importance of exploring the underlying architecture of repaired tetralogy of Fallot patients' hearts and why they could generate more global circumferential strain. We acknowledged the broader effect of this paper and its specific benefit in our country, Egypt. This paper provided insights useful for broader global health impact, especially in low-income countries.}, }
@article {pmid40296625, year = {2025}, author = {Barabadi, T and Mirjalili, ES and Mohamadi-Zarch, SM and Rahimi, H and Keshmirshekan, F and Bagheri, SM}, title = {Cell-Free DNA, a Noninvasive Biomarker for Prediction and Detection of Neurodegenerative Diseases, New Insights, and Perspectives.}, journal = {CNS &amp; neurological disorders drug targets}, volume = {24}, number = {10}, pages = {731-742}, pmid = {40296625}, issn = {1996-3181}, support = {18535//Shahid Sadoughi University of Medical Science and Health Services/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/diagnosis/blood ; Biomarkers/blood ; *Cell-Free Nucleic Acids/blood/metabolism ; Parkinson Disease/diagnosis ; Animals ; }, abstract = {Neurodegenerative diseases pose serious threats to public health worldwide. Biomarkers for neurodegenerative disorders are essential to enhance the diagnostic process in clinical settings and to aid in the creation and assessment of effective disease-modifying treatments. In recent times, affordable and readily available blood-based biomarkers identifying the same neurodegenerative disease pathologies have been created, potentially transforming the diagnostic approach for these disorders worldwide. Emerging relevant biomarkers for α-synuclein pathology in Parkinson's disease include blood-based indicators of overall neurodegeneration and glial activation. Cell-free DNA (cfDNA), an encouraging non-invasive biomarker commonly utilized in oncology and pregnancy, has demonstrated significant potential in clinical uses for diagnosing neurodegenerative disorders. In this section, we explore the latest cfDNA studies related to neurodegenerative disorders. Moreover, we present a perspective on the possible role of cfDNA as a diagnostic, therapeutic, and prognostic indicator for neurodegenerative disorders. This review provides a summary of the most recent progress in biomarkers for neurodegenerative disorders such as Alzheimer's, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, and traumatic brain injury.}, }
@article {pmid40231507, year = {2025}, author = {Tecalco-Cruz, AC and Ramirez-Jarquin, JO and Medina Abreu, KH and Palacios-Serrato, EG and Lopez-Canovas, L and Zepeda-Cervantes, J and Oropeza-Martínez, E}, title = {Molecular Interplay of ISG15/ISGylation in Neuropathologies.}, journal = {CNS &amp; neurological disorders drug targets}, volume = {24}, number = {10}, pages = {723-730}, pmid = {40231507}, issn = {1996-3181}, support = {CCyT-2024-CON-07//CCyT-UACM/ ; }, mesh = {Humans ; *Ubiquitins/metabolism ; Animals ; *Cytokines/metabolism ; *Neurodegenerative Diseases/metabolism ; }, abstract = {ISG15 is a 15 kDa ubiquitin-like protein that covalently associates with its target proteins by a sequential enzymatic process known as ISGylation. Research on protein ISGylation has increased in recent years, and some studies have suggested that ISG15 is involved in neuroprotection and neurodegeneration mechanisms. This review outlines the current state of research on the implications of ISG15/ISGylation in other neuropathies such as malignant tumors, ataxia telangiectasia, ischemia, depression, and neurodegenerative diseases such as Alzheimer's, Parkinson's diseases, multiple sclerosis, and amyotrophic lateral sclerosis. Based on the studies reported to date, ISG15/ ISGylation promotes the progression of brain tumors such as glioblastoma. Moreover, ISG15/ ISGylation seems to play a dual role in neuropathies, demonstrating a neuroprotective effect when there is acute brain damage, but ISG15/ISGylation is associated with reduced neuroprotection when there is chronic damage, such as in neurodegenerative diseases.}, }
@article {pmid41314745, year = {2025}, author = {Fatima, S and Tiwari, S and Siddiqi, B and Quadri, SN and Abdin, MZ}, title = {Biomarkers: From early detection to treatment personalization.}, journal = {Progress in brain research}, volume = {297}, number = {}, pages = {131-153}, doi = {10.1016/bs.pbr.2025.08.008}, pmid = {41314745}, issn = {1875-7855}, mesh = {Humans ; *Biomarkers/metabolism ; *Neurodegenerative Diseases/diagnosis/therapy/metabolism ; *Precision Medicine/methods ; Early Diagnosis ; }, abstract = {Neurodegenerative disorders (NDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), present increasing issues associated with the unavoidable aging of the world's population. These challenges are further highlighted by the socioeconomic consequences of these diseases. The identification and use of biomarkers for prompt diagnosis, careful observation, and efficient treatment approaches is essential to overcoming these obstacles. The primary methods for diagnosing neurodegenerative illnesses are invasive procedures like lumbar punctures to measure CSF fluid or functional brain imaging methods. Biomarkers for underlying proteinopathy in blood serum and cerebral fluid have been the focus of recent biological research, particularly in vivo. With their ability to provide novel pathways for early detection, illness progression tracking, and individualized treatment plans, biomarkers have become essential instruments in precision medicine. The classification of biomarkers including fluid, digital imaging, and molecular biomarkers is examined in this chapter, with an emphasis on their function in neurodegenerative diseases. In neurodegenerative illnesses and the aging brain, tau, amyloid-β, α-synuclein, and TDP-43 are commonly seen to be deposited together rather than separately. These may be disregarded, and it might be challenging to determine their clinicopathological significance. An overview of illness pathophysiology, diagnostic implications, and the most recent molecular and ultrastructural categories for neurodegenerative disorders are given in this chapter. Addressing these issues through interdisciplinary research and technological advancements will be crucial for the future of biomarker-driven precision medicine. This chapter provides an in-depth overview of the evolving landscape of biomarkers and their transformative impact on the early detection and personalized treatment of neurodegenerative diseases.}, }
@article {pmid41314744, year = {2025}, author = {Gunasekaran, B and Arifin, AH and Yu, WH and Hanafi, S and Rao, KDK and Salvamani, S}, title = {Precision medicine in neurodegenerative diseases: From research to clinical practice.}, journal = {Progress in brain research}, volume = {297}, number = {}, pages = {1-52}, doi = {10.1016/bs.pbr.2025.08.006}, pmid = {41314744}, issn = {1875-7855}, mesh = {Humans ; *Precision Medicine/methods ; *Neurodegenerative Diseases/therapy/genetics/diagnosis ; Biomarkers ; }, abstract = {The chapter outlines how precision medicine is reshaping the way neurodegenerative diseases (NDs) which includes Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD) are understood, diagnosed, and treated. It discusses the limitations of current therapies, which mainly address symptoms without altering disease progression. Genetic and molecular factors that influence disease development are described, including distinctions between familial and sporadic forms. The chapter also covers the roles of epigenetic changes, gene expression, protein dysfunction, mitochondrial DNA, and non-coding RNAs in NDs. Biomarkers in blood and cerebrospinal fluid, along with imaging techniques and digital tools, are presented as key elements in early diagnosis and disease monitoring. Patient stratification based on clinical features, molecular profiles, and biomarkers helps guide treatment decisions and improve outcomes. The chapter reviews ongoing developments in genotype-based drug design, gene therapy, pharmacogenomics, and personalized lifestyle strategies. Clinical case studies show how these approaches are being used in practice. The chapter also discusses challenges in applying precision medicine, such as trial design, data integration, unequal access, and regulatory hurdles. Finally, it highlights the future tools like single-cell transcriptomics, digital twins, and global research collaborations that aim to bring precision approaches into everyday care.}, }
@article {pmid41314255, year = {2025}, author = {Odonchimed, S and Imamura, K and Inoue, H}, title = {Neurodegenerative Disease and Autophagy in iPSC models.}, journal = {Neuroscience research}, volume = {}, number = {}, pages = {104991}, doi = {10.1016/j.neures.2025.104991}, pmid = {41314255}, issn = {1872-8111}, abstract = {Neurodegenerative diseases are characterized by the gradual deterioration of specific neuronal populations, ultimately resulting in motor, cognitive, or behavioral impairments. Despite the worldwide increase in disease incidence, effective therapies remain unavailable. A common pathological hallmark of neurodegenerative diseases is the accumulation of misfolded protein aggregates, which impair normal cellular function. Accordingly, numerous studies and therapeutic strategies have focused on targeting these toxic aggregates and protein quality control via autophagy, a vital cellular recycling mechanism. Autophagy dysregulation has been implicated in the pathogenesis of several neurodegenerative diseases. Induced pluripotent stem cell (iPSC) technology has emerged as a powerful platform for modeling neurodegenerative diseases, and iPSC-derived models provide human-relevant systems for studying autophagic dysfunction in vitro. In this review, we discuss the key findings of recent studies investigating autophagy in iPSC-based models of neurodegenerative diseases, including Alzheimer's disease, amyotrophic lateral sclerosis, frontotemporal dementia, and other diseases.}, }
@article {pmid41313410, year = {2025}, author = {Goel, F and Singh, P and Rai, SN and Yadav, DK}, title = {Nrf2/Keap1 Signaling Axis in the Brain: Master Regulator of Oxidative Stress in Neurodegenerative and Psychiatric Disorders.}, journal = {Molecular neurobiology}, volume = {63}, number = {1}, pages = {197}, pmid = {41313410}, issn = {1559-1182}, mesh = {Humans ; *Kelch-Like ECH-Associated Protein 1/metabolism ; *NF-E2-Related Factor 2/metabolism ; *Signal Transduction/physiology ; *Oxidative Stress/physiology ; *Mental Disorders/metabolism/pathology ; Animals ; *Neurodegenerative Diseases/metabolism/pathology ; *Brain/metabolism/pathology ; }, abstract = {Oxidative stress is a crucial factor in the development of CNS disorders, including neurodegenerative and psychiatric conditions. The Nrf2/Keap1 signaling axis plays a central role in defending against oxidative damage by regulating antioxidant and cytoprotective gene expression. Beyond its antioxidant function, Nrf2 influences neurogenesis, synaptic plasticity, mitochondrial bioenergetics, and glial neuronal interactions, all of which are vital for maintaining neural integrity and cognitive performance. Dysregulation of this pathway through altered dimerization, post-translational modifications, or impaired regulation contributes to the pathophysiology of Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, leading to protein aggregation, mitochondrial dysfunction, and neuroinflammation. Emerging evidence also implicates aberrant Nrf2 activity in psychiatric disorders such as depression, schizophrenia, and bipolar disorder, where redox imbalance and neuroimmune activation disrupt neural function. This review summarizes the molecular structure and regulation of the Nrf2/Keap1 pathway, including basal and stress-induced activation, post-translational modifications, and cross-talk with PI3K/Akt, MAPK, and NF-κB signaling. We highlight cell-type-specific roles of Nrf2 in neurons, astrocytes, and microglia, and the gene expression networks that drive CNS antioxidant and detoxification responses. Recent therapeutic strategies include natural and synthetic Nrf2 activators, gene therapy approaches, and nanotechnology-based delivery systems. While the translational potential of Nrf2-targeted interventions is considerable, challenges remain, including risks of overactivation and oncogenicity, lack of reliable biomarkers, and barriers related to blood-brain barrier permeability, dose, timing, and bioavailability. By integrating advances in neuroscience, pharmacology, and molecular medicine, this review emphasizes the promise of Nrf2 as a unifying therapeutic target across diverse CNS pathologies. Future directions include precision modulation through epigenetic regulation and circRNAs, as well as personalized pharmacotherapy. The Nrf2/Keap1 axis represents a multidisciplinary platform for developing multimodal interventions to preserve brain health in neurodegenerative and psychiatric disorders.}, }
@article {pmid41309196, year = {2025}, author = {Jamwal, RS and Sharma, B and Minerva,  and Gupta, A and Misri, S and Shankaryan, R and Shah, R and Kumar, R}, title = {Protein misfolding and its dual role in neurodegeneration and cancer progression.}, journal = {Advances in protein chemistry and structural biology}, volume = {148}, number = {}, pages = {355-377}, doi = {10.1016/bs.apcsb.2025.10.001}, pmid = {41309196}, issn = {1876-1631}, mesh = {Humans ; *Neoplasms/metabolism/pathology ; *Protein Folding ; *Neurodegenerative Diseases/metabolism/pathology ; Animals ; Disease Progression ; Unfolded Protein Response ; }, abstract = {Protein misfolding is a fundamental biological process with profound implications for human health and disease. Typically, proteins assume precise three-dimensional structures to perform their functions, a process safeguarded by the proteostasis network, which comprises molecular chaperones, the ubiquitin-proteasome system (UPS), and autophagy. However, genetic mutations, oxidative stress, and environmental insults can disrupt folding, leading to the accumulation of non-functional or toxic conformations. In neurodegenerative diseases such as Huntington's disease (HD), Parkinson's disease (PD), Alzheimer's disease (AD), Amyotrophic lateral Sclerosis (ALS), chronic misfolding results in toxic protein aggregates like amyloid-β, tau, and α-synuclein. These disrupt synaptic function, induce oxidative and nitrosative stress, and trigger apoptosis, ultimately leading to progressive neuronal loss. Dysregulation of the unfolded protein response (UPR) and weakened proteostasis with aging exacerbate disease pathology. In contrast, cancer cells utilize protein misfolding to enhance their survival and progression. Misfolded oncoproteins, such as mutant p53, not only evade degradation but also acquire oncogenic properties. Tumor cells hijack the UPR and chaperone networks, upregulate heat shock proteins, and manipulate oxidative stress responses to withstand hypoxia, nutrient deprivation, and rapid proliferation. Cancer stem cells (CSCs) further adapt to proteotoxic stress, contributing to tumor heterogeneity, therapy resistance, and immune evasion. The dual role of protein misfolding, driving degeneration in neurons while supporting proliferation in tumors, underscores its centrality in disease biology. Future research should focus on identifying early biomarkers of proteostasis imbalance and exploiting shared molecular pathways for the development of novel therapeutic interventions.}, }
@article {pmid41303502, year = {2025}, author = {Hassan, M and Shahzadi, S and Moustafa, AA and Kloczkowski, A}, title = {Neurodegeneration Through the Lens of Bioinformatics Approaches: Computational Mechanisms of Protein Misfolding.}, journal = {International journal of molecular sciences}, volume = {26}, number = {22}, pages = {}, pmid = {41303502}, issn = {1422-0067}, support = {1R01HG012117-04/NH/NIH HHS/United States ; }, mesh = {Humans ; *Computational Biology/methods ; *Neurodegenerative Diseases/metabolism ; *Protein Folding ; Animals ; Protein Aggregates ; Protein Aggregation, Pathological/metabolism ; }, abstract = {Protein and peptide aggregation has become a prominent focus in biomedical research due to its critical role in the development of neurodegenerative diseases (NDs) and its relevance to industrial applications. Neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic Lateral Sclerosis (ALS) are closely associated with abnormal aggregation processes, highlighting the need for a deeper understanding of their molecular mechanisms. In recent years, a wide range of computational methods, bioinformatics tools, and curated databases have been developed to predict and analyze sequences and structures that are prone to aggregation. These in silico approaches offer valuable insights into the underlying principles of aggregation and contribute to the identification of potential therapeutic targets. This review provides a concise overview of the current bioinformatics resources and computational techniques available for studying protein and peptide aggregation, intending to guide future research efforts in the field of neurodegenerative disease modeling and drug discovery.}, }
@article {pmid41302089, year = {2025}, author = {Anjum, F and Hulbah, MJ and Shamsi, A and Mohammad, T}, title = {Exploring TANK-Binding Kinase 1 in Amyotrophic Lateral Sclerosis: From Structural Mechanisms to Machine Learning-Guided Therapeutics.}, journal = {Life (Basel, Switzerland)}, volume = {15}, number = {11}, pages = {}, doi = {10.3390/life15111665}, pmid = {41302089}, issn = {2075-1729}, support = {KSRG-2024-446//King Salman Center for Disability Research/ ; }, abstract = {TANK-binding kinase 1 (TBK1) has emerged as one of the most compelling genetic contributors to amyotrophic lateral sclerosis (ALS), with heterozygous loss-of-function and pathogenic missense variants identified in patients across the ALS-frontotemporal dementia (FTD) spectrum. TBK1 participates in various core cellular processes associated with motor neuron vulnerability, including autophagy, mitophagy, and innate immune regulation, indicating that TBK1 is likely a key determinant of ALS pathogenesis. Structurally, TBK1 exhibits a trimodular organization comprising a kinase domain, a ubiquitin-like domain, and a scaffold/dimerization domain. Multiple experimentally resolved conformations and inhibitor-bound complexes provide a foundation for structure-guided therapeutic design. Here, we synthesize current genetic and mechanistic evidence linking TBK1 dysfunction to ALS, emphasizing its dual roles in autophagy and neuroinflammation. We also summarize advances in structure-based and AI-assisted drug discovery approaches targeting TBK1. Finally, we outline key translational challenges, including isoform selectivity, biomarker validation, and central nervous system (CNS) delivery, highlighting TBK1 as a promising yet complex therapeutic target in ALS. By integrating computational modeling, machine learning frameworks, and experimental pharmacology, future research may accelerate the translation of TBK1 modulators into clinically effective therapies.}, }
@article {pmid41300346, year = {2025}, author = {Yeasmin, A and Torrente, MP}, title = {Histone Post-Translational Modifications and DNA Double-Strand Break Repair in Neurodegenerative Diseases: An Epigenetic Perspective.}, journal = {Biology}, volume = {14}, number = {11}, pages = {}, doi = {10.3390/biology14111556}, pmid = {41300346}, issn = {2079-7737}, support = {1R15NS125394-01/NH/NIH HHS/United States ; }, abstract = {DNA damage is a hallmark of the fatal process of neurodegeneration in the central nervous system (CNS). As neurons are terminally differentiated, they accumulate metabolic and oxidative burdens over their whole life span. Unrepaired DNA develops into DNA double-strand breaks (DSBs), which are repaired through homologous recombination (HR) or non-homologous end joining (NHEJ). Being post-mitotic and unable to normally undergo HR, damage and defective repair is especially burdensome to CNS neurons. Current research has not produced treatment to prevent and halt progression of neurodegeneration. Hence, novel targeting strategies are desperately needed. Recent investigations in histone post-translational modifications (PTMs) reveal new mechanistic insight and highlight unexplored targets to ameliorate neurodegeneration. As various histone PTMs dictate and facilitate DSB repair, they represent an underexploited area in investigating DNA damage and incorrect repair aiding neurodegeneration. Here, we review the histone PTM alterations in several neurodegenerative diseases: Amyotrophic Lateral Sclerosis/Frontotemporal Dementia, Parkinson's Disease, Alzheimer's Diseases, Multiple Sclerosis, and Huntington's Disease. These findings emphasize that histone PTM alterations can enable an aberrant DNA damage response (DDR) leading to neurodegeneration. Further research into the connections between histone PTMs and DNA damage in decaying neurons will illuminate novel targets to dampen the aberrant DDR and promote neuronal survival.}, }
@article {pmid41299417, year = {2025}, author = {Wang, J and Zhu, M and Smith, RD}, title = {Prevalence, incidence and risk factors of syphilis among men who have sex with men in China from 2013 to 2025: a systematic review and meta-analysis.}, journal = {BMC infectious diseases}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12879-025-12176-8}, pmid = {41299417}, issn = {1471-2334}, abstract = {BACKGROUND: Syphilis has re-emerged in China in recent decades, particularly among men who have sex with men (MSM). We aimed to assess the prevalence, incidence, and associated factors of syphilis among MSM in China.<br><br>METHODS: We systematically searched major English (MEDLINE via PubMed, Web of Science, Embase, Scopus, Cochrane Library) and Chinese (CNKI, Wanfang, CBM, VIP, Airiti Library) databases for studies on syphilis prevalence or incidence among MSM in China published from January 1, 2013 to March 1, 2025. Study qualities were evaluated using the Hoy et al.'s risk-of-bias tool and the Newcastle-Ottawa Scale. Random-effects meta-analysis models were used to estimate pooled syphilis prevalence (%) and incidence (per 100 person-years, PYs) with 95% confidence intervals (CIs). Meta-regression analyses were performed to assess differences across subgroups.<br><br>RESULTS: A total of 441 studies (429 prevalence and 33 incidence) were included. The pooled syphilis prevalence among general MSM was 8.8% (95% CI: 8.3-9.4). Study location (R&#xb2;=0.13) and study year (R&#xb2;=0.11) each contributed significantly to the high heterogeneity observed (I&#xb2; = 98.5%) among the general MSM prevalence studies. MSM with high-risk sexual behaviors or related risk factors exhibited higher prevalence. The pooled incidence among all MSM was 7.8 per 100 PYs (95% CI: 6.0-9.8), with similarly high heterogeneity (I&#xb2; = 96.4%). Both syphilis prevalence and incidence declined over time.<br><br>CONCLUSION: Syphilis prevalence and incidence remain high among high-risk MSM subgroups in China. More rigorous studies and targeted interventions are needed to obtain more accurate estimates and to further reduce syphilis infection rates.}, }
@article {pmid41295414, year = {2025}, author = {Favari, E and Parolini, C}, title = {Marine Bioactive Components and Chronic Neuroinflammation: Focus on Neurodegenerative Disease.}, journal = {Marine drugs}, volume = {23}, number = {11}, pages = {}, pmid = {41295414}, issn = {1660-3397}, support = {NA//MUR Progetto Eccellenza/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy ; Animals ; *Neuroinflammatory Diseases/drug therapy ; *Aquatic Organisms/chemistry ; Oxidative Stress/drug effects ; Inflammation/drug therapy ; }, abstract = {Advances in neuroscience, immunology, and neuroimmunology have revealed that the nervous and immune systems form a bidirectional integrated network, ranging from regulating inflammation to directing stress responses, pivotal for the maintenance of the brain-body physiology. Like peripheral inflammation, neuroinflammation is a conserved process aimed at activating innate/adaptive immune and non-immune cells to effectively deal with bacteria, viruses, toxins, and injuries, and eventually at removing the microbial pathogens and supporting tissue repair and recovery. A failure of this process or the permanent release of pro-inflammatory mediators causes a condition called "chronic low-grade neuroinflammation" resulting in tissue damage and an increased risk of developing neurodegenerative diseases (NDD), such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS). Marine-derived bioactive components are able to modulate lipid and glucose metabolism as well as inflammation and oxidative stress. In this review, we describe the neuroinflammatory process and its involvement in the pathogenesis and progression of AD, PD, MS, and ALS. Then, we discuss the potential therapeutic efficacy of select marine-derived bioactive components.}, }
@article {pmid41294873, year = {2025}, author = {Wang, S and Feng, Z and Wu, H and Wang, S and Qin, S and Wang, X and Zhou, F and Zheng, K and Huang, X and Liu, X}, title = {The m[6]A Modification in Neurodegenerative Disease: A Cellular Perspective.}, journal = {Cells}, volume = {14}, number = {22}, pages = {}, pmid = {41294873}, issn = {2073-4409}, support = {BK20231347//Natural Science Foundation of Jiangsu Province/ ; 81971179//National Natural Science Foundation of China/ ; Z2019035//Jiangsu Commission of Health/ ; 20KJA320004//Jiangsu Provincial Department of Education/ ; KC23242//Technology Innovation Foundation of Xuzhou City/ ; JBGS202202//Open Competition Grant of Xuzhou Medical University/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/genetics/metabolism/pathology ; *Adenosine/analogs &amp; derivatives/metabolism/genetics ; Animals ; Neurons/metabolism ; }, abstract = {N6-methyladenosine (m[6]A) is the most abundant internal RNA modification in eukaryotes and plays a critical role in gene expression regulation by influencing RNA stability, splicing, nuclear export, and translation. Emerging evidence suggests that dysregulation of m[6]A contributes to neuroinflammation, neurotoxicity, and synaptic dysfunction-key features of neurodegenerative diseases. This review aims to examine the role of m6A modification in neurodegenerative diseases from a cell-type-specific perspective. We systematically reviewed recent studies investigating m[6]A modifications in neurons and glial cells. Data from transcriptomic, epitranscriptomic, and functional studies were analyzed to understand how m[6]A dynamics influence disease-related processes. Findings indicate that m[6]A modifications regulate neuroinflammation and immune responses in microglia, modulate astrocytic support functions, affect myelination through oligodendrocytes, and alter m[6]A patterns in neurons, impacting synaptic plasticity, stress responses, and neuronal survival. These cell-type-specific roles of m[6]A contribute to the progression of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and Amyotrophic lateral sclerosis (ALS). Understanding m[6]A-modulated mechanisms in specific neural cell types may facilitate the development of targeted interventions for neurodegenerative diseases.}, }
@article {pmid41294805, year = {2025}, author = {Xu, H and Zhou, K and Xia, L and Ren, K and Xu, Y}, title = {In-Depth Study of Low-Complexity Domains: From Structural Diversity to Disease Mechanisms.}, journal = {Cells}, volume = {14}, number = {22}, pages = {}, doi = {10.3390/cells14221752}, pmid = {41294805}, issn = {2073-4409}, support = {31972537//National Natural Science Foundation of China/ ; }, mesh = {Humans ; Protein Domains ; Animals ; Neurodegenerative Diseases/metabolism ; Intrinsically Disordered Proteins/chemistry/metabolism ; }, abstract = {Low-complexity domains (LCDs) are protein regions characterized by a simple amino acid composition and low sequence complexity, as they are typically composed of repeats or a limited set of a few amino acids. Historically dismissed as "garbage sequences", these regions are now acknowledged as critical functional elements. This review systematically explores the structural characteristics, biological functions, pathological roles, and research methodologies associated with LCDs. Structurally, LCDs are marked by intrinsic disorder and conformational dynamics, with their amino acid composition (e.g., G/Y-rich, Q-rich, S/R-rich, P-rich) dictating structural tendencies (e.g., β-sheet formation, phase separation ability). Functionally, LCDs mediate protein-protein interactions, drive liquid-liquid phase separation (LLPS) to form biomolecular condensates, and play roles in signal transduction, transcriptional regulation, cytoskeletal organization, and nuclear pore transportation. Pathologically, LCD dysfunction-such as aberrant phase separation or aggregation-is implicated in neurodegenerative diseases (e.g., ALS, AD), cancer (e.g., Ewing sarcoma), and prion diseases. We also summarize the methodological advances in LCD research, including biochemical (CD, NMR), structural (cryo-EM, HDX-MS), cellular (fluorescence microscopy), and computational (MD simulations, AI prediction) approaches. Finally, we highlight current challenges (e.g., structural heterogeneity, causal ambiguity of phase separation) and future directions (e.g., single-molecule techniques, AI-driven LCD design, targeted therapies). This review provides a comprehensive perspective on LCDs, illuminating their pivotal roles in cellular physiology and disease, and offering insights for future research and therapeutic development.}, }
@article {pmid41294799, year = {2025}, author = {Medigovic, G and Rachamala, HK and Dutta, SK and Pal, K}, title = {Structural and Functional Perspectives of Optineurin in Autophagy, Immune Signaling, and Cancer.}, journal = {Cells}, volume = {14}, number = {22}, pages = {}, doi = {10.3390/cells14221746}, pmid = {41294799}, issn = {2073-4409}, support = {W81XWH-21-1-0678//Department of Defense Congressionally Directed Medical Research Program/ ; R56HL160545//The National Heart, Lung, and Blood Institute/ ; }, mesh = {Humans ; *Autophagy ; *Neoplasms/immunology/metabolism/pathology ; *Membrane Transport Proteins/chemistry/metabolism ; *Signal Transduction ; *Cell Cycle Proteins/chemistry/metabolism ; Animals ; *Transcription Factor TFIIIA/metabolism/chemistry/genetics ; }, abstract = {Optineurin (OPTN) is a multifunctional adaptor protein that regulates diverse cellular processes, including inflammatory signaling, autophagy, vesicular trafficking, and immune responses. This multifaceted role of OPTN is made possible by the presence of a complex structure comprising multiple domains that interact with different proteins to exert various functions important for modulating key signaling processes. Mutations in OPTN are linked with several human pathologies including glaucoma, Paget's disease of bone, Crohn's disease, and neurodegenerative diseases such as amyotrophic lateral sclerosis, and dementia. Emerging evidence suggests that OPTN has a complex and context-dependent role in cancer biology as well. It is upregulated in pancreatic ductal adenocarcinoma and hepatocellular carcinoma but downregulated in lung and colorectal cancers, indicating its dual role as a potential oncogene or tumor suppressor depending on the cellular environment. Additionally, OPTN plays a critical role in preventing immune evasion in colorectal cancer by maintaining interferon-gamma receptor 1 (IFNGR1) expression and supporting dendritic cell-mediated T-cell priming, thereby enhancing antitumor immune responses. Despite its significance in oncogenic pathways and immune regulation, the therapeutic potential of targeting OPTN in cancer remains largely unexplored. This review aims to provide a comprehensive understanding of OPTN's pleiotropic functions, highlighting its role in autophagy, inflammation, immune surveillance, and cancer progression. By elucidating its diverse regulatory mechanisms, we seek to encourage further research into the therapeutic implications of OPTN in cancer treatment and immunotherapy.}, }
@article {pmid41291690, year = {2025}, author = {Mac Conghail, L and Parker, S and Matthews, A and Burke, S}, title = {Examining the roles, relationships and power dynamics shaping universal health system policy processes in high- and upper-middle-income countries: a scoping review.}, journal = {BMC health services research}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12913-025-13773-8}, pmid = {41291690}, issn = {1472-6963}, support = {SPHeRE/2018/1/HRBI_/Health Research Board/Ireland ; }, abstract = {BACKGROUND: Policies for universal health systems aim to provide equitable access to quality healthcare. However, achieving this remains a complex goal in high and upper-middle-income countries. Despite widespread efforts, universal health system reforms vary significantly, shaped by historical, political, and economic contexts. Understanding the policy process, including the roles of various actors and institutions, is essential to improving policy effectiveness and achieving equitable health systems. This scoping review examines the literature on policy processes, stakeholder influences, and contextual factors shaping policies for universal health system reforms.<br><br>METHODS: A systematic search of peer-reviewed and grey literature from 2014 to 2024 was conducted using five academic databases and Google Scholar. Seventy-four studies focused on policies for universal health systems in high and upper-middle-income countries. Data was examined in two phases. First, a descriptive analysis explored the geographic and economic contexts of the studies and their representation across stages of the policy cycle, including agenda-setting, formulation, adoption implementation, and evaluation. Topp et al.'s framework was then used to examine the influence of key actors, focusing on their relationships, power sources, and societal expressions of power.<br><br>RESULTS: The review revealed significant geographical disparities, representing only 30% of eligible countries. Most studies focused on early policy stages, with limited attention to implementation and evaluation. A predominance of qualitative research facilitated contextual insights, yet the underrepresentation of quantitative and mixed methods approaches restricted opportunities for integrated analysis. Crises and ideological shifts were drivers of policy momentum, catalysing changes in universal health system reforms. Governments played a central role, supported or contested by civic groups, professional associations, and academia. Media often influenced public discourse and policy perceptions, amplifying or challenging reform narratives. Persistent challenges included fragmented systems, equity-efficiency tensions, and definitional ambiguities, undermining policy coherence and sustainability.<br><br>CONCLUSIONS: The review underscores the need for a broader 'universal' framework for understanding health system reform and prioritising equity, quality, and sustainability. Adaptive health systems, robust institutions, and standardised frameworks to address political, economic, and ideological barriers are crucial. Future research must evaluate equity impacts, refine policy design, and explore mechanisms to align reforms with universal health system principles and goals.}, }
@article {pmid41291238, year = {2025}, author = {Li, H and Yu, C and Markovic, T and Nestler, EJ and Dong, Y}, title = {Chemical strategies for brain delivery of genomic therapy.}, journal = {Nature reviews. Chemistry}, volume = {}, number = {}, pages = {}, pmid = {41291238}, issn = {2397-3358}, abstract = {Genomic therapy has emerged as a transformative strategy for the prevention, diagnosis and treatment of a wide array of diseases, including Alzheimer's disease, amyotrophic lateral sclerosis and other CNS-related diseases. Recent developments in chemical strategies and delivery platforms have enhanced the potential of genomic therapies for brain disorders. In this Review, we summarize such strategies, focusing on advances in delivery platforms such as lipid nanoparticles, polymers and oligonucleotide conjugates to facilitate the brain delivery of DNA-based or RNA-based therapeutics into the CNS. We present an overview of the chemical structures and functional moieties of lipids, polymers and oligonucleotides used in these platforms. Lastly, we provide an outlook on future chemical directions to further improve the delivery of genomic medicines to the brain.}, }
@article {pmid41289739, year = {2025}, author = {Dakroub, F and Awada, B and Abdelhady, S and Shaito, AA and Eid, AH and Walker, J and Mondello, S and Bondi, CO and Moro, F and Elgendy, B and Wang, KK and Zanier, ER and Mechref, Y and Kobeissy, F}, title = {Edaravone: Advances on cytoprotective effects, pharmacological properties, and mechanisms of action.}, journal = {Pharmacological reviews}, volume = {78}, number = {1}, pages = {100101}, doi = {10.1016/j.pharmr.2025.100101}, pmid = {41289739}, issn = {1521-0081}, abstract = {Neurological diseases often lead to life-altering consequences, underscoring the urgent need for therapies that can reverse or mitigate their effects. Effective management of neurological disorders necessitates a thorough understanding of the common pathological mechanisms driving their onset and progression. Mitochondrial dysfunction and oxidative stress stand out as critical contributors to neuronal damage, implicated in traumatic brain injury, stroke, and amyotrophic lateral sclerosis. Disruptions in energy metabolism lead to the accumulation of reactive oxygen species and elevate the level of neural injury. Moreover, these imbalances disrupt cellular homeostasis and activate apoptotic pathways, further exacerbating neuronal loss and ultimately worsening the clinical prognosis. In this context, edaravone (Eda), a Food and Drug Administration-approved free radical scavenger, has emerged as a compelling candidate for the treatment of neuropathologies. This review provides a comprehensive overview of Eda, detailing its chemical structure and pharmacokinetic profile, with a focus on strategies to enhance its delivery to the central nervous system by modulating blood-brain barrier permeability or employing delivery systems that facilitate central nervous system penetration. Moreover, the review examines Eda's pharmacodynamic properties, including the signaling pathways it influences. The neurotherapeutic potential of Eda is further examined through in vitro and in vivo models of neurological disease. Insights from clinical trials are discussed to bridge the gap between preclinical findings and patient outcomes. Finally, the review highlights the synergistic effects of combining Eda with other pharmacological agents or therapeutic interventions, underscoring its promise as a versatile and indispensable treatment for neurological disorders. SIGNIFICANCE STATEMENT: Edaravone, a Food and Drug Administration-approved free radical scavenger, shows broad neuroprotective potential by mitigating oxidative stress and mitochondrial dysfunction across diverse neurological disorders, including stroke, amyotrophic lateral sclerosis, and traumatic brain injury. By synthesizing preclinical and clinical evidence, this review highlights edaravone's pleiotropic therapeutic actions, identifies translational challenges, and underscores its promise as a versatile treatment strategy for neurodegenerative and acute and chronic brain conditions.}, }
@article {pmid41287286, year = {2025}, author = {Prema, SS and Shanmugamprema, D}, title = {Empowering Parent-Focused Involvement in Early Detection and Treatment of Eating Disorders.}, journal = {European eating disorders review : the journal of the Eating Disorders Association}, volume = {}, number = {}, pages = {}, doi = {10.1002/erv.70060}, pmid = {41287286}, issn = {1099-0968}, abstract = {OBJECTIVE: To critically appraise Sidari et al.'s pilot evaluation of the Strong Foundations programme - a 6-week pre-treatment, family-centred intervention that reconceptualises the waitlist as an active window for support, and to assess whether scalable caregiver interventions can improve clinical outcomes and treatment engagement.<br><br>METHOD: Critical synthesis of the pilot study's design, implementation, and outcomes. The programme delivered structured psychoeducation to parents alongside specialist medical oversight for adolescents during the pre-treatment period. We summarise reported process and clinical indicators, assess methodological strengths and limitations, and explore adaptations such as digital delivery, peer co-facilitation and primary care integration within stepped-care frameworks.<br><br>RESULTS: Participating parents reported increased caregiving confidence and understanding of treatment pathways. Adolescents demonstrated preliminary improvements in BMI, affective symptoms and eating-disorder psychopathology. Strengths included focus on an overlooked treatment interval and integrated medical support; limitations included small sample size, absence of a control condition, selection bias, and brief follow-up. Proposed adaptations may increase scalability while preserving family-centred elements.<br><br>CONCLUSIONS: Reframing waitlists as active therapeutic intervals via brief, caregiver-focused interventions are promising for improving early outcomes, uptake and retention. Larger, controlled trials of condensed and digitally enabled formats are needed to establish effectiveness, cost-effectiveness, implementation feasibility and generalisability.}, }
@article {pmid41283496, year = {2025}, author = {D'Alatri, L and Marchese, MR and Tizio, A and Galli, J}, title = {Pathophysiology and Etiology of Brainstem-Related Dysphagia.}, journal = {Audiology research}, volume = {15}, number = {6}, pages = {}, pmid = {41283496}, issn = {2039-4330}, abstract = {BACKGROUND: Brainstem-related dysphagia represents a complex and severe form of neurogenic dysphagia (ND) arising from lesions that disrupt the central pattern generator (CPG) for swallowing located in the medulla oblongata.<br><br>METHODS: This paper explores the physiological basis of swallowing and its disruption in various brainstem pathologies.<br><br>RESULTS: The clinical presentation and electrophysiological evaluation of dysphagia are discussed, with a focus on volitional and spontaneous swallowing (SS) and the use of electromyography (EMG)-based assessment techniques.<br><br>CONCLUSIONS: Finally, therapeutic strategies are reviewed, including conventional rehabilitative methods, neuromuscular electrical stimulation, non-invasive brain stimulation, and invasive procedures such as neurobotulinum toxin-A (BoNT-A) injections, balloon dilation, and CP myotomy.}, }
@article {pmid41283303, year = {2025}, author = {Bartoshyk, P and O'Caoimh, R}, title = {Update on Disease-Modifying Pharmacological Treatments for Frontotemporal Dementia (FTD): A Scoping Review of Registered Trials.}, journal = {NeuroSci}, volume = {6}, number = {4}, pages = {}, pmid = {41283303}, issn = {2673-4087}, abstract = {Frontotemporal dementia (FTD) represents a cluster of adult-onset neurodegenerative diseases resulting from a combination of genetic and epigenetic factors. Currently, treatment is symptomatic and there are no licensed disease-modifying therapies available. The aim of this review was to provide an overview of ongoing or recently completed clinical studies targeting disease modification in FTD. A structured search of interventional trials of pharmacological compounds was conducted on three clinical trial registries (National Library of Medicine Clinical Trials, European Union Clinical Trials, and the Australian New Zealand Clinical Trials registries) up to September 2025. Twelve interventional trials were found. Half targeted autosomal-dominant progranulin (GRN) mutations (n = 6) and half examined therapies targeting neuroinflammatory-induced sporadic FTD (n = 6). The interim results of the early-phase (1/2) randomized controlled trials (RCTs), comprising three ongoing gene replacement studies (PROCLAIM, ASPIRE-FTD, upliFT-D) and one immune-modulating monoclonal antibody (INFRONT, now in phase 3)-all targeting the FTD-GRN mutation-show safety, tolerability, and effectiveness in restoring progranulin levels. Two recently completed phase 2 RCTs for sporadic FTD targeting neuroinflammation, the PEA-FTD and C9orf72 ALS/FTD trials, show disease-modifying potential. While interim results from six trials suggest clear mechanistic efficacy, prospective high-quality later-phase RCTs are required to ascertain long-term clinical efficacy. Since familial FTD encompasses less than half of the people with this disease, it is important to continue exploring the underlying pathophysiology, neuroimmunology, and treatment of epigenetic-induced sporadic FTD.}, }
@article {pmid40721287, year = {2025}, author = {Vyas, J and Johns, JR and Trivedi, A and Ali, FM and Ingram, JR and Salek, S and Finlay, AY}, title = {Systematic review of the use of the Dermatology Life Quality Index in routine clinical practice: evidence from 287 articles across 56 countries.}, journal = {Clinical and experimental dermatology}, volume = {50}, number = {12}, pages = {2456-2465}, doi = {10.1093/ced/llaf343}, pmid = {40721287}, issn = {1365-2230}, mesh = {Humans ; *Quality of Life ; *Skin Diseases/psychology ; *Dermatology ; }, abstract = {BACKGROUND: Although quality of life instruments are widely used in research, it is challenging to find evidence of their use in routine clinical use. The most widely used measure for skin disease burden is the Dermatology Life Quality Index (DLQI), and its scores have validated clinical meaning.<br><br>OBJECTIVES: To identify evidence of the use of the DLQI in routine clinical practice and explore the nature of its use.<br><br>METHODS: The study followed PRISMA guidelines, and the protocol was registered with PROSPERO. MEDLINE (Ovid), Embase, Scopus and CINAHL (EBSCO) databases were systematically searched for articles describing studies using the DLQI in routine clinical practice. Studies were excluded if participants were aged < 16&#x2005;years and if there were predetermined treatment interventions, as in a clinical trial. Information was extracted on publications' authors' opinions on the use of the DLQI in their routine practice.<br><br>RESULTS: In total, 2178 publications were screened and 287 articles met the inclusion criteria, reporting on 112 diseases and describing 66 434 patients from 56 countries, using the DLQI in at least 29 languages. Of the studies, 121 (42.2%) were reported as retrospective and 63 (22.0%) as observational. Fifty-two (18.1%) stated DLQI data were retrieved from patient records, 29 (10.1%) as 'real life', 39 (13.6%) reported 'real-world data' and 47 (16.4%) used consecutive patient recruitment. In total, 264 (92.0%) studies were conducted in a single country; 96 (33.4%) were multicentred studies, whereas 171 (59.6%) were conducted at a single site. There were 93 (32.4%) that were conducted in hospitals, 66 (23.0%) specified outpatient clinics, 38 (13.2%) tertiary care, 33 (11.5%) clinics, 4 (1.4%) in the community, 18 (6.3%) in other settings and 35 (12.2%) were unspecified. The most common diseases in the study settings were psoriasis (106 studies, 36.9%), atopic dermatitis (32, 11.1%), urticaria (24, 8.4%), hidradenitis suppurativa (22, 7.7%) and vitiligo (17, 5.9%). Thirty studies (10.5%) used Hongbo et al.'s (J Invest Dermatol 2005; 125:659-64) DLQI score banding.<br><br>CONCLUSIONS: The DLQI was widely used in routine care locations internationally, informing clinical decisions and monitoring of treatment. The DLQI was embedded into some clinics' continuing routine practice.}, }
@article {pmid41282495, year = {2025}, author = {Araújo, B and Serrenho, I and Valente da Silva, A and Marceta, BM and Baltazar, G}, title = {Mesenchymal stem cells in neurological disorders: Insights from clinical trials.}, journal = {Regenerative therapy}, volume = {30}, number = {}, pages = {1024-1035}, pmid = {41282495}, issn = {2352-3204}, abstract = {Mesenchymal stem cells (MSCs) exhibit unique properties that make them promising candidates for cell therapy, particularly in neurological disorders. They can be derived from various tissues, with bone marrow, adipose tissue, umbilical cord, and placenta being the most common sources. Evidence suggests that the tissue of origin significantly influences MSC characteristics, including secretome composition, proliferation rate, and adhesion capacity. Clinical trials have demonstrated the safety and therapeutic potential of MSCs in conditions such as spinal cord injury, multiple sclerosis, and stroke. MSC therapy has been associated with improvements in motor, sensory, and cognitive functions, as well as enhanced quality of life. Mechanistically, MSCs promote neuroprotection, reduce inflammation, and modulate immune responses. In spinal cord injury, intrathecal administration of adipose- and bone marrow-derived MSCs has led to significant functional recovery, with single high-dose treatments often yielding better outcomes than multiple lower doses. In amyotrophic lateral sclerosis, bone marrow-derived MSCs have shown potential in slowing disease progression, though higher doses do not always result in greater benefits. In multiple sclerosis, high doses of umbilical cord-derived MSCs improved quality of life and prevented disease progression, whereas lower doses of bone marrow-derived MSCs provided limited functional benefits. While MSC therapy is considered safe, patient responses vary, and a definitive correlation between administered dose and therapeutic effects remains elusive. The small number of studies using comparable protocols impedes comparison of other relevant factor, limits the drawing of conclusions and underscore the importance of developing standardized protocols to optimize MSC-based treatments and maximize their clinical efficacy.}, }
@article {pmid41277874, year = {2025}, author = {Ferreira-Junior, JR and de Lima Camandona, V and Barros, MH}, title = {From Yeast to Therapeutics: Modeling Neurodegenerative Diseases in Saccharomyces cerevisiae.}, journal = {Yeast (Chichester, England)}, volume = {}, number = {}, pages = {}, doi = {10.1002/yea.70008}, pmid = {41277874}, issn = {1097-0061}, support = {//This study was supported by grants and fellowships from Fundacao de Amparo a Pesquisa de Sao Paulo (FAPESP 2024/01152-3; 2023/14056-0), Conselho Nacional de Desenvolvimento Cient&#x131;fico e Tecnologico (CNPq 305054/2022-8), and Coordenacao de Aperfeicoamento de Pessoal de N&#x131;vel Superior-Brasil (CAPES-Finance Code 001)./ ; }, abstract = {Here, we review the use of Saccharomyces cerevisiae as a powerful model organism for studying cellular processes implicated in neurodegenerative disorders, including stress responses, proteostasis impairment, and vesicle trafficking defects. Over the last two decades, baker's yeast models have been developed for complex diseases such as Parkinson's, Alzheimer's, Huntington's, and Amyotrophic lateral sclerosis (ALS). Yeast cells expressing human proteins, such as amyloid-β, α-synuclein, huntingtin, and TDP-43, have become crucial tools for high-throughput drug screening aimed at counteracting disease progression. These yeast models have unveiled key components involved in the metabolism and toxicity of these proteins, enabling the identification of interacting partners and novel factors within each pathway. Importantly, these pathways were subsequently shown to be conserved in mammalian models. Furthermore, drug candidates identified using yeast models have provided significant leads for drug discovery, highlighting their potential for developing treatments for these neurodegenerative diseases.}, }
@article {pmid41277110, year = {2025}, author = {Lu, J and Di Florio, DN and Boya, P and Maday, S and Springer, W and Chu, CT}, title = {Autophagy and mitophagy at the synapse and beyond: implications for learning, memory and neurological disorders.}, journal = {Autophagy}, volume = {}, number = {}, pages = {1-43}, doi = {10.1080/15548627.2025.2581217}, pmid = {41277110}, issn = {1554-8635}, abstract = {The human brain is one of the most metabolically active tissues in the body, due in large part to the activity of trillions of synaptic connections. Under normal conditions, macroautophagy/autophagy at the synapse plays a crucial role in synaptic pruning and plasticity, which occurs physiologically in the absence of disease- or aging-related stressors. Disruption of autophagy has profound effects on neuron development, structure, function, and survival. Neurons are dependent upon maintaining high-quality mitochondria, and alterations in selective mitochondrial autophagy (mitophagy) are heavily implicated in both genetic and environmental etiologies of neurodegenerative diseases. The unique spatial and functional demands of neurons result in differences in the regulation of metabolic, autophagic, mitophagic and biosynthetic processes compared to other cell types. Here, we review recent advances in autophagy and mitophagy research with an emphasis on studies involving primary neurons in vitro and in vivo, glial cells, and iPSC-differentiated neurons. The synaptic functions of genes whose mutations implicate autophagic or mitophagic dysfunction in hereditary neurodegenerative and neurodevelopmental diseases are summarized. Finally, we discuss the diagnostic and therapeutic potentials of autophagy-related pathways.Abbreviations: AD: Alzheimer disease; ALS: amyotrophic lateral sclerosis; APP: amyloid beta precursor protein; ASD: autism-spectrum disorder; BDNF: brain-derived neurotrophic factor; BPAN: β-propeller protein associated neurodegeneration; CR: caloric restriction; ΔN111: deleted N-terminal region 111 residues; DLG4/PSD95: discs large MAGUK scaffold protein 4; ER: endoplasmic reticulum; FTD: frontotemporal dementia; HD: Huntington disease; LIR: LC3-interacting region; LRRK2: leucine rich repeat kinase 2; LTD: long-term depression; LTP: long-term potentiation; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; OMM: outer mitochondrial membrane; PD: Parkinson spectrum diseases; PGRN: progranulin; PINK1: PTEN induced kinase 1; PRKA/PKA: protein kinase cAMP-activated; PtdIns3P: phosphatidylinositol-3-phosphate; p-S65-Ub: ubiquitin phosphorylated at serine 65; PTM: post-translational modification; TREM2: triggering receptor expressed on myeloid cells 2.}, }
@article {pmid41276866, year = {2025}, author = {Raoufinia, R and Alyari, G and Nia, AT and Abbaszadegan, MR and Mahmoudi, A and Shafaeibajestan, S and Saburi, E and Tavakol-Afshari, J and Hassani, M and Jamali, F and Salari, S and Boroumand, AR and Rahimi, HR}, title = {Cutting-edge treatments in amyotrophic lateral sclerosis: the role of molecular pathogenesis in targeted therapies.}, journal = {Stem cell research &amp; therapy}, volume = {}, number = {}, pages = {}, doi = {10.1186/s13287-025-04781-w}, pmid = {41276866}, issn = {1757-6512}, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterized by the selective loss of motor neurons (MNs), leading to progressive muscle weakness, atrophy, and ultimately paralysis. This review provides a comprehensive overview of the molecular mechanisms underlying ALS pathogenesis, the genetic mutations associated with both familial and sporadic forms of the disease, and the latest therapeutic strategies aimed at mitigating disease progression. mutations in genes such as C9orf72, SOD1, TARDBP, and FUS have been implicated in ALS, with an intricate interplay of protein misfolding, oxidative stress, mitochondrial dysfunction, excitotoxicity, and neuroinflammation contributing to motor neuron degeneration. While current FDA-approved treatments such as Riluzole and Edaravone offer only modest benefits and do not significantly halt disease progression. Emerging therapies, including gene therapies (e.g., antisense oligonucleotides (ASOs) and CRISPR/Cas9, stem cell-based approaches, and neurotrophic factor supplementation, are demonstrating promising results in preclinical and early-phase clinical trials. novel approaches aim to target, modulate, and promote regeneration, renewed hope for future ALS treatments. However, several challenges remain, including effective delivery methods, safety concerns, and the inherent complexity of ALS pathology, ongoing research continues to explore these innovative interventions with the goal of improving clinical outcomes for patients. This review highlights the importance of personalized therapeutic approaches and underscores the necessity of continued innovation in ALS research, with the ultimate goal of developing disease-modifying therapies and, potentially, a cure for this fatal condition.}, }
@article {pmid41273627, year = {2025}, author = {Wang, W and Tan, S and Zuo, X and Gao, X and Ma, L and Sun, R and Liang, G and Yin, L and Pu, Y and Zhang, J}, title = {Brain Organoids in Neurodegenerative Disease Modeling: Advances, Applications and Future Perspectives.}, journal = {Molecular neurobiology}, volume = {63}, number = {1}, pages = {142}, pmid = {41273627}, issn = {1559-1182}, mesh = {*Organoids/pathology ; Humans ; *Neurodegenerative Diseases/pathology ; *Brain/pathology ; Animals ; Disease Models, Animal ; *Models, Biological ; }, abstract = {Neurodegenerative diseases (NDDs) represent incurable and debilitating conditions characterized by progressive deterioration of neurological function. Investigating neurodegeneration remains a critical global challenge in aging societies. Brain organoids-self-organizing three-dimensional structures derived from human pluripotent stem cells-recapitulate cell types and cytoarchitectures of the developing human brain. This in vitro model system has advanced our bridge between conventional two-dimensional cultures and in vivo models. Brain organoids emulate early neural tube formation, neuroepithelial differentiation, and whole-brain regionalization. Furthermore, region-specific organoid models now facilitate mechanistic investigation into acquired and inherited NDDs' pathogenesis, alongside drug discovery and toxicity screening. In this review, we (i) delineate the epidemiology and pathobiology of major NDDs, (ii) analyze limitations of current animal models, (iii) critically evaluate brain organoid generation methodologies, and (iv) focus on organoid applications in modeling Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS).}, }
@article {pmid41272780, year = {2025}, author = {Kumar, A and Shukla, S and Rai, A and Pathak, P and Narayan, KP}, title = {Concurrent nanotherapeutics and regulatory updates for the management of amyotrophic lateral sclerosis: a focused review for orphan drug (Tofersen).}, journal = {Orphanet journal of rare diseases}, volume = {20}, number = {1}, pages = {598}, pmid = {41272780}, issn = {1750-1172}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy ; Humans ; Genetic Therapy/methods ; Orphan Drug Production ; *Oligonucleotides/therapeutic use ; United States Food and Drug Administration ; }, abstract = {BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder affecting nerve cells in the brain and spinal cord. With a global incidence of 1.9 to 6 per 100,000 people, ALS is slightly more common in men and prevalent in individuals over 60. However, this review provides a concise update on the regulatory landscape and therapeutic advancements in managing ALS, focusing on the recent approval of Tofersen, the first gene therapy specifically targeting SOD1 mutation-related ALS.<br><br>RESULTS: It highlights Tofersen unique role as an orphan drug approved by the US FDA, emphasizing its mechanism of action, gene silencing and its impact on reducing neurodegeneration. Additionally, the review synthesizes data from ongoing clinical trials, pharmacovigilance reports, and case studies to comprehensively understand Tofersen's safety, efficacy and market exclusivity. Beyond this, it explores the emerging potential of nanotherapeutic approaches to ALS treatment, identifying critical research gaps and future directions.<br><br>CONCLUSION: Integrating regulatory updates, clinical evidence, and innovative therapeutic strategies, the review uniquely contributes to the ALS literature by bridging current treatment realities with potential future therapies, aiming to inform researchers, clinicians, and policymakers on optimizing ALS management.}, }
@article {pmid41269421, year = {2025}, author = {Asadinejad, H and Taherkhani, S and Golboos, SM and Azizi, Y and Mohammadkhanizadeh, A}, title = {Targeting Neurodegeneration with SGLT2is: From Molecular Mechanisms to Clinical Implications.}, journal = {Molecular neurobiology}, volume = {63}, number = {1}, pages = {119}, pmid = {41269421}, issn = {1559-1182}, mesh = {Humans ; *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/pharmacology ; Animals ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Neuroprotective Agents/therapeutic use/pharmacology ; }, abstract = {Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are a class of antidiabetic drugs that have demonstrated significant cardiovascular and renal benefits. Accumulating evidence suggests that SGLT2is also exert neuroprotective effects and may influence the progression of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). SGLT2is modulate glucose metabolism, reduce oxidative stress, suppress inflammation, and enhance mitochondrial function. Beyond glycemic control, they show potential therapeutic effects in ameliorating the metabolic dysregulation associated with neurodegenerative pathologies. Current preclinical and clinical evidence including metabolic regulation, anti-inflammatory actions, and neuroprotective effects mediated through SGLT2is associated molecular pathways have been critically evaluated to delineate their therapeutic potential in neurodegenerative disorders. Although preclinical studies have shown promising results, more clinical trials are needed. This review highlights key research gaps and proposes future translational applications.}, }
@article {pmid41268324, year = {2025}, author = {Thakur, DK and Padole, S and Sarkar, T and Arumugam, S and Chattopadhyay, S}, title = {Liquid-Liquid Phase Separation: Mechanisms, Roles, and Implications in Cellular Function and Disease.}, journal = {FASEB bioAdvances}, volume = {7}, number = {11}, pages = {e70054}, pmid = {41268324}, issn = {2573-9832}, abstract = {Liquid-liquid phase separation is a basic biophysical process that creates essential membraneless organelles that support different cellular activities, including chromatin organization and gene expression. The malfunction of liquid-liquid phase separation (LLPS) plays a critical role in numerous diseases, such as neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD), which involve TDP-43 and Tau, various cancers that utilize SPOP and YAP/TAZ proteins, and viral infections where pathogens use LLPS to replicate and avoid immune detection. This review brings together the fast-growing knowledge about LLPS across multiple scientific fields. The paper examines the physiological functions of LLPS along with its disease pathogenesis mechanisms and presents various experimental techniques (e.g., advanced microscopy, FRAP, FCS) for its investigation. It introduces new therapeutic approaches such as PTM modulation, small molecules like 1,6-hexanediol and Lipoamide, and advanced genetic tools including CRISPR and PROTACs like PSETAC, which also explores diagnostic applications. The thorough integration of knowledge presented here is essential to connect separate scientific findings while propelling research forward and turning LLPS discoveries into new biomedical developments.}, }
@article {pmid41263806, year = {2025}, author = {Kalkowski, K}, title = {[Genetic and Molecular Pathomechanisms of Amyotrophic Lateral Sclerosis and Therapeutic Perspectives – Current State of Knowledge].}, journal = {Postepy biochemii}, volume = {71}, number = {3}, pages = {252-259}, doi = {10.18388/pb.2021_599}, pmid = {41263806}, issn = {0032-5422}, mesh = {*Amyotrophic Lateral Sclerosis/genetics/therapy ; Humans ; Genetic Therapy ; Superoxide Dismutase-1/genetics ; C9orf72 Protein/genetics ; Mutation ; RNA-Binding Protein FUS/genetics ; DNA-Binding Proteins/genetics ; Protein Serine-Threonine Kinases/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease leading to progressive degeneration of motor neurons, muscle weakness and respiratory failure. Despite intensive research, the pathomechanisms of ALS have not been fully elucidated. This article presents the current state of knowledge on the genetic and molecular mechanisms of this disease, with a focus on mutations in the SOD1, C9ORF72, TARDBP, FUS, TBK1 genes, as well as recent discoveries in this area. Key pathogenetic processes are discussed, including disruption of RNA homeostasis, oxidative stress, mitochondrial dysfunction and protein aggregation. In addition, current therapeutic strategies are reviewed, including both registered drugs, such as riluzole and edaravone, and modern approaches, such as gene therapy, antisense oligonucleotides, immunotherapy and gene editing technologies, including CRISPR/Cas9. Special attention was given to clinical trials and their potential impact on future treatment options for ALS.}, }
@article {pmid41260310, year = {2025}, author = {Alberti, C and Parente, V and Corti, S and Sansone, VA}, title = {From molecular convergence to clinical divergence: Comparative pathogenic mechanisms and therapeutic trajectories in C9orf72-ALS/FTD and myotonic dystrophy.}, journal = {Neurobiology of disease}, volume = {217}, number = {}, pages = {107192}, doi = {10.1016/j.nbd.2025.107192}, pmid = {41260310}, issn = {1095-953X}, abstract = {Short tandem repeat expansions in C9orf72, DMPK, and CNBP genes cause amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) and myotonic dystrophy types 1 and 2 (DM1/DM2), respectively. Despite distinct clinical phenotypes, these disorders share convergent molecular mechanisms with tissue-specific vulnerability, offering a framework to inform precision therapeutic strategies. Shared pathogenic features include nuclear RNA foci sequestering RNA-binding proteins that disrupt splicing, and repeat-associated non-AUG translation generating toxic dipeptide repeat proteins. In C9orf72, GGGGCC repeats form RNA-driven condensates, including protein-free condensates, via G-quadruplex formation. Evidence also implicates autophagy-lysosome and mitochondrial dysfunction, suggesting a potential "two-hit" loss/gain-of-function model. Clinically, C9orf72 expansions primarily affect motor neurons and frontotemporal circuits, with ALS progression typically occurring over 2-5 years. Conversely, myotonic dystrophy manifests as a muscle-predominant multisystem disorder progressing over decades. Genomic instability contributes to disease variability, with anticipation and parent-of-origin effects strongest in DM1, not confirmed in DM2 and controversial in C9orf72. Sequence interruptions modulate repeat stability and phenotype, influencing diagnostic interpretation. Therapeutic development has yielded contrasting outcomes. Antisense oligonucleotides targeting C9orf72 achieved target engagement and reduced dipeptide repeat proteins but failed clinically, potentially due to sense-strand selectivity and persistence of TDP-43 pathology. In contrast, RNA-targeting conjugates for DM1 (delpacibart etedesiran and DYNE-101) received FDA Breakthrough Therapy designation. Therapeutic success depends on tissue accessibility and addressing both shared and circuit-specific pathogenic cascades. While nuclear RNA targets appear druggable in myotonic dystrophy, the bidirectional transcription and compartmentalized pathology of C9orf72 ALS/FTD may require multi-targeted approaches for precision medicine.}, }
@article {pmid41258317, year = {2025}, author = {Wang, S and Zhang, X and Zhang, }, title = {Charting the landscape and evolution of research on cell death in acute lymphoblastic leukemia: a comprehensive bibliometric analysis (1990-2024).}, journal = {Discover oncology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s12672-025-04102-w}, pmid = {41258317}, issn = {2730-6011}, abstract = {BACKGROUND: The interplay between regulated cell death pathways and Acute Lymphoblastic Leukemia (ALL) pathobiology profoundly influences disease progression and therapeutic responses.<br><br>OBJECTIVE: This study performs a comprehensive bibliometric analysis to delineate the historical trajectory, current status, and emerging research frontiers concerning cell death in ALL from 1990 to 2024.<br><br>METHODS: This bibliometric analysis maps global research on cell death in ALL (1990-2024) using 4,111 publications from the Web of Science Core Collection using search terms related to cell death and ALL. VOSviewer and CiteSpace were utilized to analyze publication trends, geographical and institutional distributions, international collaborations, journal and author productivity and impact, co-citation networks (references, authors, journals), and keyword co-occurrence, clusters, and citation bursts.<br><br>RESULTS: Publications grew slowly (1990-1992), expanded rapidly (1993-2015, peak in 2015), then moderated. The United States dominated research output (33.69% publications, 68.41 citations/paper) and collaborated strongly with China, Italy, and the UK. The University of Texas System was the most productive institution (153 articles). Blood ranked first in publications (236) and co-citations (3403). Uckun authored the most papers (31), while Pui was the most co-cited author (736 co-citations). Keyword clusters revealed evolving foci: from apoptosis (1990s) to BH3-only proteins (2000s), with current frontiers in &#x200b;ferroptosis, CAR-T cells, and drug resistance. Terwilliger et al.'s review showed the strongest citation burst.<br><br>CONCLUSION: This study dilineates the intellectual landscape of cell death research in ALL, highlighting ferroptosis, immunotherapy integration, and resistance mechanisms as critical future directions to improve therapeutic outcomes.}, }
@article {pmid41251254, year = {2025}, author = {Staehr-Rye, AK and Küchen, SHL and Salvesen, L and Blicher, J and Strange, DG and Svenstrup, K}, title = {[Chronic respiratory insufficiency in amyotrophic lateral sclerosis].}, journal = {Ugeskrift for laeger}, volume = {187}, number = {44}, pages = {}, doi = {10.61409/V03250140}, pmid = {41251254}, issn = {1603-6824}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/therapy/physiopathology ; *Respiratory Insufficiency/therapy/etiology/physiopathology ; Respiration, Artificial/methods ; Chronic Disease ; Noninvasive Ventilation ; Quality of Life ; }, abstract = {Amyotrophic lateral sclerosis is a neurodegenerative disease characterized by progressive loss of motor neurons in the brain and spinal cord. As the disease progresses, respiratory function becomes increasingly compromised. Supporting respiratory function is the treatment with the greatest potential impact on life expectancy and should align with the patient's wishes to ensure quality of life. Optimal secretion management is essential for effective non-invasive mechanical ventilation therapy, as argued in this review. Home invasive mechanical ventilation is reserved for a small subset of patients.}, }
@article {pmid41250117, year = {2025}, author = {Kulcsárová, K and Piel, JHA and Schaeffer, E}, title = {Environmental toxins in neurodegeneration - a narrative review.}, journal = {Neurological research and practice}, volume = {7}, number = {1}, pages = {93}, pmid = {41250117}, issn = {2524-3489}, abstract = {As the global incidence of neurodegenerative disorders rises at a rate beyond what can be attributed solely to population aging, the role of modifiable risk factors has come into research spotlight to inform preventive strategies. While many lifestyle interventions can be implemented at an individual level, addressing environmental pollutants that drive neurodegeneration requires a collective effort involving both public and political engagement. This narrative review summarizes current evidence on the role of selected environmental toxins-pesticides, solvents, air pollution, and heavy metals-in the development of Parkinson's Disease, Alzheimer's Disease, and Amyotrophic Lateral Sclerosis. Drawing from epidemiological and experimental studies, we highlight associations between these exposures and neurodegeneration, as well as potential converging pathophysiological mechanisms such as neuroinflammation and proteinopathy. Understanding these links may help inform public health measures aimed at reducing the burden of these diseases.}, }
@article {pmid41099526, year = {2025}, author = {Lami, R}, title = {From biocides to biology: multispecies biofilms as a sustainable, self-regenerating, and effective antifouling strategy.}, journal = {Applied and environmental microbiology}, volume = {91}, number = {11}, pages = {e0160925}, doi = {10.1128/aem.01609-25}, pmid = {41099526}, issn = {1098-5336}, mesh = {*Biofilms/drug effects/growth &amp; development ; *Disinfectants/pharmacology ; *Biofouling/prevention &amp; control ; Bacteria/drug effects ; }, abstract = {Finding antifouling strategies that are effective and environmentally safe remains a central challenge for maritime operations and ecosystem protection. Amador et al.'s article in Applied and Environmental Microbiology (91:e01392-25, 2025, https://doi.org/10.1128/aem.01392-25) proposes a bioinspired, applied-microbial-ecology solution: deliberately shaping pioneer biofilm communities, so they form a physical barrier against macrofouler settlement, avoiding biocides and low-adhesion inert coatings. Though focused on the ocean, this paradigm could inform broader anti-biofilm interventions across microbiology, reframing control as ecological steering rather than chemical suppression or materials-based design.}, }
@article {pmid41248812, year = {2025}, author = {Di Nunzio, M and Mignogna, ML and Bacigaluppi, M and Panina-Bordignon, P and Ragonese, P and Muzio, L and Summa, V and Martino, G}, title = {The role of dopaminergic signalling from physiology to neuroprotection in acute and chronic disorders.}, journal = {Neurobiology of disease}, volume = {}, number = {}, pages = {107194}, doi = {10.1016/j.nbd.2025.107194}, pmid = {41248812}, issn = {1095-953X}, abstract = {The dopaminergic system plays a central role in neuromodulation, involving motor control, reward, and cognition, and exerting its effects through five G protein-coupled receptors (DRD1-DRD5) with distinct tissue distributions and signalling mechanisms. While dopaminergic alterations are known to be associated to neuropsychiatric and movement disorders such as schizophrenia, Parkinson's disease, and Huntington's disease, growing evidence highlights a broader role in neurological and neurodegenerative conditions. This review explores the dopaminergic system's pathophysiological involvement in acute and chronic diseases such as stroke, spinal cord (SCI), traumatic brain (TBI) injury, and amyotrophic lateral sclerosis (ALS). Beyond characterizing its dysfunction, we aim to examine how this disrupted signalling contributes to the neurodegeneration underlying the neurological and neurodegenerative disorders discussed here, along with the associated pathophysiological factors of inflammation and altered plasticity. We further discuss emerging data supporting the potential of dopamine-based interventions not only to modulate disease mechanisms, but also to confer neuroprotection and reduce tissue damage in both acute and progressive neurodegeneration, while also considering sex-related dopamine alterations. By integrating findings across diverse conditions, we underscore the importance of advancing dopaminergic research beyond classical disease models into novel therapeutic territory.}, }
@article {pmid41246746, year = {2025}, author = {Bethea, JP and Sharma, H and Doberstein, N and Shenker, T and Gregory, B and Hoffman, R and Aizenman, D and Guirguis, G and Hoffmann, J and Tazani, S and Harris, Z and Costin, J}, title = {Application of Osteopathic Manipulative Treatment (OMT) in Neurodegenerative Disorders: A Scoping Review.}, journal = {Cureus}, volume = {17}, number = {10}, pages = {e94748}, doi = {10.7759/cureus.94748}, pmid = {41246746}, issn = {2168-8184}, abstract = {Neurodegenerative diseases are comprised of a host of chronic conditions that impair the central nervous system. Osteopathic manipulative treatment (OMT) consists of many non-invasive modalities that can be used to treat a wide variety of ailments and conditions. OMT is reported to increase the range of motion and lymphatic flow, as well as decrease pain in a wide array of disorders. However, the efficacy of using OMT in neurodegenerative disorders has not been well established. The objective of this scoping review is to map the evidence that pertains to the application of OMT in treating neurodegenerative disorders and identify the gaps in the literature on this subject. This study was designed according to the Joanna Briggs Institute (JBI) guidelines for scoping reviews to gather information on OMT's potential efficacy in managing Parkinson's disease (PD), Alzheimer's disease (AD) dementia, amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD). Peer-reviewed literature was collected through the Excerpta Medica database (EMBASE), Ovid Medical Literature Analysis and Retrieval System Online (MEDLINE), and Web of Science. The criteria were limited to papers in English published between 1999 and 2023. The following search string was utilized: "osteopathic manipulative treatment" OR "osteopathic manipulation" AND "neurodegenerative disorders" OR "Alzheimer's disease" OR "dementia" OR "amyotrophic lateral sclerosis" OR "Parkinson's disease" OR "Huntington's chorea". One hundred and forty-three articles were identified following final screening and critical appraisal, with eleven articles selected for analysis in this study. Data from the selected articles demonstrated that OMT can possibly attenuate symptoms in patients diagnosed with neurodegenerative diseases. Studies in rats showed that OMT techniques were found to alter cholinergic neuronal genes, improve spatial learning and memory, reduce amyloid β protein levels, modulate synaptic transmission, and increase levels of the cytokines IL-1, IL-10, IL-13, RANTES, IL-17A, and EOTAXIN effects in AD dementia. ALS patients demonstrated a high level of satisfaction with OMT and did not report any adverse effects, though there was no decrease in pain or increased quality of life reported. PD patients reported improved postural stability, balance, and gait after OMT. No results were returned regarding OMT's effects on HD. Preliminary results in human PD and ALS patients who received OMT as an adjunct to traditional treatment regimens showed promising results, though few studies were found that address the topic, and the sample sizes of the studies that were found were small. There were no studies of the effects of OMT on human patients with AD or HD found, though preclinical studies in rats supported their trial in subsequent human studies. While current research on the impact of OMT on these neurodegenerative diseases is promising, there remain large gaps in the literature. Further research is necessary to support the use of and long-term efficacy of OMT in neurodegenerative diseases.}, }
@article {pmid41246229, year = {2025}, author = {Şahin, T&#xd6; and Cemali, &#xd6; and Özdemir, M and Ayten, &#x15e; and Ağagündüz, D}, title = {Flavonoids and phenolic compounds: a promising avenue for neurodegenerative disease therapy.}, journal = {Turkish journal of biology = Turk biyoloji dergisi}, volume = {49}, number = {5}, pages = {635-659}, doi = {10.55730/1300-0152.2767}, pmid = {41246229}, issn = {1303-6092}, abstract = {BACKGROUND/AIM: Neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, and ALS are characterized by a progressive loss of nerve cells, for which no definitive cure currently exists. These conditions share common pathological mechanisms, including chronic neuroinflammation, oxidative stress, protein aggregation, and mitochondrial dysfunction. Flavonoids and other plant-derived phenolic compounds have recently attracted attention for the treatment of such conditions due to their antiinflammatory and antioxidant properties. This review explores the neuroprotective mechanisms of flavonoids and evaluates their potential for the prevention and treatment of neurodegenerative diseases.<br><br>MATERIALS AND METHODS: A literature search of the Web of Science, PubMed, and ScienceDirect databases was conducted to evaluate the therapeutic potential of flavonoids and phenolic compounds against neurodegenerative diseases. The search terms included "polyphenols", "flavonoids", and related compounds, along with "Alzheimer's", "Parkinson's", "Huntington's", and "Amyotrophic lateral sclerosis". Eligible studies included clinical trials, randomized controlled trials, and in vitro and in vivo research published in English. Priority was given to studies from the last decade, although older but significant publications were also included.<br><br>RESULTS: The findings of multiple studies report the ability of flavonoid compounds such as quercetin, myricetin, apigenin, and epigallocatechin gallate (EGCG) to modulate critical signaling pathways, reduce oxidative stress, prevent the accumulation of neurotoxic proteins, and support mitochondrial function. These bioactive molecules have exhibited significant potential in slowing disease progression and preserving neuronal integrity. Their therapeutic application, however, has been limited by their poor bioavailability, low stability, and rapid metabolism.<br><br>CONCLUSION: Flavonoids have shown promise as naturally derived agents with multi-targeted activity against neurodegenerative processes. Enhancing their absorption and stability through novel delivery systems and structural modifications could significantly improve their clinical efficacy. When administered early or as a complementary therapy, flavonoids can be considered a safe and effective approach to the management of neurodegenerative diseases.}, }
@article {pmid41245603, year = {2025}, author = {Almalki, S and Salama, M and Taylor, MJ and Ahmed, Z and Tuxworth, RI}, title = {FUS-related amyotrophic lateral sclerosis-frontotemporal dementia and links to the DNA damage response: a systematic review.}, journal = {Frontiers in molecular neuroscience}, volume = {18}, number = {}, pages = {1671910}, doi = {10.3389/fnmol.2025.1671910}, pmid = {41245603}, issn = {1662-5099}, abstract = {Mutations in Fused in Sarcoma (FUS) are associated with neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). This systematic review examined the connections between DNA damage in the central nervous system (CNS), dysfunction of DNA repair processes and the FUS proteinopathy. Twelve peer-reviewed publications were analyzed, investigating this question across a range of models, including immortalized cell lines, ALS-FTD patient-derived induced pluripotent stem cells, mouse tissues and post-mortem samples from ALS-FTD patients. The studies also explored the impact of inducing DNA damage using several agents, including calicheamicin and etoposide, on FUS pathology. Our findings indicated that accumulated DNA damage was documented in all twelve studies, with a key finding being the disruption of interactions between FUS and the DNA damage response (DDR). FUS interactions with various DDR and DNA repair proteins involved in sensing DNA damage and executing the major repair pathways were impaired, resulting in elevated levels of DNA damage in both the nucleus and mitochondria. Therefore, FUS is an essential protein for the preservation of genomic integrity and this loss of genome stability is likely to be a key contributor to the neurodegeneration in ALS-FTD.}, }
@article {pmid41239797, year = {2025}, author = {Garg, N and Dhankhar, S and Dhariya, A and Parkash, C and Chauhan, S and Singh, TG}, title = {Role of Liposomes in the Treatment of Neurodegenerative Disorders: A Comprehensive Review.}, journal = {Central nervous system agents in medicinal chemistry}, volume = {25}, number = {4}, pages = {496-512}, pmid = {41239797}, issn = {1875-6166}, mesh = {Humans ; *Liposomes/metabolism/chemistry ; *Neurodegenerative Diseases/drug therapy/metabolism ; Animals ; *Drug Delivery Systems/methods ; *Neuroprotective Agents/administration &amp; dosage/therapeutic use ; Blood-Brain Barrier/metabolism/drug effects ; }, abstract = {The complex etiology and limited therapy options of neurodegenerative illnesses pose daunting challenges to modern medicine. Nonetheless, novel treatment approaches have exciting new possibilities because of developments in nanotechnology. Liposomes have garnered a lot of interest as a potential treatment for neurological illnesses due to the fact that they are able to adapt to their role as nanocarriers. This review article discusses various uses of liposomes, including their ability to help treat neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's disease, as well as their diagnostic and neuroprotective uses. Liposomes allow for the targeted delivery of medicines to specific brain areas with minimal systemic side effects since they encapsulate and carry therapeutic molecules across the blood-brain barrier. Due to the fact that they are biocompatible, have surface features that can be adjusted, and have the ability to co-deliver many drugs, liposomes are excellent candidates for combination therapy and personalized medicine procedures. In spite of this, there is a growing body of research that suggests liposomes could serve as a versatile platform for the improvement of neurodegenerative disease treatment. This is a positive sign for the future results of patients and their quality of life.}, }
@article {pmid40972307, year = {2026}, author = {Singh, S and Mohammed, AS and DeJonge, J and Puskoor, AV and Desai, R and Ghani, MU and Ghantasala, P and Fattal, PG and Sareen, N}, title = {Impact of moderate to severe tricuspid regurgitation on long-term clinical outcomes in heart failure: A systematic review and meta-analysis of 456,353 patients.}, journal = {Heart &amp; lung : the journal of critical care}, volume = {75}, number = {}, pages = {90-97}, doi = {10.1016/j.hrtlng.2025.09.015}, pmid = {40972307}, issn = {1527-3288}, mesh = {Humans ; *Tricuspid Valve Insufficiency/complications/mortality/physiopathology ; *Heart Failure/mortality/complications/physiopathology ; Severity of Illness Index ; Global Health ; Hospitalization/statistics &amp; numerical data ; Time Factors ; }, abstract = {INTRODUCTION: Tricuspid regurgitation (TR) may have detrimental effects on heart failure (HF) patients clinically. We aimed to study the impact of severity of TR on the long-term outcomes in patients with HF.<br><br>OBJECTIVES: To understand the association between moderate-to-severe TR and long-term clinical outcomes, including mortality and HF-related hospitalizations, in adults with HF.<br><br>METHODS: We screened PubMed, SCOPUS, and Google Scholar databases up to May 2024 using appropriate keywords. Pooled odds ratios (OR) and confidence intervals (95 % CI) were estimated using a binary random effects model. Heterogeneity was assessed using I2 statistics, and a leave-one-out analysis was performed.<br><br>RESULTS: Ten studies with 456,353 HF patients were included. The mean age was 71.2 years. Severe TR showed a significant association with higher odds of 1-year mortality (OR=1.25 [1.02-1.52], p = 0.03; I2=78.15 %), 2-year mortality (OR=1.63 [1.28-2.09], p < 0.01; I2=0 %), HF hospitalization (OR=1.39 [1.14-1.71], p < 0.01; I2=61.58 %), and composite events (OR=1.44 [1.10-1.88], p < 0.01; I2=73.46 %). However, it showed no association with cardiovascular deaths (OR=1.35 [0.82-2.24], p = 0.24; I2=78.31 %). Upon performing a leave-one-out sensitivity analysis, we found that excluding Adamo et al.'s 2024 study changed the overall OR to 1.34 (95 % CI: 1.29, 1.39), indicating its influence on the estimate.<br><br>CONCLUSION: Severe TR is associated with a higher risk of 1-year and 2-year mortality, HF hospitalizations, and composite events among HF patients. Therefore, HF patients with comorbid TR should be promptly screened and managed [Figure 1].}, }
@article {pmid41239791, year = {2025}, author = {Bassi, P and Rana, S and Sapra, V and Raina, A and Kumar, P and Devi, S}, title = {Exploring Novel Therapeutic Avenues: Drug Repurposing for Neurodegenerative Movement Disorders.}, journal = {Current drug research reviews}, volume = {17}, number = {3}, pages = {375-393}, pmid = {41239791}, issn = {2589-9783}, mesh = {Humans ; *Drug Repositioning/methods ; *Neurodegenerative Diseases/drug therapy ; Animals ; *Movement Disorders/drug therapy ; }, abstract = {Neurodegenerative movement disorders, encompassing conditions such as Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, represent a significant burden on individuals, families, and healthcare systems globally. Traditional drug discovery approaches for these disorders have encountered challenges, including high costs and lengthy timelines. Drug repurposing has emerged in recent years as a promising approach to expedite the discovery of new treatments by leveraging existing drugs approved for other indications. This review explores the landscape of drug repurposed for neurodegenerative movement disorders, highlighting promising candidates, underlying mechanisms, and clinical implications. The rationale behind repurposing, including the advantages of utilizing existing pharmacological agents with established safety profiles and known pharmacokinetics, along with techniques utilized for repurposing (computational and experimental), have been elaborated. Several studies on the potential of pre-existing drugs such as isradipine, tetracycline, ambroxol, metformin, deferiprone, simvastatin, etc., which have been repurposed for neurodegenerative movement disorders, including Parkinson's disease, Huntington's disease, Alzheimer's disease, Multiple Sclerosis, etc. have been discussed. Further, the current scenario and future prospective of drug repurposing have also been touched upon.}, }
@article {pmid41238318, year = {2025}, author = {Soriani, MH and Blasco, H and Corcia, P and Danel-Brunaud, V and Desmaison, A and Pradat, PF and Querin, G and Vourch, P and Guy, N}, title = {Markers of presymptomatic amyotrophic lateral sclerosis: State of the art, practical implications and perspectives.}, journal = {Revue neurologique}, volume = {181}, number = {9}, pages = {893-908}, doi = {10.1016/j.neurol.2025.07.008}, pmid = {41238318}, issn = {0035-3787}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics/therapy/blood ; *Biomarkers/analysis/blood ; C9orf72 Protein/genetics ; Superoxide Dismutase-1/genetics ; Mutation ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with an identified genetic origin in 10-15% of cases, mainly involving C9orf72 and SOD1 mutations. The increasing number of genetically confirmed ALS cases has led to a growing identification of asymptomatic mutation carriers. While riluzole remains the standard treatment, mutation-specific therapies such as tofersen, that was recently approved in SOD1-ALS, are emerging. In this context, the identification of presymptomatic biomarkers is crucial for monitoring genetically at-risk individuals. Plasma neurofilament light chain can increase up to 3.5years before symptom onset in C9orf72 carriers. Metabolic and neuroimaging alterations together with cognitive or behavioral changes, that are sometimes detectable decades prior to diagnosis, have also been observed. These biomarkers may support early surveillance and intervention strategies. The present review provides an overview of current evidence on presymptomatic biomarkers in ALS mutation carriers and their potential role in genetic counseling, monitoring, and early therapeutic decisions.}, }
@article {pmid38879765, year = {2025}, author = {Sharma, A and Kakkar, A and Khanna, M and Devi, S}, title = {Arbutin's Potential in Neuroprotection: A Promising Role in Mitigating Neurodegenerative Diseases.}, journal = {Current drug research reviews}, volume = {17}, number = {3}, pages = {343-351}, pmid = {38879765}, issn = {2589-9783}, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy ; *Neuroprotective Agents/pharmacology/therapeutic use/pharmacokinetics ; *Arbutin/pharmacology/therapeutic use/pharmacokinetics ; Animals ; Oxidative Stress/drug effects ; Blood-Brain Barrier/metabolism ; Neuroprotection/drug effects ; }, abstract = {Naturally occurring glycosylated hydroquinone Arbutin, has drawn interest due to its possible function in reducing the risk of neurodegenerative diseases such as Huntington's disease, amyotrophic lateral sclerosis, Parkinson's disease, and Alzheimer's disease. Arbutin is well-known for its anti-inflammatory and antioxidant properties, which are essential in preventing oxidative stress and neuroinflammation. Research has shown that arbutin might alter important physiological pathways connected to protein misfolding, synapse function, and neuronal survival processes linked to the development of neurodegenerative diseases. Arbutin can also penetrate the blood- -brain barrier, which increases its therapeutic potential. Arbutin's neuroprotective properties and promise as a therapeutic agent for neurodegenerative illnesses are summarized in this review, which also emphasizes the need for further study into the molecular processes behind these effects.}, }
@article {pmid41238313, year = {2025}, author = {Rival, M and Thouvenot, E}, title = {Tracing Neurological Diseases in the presymptomatic phase: moving forward a detection panel.}, journal = {Revue neurologique}, volume = {181}, number = {9}, pages = {821-828}, doi = {10.1016/j.neurol.2025.08.004}, pmid = {41238313}, issn = {0035-3787}, mesh = {Humans ; Biomarkers/analysis ; *Nervous System Diseases/diagnosis ; Neurodegenerative Diseases/diagnosis ; Early Diagnosis ; Disease Progression ; *Prodromal Symptoms ; Asymptomatic Diseases ; }, abstract = {Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS) often exhibit a prolonged presymptomatic phase during which neuropathological changes silently progress. Recent advances in biomarker research have revealed molecular and imaging signatures that precede clinical onset by years, offering a critical window for early intervention. This review synthesizes current knowledge on the most promising presymptomatic biomarkers across these conditions, highlighting their biological origins, diagnostic performance, and clinical utility. Particular emphasis is placed on the development and validation of biomarker panels, which combine multiple markers to enhance diagnostic sensitivity and specificity, enabling more accurate detection of disease in its earliest stages. Minimally invasive approaches, such as blood-based assays, are also discussed for their potential to facilitate widespread screening and longitudinal monitoring. As these biomarkers begin to integrate into clinical workflows, particularly in AD and MS, international collaboration will be essential to standardize methodologies and ensure equitable implementation. Ultimately, presymptomatic biomarkers hold transformative potential for shifting neurology toward a proactive and precision-based paradigm.}, }
@article {pmid41238191, year = {2025}, author = {Yang, Y and Wang, Q and Wang, Z and Wang, Y and Liu, B and Zhang, Y and Mao, X and Sun, H}, title = {The Role of Fatty Acids in Neurodegenerative Diseases: Mechanistic Insights and Therapeutic Strategies.}, journal = {Journal of lipid research}, volume = {}, number = {}, pages = {100944}, doi = {10.1016/j.jlr.2025.100944}, pmid = {41238191}, issn = {1539-7262}, abstract = {Fatty acids (FAs) play multifaceted roles in neurodegenerative diseases (NDDs), including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). This review systematically summarizes current understanding of fatty acid metabolism and its diverse implications in NDD pathology. Short-chain fatty acids (SCFAs), primarily generated by gut microbiota, regulate neuroinflammation, gut-brain communication, and blood-brain barrier (BBB) integrity via epigenetic modifications and immune modulation. Medium-chain fatty acids (MCFAs) exhibit therapeutic potential by improving energy metabolism and neuromuscular function, particularly in ALS models. Long-chain polyunsaturated fatty acids (PUFAs), notably docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), contribute to neuronal membrane integrity, synaptic plasticity, and antioxidant defense, mitigating oxidative stress and neuroinflammation. Conversely, saturated and certain n-6 fatty acids may exacerbate neurodegeneration through pro-inflammatory and oxidative pathways. Emerging evidence highlights fatty acid involvement in key pathological processes such as lipid peroxidation, mitochondrial dysfunction, ferroptosis, and BBB disruption. Therapeutically, targeted supplementation, dietary modification, microbiome manipulation, and advanced nanotechnology-based delivery systems are promising strategies. Nevertheless, precise therapeutic efficacy depends critically on disease stage, dosage, genetic background, and individual metabolic context. Integrating personalized medicine with precision nutritional strategies and novel drug-delivery platforms offers promising avenues to translate fatty acid-based interventions into clinical practice, potentially improving patient outcomes in the aging global population.}, }
@article {pmid41238102, year = {2025}, author = {Long, J and Liu, S and Shi, Y and Zhang, C and Qin, L and Ai, Q}, title = {Targeting lipid metabolism in neurodegenerative diseases: From experimental to clinical.}, journal = {Metabolism: clinical and experimental}, volume = {}, number = {}, pages = {156436}, doi = {10.1016/j.metabol.2025.156436}, pmid = {41238102}, issn = {1532-8600}, abstract = {The human brain, despite accounting for only 2 % of total body weight, exhibits an exceptionally high lipid content (approximately 20 % of its mass), highlighting the critical role of lipid metabolism in maintaining neural homeostasis and function. Neurodegenerative diseases-including Alzheimer's disease (AD), Parkinson's disease (PD), stroke, Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS)-are characterized by progressive neuronal dysfunction and myelin degeneration. These conditions predominantly affect aging populations and represent a growing global health challenge. While aging remains the primary risk factor, compelling evidence now underscores the involvement of dysregulated lipid metabolism in their pathogenesis. However, the precise mechanisms linking dynamic lipid metabolic alterations to disease progression remain incompletely elucidated. This review systematically examines the multifaceted contributions of lipid metabolism to neurodegenerative processes and critically assesses emerging therapeutic strategies that target lipid pathways for the treatment of neurodegenerative disorders.}, }
@article {pmid41234489, year = {2025}, author = {Chan, JM and Romano, C and Lee, AY and Wang, S and Lombardo, D and Kamdar, F and Dora, M and Khan, S and Mammen, P and Kimonis, V}, title = {Cardiomyopathy in valosin-containing protein multisystem proteinopathy: Evaluation, diagnosis, and management.}, journal = {American heart journal plus : cardiology research and practice}, volume = {60}, number = {}, pages = {100644}, pmid = {41234489}, issn = {2666-6022}, abstract = {Valosin-containing protein (VCP)-associated multisystem proteinopathy is a rare, autosomal dominant disease that affects skeletal muscle, bone, central nervous system, and the heart. While VCP mutations are well established as causing inclusion body myopathy, Paget's disease of bone, frontotemporal dementia, and amyotrophic lateral sclerosis, their role in cardiomyopathy remains underrecognized. This review aims to evaluate the pathophysiology, diagnostic approach, and management of VCP-associated cardiomyopathy to provide a framework for clinical care and future research. Emerging evidence from animal models and human case studies suggests that VCP dysfunction disrupts cardiomyocyte homeostasis, impairs protein degradation, and alters mitochondrial function, leading to maladaptive cardiac remodeling and susceptibility to dilated or hypertrophic cardiomyopathy. Echocardiographic studies in patients with VCP variants reveal a significant prevalence of diastolic dysfunction, conduction abnormalities, and variable degrees of systolic impairment. Despite these findings, there are no standardized guidelines for the diagnosis and management of VCP-associated cardiomyopathy. Current treatment strategies are extrapolated from heart failure guidelines, incorporating neurohormonal blockades with angiotensin-converting enzyme inhibitors, beta-blockers, and mineralocorticoid receptor antagonists. Our review highlights the need for systematic screening protocols, genotype-phenotype correlation studies, and the development of targeted therapies. Future research should focus on identifying biomarkers for early detection, elucidating the molecular mechanisms underlying cardiac dysfunction, and assessing the efficacy of novel treatment strategies. Recognizing VCP-associated cardiomyopathy as a distinct clinical entity will facilitate earlier diagnosis, improve patient outcomes, pave the way for disease-specific therapeutic interventions and insights into the mechanism for isolated cardiomyopathy.}, }
@article {pmid41229731, year = {2025}, author = {Nasir, AR and Delpirou Nouh, C}, title = {TDP-43-proteinopathy at the crossroads of tauopathy: on copathology and current and prospective biomarkers.}, journal = {Frontiers in cellular neuroscience}, volume = {19}, number = {}, pages = {1671419}, pmid = {41229731}, issn = {1662-5102}, abstract = {Though usually described as isolated models, neurodegenerative diseases exist in a significant proportion of cases as mixed pathologies, particularly in older adults. The presence of co-pathologies may influence phenotypes and progression, and the correct classification in vivo has proven to be challenging, particularly without proper biomarker panels. Recent breakthroughs in biomarkers, enabling earlier detection in Alzheimer's disease and, more recently, in synuclein-related diseases, are promising as a first step toward the wider detection of all other abnormal proteins involved in neurodegenerative diseases. Over the past decade, the growing body of research on TDP-43 pathology has led to considering TDP-43 as a potential major contributor to the neurodegenerative process. TDP-43's normal function is essential for neuronal survival and the regulation of RNA processing and cellular stress response; abnormal TDP-43 protein leads to altered cell function and survival. TDP-43 is notably the neuropathological hallmark of amyotrophic lateral sclerosis (ALS) as well as some form of frontotemporolobar degeneration (FTLD). Tauopathies, divided in primary or secondary tauopathies cover other forms of FTLD including Pick disease (PiD), corticobasal degeneration (CBD), progressive supranuclear palsy (PSP) but also non-FTLD diseases like Alzheimer's disease (AD) which can be classified as secondary tauopathy. As the importance of copathology is more and more recognized, TDP-43 is also frequently observed in conjunction with other proteinopathies, possibly with a synergistic or additive effect, although the exact mechanism is still unclear. In Alzheimer's disease, the limbic predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) co-occurrence with Alzheimer's disease neuropathologic changes (ADNC) lead to a more rapid course. Although there are currently no approved and validated biomarkers for its early detection, several promising tools, including neuroimaging and biofluid biomarkers, are under development, offering hope for the earlier detection of TDP-43 pathology in vivo. Accurate identification of the underlying proteinopathies and pathological processes could lead to better diagnosis and classification, more precise selection of clinical trial candidates, and ultimately, disease-specific tailored treatments.}, }
@article {pmid41227379, year = {2025}, author = {Spedding, M}, title = {Does Amyotrophic Lateral Sclerosis (ALS) Have Metabolic Causes from Human Evolution?.}, journal = {Cells}, volume = {14}, number = {21}, pages = {}, doi = {10.3390/cells14211734}, pmid = {41227379}, issn = {2073-4409}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/genetics ; Animals ; *Biological Evolution ; Mixed Function Oxygenases/metabolism/genetics ; }, abstract = {As so many drugs have failed in ALS a new approach is needed. The author proposes that recent human genetic variants may play major roles in the disease, changing metabolism. Evolution of hominins was accelerated 3-2.5 Mya, by cytidine monophospho-N-acetylneuraminic acid hydroxylase (CMAH) becoming a unitary pseudogene after a pathogenic infection, changing the sialome, and hence metabolism, brain development and neuromuscular junctions (NMJs). This was when hominins evolved to run in Africa and develop bigger brains. Deletion of CMAH in mice allows them to run for longer (~50%). The enzyme CMAH is critical for the sialome, particularly the neurotrophin GM1, a critical hub for viral infection and for NMJ stability, but which is lost from NMJs at the beginning of denervation, probably due a 10-fold increase in spinal cord glucosylceramidases (non-lysosomal GBA2). A GBA2 inhibitor, ambroxol, is currently in phase II for ALS. Human-specific GM1 may be critical for human evolution, lactate metabolism and ALS. Lipid/lactate metabolism changed to support these evolutionary changes and lactate is a major body/brain fuel, but compromised in ALS patients and a marker of disease progression. Recent progress in sports science involving lactate metabolism and human performance may also be relevant to ALS therapies, and incidence.}, }
@article {pmid41226260, year = {2025}, author = {Cutter, LR and Ren, AR and Banerjee, IA}, title = {Advances in Naturally and Synthetically Derived Bioactive Sesquiterpenes and Their Derivatives: Applications in Targeting Cancer and Neurodegenerative Diseases.}, journal = {Molecules (Basel, Switzerland)}, volume = {30}, number = {21}, pages = {}, pmid = {41226260}, issn = {1420-3049}, support = {N/A//Henry Luce Foundation/ ; N/A//Fordham University/ ; }, mesh = {Humans ; *Sesquiterpenes/chemistry/pharmacology/therapeutic use/chemical synthesis ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Neoplasms/drug therapy/metabolism ; Animals ; *Biological Products/chemistry/pharmacology/therapeutic use ; *Antineoplastic Agents/pharmacology/chemistry ; Antioxidants/chemistry/pharmacology ; }, abstract = {Sesquiterpenes are a diverse class of natural products that have garnered considerable interest for their potent bioactivity and structural variability. This review highlights advances in the derivatization of various sesquiterpene lactones, quinones, and alcohols, particularly in targeting cancer and neurodegenerative diseases. The structural modifications discussed include the incorporation of triazole, arylidene, or thiol moieties with eudesmane, guaiane, and germacranolide-type sesquiterpenes, among others. In addition, the conjugation with chemotherapeutics, as well as the development of nanoscale therapeutics, is also discussed. Such modifications have expanded the pharmacological potential, enabling improved specificity, cytotoxicity profiles, and sensitization toward tumor cells. Additionally, sesquiterpenes such as parthenolide (20), pterosinsade A (176), and cedrol (186) have demonstrated potential in mitigating neurodegeneration via anti-inflammatory and antioxidant signaling pathway-modulation mechanisms, with potential applications in Alzheimer's, Parkinson's, and ALS diseases. Mechanistic insights into redox signaling modulation, NF-κB inhibition, ROS regulation, and disruption of aggregation underscore their multifaceted modes of action. This review highlights the translational promise of sesquiterpene derivatives as dual-action agents for potential drug development in a plethora of diseases that are caused by inflammation and free-radical damage. It provides a framework for future rational design of multifunctional drug candidates and therapeutics.}, }
@article {pmid41224659, year = {2025}, author = {Moss, KR and Darvishi, FB and Badawi, Y and Fish, LA and Funke, JR and Pedersen, TH and Robitaille, R and Arnold, WD and Burgess, RW and Meriney, SD and Nishimune, H and Saxena, S}, title = {The Neuromuscular Junction: A Shared Vulnerability in Aging and Disease.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {45}, number = {46}, pages = {}, doi = {10.1523/JNEUROSCI.1353-25.2025}, pmid = {41224659}, issn = {1529-2401}, mesh = {Humans ; *Neuromuscular Junction/pathology/physiopathology/physiology ; *Aging/pathology/physiology ; Animals ; *Neuromuscular Diseases/physiopathology/pathology ; Schwann Cells ; }, abstract = {The neuromuscular junction (NMJ) is a specialized synapse essential for effective motor neuron-muscle communication and is increasingly recognized as a vulnerable site in aging and neuromuscular disease. While traditionally considered a final common pathway for motor deficits, accumulating evidence demonstrates that NMJ dysfunction is an early and critical driver of disease onset and progression in conditions such as amyotrophic lateral sclerosis and Charcot-Marie-Tooth disease. This review highlights shared and disease-specific mechanisms contributing to NMJ impairment, including presynaptic, postsynaptic, and perisynaptic Schwann cell defects in these diseases. We also discuss age-related changes at the NMJ, emphasizing its role in sarcopenia and muscle weakness in older adults. Furthermore, we explore emerging molecular drivers of NMJ dysfunction uncovered through studies in congenital myasthenic syndromes, autoimmune disorders, and advanced omics approaches. By integrating insights across diseases and aging, we underscore the potential for shared therapeutic strategies aimed at stabilizing NMJ function. Promising interventions targeting presynaptic neurotransmitter release, postsynaptic excitability, and perisynaptic Schwann cells are discussed as avenues to improve neuromuscular transmission and maintain muscle strength. Finally, we discuss the challenges and opportunities in translating these mechanistic insights into clinical therapies and highlight how novel human neuromuscular organoid models and advanced molecular profiling can bridge this gap. Together, these insights establish the NMJ as a critical, modifiable target for preserving motor function across neuromuscular diseases and aging.}, }
@article {pmid41219095, year = {2025}, author = {Pu, S and Sawyer, A and Levinson, C and Putrino, D and Kirke, DN}, title = {Exploring Voice Banking as an Alternative Augmentative Communication Strategy for Individuals with Dysphonia, Aphonia, and Dysarthria: A Scoping Review.}, journal = {Journal of voice : official journal of the Voice Foundation}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jvoice.2025.10.018}, pmid = {41219095}, issn = {1873-4588}, abstract = {OBJECTIVES: This scoping review sought to: (i) review studies involving people diagnosed with dysphonia, aphonia, and dysarthria who have used voice banking technology in a hospital or community setting, and (ii) understand the scope of research surrounding existing voice banking technology and software in the clinical setting.<br><br>METHODS: This scoping review was conducted according to the preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews. An electronic search of databases, including Ovid MEDLINE(R), Embase (Ovid), APA PsycINFO (Ovid), and CINAHL was conducted. Title, abstract, and full text screening were completed using Covidence (Veritas Health Innovation, Melbourne, Australia) by two reviewers.<br><br>RESULTS: After deduplication, 1336 studies underwent title and abstract screening. Of these, the full texts of 65 studies were reviewed, and 23 were included. Three distinct topics were identified in the search: (i) message banking, in which discrete messages or phrases are recorded for later use, without the ability to create novel phrases outside of those previously recorded; (ii) voice banking, in which all the necessary phonemes in the target language are captured, with the goal of generating a personalized synthetic voice that can generate novel phrases; (iii) and voice conversion or voice reconstruction, in which pathologic voices or speech are "converted" into a personalized synthetic voices.<br><br>DISCUSSION AND CONCLUSION: This scoping review summarized the evidence for voice banking technology use in people diagnosed with dysphonia and dysarthria and sought to understand the research landscape of existing types of voice banking technology and software use in a clinical setting. The included papers were highly heterogeneous in terms of the population and type (research vs clinical program vs review/other). There is a pressing need for the publication of clinical programs and models facilitating the adoption of voice banking, especially within populations affected by conditions such as amyotrophic lateral sclerosis and laryngectomy, to address existing gaps and foster broader implementation and accessibility.}, }
@article {pmid40920400, year = {2025}, author = {Urso, D and Giannoni-Luza, S and Brayne, C and Ray, N and Logroscino, G}, title = {Incidence and Prevalence of Frontotemporal Dementia: A Systematic Review and Meta-Analysis.}, journal = {JAMA neurology}, volume = {82}, number = {11}, pages = {1144-1152}, pmid = {40920400}, issn = {2168-6157}, mesh = {Humans ; *Frontotemporal Dementia/epidemiology ; Incidence ; Prevalence ; }, abstract = {IMPORTANCE: Comprehensive incidence and prevalence rates of frontotemporal dementia are currently not available.<br><br>OBJECTIVE: To estimate the incidence and prevalence of frontotemporal dementia and its clinical variants in the overall population and age subgroups.<br><br>We systematically searched PubMed, EMBASE, and Scopus between January 1, 1990, and October 22, 2024, for population-based studies estimating the incidence and/or prevalence of FTD.<br><br>DATA EXTRACTION AND SYNTHESIS: Studies and data were screened and extracted independently by 2 investigators in accordance with PRISMA guidelines. Incident and prevalent cases together with the population at risk were pooled using random-effects meta-analysis. Differences in heterogeneity by FTD variants and populations at risk were estimated.<br><br>MAIN OUTCOMES AND MEASURES: Prevalent and incident cases as numerator were based on well-defined clinical criteria. Denominators were derived either from census population data or from author-defined populations at risk.<br><br>RESULTS: From 1854 screened articles, 32 eligible population-based studies were identified. Sixteen were on prevalence and 22 on incidence reporting FTD measures, including those with estimates for the whole population and for specific age subgroups. Pooled crude incidence for FTD was 2.28 (95% CI, 1.55-3.36) per 100&#x202f;000 person-years and prevalence, 9.17 (95% CI, 3.59-23.42) per 100&#x202f;000 people. The behavioral-variant FTD pooled crude incidence was 1.20 (95% CI, 0.67-2.16) per 100&#x202f;000 person-years and prevalence, 9.74 (95% CI, 2.90-32.73) per 100&#x202f;000 people. The primary progressive aphasia variant pooled crude incidence was 0.52 (95% CI, 0.35-0.79) per 100&#x202f;000 person-years and prevalence, 3.67 (95% CI, 3.05-4.43). FTD incidence among individuals younger than 65 years was 1.84 (95% CI, 0.79-4.30) per 100&#x202f;000 person-years and prevalence, 7.47 (95% CI, 4.13-13.49) per 100&#x202f;000 people. The denominator based on census data showed less heterogeneity than the population at risk defined by the authors (I2: for incidence, 91.6% vs 97.6%, respectively, and for prevalence, 98.8% vs 99.2%, respectively).<br><br>CONCLUSIONS AND RELEVANCE: In this systematic review and meta-analysis, estimates indicate that FTD is comparable in frequency to dementia with Lewy bodies and occurs at higher rates than progressive supranuclear palsy, corticobasal syndrome, and amyotrophic lateral sclerosis. These results provide a foundation for future research and public health strategy, especially for underrepresented populations, to better comprehend the global burden of FTD. Our findings provide robust pooled estimates of the incidence and prevalence of FTD and its subtypes, offering a foundation for future research and public health planning.}, }
@article {pmid40778462, year = {2025}, author = {Schvey, NA and Tanofsky-Kraff, M}, title = {Commentary on: The Prevalence of Eating Disorders and Disordered Eating in Adults Seeking Obesity Treatment: A Systematic Review With Meta-Analyses by Melville et al.}, journal = {The International journal of eating disorders}, volume = {58}, number = {11}, pages = {2062-2065}, doi = {10.1002/eat.24522}, pmid = {40778462}, issn = {1098-108X}, mesh = {Humans ; *Feeding and Eating Disorders/epidemiology ; *Obesity/therapy/epidemiology ; Prevalence ; Adult ; }, abstract = {Melville et al.'s 2025 systematic review and meta-analysis highlight the prevalence of eating disorders and disordered eating among adults seeking obesity treatment. Findings showed that the prevalence of binge-eating disorder in obesity treatment-seeking samples exceeds community norms. Results corroborate prior research suggesting that high body weight and eating pathology frequently co-occur and that individuals seeking weight management may be a high-risk population for both sub- and full-threshold eating disorders. Although concerns persist that weight loss efforts may promote or worsen eating disorder symptoms, research indicates that structured, evidence-based interventions typically have neutral or positive effects on disordered eating outcomes. However, rigorous and consistent screening for eating disorders among individuals with high weight is lacking. Importantly, obesity and eating disorders share many common etiological factors, suggesting that integrated intervention is both feasible and highly beneficial. Despite this, the fields of obesity and eating disorders remain siloed. This bifurcation disproportionately impacts youth and adolescents who are at high risk for the onset of both conditions. Currently, standards of care fail to include screening for eating disorders, particularly in youth with high weight, who may be overlooked or misdiagnosed due, in part, to weight-based stigma. Universal, developmentally sensitive screening tools and comprehensive assessment of eating disorder risk factors are urgently needed in pediatric primary care settings. As evidence mounts for concurrent treatment models of high weight and eating disorders, integration across science and clinical care is vital to improve outcomes for youth affected by both conditions.}, }
@article {pmid41214238, year = {2025}, author = {Mushtaq, U and Ahmad, B and Khanday, FA and Ahmad, M}, title = {CHI3L1: An Emerging Player in Neuroinflammation and Neurodegeneration.}, journal = {Molecular neurobiology}, volume = {63}, number = {1}, pages = {23}, pmid = {41214238}, issn = {1559-1182}, abstract = {Neuroinflammation is now being identified as the major factor in the development of various neurological disorders. It is a vital process in neurons and the brain that maintains homeostasis under normal and healthy conditions. However, in hyperactivated states, neuroinflammation can also go awry when microglia and astrocytes enter a toxic, reactive state that can release chemicals that damage neurons. When innate immune cells encounter pathogens, infection, cell debris, or misfolded proteins, they release certain chemokines and cytokines to eliminate the intruding particles and protect the brain. However, persistent inflammatory reactions are harmful and can lead to neurodegeneration by continuously releasing toxic chemicals and proteins. Chitinase-3-like protein 1 (CHI3L1), a secretory protein, is emerging as a key inflammatory molecule that is strongly upregulated during neuroinflammation and has been implicated in the pathogenesis of many diseases. The brain's activated astrocytes are the main source of CHI3L1 and are a dependable biomarker for inflammatory pathologies affecting the central nervous system (CNS), including neurodegeneration and autoimmune diseases. The protein has been implicated in many neurological disorders, including Alzheimer's Disease, Parkinson's Disease, Amyotrophic Lateral Sclerosis, and others, mediating neuroinflammation and neurodegeneration. CHI3L1 has contrasting functions in the CNS and other tissues. While the protein promotes cell proliferation and migration in various non-neuronal cancers, at the same time, it simultaneously promotes neurodegeneration and apoptosis in the CNS. This paper reviews the current developments in our knowledge of the pathogenic role of the CHI3L1 protein in various neurological disorders.}, }
@article {pmid41213329, year = {2025}, author = {Adachi, M and Banno, H and Inoue, H}, title = {Drug discovery research with the iPSC models of neurodegenerative diseases.}, journal = {Neuroscience research}, volume = {}, number = {}, pages = {104985}, doi = {10.1016/j.neures.2025.104985}, pmid = {41213329}, issn = {1872-8111}, abstract = {Induced pluripotent stem cells (iPSCs) are widely used in research because they can be used to create models of diseases with the same genomic background as in patients. Recently, it has become recognized that the use of iPSCs for screening can promote drug discovery research. Additionally, research is being conducted to develop high-quality models for drug discovery and to link translational research with clinical studies. The present work focuses on neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD), and broadly introduces the latest research using iPSCs, from disease mechanism studies to drug discovery research. In addition, clinical trials based on research with iPSCs have been conducted: bosutinib, ropinirole and ezogabine for ALS, WVE-004 and BIIB078 for ALS with frontotemporal dementia (ALS/FTD), and bromocriptine for familial AD. Finally, we also wish to mention screening studies utilizing artificial intelligence (AI).}, }
@article {pmid41213077, year = {2025}, author = {Cai, S and Liu, Y and Liu, B and Liao, H and Li, K}, title = {Hexokinase as a Central Hub in Neurodegeneration: From Metabolic Dysfunction to Therapeutic Innovation.}, journal = {Aging and disease}, volume = {}, number = {}, pages = {}, doi = {10.14336/AD.2025.0891}, pmid = {41213077}, issn = {2152-5250}, abstract = {Neurodegenerative diseases represent an escalating global health crisis affecting more than 55 million people worldwide; however, underlying mechanisms remain unclear, and therapeutic breakthroughs are elusive. Emerging evidence indicates that hexokinase (HK), the rate-limiting glycolytic enzyme, functions as a master regulator orchestrating neuronal survival through metabolic‒mitochondrial coupling. This review consolidates emerging paradigms revealing that HK maintains neuronal viability through its obligate interaction with mitochondrial VDAC1, forming a metabolic checkpoint that integrates energy status with survival signaling. Disease-specific HK dysfunction patterns precede clinical manifestations and drive pathological cascades across primary neurodegenerative conditions. Pathological proteins characteristic of neurodegeneration-amyloid-β in AD, α-synuclein in PD, mutant SOD1 in ALS, and huntingtin in HD-converge to disrupt the HK-VDAC1 axis through distinct molecular mechanisms, triggering mitochondrial permeabilization, bioenergetic collapse, and inflammatory activation. This uncoupling event promotes VDAC1 oligomerization, enabling the cytosolic release of mtDNA, which in turn activates the NLRP3 inflammasome while depleting antioxidant capacity, establishing self-perpetuating neuroinflammatory cycles. The literature reveals that HK functions as a molecular rheostat, determining neuronal fate through glucose-6-phosphate-mediated feedback control, modulation of growth factor signaling, and regulation of apoptosis/survival pathways. Therapeutic targeting of HK through peptide interventions, enzymatic modulation, and gene therapy demonstrates robust neuroprotective effects across multiple disease models. Meanwhile, combination strategies addressing metabolic-inflammatory networks show synergistic efficacy. These insights position HK as a convergent therapeutic nexus offering unprecedented opportunities for precision intervention in neurodegeneration, with potential for early diagnostic applications and preventive strategies that could transform treatment paradigms for conditions affecting millions worldwide.}, }
@article {pmid41212342, year = {2025}, author = {Zhong, R and Yang, H and Li, X and Wang, F and Zhai, L and Gao, J}, title = {Mitochondria-Mediated Mechanisms of Ferroptosis in Neurological Diseases.}, journal = {Neurochemical research}, volume = {50}, number = {6}, pages = {354}, pmid = {41212342}, issn = {1573-6903}, support = {202403070986//Health Science and Technology Project of Shandong Province/ ; RZ1900011598//post-doctoral foundation of Qingdao University/ ; }, abstract = {Ferroptosis, a regulated form of cell death driven by iron-dependent lipid peroxidation, is increasingly recognized as a critical contributor to the pathogenesis of various neurological disorders. Mitochondria, the powerhouses of cells, play dual roles as both initiators and mediators of ferroptosis by integrating lipid peroxidation cascades, oxidative stress responses, and iron homeostasis dysregulation. This review first comprehensively explores the multifaceted mechanisms by which mitochondria mediate ferroptosis in neurological diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Friedreich's ataxia (FRDA), amyotrophic lateral sclerosis (ALS), epilepsy, stroke, and brain injury, with a focus on mitochondrial lipid peroxidation and iron metabolism dysregulation. Building on these mechanistic insights, we further discuss emerging evidence suggesting that targeting mitochondrial pathways may represent a promising therapeutic strategy for mitigating ferroptosis-associated neuronal damage. By synthesizing these findings, our review establishes a conceptual foundation for developing innovative neuroprotective interventions through precise modulation of mitochondrial function within ferroptotic pathways.}, }
@article {pmid41207217, year = {2025}, author = {Wu, Y and Huang, S and Sha, Q and Yu, J}, title = {Emerging and Re-emerging viruses as triggers of human endogenous retrovirus activation: Implications for aging and age-related pathologies.}, journal = {Molecular aspects of medicine}, volume = {106}, number = {}, pages = {101422}, doi = {10.1016/j.mam.2025.101422}, pmid = {41207217}, issn = {1872-9452}, abstract = {The human genome contains a substantial legacy of ancient retroviral infections known as Human Endogenous Retroviruses (HERVs), composing 8 % of our DNA. In healthy young individuals, these elements are kept dormant by robust epigenetic mechanisms, primarily DNA methylation and repressive H3K9me3 histone marks. However, this epigenetic silencing deteriorates with age, leading to the reactivation of HERVs, particularly the youngest HERV-K subfamily. This report posits that this HERV awakening is not a passive byproduct of aging but an active, transmissible driver of pathology. The reactivation of HERVs leads to the production of retrovirus-like particles (RVLPs) that can induce senescence in healthy neighboring cells, propagating a contagious aging phenomenon. Furthermore, the accumulation of HERV-derived dsRNA and reverse-transcribed DNA triggers chronic innate immune responses through pathways including cGAS-STING and IFIH1-MAVS, fueling the systemic, low-grade inflammation characteristic of inflammaging, catalytically accelerated by exogenous viral infections. Pathogens such as SARS-CoV-2, Epstein-Barr Virus (EBV), and Herpes Simplex Virus (HSV-1) can directly transactivate HERVs via their own viral proteins, overwhelming the already compromised epigenetic controls in an aging host. This mechanistic link between viral triggers and endogenous retroviral activity is strongly implicated in a range of age-related diseases, including neurodegenerative disorders such as Alzheimer's disease and Amyotrophic Lateral Sclerosis (ALS), where the HERV-K envelope protein is directly neurotoxic. It is also linked to autoimmune diseases like Multiple Sclerosis and various cancers. This report synthesizes these findings and identifies a novel mechanistic link between viral activity, chronic inflammation, and the onset of age-related diseases.}, }
@article {pmid41205733, year = {2025}, author = {Hendricus Maes, KJ and Briedé, JJ}, title = {Repurposing immunomodulatory drugs targeting microglia for amyotrophic lateral sclerosis.}, journal = {Brain research}, volume = {}, number = {}, pages = {150032}, doi = {10.1016/j.brainres.2025.150032}, pmid = {41205733}, issn = {1872-6240}, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder that progressively affects upper and lower motor neurons, leading to symptoms including dysarthria, muscle weakness, and paralysis. The disease is multifactorial, with a variety of contributing pathways, including excitotoxicity, oxidative stress, and neuroinflammation. Current treatments target only two of these pathways with limited efficacy, highlighting the need for alternative approaches. Increasing evidence highlights the involvement of immune dysregulation, particularly microglial-mediated neuroinflammation, in ALS pathology. Fortunately, many immunomodulatory drugs acting on microglia are already available for other diseases, indicating promising opportunities for drug repurposing. This literature review provides an overview of existing drugs under investigation for ALS, including those that have failed, and highlights new microglia-targeting candidates with repurposing potential. Compounds such as ibudilast, fingolimod, and modafinil have shown encouraging initial clinical results, whereas others were well-tolerated but underpowered or failed to demonstrate efficacy. New candidates, such as azithromycin, naltrexone, montelukast, doxycycline, tofacitinib, quercetin, belinostat, and several kinase inhibitors, have demonstrated positive preclinical results, supporting their advancement toward clinical evaluation. Overall, these findings emphasize the potential of microglia-targeting therapies for ALS. To realize this potential, future studies must include larger cohorts, assess effects across disease stages and patient subgroups, and examine sex differences. This is essential to address patient heterogeneity and improve personalized treatment in ALS.}, }
@article {pmid41203507, year = {2025}, author = {Zhang, YP and Kedia, S and Klenerman, D}, title = {Rethinking neurodegeneration through a co-proteinopathy lens.}, journal = {Trends in neurosciences}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tins.2025.10.006}, pmid = {41203507}, issn = {1878-108X}, abstract = {Neurodegenerative diseases have long been considered distinct proteinopathies: amyloid-β and tau in Alzheimer's disease, α-synuclein in Parkinson's disease, and TDP-43 in amyotrophic lateral sclerosis. This single-protein paradigm has guided therapeutic development for decades; yet clinical outcomes remain modest. Mounting evidence, however, reveals that protein aggregates rarely occur in isolation; instead, they coexist, colocalise, and modulate each other's pathogenicity. Here, we propose a co-proteinopathy framework that views neurodegeneration as an interactive network of misfolded proteins rather than as isolated disorders. Adopting this framework demands multiplexed quantification of protein aggregates and disease models that better reflect the biological complexity of human neurodegeneration. The co-proteinopathy perspective offers a more realistic foundation for next-generation approaches to neurodegeneration research and treatment.}, }
@article {pmid41201719, year = {2025}, author = {Gautam, P and Vishwakarma, RK and Nath, M and Nath, G and Pathak, A}, title = {Microbiota Dysbiosis in Amyotrophic Lateral Sclerosis: A Systematic Review of Human Studies.}, journal = {Molecular neurobiology}, volume = {63}, number = {1}, pages = {10}, pmid = {41201719}, issn = {1559-1182}, mesh = {*Amyotrophic Lateral Sclerosis/microbiology/complications ; Humans ; *Dysbiosis/microbiology/complications ; *Gastrointestinal Microbiome/physiology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive motor neuron degeneration. Despite intensive research, its pathogenesis remains poorly understood. Recent insights suggest a pivotal role of the gut microbiota in modulating neuroinflammation and neurodegeneration via the gut-brain axis. This systematic review aims to synthesize clinical evidence on gut microbiota dysbiosis in ALS, exploring microbial and metabolic alterations and their associations with disease progression and severity. A comprehensive literature search was conducted across PubMed, Embase, Scopus, Web of Science, and other databases up to May 10, 2024, adhering to PRISMA 2020 guidelines. Eighteen eligible human studies were selected based on predefined inclusion criteria. Data on microbial diversity, taxonomic shifts, metabolite profiles, and clinical correlations were extracted and assessed using a modified Newcastle-Ottawa Scale. Most studies reported altered microbial diversity, reduced butyrate-producing bacteria (e.g., Faecalibacterium, Roseburia), and increased pro-inflammatory taxa (e.g., Escherichia coli, Bacteroides) in ALS. Integrated microbiome-metabolome analyses revealed disruptions in SCFAs, bile acids, and lipid metabolism, some correlating with ALSFRS-R scores and cognitive impairment. Although some studies showed minimal or no differences, the overall evidence supports a link between dysbiosis and ALS pathophysiology. Probiotic trials demonstrated limited efficacy, highlighting the need for targeted, patient-specific interventions. Gut microbiota dysbiosis is increasingly recognized as a contributor to ALS progression. However, methodological variability, small sample sizes, and limited longitudinal data restrict definitive conclusions. Future research should employ standardized, multi-omics approaches and larger cohorts to clarify causal links and develop microbiome-informed diagnostics and therapies for ALS.}, }
@article {pmid41196032, year = {2025}, author = {Mansoor, N and Heiman-Patterson, T and Feldman, EL and Wicks, P and Benatar, M and Vieira, F and Glass, J and Levine, T and Bertorini, T and Barkhaus, P and Mascias Cadavid, J and Jackson, C and Jhooty, S and Brown, A and Pattee, G and Sane, H and Mcdermott, CJ and Carter, G and Beauchamp, M and Wang, O and Ratner, D and Bedlack, R and Li, X}, title = {ALSUntangled #81: Pyridostigmine (mestinon[®]).}, journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration}, volume = {}, number = {}, pages = {1-5}, doi = {10.1080/21678421.2025.2582830}, pmid = {41196032}, issn = {2167-9223}, abstract = {Pyridostigmine (Mestinon[®], Bausch Health, Canada Inc.) increases acetylcholine availability at the neuromuscular junction, enhancing transmission. Preclinical studies suggest that neuromuscular junction dysfunction develops early in ALS, and pyridostigmine may temporarily improve neuromuscular transmission. However, altered neuromuscular junction transmission has uncertain benefits in ALS progression. Pyridostigmine does not have other plausible mechanisms that truly modify ALS pathophysiology. People with ALS (PALS) who have positive acetylcholine receptor autoantibodies and no myasthenia symptoms are unlikely to respond to pyridostigmine treatment. Clinical trials on pyridostigmine in PALS are lacking, but two clinical trials of other similar anticholinesterase agents did not effectively slow ALS progression. Muscarinic cholinergic side effects, including gastrointestinal symptoms, are common. Given the lack of mechanistic plausibility and efficacy, we do not support the use of pyridostigmine for slowing ALS progression.}, }
@article {pmid41194800, year = {2025}, author = {Su, Z and Xiang, L}, title = {Targeting ER stress in skeletal muscle through physical activity: a strategy for combating neurodegeneration-associated muscle decline.}, journal = {Frontiers in molecular neuroscience}, volume = {18}, number = {}, pages = {1639114}, pmid = {41194800}, issn = {1662-5099}, abstract = {The pathophysiology of neurodegenerative diseases is largely driven by ER stress, contributing to cellular dysfunction and inflammation. Chronic ER stress in skeletal muscle is associated with a deterioration in muscle function, particularly in diseases such as ALS, PD, and AD, which are often accompanied by muscle wasting and weakness. ER stress triggers the UPR, a cellular process designed to restore protein homeostasis, but prolonged or unresolved stress can lead to muscle degeneration. Recent studies indicate that exercise may modulate ER stress, thereby improving muscle health through the enhancement of the adaptive UPR, reducing protein misfolding, and promoting cellular repair mechanisms. This review examines the influence of exercise on the modulation of ER stress in muscle cells, with a particular focus on how physical activity influences key pathways contributed to mitochondrial function, protein folding, and quality control. We discuss how exercise-induced adaptations, including the activation of stress-resilience pathways, antioxidant responses, and autophagy, can help mitigate the negative effects of ER stress in muscle cells. Moreover, we examine the potential therapeutic implications of exercise in neurodegenerative diseases, where it may improve muscle function, reduce muscle wasting, and alleviate symptoms associated with ER stress. By integrating findings from neurobiology, muscle physiology, and cellular stress responses, this article highlights the therapeutic potential of exercise as a strategy to modulate ER stress and improve muscle function in neurodegenerative diseases.}, }
@article {pmid41194479, year = {2025}, author = {Das, S and Patel, M and Khandelwal, S and Rawat, R and Shukla, S and Kumari, AP and Singh, K and Kumar, A}, title = {From Mutations to Microbes: Investigating the Impact of the Gut Microbiome on Repeat Expansion Disorders.}, journal = {Journal of neurochemistry}, volume = {169}, number = {11}, pages = {e70278}, doi = {10.1111/jnc.70278}, pmid = {41194479}, issn = {1471-4159}, mesh = {*Gastrointestinal Microbiome/physiology/genetics ; Humans ; Animals ; *Mutation/genetics ; Dysbiosis/genetics ; *DNA Repeat Expansion/genetics ; }, abstract = {Repeat expansion disorders (REDs) are a diverse array of genetic disorders characterized by the expansion of specific DNA sequences. These expansions are frequently dynamic and are susceptible to further expansion across generations. They contribute to disease progression by leading symptoms to become more severe and manifest earlier in subsequent generations. Despite a substantial understanding of their molecular mechanisms, the exact etiology of REDs remains tricky. Emerging evidence indicates that gut microbiome dysbiosis significantly impacts REDs by regulating various biochemical pathways. Alterations in microbial diversity and composition have been observed across multiple REDs; however, a comprehensive understanding of the complete scenario remains a significant challenge. To elucidate these dynamic interactions, future research should utilize multifaceted approaches. This review focuses on the key modifications in the gut microbiome that contribute to the pathogenesis of REDs and discusses potential gut microbiome-targeted therapeutic strategies that could be effectively employed to treat these disorders.}, }
@article {pmid41192771, year = {2025}, author = {Shima, S and Kondo, T and Inoue, H}, title = {iPSC-derived neural organoids in dementia research: recent advances and future directions.}, journal = {Neuroscience research}, volume = {}, number = {}, pages = {104980}, doi = {10.1016/j.neures.2025.104980}, pmid = {41192771}, issn = {1872-8111}, abstract = {Neural organoids are self-assembled three-dimensionally shaped aggregates generated from pluripotent stem cells for the purpose of generating brain-like structures. Organoids derived from patient induced pluripotent stem cells (iPSCs) can recapitulate the features of the disease from molecular to functional levels, which are not fully reproduced by other culture systems or in vivo models. Neural organoids have been applied to model dementia including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis/frontotemporal dementia, and they have recapitulated aspects of their complex pathophysiology, including neuronal network dysfunction and accumulation of pathogenic proteins. Although there are some challenges for the research using neural organoids, including their heterogeneity and the lack of cells of non-neural lineage, researchers have tried to overcome these limitations and have demonstrated their utility in conjugation with gene editing technologies and the assembly system of organoids and specific types of cells. This article reviews current research on iPSC-derived organoids for dementia, discussing both the technical hurdles and the potential for translational applications.}, }
@article {pmid41165282, year = {2025}, author = {Roedl, K and Genbrugge, C}, title = {Managing cardiac arrest in the intensive care unit.}, journal = {Current opinion in critical care}, volume = {31}, number = {6}, pages = {729-734}, doi = {10.1097/MCC.0000000000001319}, pmid = {41165282}, issn = {1531-7072}, mesh = {Humans ; *Heart Arrest/therapy/epidemiology/etiology/mortality ; *Intensive Care Units ; *COVID-19/epidemiology ; *Cardiopulmonary Resuscitation/methods ; SARS-CoV-2 ; *Critical Care/methods ; }, abstract = {PURPOSE OF REVIEW: This review aims to explore the distinct clinical characteristics, epidemiology, treatment approaches, and research needs concerning cardiac arrest in the intensive care unit (ICU-CA), a specific subset of in-hospital cardiac arrest (IHCA). While IHCA remains a major cause of mortality, recent data indicate improved outcomes, with a notable variation in incidence and survival depending on the location, particularly within the ICU setting.<br><br>RECENT FINDINGS: Recent studies underscore that ICU-CA differs significantly from general IHCA in etiology, monitoring, and treatment environment. Although incidence rates vary widely (4-78 per 1000 ICU admissions), recent data suggest a stabilization. Causes of ICU-CA often involve noncardiac factors such as septic shock and respiratory failure. Treatment is typically guided by general advanced life support (ALS) protocols, but ICU-specific resources such as real-time monitoring, invasive pressure measurements, transesophageal echocardiography, and the potential for extracorporeal cardiopulmonary resuscitation offer unique advantages. The COVID-19 pandemic highlighted the vulnerability of ICU patients, with respiratory causes dominating and extremely poor outcomes reported.<br><br>SUMMARY: In summary, ICU-CA represents a distinct clinical entity requiring tailored research. Future directions should prioritize international registries, validation of predictive models using artificial intelligence, and clarification of do-not-resuscitate practices to improve outcomes and resource allocation in this critically ill population.}, }
@article {pmid41191158, year = {2025}, author = {Pal, B and Panda, S and Bashir, B and Vishwas, S and Chaitanya, M and Hussain, MS and Gupta, G and Kumbhar, P and Gupta, S and Singh, SK}, title = {Nanomedicine-enabled neuroprotection: therapeutic role of berberine in neurodegenerative diseases.}, journal = {Molecular biology reports}, volume = {53}, number = {1}, pages = {49}, pmid = {41191158}, issn = {1573-4978}, mesh = {Humans ; *Berberine/therapeutic use/pharmacology ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Neuroprotective Agents/therapeutic use/pharmacology ; *Nanomedicine/methods ; Animals ; *Neuroprotection/drug effects ; Nanoparticles/chemistry ; Oxidative Stress/drug effects ; Blood-Brain Barrier/metabolism/drug effects ; }, abstract = {Neurodegenerative diseases (NDs), including Alzheimer's, Amyotrophic lateral sclerosis, Huntington's, and Parkinson's, present an increasingly widespread health burden globally with limited curative or treatment modalities, mostly having symptomatic attenuation. Berberine (BBR) is an isoquinoline alkaloid that occurs naturally and has been proposed as a potential neuroprotectant, since it has been found to exert multiple effects to modulate most of the pathological hallmarks of NDs, including neuroinflammation, oxidative stress, mitochondrial dysfunction, and protein aggregation. Although it shows promise, the practical utilization of BBR is marred by low oral bioavailability, high rate of oxidation, and low blood-brain barrier permeability. To combat these issues, recent developments in nanotechnology, especially in the use and creation of lipidic, inorganic, and polymeric nano-particles, have dramatically altered the pharmacokinetics and pharmacodynamics of BBR. This article summarizes recent advances in BBR-based nanoformulations and emphasizes the translational potential of BBR-based nanopreparations to improve treatment response in NDs. It also describes the molecular foundation of the neuroprotective effects of BBR and its possible place in clinical practice. Future nanocarrier development and investigation of BBR mechanisms will be essential to the development of the next generations of therapeutics in NDs.}, }
@article {pmid41190025, year = {2025}, author = {Alhassan, HH and Janiyani, K and Surti, M and Adnan, M and Patel, M}, title = {The dual role of glycogen synthase kinase-3 beta (GSK3β) in neurodegenerative pathologies: interplay between autophagy and disease progression.}, journal = {Frontiers in pharmacology}, volume = {16}, number = {}, pages = {1693805}, pmid = {41190025}, issn = {1663-9812}, abstract = {Glycogen Synthase Kinase-3 Beta (GSK3β), a multifunctional serine/threonine kinase, plays a central role in cellular signaling pathways and autophagy regulation, processes critical to neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease and Amyotrophic Lateral Sclerosis (ALS). Dysregulation of autophagy leads to the toxic accumulation of misfolded proteins and damaged organelles, contributing to neuronal loss in these disorders. This review explores the mechanistic interplay between GSK3β and autophagy, highlighting its modulation through key pathways, including mTOR, AMPK and Bcl-2 and its direct impact on autophagy-related proteins such as Beclin-1 and LC3. This review systematically discusses the disease-specific roles of GSK3β in autophagy dysregulation and protein aggregation, providing evidence from recent studies on neurodegenerative models. Additionally, therapeutic approaches targeting GSK3β are evaluated, including preclinical and clinical trials of GSK3β inhibitors and combination therapies with autophagy modulators, emphasizing their potential for improving neuroprotection and cellular homeostasis. Despite its promise, challenges such as off-target effects and pathway complexity remain significant. This review highlights the importance of GSK3β as both a therapeutic target and a biomarker, offering avenues for future research into selective GSK3β modulators that enhance autophagy and mitigate ND progression.}, }
@article {pmid41189652, year = {2025}, author = {Guo, H and Yang, Z and Zhang, G and Lv, L and Zhao, X}, title = {Meta analysis of the diagnostic efficacy of transformer-based multimodal fusion deep learning models in early Alzheimer's disease.}, journal = {Frontiers in neurology}, volume = {16}, number = {}, pages = {1641548}, pmid = {41189652}, issn = {1664-2295}, abstract = {INTRODUCTION: This study aims to systematically evaluate the diagnostic efficacy of Transformer-based multimodal fusion deep learning models in early Alzheimer's disease (AD) through a Meta-analysis, providing a scientific basis for clinical applications.<br><br>METHODS: Following PRISMA guidelines, databases such as PubMed and Web of Science were searched, and 20 eligible clinical studies (2022-2025) involving 12,897 participants were included. Study quality was assessed using the modified QUADAS-2 tool, statistical analyses were performed with Stata 16.0, effect sizes were pooled via random-effects models, and subgroup analyses, sensitivity analyses, and publication bias tests were conducted.<br><br>RESULTS: Results showed that Transformer-based multimodal fusion models exhibited excellent overall diagnostic performance, with a pooled AUC of 0.924 (95% CI: 0.912-0.936), sensitivity of 0.887 (0.865-0.904), specificity of 0.892 (0.871-0.910), and accuracy of 0.879 (0.858-0.897), significantly outperforming traditional single-modality methods. Subgroup analyses revealed that: Three or more modalities achieved a higher AUC (0.935 vs. 0.908 for two modalities, p&#x202f;=0.012). Intermediate fusion strategies (feature-level, AUC=0.931) significantly outperformed early (0.905) and late (0.912) fusion (p&#x202f;<0.05 for both). Multicenter data improved AUC (0.930 vs. 0.918 for single-center, p&#x202f;=0.046), while sample size stratification (<200 vs. &#x2265;200 cases) showed no significant difference (p&#x202f;=0.113). Hybrid Transformer models (Transformer +CNN) trended toward higher AUC (0.928 vs. pure Transformer 0.917, p&#x202f;=0.068) but did not reach statistical significance.<br><br>DISCUSSION: Notable studies included Khan et al.'s (2024) Dual-3DM[3]AD model (AUC=0.945 for AD vs. MCI) and Gao et al.'s (2023) generative network (AUC=0.912 under data loss), validating model robustness and feature complementarity. Sensitivity analysis confirmed stable results (AUC range: 0.920-0.928), and Egger's test (p&#x202f;=0.217) and funnel plot symmetry indicated no significant publication bias. Limitations included a high proportion of single-center data and insufficient model interpretability. Future research should focus on multicenter data integration, interpretable module development, and lightweight design to facilitate clinical translation. Transformer-based multimodal fusion models demonstrate exceptional efficacy in early AD diagnosis, with multimodal integration, feature-level fusion, and multicenter data application as key advantages. They hold promise as core tools for AD "early diagnosis and treatment" but require further optimization for cross-cohort generalization and clinical interpretability.}, }
@article {pmid41187881, year = {2025}, author = {Ge, TQ and Wang, P and Guan, PP}, title = {Targeting the C5-C5aR1 axis: A promising therapeutic strategy for Alzheimer's disease and amyotrophic lateral sclerosis by unlocking neuroprotection.}, journal = {Biochemical pharmacology}, volume = {243}, number = {Pt 1}, pages = {117518}, doi = {10.1016/j.bcp.2025.117518}, pmid = {41187881}, issn = {1873-2968}, abstract = {C5aR1 is a G protein-coupled receptor (GPCR) which is involved in exacerbating neurodegenerative diseases, including Alzheimer's disease (AD) and Amyotrophic Lateral Sclerosis (ALS). This review highlights the critical role of the C5-C5aR1 axis, in the pathogenesis of neurodegenerative diseases such as AD and ALS. In AD and ALS, abnormal protein aggregates activate the complement system (CS), leading to increased production of C5a. C5a activates C5aR1 on microglia, triggering the release of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6) that induce synaptic loss. Concurrently, the C5-C5aR1 axis impairs microglial phagocytic capacity, promoting damage-associated molecular patterns (DAMPs) accumulation and forming a vicious cycle of inflammation and complement activation. Additionally, excessive complement molecule assembles into the terminal complement complex (TCC), which exerts direct neurotoxic effects and drives neuronal apoptosis. Preclinical studies show that C5aR1 antagonists, such as PMX205, mitigate disease progression in AD and ALS animal models by reducing neuroinflammation and preserving synaptic function. These findings underscore the C5-C5aR1 axis as a promising target for neurodegenerative disease therapy and highlight the need for further development of potential antagonists of C5aR1.}, }
@article {pmid41117139, year = {2025}, author = {Pedro, KM and Alvi, MA and Goulart, GR and Fehlings, MG}, title = {Riluzole as a pharmacological therapy for spinal cord injury: where does this therapy stand?.}, journal = {Current opinion in neurology}, volume = {38}, number = {6}, pages = {625-634}, doi = {10.1097/WCO.0000000000001434}, pmid = {41117139}, issn = {1473-6551}, mesh = {*Riluzole/therapeutic use/pharmacology ; Humans ; *Spinal Cord Injuries/drug therapy ; *Neuroprotective Agents/therapeutic use/pharmacology ; Animals ; }, abstract = {PURPOSE OF REVIEW: Spinal cord injury (SCI) remains a disabling condition associated with long term neurological impairment, functional disability, and reduced quality of life. Despite decades of research, pharmacological interventions with proven clinical efficacy remain limited. This review critically evaluates the current evidence supporting riluzole as a neuroprotective agent for acute traumatic and nontraumatic SCI. We synthesize findings from preclinical and clinical studies, assess the progress towards clinical translation, and outline key challenges and research opportunities for future implementation.<br><br>RECENT FINDINGS: Riluzole, an FDA-approved agent for amyotrophic lateral sclerosis (ALS), inhibits voltage-gated sodium channels and modulates glutaminergic transmission, two mechanisms central to the pathogenesis of secondary injury in SCI and in nerve cell degeneration in nontraumatic forms of SCI, including degenerative cervical myelopathy (DCM). Preclinical studies consistently demonstrate functional and histopathological improvements following riluzole administration. Phase I/II trials have provided evidence for its safety and tolerability in acute SCI patients, while the RISCIS and CSM-PROTECT trials, two landmark multicenter randomized controlled studies, along with their secondary analyses, revealed promising multidomain improvements in motor function, independence, and quality of life indices. Sub-studies have also established pharmacokinetic and pharmacodynamic frameworks for individualized dosing, and early biomarker analysis suggests potential for predictive stratification.<br><br>SUMMARY: Riluzole represents a promising candidate for neuroprotection in traumatic and nontraumatic SCI. The consistency of favorable trends across multiple domains and strong support from preclinical studies highlight riluzole's value in orphan diseases such as SCI. Future directions should focus on refining the therapeutic window, optimizing PK/PD modeling, and identifying patient subgroups most likely to benefit. Its implementation in a multimodal treatment paradigm for acute SCI will be crucial for optimizing management protocols in this highly disabling condition.}, }
@article {pmid40960157, year = {2025}, author = {Wang, J and Dai, L and Zhang, Z}, title = {Protein aggregation in neurodegenerative diseases.}, journal = {Chinese medical journal}, volume = {138}, number = {21}, pages = {2753-2768}, pmid = {40960157}, issn = {2542-5641}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism ; alpha-Synuclein/metabolism ; Amyloid beta-Peptides/metabolism ; tau Proteins/metabolism ; *Protein Aggregation, Pathological/metabolism ; DNA-Binding Proteins/metabolism ; Animals ; *Protein Aggregates/physiology ; }, abstract = {Neurodegenerative diseases constitute a group of chronic disorders characterized by the progressive loss of neurons. Major neurodegenerative conditions include Alzheimer's disease, Parkinson's disease, Huntington's disease, frontotemporal lobar degeneration, and amyotrophic lateral sclerosis. Pathologically, these diseases are marked by the accumulation of aggregates formed by pathological proteins such as amyloid-β, tau, α-synuclein, and TAR DNA-binding protein 43. These proteins assemble into amyloid fibrils that undergo prion-like propagation and dissemination, ultimately inducing neurodegeneration. Understanding the biology of these protein aggregates is fundamental to elucidating the pathophysiology of neurodegenerative disorders. In this review, we summarize the molecular mechanisms underlying the aggregation and transmission of pathological proteins, the processes through which these protein aggregates trigger neurodegeneration, and the interactions between different pathological proteins. We also provide an overview of the current diagnostic approaches and therapeutic strategies targeting pathological protein aggregates.}, }
@article {pmid40794569, year = {2025}, author = {Benatar, M and Staffaroni, AM and Wuu, J and McDermott, MP and Quintana, M and Swidler, J and Andersen, G and Huey, ED and Turner, MR and Macklin, EA and Berry, JD and McMillan, CT and Gendron, T and Onyike, C and Rosen, H and Heuer, HW and Grignon, AL and Dave, KD and Balas, C and Gleixner, A and Satlin, A and Dunn, B and Dacks, P and Boxer, AL}, title = {Design considerations for C9orf72 disease prevention trials.}, journal = {Brain : a journal of neurology}, volume = {148}, number = {11}, pages = {3844-3855}, doi = {10.1093/brain/awaf290}, pmid = {40794569}, issn = {1460-2156}, support = {//Association for Frontotemporal Degeneration/ ; //ALS Association/ ; }, mesh = {Humans ; *C9orf72 Protein/genetics ; *Amyotrophic Lateral Sclerosis/genetics/prevention &amp; control ; *Frontotemporal Dementia/genetics/prevention &amp; control ; *Clinical Trials as Topic/methods ; DNA Repeat Expansion/genetics ; Research Design ; }, abstract = {The idea that it might be possible to prevent some forms of amyotrophic lateral sclerosis and frontotemporal dementia has finally come of age. The hexanucleotide repeat expansion in the C9orf72 gene accounts for ∼10% of all amyotrophic lateral sclerosis and 10%-15% of all frontotemporal dementia diagnoses, with the two clinical syndromes co-manifesting in a significant number of patients. As a result, clinically unaffected carriers of pathogenic C9orf72 repeat expansions are currently the largest identifiable population at significantly elevated risk for both amyotrophic lateral sclerosis and frontotemporal dementia, and in whom it might be possible to prevent the emergence of clinically manifest disease. Strategies for the design of disease prevention trials among clinically unaffected C9orf72 carriers have begun to emerge separately in the amyotrophic lateral sclerosis and frontotemporal dementia fields. However, recognition of the need to define neurodegenerative diseases based on biology underscores the need to consider all potential clinical manifestations of a C9orf72 repeat expansion together, rather than the traditional siloed approach of focusing on only amyotrophic lateral sclerosis or only frontotemporal dementia. Indeed, emerging clinical and biological markers that might be used to quantify pre-symptomatic disease progression and to predict the short-term risk of phenoconversion to clinically manifest disease are shared across the phenotypic spectrum. Given the anticipated progress in the development of therapeutic strategies to target the C9orf72 repeat expansion, and the enthusiasm for prevention trials among the unaffected C9orf72 repeat expansion carrier population, now is the time to begin work on the design of disease prevention trials. To this end, The Association for Frontotemporal Degeneration and The ALS Association supported a multi-stakeholder workshop (in Washington D.C., June 2024) to unify efforts to design a prevention trial for the population at elevated genetic risk for the phenotypic spectrum of C9orf72 disease. Here we describe recommendations emanating from this workshop for the selection of outcome measures, delineation of eligibility criteria, optimal use of biomarkers and digital health technologies, potential analytic frameworks and relevant regulatory considerations related to C9orf72 disease prevention trials. We also emphasize the importance of the amyotrophic lateral sclerosis and frontotemporal dementia communities working together in partnership with the C9orf72 repeat expansion carrier community, the regulatory authorities and the broader drug development community.}, }
@article {pmid41186720, year = {2025}, author = {Aijaz, M and Ahmad, M and Ahmad, S and Afzal, M and Kothiyal, P}, title = {The gut-brain axis: role of gut microbiota in neurological disease pathogenesis and pharmacotherapeutics.}, journal = {Naunyn-Schmiedeberg's archives of pharmacology}, volume = {}, number = {}, pages = {}, pmid = {41186720}, issn = {1432-1912}, abstract = {The gut-brain axis is a highly complex, bidirectional communication link between the gut and the central nervous system (CNS), mainly through neural, endocrine, immunological, and metabolic pathways. This review outlines the growing contribution of gut microbiota in the remediation of neurological health and also emphasizes the controlling role of gut microbiota on the synthesis of neurotransmitters. Emerging evidence indicates that dysbiosis of the gut is related to a variety of neurodegenerative and neuropsychiatric diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), autism spectrum disorders (ASD), depression, and glioblastoma. Mechanistic understandings show that gut microbes critically contribute to neuroimmune and blood-brain barrier (BBB) signaling. The peripheral association of gut microflora, networked with inflammasome activation, nuclear factor kappa B (NF-κB), and type-I IFN pathways highlights their role in CNS inflammation. Microbiota-targeted interventions with probiotics, prebiotics, synbiotics, antibiotics, dietary modifications, and fecal microbiota transplantation are examined for their therapeutic potential. These strategies appear to be promising to reinstate microbial balance, enhance neuroplastic responses, and ameliorate the disease symptoms. The review highlights personalized microbiome-based algorithms, underpinned by integrated multi-omics technologies and machine-learning-driven diagnostics. Future research should address underlying microbial mechanisms and perform large, randomized controlled trials in order to establish microbiota-based therapies for neurological disorders.}, }
@article {pmid41184709, year = {2025}, author = {Kiecka, A and Szczepanik, M}, title = {Dietary modulation of the gut microbiome as a supportive strategy in the treatment of amyotrophic lateral sclerosis - a narrative review.}, journal = {Pharmacological reports : PR}, volume = {}, number = {}, pages = {}, pmid = {41184709}, issn = {2299-5684}, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease leading to permanent damage to the central and peripheral motor neurons. Currently, there is no effective treatment for ALS, and therapy focuses solely on slowing the progression of the disease. Recent studies show that gut microbiota plays an important role in the development of neurodegenerative diseases. Altered gut microbiota has also been found in ALS. These changes have prompted the search for alternative forms of ALS treatment, focusing on changing the microbial composition of the gut. It has been noted that diet, probiotics, prebiotics and vitamins can all influence the course of ALS. Another interesting issue is fecal microbiota transplantation, which is already used in the treatment of certain intestinal diseases and could potentially be useful in the treatment of ALS. This review summarizes current knowledge on the impact of gut microbiota on the neurodegenerative process in ALS, with particular emphasis on the role of diet and probiotics. It also discusses potential mechanisms and highlights future research directions in this emerging field.}, }
@article {pmid41183377, year = {2025}, author = {Morris, AC and Seker, A and Telesia, L and Wickersham, A and Ching, BC and Roy, R and Epstein, S and Matcham, F and Sonuga-Barke, E and Downs, J}, title = {Adherence to Actigraphic Devices in Elementary School-Aged Children: Systematic Review and Meta-Analysis.}, journal = {Journal of medical Internet research}, volume = {27}, number = {}, pages = {e79718}, doi = {10.2196/79718}, pmid = {41183377}, issn = {1438-8871}, mesh = {Humans ; Child ; *Actigraphy/instrumentation ; *Patient Compliance/statistics &amp; numerical data ; Child, Preschool ; Female ; Schools ; Male ; }, abstract = {BACKGROUND: Consistent wear is essential for valid and reliable actigraphy data. Adherence to actigraphy may be challenging in primary school children due to developmental and design considerations, yet no quantitative synthesis of adherence in this age group exists.<br><br>OBJECTIVE: The aim of this study was to provide the first pooled estimate of actigraphy adherence in primary school-aged children and examine the impact of individual, device, and study-specific factors on adherence.<br><br>METHODS: We searched seven electronic databases for studies reporting adherence to actigraphy in primary school-aged children. Searches were conducted in Embase, MEDLINE, PsycINFO, Social Policy and Practice via OVID, Education Resources Information Center, British Education Index, and CINAHL via EBSCO using database-specific search strategies conducted between January 2018 and January 24, 2023. Forward and backward citation searches were completed on the Web of Science Core Collection and Google Scholar. Gray literature searches were undertaken in PsycEXTRA and Healthcare Management Information Consortium. Empirical studies reporting quantitative data on adherence to community-based actigraphy in children aged 5-11 years (or if &#x2265;50% of the average age fell within this range) were included. Eligible studies were written in English and could be published or unpublished. Risk of bias was assessed using an 8-item checklist adapted from Berger et al's actigraphy reporting standards. All included studies were narratively synthesized, and adherence data were pooled in a proportional meta-analysis. Adherence was calculated as the proportion of children meeting wear-time criteria to be included in the analysis compared to the number of children invited to use the device at baseline. Meta-regression was used to examine the impact of individual, device, and study-specific factors on adherence. Prediction intervals were calculated to estimate the range of adherence expected across future studies.<br><br>RESULTS: Data were extracted from 235 studies (N=148,161); of these, 135 studies (n=64,541) provided adherence data for proportional meta-analysis. Pooled adherence, measured across 1-140 days, was 81.6% (95% CI 78.7%-84.4%; I2=98.8%). The prediction intervals (42.8%-100%) indicated substantial variability in adherence estimates across studies. Meta-regression suggested that individual characteristics contributed to observed heterogeneity as children with a physical health diagnosis (b=0.236, 95% CI 0.009-0.464; P=.04) and those with neurodevelopmental or mental health diagnosis (b=0.395, 95% CI 0.125-0.665; P=.004) demonstrated higher adherence than undiagnosed children, though these effects were of modest magnitude. No significant effects were found for age, placement, protocol length, protocol deviation, or incentivization. Reporting quality was poor, with only 3.4% of studies satisfying all criteria.<br><br>CONCLUSIONS: This review demonstrates generally high actigraphy adherence in primary school-aged children, particularly those with health conditions. However, observed variability indicates that adherence was much lower in some contexts, underscoring that the reported pooled adherence cannot be assumed across future actigraphy applications within this age group. Future research should use standardized adherence reporting and should plan for adherence variability.}, }
@article {pmid41182353, year = {2025}, author = {Cai, Y and Huang, S and Dong, Y and Li, S and Jin, X}, title = {PIWI-Interacting RNAs in brain health and disease: biogenesis, mechanisms, and therapeutic horizons.}, journal = {Psychopharmacology}, volume = {}, number = {}, pages = {}, pmid = {41182353}, issn = {1432-2072}, support = {81971083//National Natural Science Foundation of China/ ; 25JCLZJC00190//Tianjin Natural Science Foundation Project/ ; }, abstract = {PIWI-interacting RNAs (piRNAs), a class of small non-coding RNAs originally identified for their role in transposon silencing in germ cells, have recently been recognized as pivotal regulators of gene expression in the central nervous system. Beyond their canonical functions in genome defense, emerging evidence highlights piRNAs as key modulators of neuronal development, synaptic plasticity, axonal regeneration, and neuroimmune interactions-processes central to brain function and dysfunction. This review provides a comprehensive overview of piRNA biogenesis, molecular mechanisms, and regulatory pathways relevant to neurobiology. We focus on the growing body of evidence implicating piRNA dysregulation in major neurological and neuropsychiatric disorders, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, stroke, glioma, autism spectrum disorder, and schizophrenia. Importantly, we discuss the neuropharmacological implications of piRNA pathways as novel targets for therapeutic intervention and their potential utility as biomarkers for early diagnosis and treatment stratification. By integrating mechanistic insights with emerging translational evidence, this review highlights piRNAs as promising molecular targets in the development of next-generation neurotherapeutics aimed at modifying disease progression and improving brain health.}, }
@article {pmid41180593, year = {2025}, author = {Civita, E and Nicolella, V and Fiorenza, M and Cosimato, V and Castaldo, G and Morra, VB and Moccia, M and Terracciano, D}, title = {Advancing Clinical Use of Neurofilament Light Chain: Translational Insights From Research to Routine Practice.}, journal = {Biomarker insights}, volume = {20}, number = {}, pages = {11772719251364018}, pmid = {41180593}, issn = {1177-2719}, abstract = {Neurofilament Light Chain (NfL) has emerged as a promising biomarker for neurological diseases. NfL, a structural component of axons, is released into cerebrospinal fluid (CSF) and blood following neuro-axonal damage. Highly sensitive immunometric assays have enabled its reliable quantification in blood, facilitating non-invasive monitoring. Several studies demonstrated strong correlations between NfL levels and the risk of developing different neurological diseases and, in individuals already living with a neurological disease, with the risk of worsening. However, interpretation is affected by factors like age, BMI, renal function, and comorbidities. NfL is already utilized as a diagnostic and prognostic biomarker in clinical practice, particularly in specialized centers and research settings, although no FDA-cleared assay is currently available for routine use. Recent research has highlighted that NfL may represent the first of a new generation of neurological biomarkers, with many more ready to come, such as glial fibrillary acidic protein (GFAP), further improving diagnostic and prognostic accuracy. Despite its promising role in the landscape of biomarkers, challenges remain to implement NfL in daily clinical practice, including standardization of assays, defining reference values, and ensuring methodological consistency. Addressing these limitations will be essential for integrating NfL into routine clinical practice, ultimately advancing precision medicine in neurology.}, }
@article {pmid41180498, year = {2025}, author = {Shamsi, A and Alrouji, M and AlOmeir, O and Tasqeruddin, S and Dinislam, K and Zuberi, A}, title = {CRISPR-Cas9: bridging the gap between aging mechanisms and therapeutic advances in neurodegenerative disorders.}, journal = {Frontiers in cellular neuroscience}, volume = {19}, number = {}, pages = {1681891}, pmid = {41180498}, issn = {1662-5102}, abstract = {Neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, ALS, and spinocerebellar ataxia are becoming more prevalent as populations age, posing major global health challenges. Despite decades of research, effective treatments that halt or reverse these conditions remain elusive. Aging is the most significant risk factor in the development of these diseases, intertwining with molecular processes like DNA damage, mitochondrial dysfunction, and protein aggregation. Recent advances in gene-editing technologies, particularly CRISPR-Cas9, are beginning to shift the therapeutic landscape. This revolutionary tool allows for precise correction of genetic mutations associated with neurodegeneration, offering the potential for disease modification rather than symptom management alone. In this review, we explore how CRISPR-Cas9 is being leveraged to target key genes implicated in various neurodegenerative conditions and how it may overcome barriers posed by aging biology. We also examine the delivery systems and safety challenges that must be addressed before clinical application. With continued progress, CRISPR-Cas9 could mark a turning point in our ability to treat or even prevent age-related neurological decline.}, }
@article {pmid41179113, year = {2025}, author = {Luo, Y and Xu, Z and Li, Z}, title = {Advances in Induced Pluripotent Stem Cell Reprogramming and Its Application in Amyotrophic Lateral Sclerosis: A Review.}, journal = {FASEB bioAdvances}, volume = {7}, number = {11}, pages = {e70065}, pmid = {41179113}, issn = {2573-9832}, abstract = {Since Yamanaka's landmark achievement in reprogramming somatic cells into induced pluripotent stem cells (iPSCs) using the four key transcription factors-OCT4, SOX2, KLF4, and c-Myc (OSKM)-iPSC technology has made significant strides. Notable advancements include refining reprogramming factors, delivery systems, somatic cell selection, and optimization of reprogramming conditions, along with developing chemical reprogramming methods. With their unparalleled proliferative capacity and near-pluripotent differentiation potential, iPSCs have become invaluable tools for investigating neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Neuronal models derived from ALS patient-specific iPSCs, particularly iPSC-derived motor neurons (iPSC-MNs), offer a robust platform to recapitulate disease-specific pathology and investigate the molecular mechanisms underpinning ALS, thereby accelerating the discovery of novel therapeutic strategies. This review highlights the evolution of iPSC technology and its transformative applications in ALS modeling, drug discovery, and therapeutic development.}, }
@article {pmid41178826, year = {2025}, author = {Stern, C and Semendric, I and Shrestha, N and Beasley-Hall, J and Hasanoff, S and Barker, T and Pollock, D and Schubert, C and Giles, L and Vucic, S and Merlin, T and Munn, Z}, title = {Guidelines addressing Motor Neurone Disease (MND): a scoping review.}, journal = {Neurodegenerative disease management}, volume = {}, number = {}, pages = {1-16}, doi = {10.1080/17582024.2025.2573608}, pmid = {41178826}, issn = {1758-2032}, abstract = {INTRODUCTION: Motor Neurone Disease (MND) is a debilitating neurodegenerative condition affecting individuals, families, and carers. Evidence-informed care can improve outcomes, and guidelines play a key role in supporting this. A preliminary search showed limited guidelines exist, with none developed for the Australian context. This review aimed to identify existing health and social care guidelines for MND.<br><br>METHODS: A scoping review was conducted using Joanna Briggs Institute (JBI) methodology. Guidelines addressing health and social care for people with MND, gene carriers, family members, or carers were included regardless of publication status. Five databases and additional sources were searched. Two reviewers independently screened citations, and data were extracted and analysed descriptively, with qualitative content analysis grouping guideline questions. Reporting followed PRISMA-ScR.<br><br>RESULTS: Forty-two guidelines covering 133 questions were included. Most focused on symptom management for people with MND and were produced by professional bodies. Few used GRADE methodology or systematic reviews, and only seven assessed risk of bias. No guideline was developed for Australia.<br><br>CONCLUSIONS: A high-quality, evidence-based MND guideline following best practice development methods is needed.}, }
@article {pmid41178159, year = {2025}, author = {Mosna, S and Dormann, D}, title = {TDP-43 Phosphorylation: Pathological Modification or Protective Factor Antagonizing TDP-43 Aggregation in Neurodegenerative Diseases?.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {}, number = {}, pages = {e70084}, doi = {10.1002/bies.70084}, pmid = {41178159}, issn = {1521-1878}, support = {//Deutsche Forschungsgemeinschaft (DFG)/ ; //VERUM Foundation/ ; }, abstract = {TDP-43 is a ubiquitously expressed RNA-binding protein that aggregates in the brains of patients suffering from neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and Alzheimer's disease. Aggregated TDP-43 in these diseases is hyperphosphorylated in its C-terminal intrinsically disordered region, while physiological TDP-43 is normally unphosphorylated. Whether TDP-43 phosphorylation is a pathological driver, or rather a protective antagonist of TDP-43 aggregation and consequently neurodegeneration, is still debated and a matter of ongoing research. Here, we review current knowledge about TDP-43 phosphorylation in disease and the kinases and phosphatases that regulate this post-translational modification. We discuss how TDP-43 phosphorylation is thought to shape TDP-43's phase separation, aggregation and toxicity in neurodegenerative diseases. We highlight recent research that provides evidence that hyperphosphorylation antagonizes TDP-43 phase separation and aggregation, and speculate about a potential role of condensates in TDP-43 phosphorylation.}, }
@article {pmid41176929, year = {2025}, author = {Akan, T and Akan, S and Alp, S and Ledbetter, CR and Tafti, AP and Arevalo, O and Bhuiyan, MAN}, title = {Deep Learning in neuroimaging for neurodegenerative diseases: State-of-the art, Challenges, and Opportunities.}, journal = {Journal of the neurological sciences}, volume = {478}, number = {}, pages = {123735}, doi = {10.1016/j.jns.2025.123735}, pmid = {41176929}, issn = {1878-5883}, abstract = {Neuroimaging is commonly used to diagnose neurodegenerative diseases (NDDs), providing crucial insights into brain changes before clinical symptoms manifest. Deep learning (DL) for neuroimaging can improve early diagnosis and disease monitoring. Clinical implementation of DL faces challenges in accurately representing real-world data. Recent models, particularly those focused on diagnostic categorization, have achieved high accuracy, but their applicability to patients is limited. Conflicting inferences have been reported, with findings from small cohorts generalizing conclusions without considering inter-scanner, intra- and inter-site variations. A theoretically feasible method involves gathering a comprehensive dataset that encompasses all patient demographics, but this presents practical challenges including harmonization, data incompleteness, class imbalance, and substantial costs. Existing research has also mostly focused on common NDDs like Alzheimer's Disease (AD) and Parkinson's Disease (PD). This contribution expands the literature by looking at a wider range of NDDs, exploring the latest advancements in applying deep learning algorithms to neuroimaging analysis for the diagnosis and monitoring of NDDs, including AD, Frontotemporal Dementia (FTD), Lewy Body Dementia, PD, Huntington's Disease, Amyotrophic Lateral Sclerosis, and Multiple Sclerosis. We emphasize how these approaches are handling spatial/temporal information available in brain volume imaging data. We conclude by discussing the challenges associated with the use of voxel-based, patch-based, ROI-based, and slice-based approaches in brain volume imaging. These challenges are further compounded by issues such as inter-site and inter-scanner variability, class imbalances in medical datasets, and the scarcity of accurately annotated data, all of which impact the performance and generalizability of deep learning models.}, }
@article {pmid41165792, year = {2025}, author = {Goerdt, LA and Brandl, C and Schuster, AK and Rauscher, FG and Finger, RP and Mauschitz, MM}, title = {[Neurodegeneration and retinal changes-A literature overview].}, journal = {Zeitschrift fur Gerontologie und Geriatrie}, volume = {}, number = {}, pages = {}, pmid = {41165792}, issn = {1435-1269}, abstract = {BACKGROUND: The eyes and the central nervous system (CNS) develop from the same embryonic tissue which explains why retinal changes have been observed in various neurological and neurodegenerative diseases. These changes can be visualized in vivo on a cellular and subcellular level using optical coherence tomography (OCT). This article summarizes which retinal changes occur and how these could be used as potential biomarkers of neurodegenerative diseases.<br><br>OBJECTIVE: The article gives an overview of the literature on the relationship between neurodegeneration, OCT-based retinal characteristics and cognitive functions.<br><br>METHODS: A literature search was carried out in PubMed until February 2025. The search terms "neurodegeneration", "dementia", "mild cognitive impairment", "mild neurocognitive disorder", "OCT", "OCT angiography (OCT-A)", "retinal biomarkers", "retinal layer", "RNFLT", and "GCL" were used. Relevant publications were reviewed, analyzed and summarized.<br><br>RESULTS: In OCT&#x2011;A Alzheimer's disease, frontotemporal dementia, vascular dementia, amyotrophic lateral sclerosis, multiple sclerosis (MS) and Parkinson's disease demonstrate an association with a&#xa0;reduced retinal nerve fiber layer (RNFL) and the ganglion cell layer (GCL) thickness as well as an enlarged foveal avascular zone.<br><br>CONCLUSION: So far retinal changes could not be specifically assigned to a&#xa0;particular form of neurodegenerative disease,; however, they could be meaningful in neuropsychological/radiological examinations and for longitudinal monitoring, as already recommended for MS. Further longitudinal studies are needed to identify and validate retinal biomarkers (patterns).}, }
@article {pmid40975951, year = {2025}, author = {von Quednow, E and Husain, N and Łajczak, P and Linha Secco, G and Koppanatham, A}, title = {Diagnostic accuracy of the Gold Coast Criteria for amyotrophic lateral sclerosis: a systematic review and meta-analysis.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {179}, number = {}, pages = {2111005}, doi = {10.1016/j.clinph.2025.2111005}, pmid = {40975951}, issn = {1872-8952}, mesh = {*Amyotrophic Lateral Sclerosis/diagnosis ; Humans ; Sensitivity and Specificity ; }, abstract = {OBJECTIVE: To compare the diagnostic accuracy of Gold Coast Criteria (GCC) with Revised El Escorial Criteria (rEEC) and Awaji Criteria (AC) in suspected amyotrophic lateral sclerosis (ALS).<br><br>METHODS: PubMed, EMBASE, Web of Science, Cochrane Library, and Google Scholar were searched through December 2024. Eligible studies assessed patients using GCC, rEEC, and/or AC, reporting or allowing calculation of sensitivity and specificity. Quality was evaluated using QUADAS-2 and STARD. "Probable+" included probable and definite classifications; "Possible+" encompassed possible to definite. Sensitivity analyses excluded the largest study with imputed data and included a sensitivity-only model. PRISMA-DTA compliant; PROSPERO CRD42025623678.<br><br>RESULTS: Nine studies (n&#xa0;=&#xa0;9656), all from ALS referral centers, were included. GCC showed higher sensitivity (&#x223c;95&#xa0;%) than rEEC and AC Probable+ (59&#xa0;% and 54&#xa0;%) and Possible+ (84&#xa0;% and 85&#xa0;%), but lower specificity (66&#xa0;%) vs. rEEC (Probable+&#xa0;94&#xa0;%, Possible+&#xa0;77&#xa0;%) and AC (Probable+&#xa0;94&#xa0;%, Possible+&#xa0;82&#xa0;%). GCC achieved the highest AUC (0.95) and diagnostic odds ratio (36.1). Sensitivity-only analysis confirmed GCC performance (97&#xa0;%).<br><br>CONCLUSIONS: GCC demonstrated superior sensitivity, potentially facilitating earlier recognition and trial inclusion. Their lower specificity requires caution, particularly in low-prevalence contexts. Applicability in unselected neurology populations remains uncertain.<br><br>SIGNIFICANCE: GCC may enable earlier ALS diagnosis and timely trial enrollment in referral centers.}, }
@article {pmid40998074, year = {2025}, author = {Fischer, I}, title = {Considering Big tau as a novel and specific biomarker for spinal motor neuron pathology.}, journal = {Neurobiology of disease}, volume = {216}, number = {}, pages = {107118}, doi = {10.1016/j.nbd.2025.107118}, pmid = {40998074}, issn = {1095-953X}, mesh = {Humans ; *tau Proteins/metabolism ; Biomarkers/metabolism ; *Motor Neurons/pathology/metabolism ; Animals ; *Spinal Cord/pathology/metabolism ; *Motor Neuron Disease/metabolism/pathology/diagnosis ; Amyotrophic Lateral Sclerosis/metabolism/pathology ; }, abstract = {Big tau is an isoform of tau that includes the large 4 A exon, resulting in an extended projection domain and an overall increase in apparent molecular weight from 40 to 65 kDa to 95-110 kDa. Its expression is highly restricted to the peripheral and autonomic nervous systems and select regions of the central nervous system. Although the precise function of Big tau remains unclear, we have proposed that the expanded projection domain of low molecular weight (LMW) tau by 250 amino acids of exon 4a and its structural properties may enhance axonal transport in long-projecting neurons and confer resistance to aggregation. Here, we propose a clinical perspective based on the properties of Big tau: the selective expression of Big tau in spinal motor neurons, but not in upper motor neurons or other spinal neuronal populations, is likely to make Big tau a specific biomarker for spinal motor neuron pathology. This expression pattern may be particularly valuable for tracking disease prognosis and progression in conditions such as amyotrophic lateral sclerosis (ALS) and related disorders, to identify when degeneration advances to lower motor neurons. Big tau could thus serve as a more specific biomarker to neurofilament or LMW tau proteins or can be used in combination with other biomarkers to enhance the specificity and sensitivity. This hypothesis can be readily tested using existing samples and assays applied to cerebrospinal fluid (CSF) and blood samples from patients. If validated through clinical studies, Big tau may provide clinicians with a new tool to better diagnose and monitor a variety of motor neuron degenerative disorders. To accelerate research in this area, I offer to share experimental data and an inventory of polyclonal antibodies specific to Big tau to the research community to enable further investigation of Big tau as a clinical biomarker.}, }
@article {pmid41164103, year = {2025}, author = {}, title = {Edaravone for amyotrophic lateral sclerosis.}, journal = {Australian prescriber}, volume = {48}, number = {5}, pages = {182-183}, pmid = {41164103}, issn = {0312-8008}, }
@article {pmid41158661, year = {2025}, author = {Tao, F and Lin, M and Meng, X and Huang, L and Zhuo, B and Jiang, S and Deng, S and Meng, Z and Shi, J}, title = {Copper homeostasis and cuproptosis: implications for neurodegenerative diseases.}, journal = {Frontiers in aging neuroscience}, volume = {17}, number = {}, pages = {1688554}, pmid = {41158661}, issn = {1663-4365}, abstract = {Copper (Cu) is a vital trace element required for sustaining life and is involved in numerous critical metabolic processes within the body. Cuproptosis, a newly recognized type of Cu-dependent cell death, is mechanistically distinct from apoptosis, autophagy, pyroptosis, and ferroptosis. It is characterized by abnormal Cu accumulation and aberrant interactions with key enzymes of the tricarboxylic acid (TCA) cycle, which lead to protein aggregation, loss of iron-sulfur cluster proteins, and proteotoxic stress, ultimately leading to cell death. Recent studies have revealed that Cu dyshomeostasis and cuproptosis are intricately linked to the pathological progression of several neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), Wilson's disease (WD), and Menkes disease (MD). In this review, we systematically elucidate the systemic Cu metabolism, the molecular mechanisms of cuproptosis, and its intricate interplay with different neurodegenerative disorders. We also examined the relationship between cuproptosis and other types of cell death. Finally, we discuss therapeutic strategies targeting cuproptosis and Cu dyshomeostasis to combat neurodegenerative diseases and propose potential directions for future research.}, }
@article {pmid40975292, year = {2025}, author = {Lewis, KN and Gonsalvez, DG and Turner, BJ and Barton, SK}, title = {Schwann cells as a therapeutic target for amyotrophic lateral sclerosis: A TDP-43 focussed review.}, journal = {Neurochemistry international}, volume = {190}, number = {}, pages = {106055}, doi = {10.1016/j.neuint.2025.106055}, pmid = {40975292}, issn = {1872-9754}, mesh = {Humans ; *Schwann Cells/metabolism/drug effects/pathology ; *Amyotrophic Lateral Sclerosis/metabolism/therapy/pathology ; Animals ; *DNA-Binding Proteins/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is an incurable, lethal neurodegenerative disease and a proteinopathy with >97 % of cases characterised by pathological accumulation of TDP-43. TDP-43 is ubiquitously expressed and its pathological accumulation has now been identified in non-neuronal cells in both the central and peripheral nervous systems. Thus, the expansion to exploring other cells and their contribution to ALS pathogenesis may be the key to finding more effective treatments. Schwann cells are the myelinating cells of the peripheral nervous system, that encase neuronal axons to propagate action potentials, maintain neuronal health, and respond to neuronal activity in the extracellular environment. Despite Schwann cells being identified to exhibit aberrant TDP-43 proteinopathy in ALS patients, their role in disease remains elusive. Here, we review the potential contributions of Schwann cells to ALS as well as the prospective benefits of harnessing Schwann cells treat the disease.}, }
@article {pmid41157172, year = {2025}, author = {Carata, E and Destino, M and Tenuzzo, BA and Panzarini, E}, title = {Inter-Organ Crosstalk in Neurodegenerative Disease.}, journal = {Life (Basel, Switzerland)}, volume = {15}, number = {10}, pages = {}, doi = {10.3390/life15101499}, pmid = {41157172}, issn = {2075-1729}, abstract = {Inter-organ communication plays a vital role in the pathogenesis of neurodegenerative diseases (ND), including Alzheimer's disease (AD), Parkinson's disease (PD), and Amyotrophic Lateral Sclerosis (ALS). Emerging research highlights the involvement of the gut-brain axis, immune system, and peripheral metabolic systems in modulating neuroinflammation, protein misfolding, and neuronal dysfunction by releasing cytokines, adipokines, growth factors, and other soluble factors, which in turn affect neuronal health and systemic inflammation. This review explores the complex bidirectional interactions between the brain and peripheral organs, including the gut, adipose tissue, liver, muscle, bone and immune system. Notably, the gut microbiome's role in neurodegenerative diseases through the gut-brain axis, the impact of adipose tissue in inflammation and metabolic regulation, and the muscle-brain axis with its neuroprotective myokines are also discussed. Additionally, we examine the neuro-immune axis, which mediates inflammatory responses and exacerbates neurodegeneration, and liver-brain axis that is implicated in regulating neuroinflammation and promoting disease progression. Dysregulation of inter-organ pathways contributes to the systemic manifestations of neurodegenerative diseases, offering insights into both potential biomarkers and therapeutic targets, and, in turn, promising strategies for preventing, diagnosing, and treating neurodegenerative diseases.}, }
@article {pmid41155689, year = {2025}, author = {Ruffo, P and Perrone, B and Perrone, F and De Amicis, F and Iuliano, R and Bucci, C and Messina, A and Conforti, FL}, title = {The Other Side of the Same Coin: Beyond the Coding Region in Amyotrophic Lateral Sclerosis.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {18}, number = {10}, pages = {}, doi = {10.3390/ph18101573}, pmid = {41155689}, issn = {1424-8247}, support = {2022XTM2S3//Ministero dell'universit&#xe0; e della ricerca/ ; P20225J5NB//Ministero dell'universit&#xe0; e della ricerca/ ; }, abstract = {Transposable elements (TEs), once regarded as genomic "junk," are now recognized as powerful regulators of gene expression, genome stability, and innate immunity. In the context of neurodegeneration, particularly Amyotrophic Lateral Sclerosis (ALS), accumulating evidence implicates TEs as active contributors to disease pathogenesis. ALS is a fatal motor neuron disease with both sporadic and familial forms, linked to genetic, epigenetic, and environmental factors. While coding mutations explain a subset of cases, advances in long-read sequencing and epigenomic profiling have unveiled the profound influence of non-coding regions-especially retrotransposons such as LINE-1, Alu, and SVA-on ALS onset and progression. TEs may act through multiple mechanisms: generating somatic mutations, disrupting chromatin architecture, modulating transcriptional networks, and triggering sterile inflammation via innate immune pathways like cGAS-STING. Their activity is normally repressed by epigenetic regulators, including DNA methylation, histone modifications, and RNA interference pathways; however, these controls are compromised in ALS. Taken together, these insights underscore the translational potential of targeting transposable elements in ALS, both as a source of novel biomarkers for patient stratification and disease monitoring, and as therapeutic targets whose modulation may slow neurodegeneration and inflammation. This review synthesizes the current knowledge of TE biology in ALS; integrates findings across molecular, cellular, and systems levels; and explores the therapeutic potential of targeting TEs as modulators of neurodegeneration.}, }
@article {pmid41155541, year = {2025}, author = {Perez, DM}, title = {α1A-Adrenergic Receptor as a Target for Neurocognition: Cautionary Tale from Nicergoline and Quinazoline Non-Selective Blockers.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {18}, number = {10}, pages = {}, doi = {10.3390/ph18101425}, pmid = {41155541}, issn = {1424-8247}, support = {RO1AG066627/GF/NIH HHS/United States ; }, abstract = {Decades ago, previous studies that used non-selective ergot derivatives suggested that blockage of the α1A-adrenergic receptor mildly increased cognition through increased blood flow to the brain due to vasodilation and, thus, could be used as a treatment for dementia. However, further studies indicated that nicergoline was non-specific and hit many different targets. Today, a similar scenario is developing with the use of non-selective α1-AR antagonists of the quinazoline class, referred to as "osins", as potential treatments for COVID-19/SARS, post-traumatic stress disorder, cancer, and neurodegenerative disorders, such as Parkinson's, Alzheimer's, and amyotrophic lateral sclerosis. While there is extensive evidence of neuroprotection from many clinical trials, the mechanism of action of quinazolines is often not α1-AR-mediated but keyed to its glycolysis-enhancing effects through activation of the enzyme phosphoglycerate kinase 1 (PGK1). These studies have incorrectly labeled the α1A-adrenergic receptor as an "old target" to treat Alzheimer's and other neurocognitive diseases, hampering drug development. This review will summarize these and other studies to indicate that activation, not blockage, of norepinephrine's actions, through α1A-AR, mediates cognitive, memory, and neuroprotective functions that may reverse the progression of neurocognitive diseases.}, }
@article {pmid41155167, year = {2025}, author = {Sharbafshaaer, M and Pepe, R and Notariale, R and Canale, F and Tedeschi, G and Tessitore, A and Bergamo, P and Trojsi, F}, title = {Beyond Antioxidants: The Emerging Role of Nrf2 Activation in Amyotrophic Lateral Sclerosis (ALS).}, journal = {International journal of molecular sciences}, volume = {26}, number = {20}, pages = {}, doi = {10.3390/ijms26209872}, pmid = {41155167}, issn = {1422-0067}, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; Humans ; *NF-E2-Related Factor 2/metabolism/genetics ; Animals ; *Antioxidants/metabolism ; Oxidative Stress ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder involving the progressive degeneration of upper and lower motor neurons. While oxidative stress, RNA-binding protein (RBP) pathology, mitochondrial dysfunction, and glial-neuronal dysregulation is involved in ALS pathogenesis, current therapies provide limited benefit, underscoring the need for multi-target disease-modifying strategies. Nuclear factor erythroid 2-related factor 2 (Nrf2), classically regarded as a master regulator of redox homeostasis, has recently emerged as a central integrator of cellular stress responses relevant to ALS. Beyond its canonical antioxidant function, Nrf2 regulates critical pathways involved in mitochondrial quality control, proteostasis, nucleocytoplasmic transport, RNA surveillance, and glial reactivity. Experimental models demonstrate that astrocyte-specific Nrf2 activation enhances glutathione metabolism, suppresses neuroinflammation, promotes stress granule disassembly, and reduces RBP aggregation. In C9orf72-linked ALS, Nrf2 activation mitigates dipeptide repeat protein toxicity and restores RNA processing fidelity via modulation of nonsense-mediated decay and R-loop resolution. Recent advances in Nrf2-targeted interventions including Keap1-Nrf2 protein-protein interaction inhibitors, dual Nrf2/HSF1 activators, and cell-type-selective Adeno-associated virus 9 (AAV9) vectors show promise in preclinical ALS models. These multimodal approaches highlight Nrf2's therapeutic versatility and potential to address the upstream convergence points of ALS pathogenesis. Taken together, positioning Nrf2 as a systems-level regulator offers a novel framework for developing precision-based therapies in ALS. Integrating Nrf2 activation with RNA- and glia-directed strategies may enable comprehensive modulation of disease progression at its molecular roots.}, }
@article {pmid41154657, year = {2025}, author = {Nhieu, J and Wei, LN}, title = {Targeting CRABP1 Signalosomes in Managing Neurodegeneration.}, journal = {Biomolecules}, volume = {15}, number = {10}, pages = {}, doi = {10.3390/biom15101428}, pmid = {41154657}, issn = {2218-273X}, support = {R01NS132277//National Institute of Health/ ; }, mesh = {Humans ; Animals ; *Receptors, Retinoic Acid/metabolism/genetics ; *Neurodegenerative Diseases/metabolism/drug therapy ; Signal Transduction/drug effects ; Tretinoin/metabolism/pharmacology ; }, abstract = {Retinoic acid (RA) binds RA (RAR) and Retinoid X (RXR) receptors to elicit biological effects by regulating transcription. RA is also known to have non-canonical activities mediated, primarily, by cellular retinoic acid-binding protein 1 (CRABP1) which forms protein complexes named "CRABP1 signalosomes" to regulate cytosolic signaling independent of RARs/RXRs. This review focuses on therapeutic applications in neurodegeneration by targeting CRABP1 signalosomes including CRABP1-MAPK, CRABP1-CaMKII, CRABP1-eIF2α, and others recently identified from our proteomic studies. The mouse Crabp1 gene is regulated by various epigenetic factors and is important for the health of multiple cell types including motor neurons (MNs). In humans, CRABP1 gene expression is reduced in ALS- and SMA-patient MNs. RA is a therapeutic agent for leukemias and dermatological disorders and is being investigated for managing neurodegenerative diseases, but its therapeutic effects are accompanied by RAR-mediated toxic effects. We have uncovered a novel class of synthetic retinoids that bind CRABP1 without acting on RARs, circumventing RAR-mediated toxic effects. These first-generation CRABP1-selective compounds C3, C4, and C32 target CRABP1-MAPK and/or CRABP1-CaMKII signalosomes. This knowledge, together with emerging structural information, sheds lights on the strategies in designing next-generation CRABP1-signalosome-selective retinoids for the management of neurodegenerative diseases.}, }
@article {pmid41151740, year = {2025}, author = {Bhatia, T and Godad, A}, title = {Disrupted proteostasis and ionic imbalance in TDP-43 and tauopathies: Dual drivers of neurodegeneration.}, journal = {Life sciences}, volume = {382}, number = {}, pages = {124055}, doi = {10.1016/j.lfs.2025.124055}, pmid = {41151740}, issn = {1879-0631}, abstract = {Neurodegenerative diseases (NDDs), including Alzheimer's Disease (AD), frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS), are characterized by progressive neuronal dysfunction and protein aggregation. There is a growing body of evidence suggesting that the collapse of proteostasis, the failure of protein homeostasis, is an important contributor to neurotoxicity. In this review, we suggest that this collapse is exacerbated by ionic dysregulation, an important but under-addressed cause of neurodegeneration. Importantly, breakdowns in chloride, bicarbonate, sodium, and calcium homeostasis alter fundamental aspects of cellular physiology, including important aspects of TDP-43 phase separation and tau hyperphosphorylation and aggregation. We suggest that the relationship of proteostasis failure and ionic dysregulation is a bidirectional feedback loop that accelerates the progression of neurodegeneration. Some therapeutic strategies aimed at correcting these mechanisms-including small-molecule chaperone inducers, autophagy inducers, and ion-channel modulators-might hold the potential for disease modification. In this review, we document the complex intersections of proteostasis failure and ionic dysregulation in TDP-43 and tauopathies and provide new ideas for therapies and future studies.}, }
@article {pmid41149991, year = {2025}, author = {Kwiatkowska, A and Grzeczkowicz, A and Lipko, A and Kazimierczak, B and Granicka, LH}, title = {Emerging Approaches to Mitigate Neural Cell Degeneration with Nanoparticles-Enhanced Polyelectrolyte Systems.}, journal = {Membranes}, volume = {15}, number = {10}, pages = {}, doi = {10.3390/membranes15100313}, pmid = {41149991}, issn = {2077-0375}, abstract = {Counteracting neurodegenerative diseases (NDs) presents a multifaceted challenge in the aging societies of Western countries. Each year, millions of people worldwide are affected by such ailments as Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD), multiple sclerosis (MS), spinal cord injury, ischemic stroke, motor neuron disease, spinal muscular atrophy, spinocerebellar ataxia, and amyotrophic lateral sclerosis (ALS). Advancements in modern biomaterial technologies present substantial opportunities for the field of regenerative medicine. Nevertheless, limitations arise from the requirement that biomaterial design be tailored to the specific biological parameters of the target cell types with which they are intended to interact. Such an opportunity creates nanomaterials involving nanoparticles. The surface chemistry of nanoparticles, especially when functionalized with bioactive agents, enhances biocompatibility and facilitates interactions with nervous cells. Herein, we review contemporary strategies in the application of biomaterials for nerve regeneration, with particular emphasis on nanomaterials and biocompatible polyelectrolyte layers, which the authors identify as having the most significant potential to drive transformative advances in regenerative medicine in the near future.}, }
@article {pmid41149102, year = {2025}, author = {Mauriello, L and Cuozzo, A and Pezzella, V and Isola, G and Spagnuolo, G and Iorio-Siciliano, V and Ramaglia, L and Blasi, A}, title = {Oral Health Status in Patients with Amyotrophic Lateral Sclerosis: A Scoping Review.}, journal = {Dentistry journal}, volume = {13}, number = {10}, pages = {}, doi = {10.3390/dj13100455}, pmid = {41149102}, issn = {2304-6767}, abstract = {Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative syndrome which often leads to progressive muscular dysfunction and therefore oral health deterioration. The aim of this scoping review is to evaluate oral health status in ALS patients focusing on the importance of dental care in improving patient's quality of life. Methods: A comprehensive literature search was conducted on PubMed, Scopus, Web of Science, and Embase databases until June 2025 using a combination of keywords and MeSH terms related to ALS and oral health. Studies were screened and selected based on inclusion and exclusion criteria, focusing on human clinical data reporting oral health outcomes in ALS. Results: Eight studies met the inclusion criteria. The findings showed a high prevalence of oral complications in bulbar-onset ALS patients. Common issues included reduced tongue mobility, poor oral hygiene, sialorrhea, and decreased masticatory function were evaluated. Conclusions: Oral health impairment in ALS patients frequently contributes to systemic risks and reduced quality of life. A dental expert may play an important role in multidisciplinary care teams in terms of early diagnosis and conservative treatment of oral diseases ranging from periodontal disease to temporomandibular disorders (TMD). Personalized oral hygiene strategies and adjunctive therapies may serve as key elements in maintaining overall health and patient comfort in ALS. Therefore, the objective of the following review was to evaluate oral health complication in patients with ALS, highlighting the impact of oral care on patients' quality of life.}, }
@article {pmid41148800, year = {2025}, author = {Salmaso, V and Menin, S and Moro, S and Spalluto, G and Federico, S}, title = {Adenosine Receptors in Neuroinflammation and Neurodegeneration.}, journal = {Cells}, volume = {14}, number = {20}, pages = {}, doi = {10.3390/cells14201585}, pmid = {41148800}, issn = {2073-4409}, mesh = {Humans ; *Receptors, Purinergic P1/metabolism ; *Neurodegenerative Diseases/metabolism ; Animals ; *Neuroinflammatory Diseases/metabolism ; Adenosine/metabolism ; *Inflammation/metabolism ; }, abstract = {Adenosine plays a crucial role in various pathophysiological conditions, including neuroinflammation and neurodegeneration. Neuroinflammation can be either beneficial or detrimental to the central nervous system, depending on the intensity and duration of the inflammatory response. Across a wide range of brain disorders, neuroinflammation contributes to both the onset and progression of disease. Notably, neuroinflammation is not limited to conditions primarily classified as neuroinflammatory but is also a key factor in other neurological disorders, including life-threatening neurodegenerative diseases. All four adenosine receptor subtypes (A1, A2A, A2B, and A3) are implicated, to varying degrees, in these conditions. This review aims to summarize the roles of individual adenosine receptor subtypes in neuroinflammation and neurodegenerative diseases, emphasizing their therapeutic potential. While some therapeutic applications are well-established with clinically approved drugs, others warrant further investigation due to their promising potential.}, }
@article {pmid41148458, year = {2025}, author = {Goel, F and Kumar, D and Singh, P and Rai, SN and Yadav, DK}, title = {Molecular crosstalk between miRNAs and lncRNAs in neurodegenerative disease pathways.}, journal = {Molecular biology reports}, volume = {53}, number = {1}, pages = {16}, pmid = {41148458}, issn = {1573-4978}, mesh = {Humans ; *RNA, Long Noncoding/genetics/metabolism ; *MicroRNAs/genetics/metabolism ; *Neurodegenerative Diseases/genetics/metabolism/therapy ; Gene Expression Regulation ; Animals ; Signal Transduction ; Gene Regulatory Networks ; }, abstract = {Neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic Lateral Sclerosis (ALS), are characterized by progressive neuronal degeneration and dysfunction. Of recent interest, a series of studies have been targeting the role of non-coding RNAs, particularly miRNAs and lncRNAs, in regulating gene expression and influencing cellular pathways that may play a critical role in the pathogenesis of these diseases. miRNAs regulate many biological processes by degrading or repressing the translation of target mRNAs, whereas lncRNAs act as scaffolds, sponges, and guides to control gene expression and cellular activities. Both miRNAs and lncRNAs participate in neurodegenerative mechanisms such as protein aggregation, inflammation, oxidative stress, and neuroinflammation. While targeting miRNAs and lncRNAs holds promise for potential therapeutic benefits, problems persist with their efficient delivery, specificity, and off-target effects. New techniques like viral vectors, lipid nanoparticles, and CRISPR-based gene editing will further enhance the development of therapies based on miRNA and lncRNA. Moreover, their interaction with regulatory networks may present new avenues toward understanding disease mechanisms and guiding therapeutic design. This review covers the role of miRNAs and lncRNAs in neurodegenerative disorders, their therapeutic potential, challenges, and future directions in ncRNA-based treatment approaches.}, }
@article {pmid41146616, year = {2025}, author = {Roberts, L and Trakman, G and Furness, K and Farrugia, E}, title = {Risks and Benefits of Gastrostomy in Non-Motor Neurone Disease Progressive Neurological Diseases: A Systematic Review.}, journal = {Journal of human nutrition and dietetics : the official journal of the British Dietetic Association}, volume = {38}, number = {6}, pages = {e70144}, doi = {10.1111/jhn.70144}, pmid = {41146616}, issn = {1365-277X}, support = {//The authors received no specific funding for this work./ ; }, mesh = {Humans ; *Gastrostomy/adverse effects/methods ; Parkinson Disease/surgery ; Risk Assessment ; Enteral Nutrition ; Multiple Sclerosis/surgery/therapy ; *Nervous System Diseases/surgery ; Adult ; Huntington Disease/surgery ; }, abstract = {OBJECTIVES: This review aimed to synthesise current evidence on the effects of gastrostomy in Parkinson's disease (PD) and parkinsonism, Multiple Sclerosis (MS) and Huntington's disease (HD).<br><br>PURPOSE: Evidence regarding the risks and benefits of gastrostomy insertion and use in progressive neurological diseases, excluding Motor Neurone Disease (MND), is lacking, causing gastrostomy decision-making discussions to arise as a matter of debate in practice.<br><br>METHODS: Three databases (Web of Science, Ovid Medline and Embase) were searched for research on the impacts of gastrostomy, including survival, complication rates, nutrition changes, in adults with progressive neurological diseases, excluding MND. Quality was assessed using the Academy of Nutrition and Dietetics Quality Criteria Checklist: Primary Research, and a narrative synthesis was conducted.<br><br>RESULTS: Twelve (n&#x2009;=&#x2009;12) studies were eligible for inclusion, with either retrospective cohort (n&#x2009;=&#x2009;12) or cross-sectional (n&#x2009;=&#x2009;1) design, examining the effects of percutaneous endoscopic gastrostomy (PEG) (n&#x2009;=&#x2009;8), radiologically inserted gastrostomy (RIG) (n&#x2009;=&#x2009;1) or gastrostomy not further defined (n&#x2009;=&#x2009;4) in adults with PD (n&#x2009;=&#x2009;6), parkinsonism (n&#x2009;=&#x2009;3), MS (n&#x2009;=&#x2009;3), or HD (n&#x2009;=&#x2009;3). There was variability in outcomes and comparators with inconclusive results. Quality was assessed as positive (n&#x2009;=&#x2009;3) or neutral (n&#x2009;=&#x2009;9). Gastrostomy appears to be associated with increased care needs in the population of interest.<br><br>CONCLUSIONS: Gastrostomy insertion and use in this cohort is poorly investigated. High-quality prospective studies, especially with well-defined nutrition-related outcome measures, and robust statistical analyses are needed to determine the potential benefits of gastrostomy in this population.<br><br>TRIAL REGISTRATION: PROSPERO: CRD42024604136.}, }
@article {pmid41144030, year = {2025}, author = {Yang, D and Lei, X and Yang, L and He, D}, title = {A novel frameshift mutation in the NEK1 gene causing amyotrophic lateral sclerosis: A case report and literature review.}, journal = {Neurogenetics}, volume = {26}, number = {1}, pages = {75}, pmid = {41144030}, issn = {1364-6753}, mesh = {Humans ; *NIMA-Related Kinase 1/genetics ; *Amyotrophic Lateral Sclerosis/genetics ; *Frameshift Mutation ; Male ; Aged ; Female ; Middle Aged ; }, abstract = {To investigate a novel NIMA Related Kinase 1 (NEK1) frameshift mutation in amyotrophic lateral sclerosis (ALS), assess its pathogenicity using computational algorithms and genetic databases, and analyze the clinical manifestations of cases carrying the NEK1 genetic mutation. A 65-year-old man with sporadic ALS (sALS) carrying a NEK1 c.2413dup (p.Thr805Asnfs*7) mutation was studied. Clinical and genetic data were evaluated using Mutation Taster and ACMG guidelines. A literature review was conducted in PubMed and CNKI to identify ALS cases with NEK1 mutations. Whole-exome sequencing identified a NEK1 mutation, c.2413dup (p.Thr805Asnfs*7),which is predicted to lead to a truncated protein. A literature review found 19 articles covering 89 mutation sites. Among the recorded cases, sex was reported for 79 cases (47 male,32 female), and age of onset was available for 80 cases, with an average of 56.94 ± 11.88 years. Onset type data were available for 77 cases, of which 49.35% (38/77) had lower motor neuron onset,41.56% (32/77) had upper motor neuron onset, and 9.09% (7/77) had both. Among those with lower motor neuron onset (n = 38),28.95% (11/38) had bulbar onset, and 2.63% (1/38) had respiratory onset. The c.2413dup (p.Thr805Asnfs*7) frameshift mutation in the NEK1 gene is likely pathogenic and may contribute to the onset of ALS. ALS associated with NEK1 mutations appears to be more common in men than women and typically affects individuals in late middle age.}, }
@article {pmid41141079, year = {2025}, author = {Jeong, E and Li, D}, title = {Antisense Oligonucleotide Therapy for Amyotrophic Lateral Sclerosis (ALS): An Umbrella Review.}, journal = {Cureus}, volume = {17}, number = {9}, pages = {e93140}, pmid = {41141079}, issn = {2168-8184}, abstract = {Amyotrophic lateral sclerosis, also known as ALS or Lou Gehrig's disease, is a fatal neurodegenerative disease prominent in the elderly population. To this point, no completely effective treatments have been procured; however, antisense oligonucleotide therapies, or ASOs, are a promising venue. In order to investigate the efficacy of ASOs in the treatment of ALS by targeting specific genetic mutations, we conducted an umbrella review utilizing keywords such as "ALS" and "ASO" in the PubMed database, excluding sources published more than 10 years ago for relevance. Results revealed that of multiple tentative ASO treatments, for multiple specific gene mutations, only one, Tofersen, was approved for the wider population. The main cause of failure was an inability to meet efficacy endpoints, resulting in the discontinuation of the product. Tofersen is able to treat mutations in the SOD1 gene, but not any others. While initially discouraging, the production of ASOs is a relatively new and advanced process, and slow progress is expected. However, there remains the problem of identifying and treating the much more prevalent sporadic ALS, which is much more common compared to familial ALS.}, }
@article {pmid41140053, year = {2025}, author = {Obara, K and Ito, D and Nilsson, C and Janelidze, S and Santillo, A and Katsuno, M and Mattsson-Carlgren, N}, title = {Diagnostic and Prognostic Value of Blood and Cerebrospinal Fluid Biomarkers in Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis.}, journal = {European journal of neurology}, volume = {32}, number = {10}, pages = {e70382}, doi = {10.1111/ene.70382}, pmid = {41140053}, issn = {1468-1331}, support = {//Elsa Schmitz stiftelse f&#xf6;r neurologisk och neurokirurgisk forskning/ ; JPMJSP2125//Japan Science and Technology Agency (JST) SPRING/ ; //Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/cerebrospinal fluid/blood/diagnosis ; Biomarkers/cerebrospinal fluid/blood ; Prognosis ; Neurofilament Proteins/cerebrospinal fluid/blood ; }, abstract = {BACKGROUND: Reliable biomarkers for amyotrophic lateral sclerosis (ALS) are urgently needed due to diagnostic and prognostic challenges. This systematic review and meta-analysis aimed to synthesize recent evidence on the utility of blood and cerebrospinal fluid (CSF) biomarkers for ALS.<br><br>METHODS: We systematically reviewed studies published from January 1, 2019 to March 25, 2025, that evaluated blood or CSF biomarkers for ALS. Eligible studies reported diagnostic performance, group-level biomarker values, hazard ratios (HRs) for survival, or correlations with functional rating scales&#xa0;or disease progression rates. Study quality was assessed using the QUADAS-2 and QUIPS frameworks. Random-effects models were employed to pool summary receiver operating characteristic (SROC) curves, HRs, standardized mean differences, and correlation coefficients.<br><br>RESULTS: We included 47 studies in the SROC analysis and 27 in the HR analysis, covering 9078 participants (5556 ALS and 3522 controls). Neurofilament light chain (NfL) consistently demonstrated the highest diagnostic accuracy (sensitivity/specificity: 0.81-0.87 vs. ALS mimics) and high prognostic value (pooled HRs: 2.8-4.3) in both blood and CSF. CSF chitinases and the p-tau/t-tau ratio showed moderate utility. Other biomarkers, including interleukins, had limited clinical relevance. Most studies showed moderate to high risk of bias, with methodological heterogeneity and limited transparency.<br><br>CONCLUSIONS: NfL is the most validated biomarker for ALS diagnosis and prognosis, in both blood and CSF. However, its limited accuracy when used alone carries a considerable risk of misclassification. Future studies should adopt prevalence-specific strategies and integrate biomarkers within&#xa0;multimodal frameworks to enhance diagnostic and prognostic precision.}, }
@article {pmid41136086, year = {2025}, author = {Tran, K and Lussier, BL}, title = {Noninvasive Ventilation in Amyotrophic Lateral Sclerosis.}, journal = {Sleep medicine clinics}, volume = {20}, number = {4}, pages = {547-555}, doi = {10.1016/j.jsmc.2025.07.007}, pmid = {41136086}, issn = {1556-4088}, mesh = {*Amyotrophic Lateral Sclerosis/therapy/complications ; Humans ; *Noninvasive Ventilation/methods ; *Respiratory Insufficiency/therapy/etiology ; }, abstract = {This article explores the role of early noninvasive ventilation in improving the quality of life and survival rates in patients with amyotrophic lateral sclerosis (ALS). It discusses how the goals of ventilatory support may vary depending on whether hospitalization is elective or emergent. The article emphasizes the importance of protocol-based optimization of nocturnal noninvasive positive pressure ventilation, focusing on patient tolerance and neuromuscular considerations. Additionally, it highlights the different approaches required for nocturnal and daytime ventilatory support, underscoring the need for tailored management strategies in ALS care.}, }
@article {pmid39328135, year = {2025}, author = {Sharma, S and Mehan, S and Khan, Z and Tiwari, A and Kumar, A and Gupta, GD and Narula, AS and Kalfin, R}, title = {Exploring the Neuroprotective Potential of Icariin through Modulation of Neural Pathways in the Treatment of Neurological Diseases.}, journal = {Current molecular medicine}, volume = {25}, number = {8}, pages = {962-979}, pmid = {39328135}, issn = {1875-5666}, support = {CRG/2021/001009//DST-SERB, Govt. Of India/ ; }, mesh = {Humans ; *Flavonoids/therapeutic use/pharmacology/chemistry ; *Neuroprotective Agents/therapeutic use/pharmacology ; Animals ; Signal Transduction/drug effects ; *Nervous System Diseases/drug therapy/metabolism ; *Neurodegenerative Diseases/drug therapy/metabolism ; }, abstract = {Neuropathological diseases involve the death of neurons and the aggregation of proteins with altered properties in the brain. Proteins are used at the molecular level to categorize neurodegenerative disorders, emphasizing the importance of protein-processing mechanisms in their development. Natural herbal phytoconstituents, such as icariin, have addressed these neurological complications. Icariin, the principal compound in Epimedium, has been studied for its antineuroinflammatory, anti-oxidative, and antiapoptotic properties. Recent scientific investigations have shown that icariin exhibits promising therapeutic and preventive properties for mental and neurodegenerative disorders. In preclinical, icariin has been shown to inhibit amyloid development and reduce the expression of APP and BACE-1. Previous preclinical studies have demonstrated that icariin can regulate proinflammatory responses in neurological conditions like Parkinson's disease, depression, cerebral ischemia, ALS, and multiple sclerosis. Studies have shown that icariin possesses neuroprotective properties by modulating signaling pathways and crossing the blood-brain barrier, suggesting its potential to address various neurocomplications. This review aims to establish a foundation for future clinical investigations by examining the existing literature on icariin and exploring its potential therapeutic implications in treating neurodegenerative disorders and neuropsychiatric conditions. Future research may address numerous concerns and yield captivating findings with far-reaching implications for various aspects of icariin.}, }
@article {pmid41135633, year = {2025}, author = {Vu, TD and Sung, H}, title = {Endoplasmic reticulum in the axon: Insights into structural dynamics and implications in neurodegeneration.}, journal = {Neurobiology of disease}, volume = {}, number = {}, pages = {107152}, doi = {10.1016/j.nbd.2025.107152}, pmid = {41135633}, issn = {1095-953X}, abstract = {The endoplasmic reticulum (ER) is an interconnected and highly dynamic organelle essential for multiple cellular functions. In neurons, the ER extends into axons, where it plays a pivotal role in maintaining neuronal polarity. The unique structural and dynamic adaptations of the axonal ER enable it to meet the specialized demands of neurons, ranging from compartmentalized physiological regulation to long-distance intracellular communication. Recent studies have shown that axonal ER supports the regulation of organelle remodeling and trafficking in a spatiotemporal manner, processes that become compromised in aged neurons. Moreover, disruptions in the structure and dynamics of the axonal ER have increasingly become associated with neurodegenerative diseases, including hereditary spastic paraplegia, amyotrophic lateral sclerosis, and peripheral neuropathies. This review synthesizes current knowledge of axonal ER biology, highlighting its structural and dynamic characteristics, its impact on organelle arrangement and distribution, and its pathological implications in neurodegeneration. By consolidating recent advances, this review outlines emerging questions and future directions in axonal ER research, a field gaining recognition for its contribution to neuronal dysfunction and neurodegenerative pathomechanisms.}, }
@article {pmid41133655, year = {2025}, author = {Di Fronzo, P and Gaetti, G and Marcassa, D and Gervasi, V and Dardour, O and Pedretti, A and Gambolò, L}, title = {The Impact of ACLS Training in the Management of Cardiac Arrest: A Narrative Review.}, journal = {Epidemiologia (Basel, Switzerland)}, volume = {6}, number = {4}, pages = {}, doi = {10.3390/epidemiologia6040061}, pmid = {41133655}, issn = {2673-3986}, abstract = {BACKGROUND: Cardiac arrests can occur both in and out of hospital settings. Over the years, several protocols have been developed to standardize the behavior of healthcare professionals called upon to deal with these emergencies. Advanced Cardiac Life Support (ACLS) algorithms enable healthcare professionals to effectively manage cardiac arrest and achieve better patient outcomes, particularly at the time of discharge.<br><br>METHODS: We conducted a narrative review. Three databases (PubMed, Embase, Cochrane) were searched for relevant articles. The articles were screened and analyzed in accordance with the PRISMA guidelines.<br><br>RESULTS: A total of 1252 articles were initially identified. After screening, 11 papers were included in the review. From the selected studies, it has emerged that ACLS training had several positive effects, including an overall decrease in mortality rates. Adherence to ACLS protocols throughout an event is associated with increased Return of Spontaneous Circulation (ROSC) in the setting of In-Hospital Cardiac Arrest (IHCA). Advanced Life Support (ALS) response interval in out-of-hospital cardiac arrest was associated with decreased survival and a favorable neurological outcome. ALS response &#x2264; 10 min was associated with improved survival and favorable neurological outcomes.<br><br>CONCLUSIONS: This review underscores the importance of adherence to ALS/ACLS guidelines in the resuscitation of patients who suffer in-hospital and out-of-hospital cardiac arrest.}, }
@article {pmid41131592, year = {2025}, author = {Theunissen, F and Flynn, L and Iacoangeli, A and Al Khleifat, A and Al-Chalabi, A and Giordano, JJ and Strømme, M and Akkari, PA}, title = {Entering the era of precision medicine to treat amyotrophic lateral sclerosis.}, journal = {Molecular neurodegeneration}, volume = {20}, number = {1}, pages = {111}, pmid = {41131592}, issn = {1750-1326}, mesh = {*Amyotrophic Lateral Sclerosis/genetics/drug therapy/therapy ; Humans ; *Precision Medicine/methods ; }, abstract = {With the disease modifying therapy Qalsody (tofersen) which targets the RNA product of the SOD1 gene, having been shown effective in amyotrophic lateral sclerosis (ALS), the present perspective seeks to explore progress towards the implementation of precision medicine principles in ALS drug development. We address the advances in our understanding of the complex genetic architecture of ALS, including the varying models of genetic contribution to disease, and the importance of understanding population genetics and genetic testing when considering patient selection for clinical studies. Additionally, we discuss the advances in long-read whole-genome sequencing technology and how this method can improve streamlined genetic testing and our understanding of the genetic heterogeneity in ALS. We highlight the recent advances in omics-data for understanding ALS patient sub-groups and how this knowledge should be applied to pre-clinical drug development in a proposed patient profiling workflow, particularly for gene targeted therapies. Finally, we summarise key ethical considerations that are pertinent to equitable care for patients, as we enter the era of precision medicine to treat ALS.}, }
@article {pmid41126230, year = {2025}, author = {Lai, YH and Lin, KH and Huang, HK and Huang, TW and Kuo, YS}, title = {The first case of diaphragm pacing system implantation in a patient with high cervical spinal cord injury in taiwan: a case report and literature review.}, journal = {Journal of cardiothoracic surgery}, volume = {20}, number = {1}, pages = {377}, pmid = {41126230}, issn = {1749-8090}, mesh = {Humans ; *Diaphragm/innervation/physiopathology ; *Spinal Cord Injuries/complications ; Taiwan ; Male ; Laparoscopy/methods ; Middle Aged ; Cervical Vertebrae/injuries ; *Electric Stimulation Therapy/methods ; *Respiratory Insufficiency/etiology/therapy ; }, abstract = {INTRODUCTION: This report presents the first case of a patient with high cervical spinal cord injury who underwent successful laparoscopic implantation of a diaphragm pacing system in Taiwan. It also compares the pros and cons of laparoscopic and thoracoscopic implantation and discusses postoperative care.<br><br>BACKGROUND: The diaphragm pacing system (DPS) represents a substantial advancement in respiratory support technology, particularly for patients with chronic respiratory insufficiency. It electrically stimulates the phrenic nerve, which in turn activates the diaphragm-the primary muscle involved in respiration [1]. This stimulation mimics the natural neural impulses that drive diaphragmatic contractions, thereby promoting inhalation and a more efficient lung ventilation. The DPS typically consists of implanted electrodes, an external pulse generator, and connecting leads [2]. It is mainly used in patients with high spinal cord injuries, amyotrophic lateral sclerosis, and central hypoventilation syndrome. These conditions often result in compromised neural control of the diaphragm, leading to severe respiratory insufficiency. By restoring diaphragm function, DPS can enhance the patients' quality of life, reduce dependence on mechanical ventilators, and lower the risk of ventilator-associated complications [3]. Despite its benefits, DPS is not without challenges. Patient selection and the surgical approach are critical to perform successful DPS implantation for the restoration of diaphragm function [4]. This report presents the first case of a patient with cervical spine injury who underwent successful laparoscopic implantation of DPS in Taiwan. Furthermore, it discusses postoperative ICU care and reviews the pros and cons of different surgical approaches to performing DPS implantation.}, }
@article {pmid41124800, year = {2025}, author = {Sergeeva, OS and Neklesova, MV and Reushev, VA and Artemov, AV and Kuznetsova, IM and Turoverov, KK and Uversky, VN and Fonin, AV}, title = {On the potential roles of TDP-43 in the formation of membraneless organelles and their transformation into toxic aggregates.}, journal = {Biochemical and biophysical research communications}, volume = {788}, number = {}, pages = {152808}, doi = {10.1016/j.bbrc.2025.152808}, pmid = {41124800}, issn = {1090-2104}, abstract = {Trans-activation response (TAR) DNA-binding protein 43 (TDP-43) is an RNA-binding protein involved in the processing, transport, and regulation of mRNA translation. It is distributed in many tissues, including the brain, where it is found mainly in hippocampal neurons. Abnormal localization, hyperphosphorylation, and aggregation of TDP-43 are pathological signs of a group of neurodegenerative diseases known as TDP-43 proteinopathies. Despite the growing understanding of the physiological role of TDP-43 in ensuring neuronal plasticity and the formation of long-term memory, to date, there is no comprehensive data on the molecular and cellular mechanisms of the transformation of functional membraneless organelles (MLOs) containing TDP-43 into toxic aggregates and the pathogenesis of associated diseases, such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). This review is devoted to highlighting the role of MLOs in the formation of irreversible aggregates, the role of TDP-43 in the formation of MLOs and their relationship with pathological forms of TDP-43, most often found in people suffering from neurodegenerative diseases.}, }
@article {pmid41122379, year = {2025}, author = {Takahashi, H and Kasai, T and Miyagawa-Hayashino, A and Ohara, T}, title = {Emerging roles of primary cilia in the pathogenesis of amyotrophic lateral sclerosis.}, journal = {Frontiers in neuroscience}, volume = {19}, number = {}, pages = {1688839}, pmid = {41122379}, issn = {1662-4548}, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease primarily affecting motor neurons, for which effective disease-modifying therapies remain elusive. Primary cilia are solitary microtubule-based organelles critical for signal transduction and have recently been implicated in ALS pathogenesis. In this review, we provide a basic overview of the structure, dynamics, and functions of primary cilia, particularly in the brain. We highlight accumulating evidence from ALS models showing altered ciliary structure and function and explore how mutations in ALS-associated genes such as NEK1, C21orf2, and C9orf72 disrupt ciliogenesis and ciliary signaling. Moreover, we examine the interplays between primary cilia dysfunction and known ALS-related mechanisms, including loss of proteostasis, abnormal RNA metabolism, microtubule dysfunction, neuroinflammation, and mitochondrial dysfunction. Collectively, the evidence suggests a bidirectional relationship in which ciliary impairment and ALS pathomechanisms reinforce one another in a vicious cycle. We further discuss emerging therapeutic strategies targeting ciliary function, as well as the potential for primary cilia as novel clinical applications. Our review highlights primary cilia as a previously underappreciated yet potentially important component of ALS biology, offering novel insights into disease mechanisms and future therapeutic development.}, }
@article {pmid41118343, year = {2025}, author = {Cheng, YH and Ho, MS}, title = {Disease-associated microglia in neurodegenerative diseases: Friend or foe?.}, journal = {PLoS biology}, volume = {23}, number = {10}, pages = {e3003426}, pmid = {41118343}, issn = {1545-7885}, mesh = {*Microglia/metabolism/pathology ; Humans ; Animals ; *Neurodegenerative Diseases/pathology/metabolism ; Alzheimer Disease/pathology/metabolism ; Mice ; Disease Models, Animal ; Aging ; Amyotrophic Lateral Sclerosis/pathology/metabolism ; Phagocytosis/genetics ; Lipid Metabolism ; Transcriptome ; }, abstract = {Recent advances in single-cell transcriptomics have led to the identification of disease-associated microglia (DAM) as a distinct, conserved microglia state associated with mouse models of Alzheimer's disease (AD) and amyotrophic lateral sclerosis, and with aging. DAM are characterized by downregulation of homeostatic genes and upregulation of lipid metabolism and phagocytosis genes, including key risk factors for AD in humans. Although characterized in models of AD, whether DAM acts as universal sensor across all neurodegenerative diseases remains unknown. This Essay discusses the dynamics, origins, and therapeutic potential of DAM in neurodegeneration, alongside evidence supporting a protective role for them in regulating disease processes.}, }
@article {pmid41016762, year = {2025}, author = {Riku, Y and Kobayashi, R}, title = {[Pathomechanisms of frontotemporal lobar degeneration: from view of clinical neuropathology].}, journal = {Rinsho shinkeigaku = Clinical neurology}, volume = {65}, number = {10}, pages = {711-720}, doi = {10.5692/clinicalneurol.cn-002103}, pmid = {41016762}, issn = {1882-0654}, mesh = {Humans ; *Frontotemporal Lobar Degeneration/pathology/genetics/etiology ; tau Proteins/metabolism ; }, abstract = {Frontotemporal lobar degeneration (FTLD) encompasses frontotemporal dementia and related neurological disorders including motor neuron disease and movement disorders. During the 21th century, analyses of aggregative proteins suggested powerful hypotheses of gain-of-neurotoxicity or loss-of-function for aggregation-related proteins. However, recent translational researches in collaboration of basic studies and human pathology indicate that FTLD arises from more complex molecular mechanisms than dyshomeostasis of single molecules. Additionally, accumulation of clinicopathological evidences from various countries, genetic backgrounds or clinical specialties (e.g. neurology and psychiatry), suggests diverse phenotypes of FTLD, which are indicative of future paradigm-shift in the concept of FTLD. In this paper, we discuss FTLD pathomechanism on the basis of human pathology.}, }
@article {pmid41113933, year = {2025}, author = {Wang, Z and Cao, W and Fan, D}, title = {Role of lipocalin-2 in amyotrophic lateral sclerosis.}, journal = {Frontiers in aging neuroscience}, volume = {17}, number = {}, pages = {1672903}, pmid = {41113933}, issn = {1663-4365}, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized pathologically by degeneration of upper and lower motor neurons, ultimately leading to muscle weakness and respiratory failure. Lipocalin-2 (LCN2) is a secreted protein involved in lipid transport that plays a key role in inflammatory responses and the regulation of iron homeostasis. The role of LCN2 in ALS has attracted increasing attention, as significantly elevated LCN2 expression has been observed in the blood and postmortem tissues of ALS patients. Functionally, LCN2 participates in neuroinflammation, iron dysregulation, cell death, and peripheral immune immunity, proposing a central-peripheral linkage hypothesis mediated by LCN2. Clinically, LCN2 shows promise as both a biomarker and a therapeutic target, with multiple strategies demonstrating potential to mitigate ALS pathology. Moving forward, it is essential to integrate multi-omics to deeply decipher LCN2-mediated molecular networks, advance patient stratification, and accelerate its clinical translation.}, }
@article {pmid41113424, year = {2025}, author = {Maidina, A and Wang, F}, title = {[Advances in the Structure and Function of Neurofilament Protein and Its Application in Early Diagnosis of Amyotrophic Lateral Sclerosis].}, journal = {Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition}, volume = {56}, number = {4}, pages = {1145-1151}, pmid = {41113424}, issn = {1672-173X}, mesh = {*Amyotrophic Lateral Sclerosis/diagnosis/metabolism ; Humans ; *Neurofilament Proteins/chemistry/metabolism/physiology ; Early Diagnosis ; Biomarkers ; }, abstract = {Neurofilament proteins (NFs), defined as a type Ⅳ intermediate filaments, are important components of the neuronal cytoskeleton. They play a key physiological role in maintaining the structural integrity and plasticity of axons and in ensuring the axonal transport function. Under pathological conditions, NFs detach from axons and undergo abnormal aggregation, causing axonal transport dysfunction. In addition, some components of the detached NFs leak into the peripheral circulation system. In patients with amyotrophic lateral sclerosis (ALS), the concentration of NFs is significantly elevated in the cerebrospinal fluid and blood, and the changes in NFs concentration is significantly positively correlated with the disease progression of ALS, suggesting the potential of NFs being used as early diagnostic biomarkers for ALS. In this review, we explored the relationship between NFs structure, assembly, and physiological function, focusing on the molecular mechanisms and clinical manifestations of ALS caused by abnormal assembly of NFs. We comprehensively summarized recent advances in the application of NFs as a new humoral biomarkers for early diagnosis and therapeutic monitoring of ALS. Key challenges in biomarker development-including undefined pathological neurofilament light chain (NFL) fragments, limited antibody availability, and poor assay reproducibility-are discussed. Strategies, including ultrasensitive detection technologies such as single molecule array (Simoa), antibody optimization based on pathological fragment identification, and multi-omics biomarker panels, should be integrated. These approaches may lead to breakthroughs, pave the way for precision-based ALS diagnosis, provide theoretical support for promoting its clinical translation and application, and offer ideas for future research.}, }
@article {pmid41110100, year = {2025}, author = {Yu, H and Chen, X and Yang, Y and Gu, M and Ren, K and Wei, Z}, title = {Decoding Glycosylation in Neurodegenerative Diseases: Mechanistic Insights and Therapeutic Opportunities.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {39}, number = {20}, pages = {e71160}, pmid = {41110100}, issn = {1530-6860}, support = {82301342//MOST | National Natural Science Foundation of China (NSFC)/ ; 82201455//MOST | National Natural Science Foundation of China (NSFC)/ ; 82470403//MOST | National Natural Science Foundation of China (NSFC)/ ; 82204389//MOST | National Natural Science Foundation of China (NSFC)/ ; }, mesh = {Humans ; Glycosylation ; *Neurodegenerative Diseases/metabolism/therapy/pathology ; *Protein Processing, Post-Translational ; Animals ; Biomarkers/metabolism ; }, abstract = {Glycosylation is a highly dynamic and complex post-translational modification that plays a pivotal role in regulating protein folding, trafficking, stability, and function. Accumulating evidence indicates that aberrant glycosylation is intimately involved in the pathogenesis of multiple neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). This review provides a comprehensive overview of the molecular mechanisms by which the two predominant forms of glycosylation, N-glycosylation and O-GlcNAcylation, contribute to protein misfolding, synaptic dysfunction, neuroinflammation, and impaired stress responses in the diseased nervous system. We further explore the diagnostic potential of glycosylation biomarkers and emerging therapeutic strategies targeting glycosylation pathways. Special emphasis has been placed on recent advances in glycomic technologies, artificial intelligence-driven analytics, and nanocarrier-based drug delivery platforms. By integrating mechanistic insights with translational applications, this review highlights glycosylation as both a pathological driver and a promising therapeutic target in neurodegenerative disorders.}, }
@article {pmid41107992, year = {2025}, author = {Wu, S}, title = {Fixed-effect or random-effect models? A methodological reappraisal of subgroup analyses in mesenchymal stem cell therapy for knee osteoarthritis.}, journal = {Stem cell research &amp; therapy}, volume = {16}, number = {1}, pages = {572}, pmid = {41107992}, issn = {1757-6512}, mesh = {Humans ; *Osteoarthritis, Knee/therapy ; *Mesenchymal Stem Cell Transplantation/methods ; *Mesenchymal Stem Cells/cytology ; }, abstract = {We commend Cao et al. for their systematic review demonstrating the efficacy of intra-articular mesenchymal stem cell (MSC) therapy in alleviating pain and improving function in patients with non-surgical knee osteoarthritis (OA). However, we reanalyzed their subgroup analyses to evaluate the methodological implications of statistical model selection (fixed-effect vs. random-effect models) on result reliability. In dose-stratified analyses, Cao et al. applied fixed-effect models to low-dose (I[2] = 0%) and high-dose (I[2] = 80%) MSC subgroups. Upon reanalysis using random-effect models, the high-dose group showed no statistically significant differences in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total scores compared to the control group at 6 months [MD = 8.75; 95% CI (-2.10, 19.61); P = 0.11] or 12 months [MD = 12.68; 95% CI (-4.96, 30.32); P = 0.16], contrasting with Cao et al.'s original findings. The low-dose subgroup, with no heterogeneity, yielded identical results across both models. Similarly, in cell-source stratification (adipose-derived MSCs [ADMSCs] vs. bone marrow-derived MSCs [BM-MSCs]), reanalysis of ADMSCs using random-effect models demonstrated significant 6-month WOMAC improvement [MD = 9.32; 95% CI (3.73, 14.92); P = 0.001] but non-significant 12-month differences [MD = 12.90; 95% CI (-1.76, 27.55); P = 0.08], diverging from Cao et al.'s conclusions. BM-MSCs results remained consistent due to negligible heterogeneity (I[2] = 0%). These findings underscore that fixed-effect models artificially narrow confidence intervals in heterogeneous populations, overestimating clinical significance. Our results align with Cochrane guidelines, emphasizing that random-effect models better accommodate inter-study diversity, yielding conservative and clinically generalizable estimates. This critique reinforces the necessity of transparent statistical model selection in meta-analyses, particularly when subgroup heterogeneity may influence therapeutic interpretations.}, }
@article {pmid41104042, year = {2025}, author = {Yassin, LK and Skrabulyte-Barbulescu, J and Alshamsi, SH and Saeed, S and Alkuwaiti, SH and Almazrouei, S and Alnuaimi, A and BaniYas, S and Aldhaheri, D and Alderei, M and Shehab, S and Hamad, MIK}, title = {The microbiota-gut-brain axis in mental and neurodegenerative disorders: opportunities for prevention and intervention.}, journal = {Frontiers in aging neuroscience}, volume = {17}, number = {}, pages = {1667448}, pmid = {41104042}, issn = {1663-4365}, abstract = {The microbiota-gut-brain axis (MGBA) is increasingly recognized as a critical regulator of brain health, influencing both neurodevelopment and age-related neurological decline. Disruptions in this axis, driven by gut dysbiosis, have been implicated in the pathogenesis of a wide range of neurodegenerative and neuropsychiatric disorders. This review synthesizes current evidence linking microbiota alterations to Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and stroke-including post-stroke cognitive impairment (PSCI), as well as major depressive disorder (MDD), bipolar disorder (BD), anxiety disorders, post-traumatic stress disorder (PTSD), and chronic fatigue syndrome (CFS). Common findings include reduced microbial diversity, depletion of short-chain fatty acid (SCFA)-producing genera, and enrichment of pro-inflammatory taxa. These changes contribute to neuroinflammation, blood-brain barrier (BBB) dysfunction, microglial activation, and neurotransmitter imbalances. The review further explores the neurotoxic effects of external factors such as radiation and xenobiotics on the MGBA. Despite disorder-specific variations, shared microbial and immunological mechanisms emerge across the spectrum of conditions. Importantly, we present current and emerging strategies aimed at restoring gut-brain communication, including dietary interventions such as fiber-rich and Mediterranean diets, SCFA supplementation, probiotics, and fecal microbiota transplantation (FMT). These approaches show promise in alleviating cognitive and emotional symptoms, modulating immune responses, and potentially slowing disease progression. By integrating mechanistic insights with therapeutic perspectives, this review underscores the gut microbiota as a modifiable factor in neuropsychiatric and neurodegenerative disease. Targeting the MGBA offers a novel, translational approach to intervention that may ultimately contribute to healthier brain aging and improved outcomes across the lifespan.}, }
@article {pmid41102629, year = {2025}, author = {Masbi, M and Tavkoli, N and Payrovi, H and Dowlati, M}, title = {Special care services delivery at disaster scenes: a systematic review.}, journal = {International journal of emergency medicine}, volume = {18}, number = {1}, pages = {206}, pmid = {41102629}, issn = {1865-1372}, abstract = {BACKGROUND: Disasters create strain on health systems and require significant preparedness to reduce mortality and morbidity. Special care services; e.g. Advanced Life Support, critical care interventions (intubation; vasopressor therapy) and point of care diagnostics (ultrasound) may be provided in disaster-settings, although actual use of services is dependent on logistical, operational and contextual issues. This systematic review identifies an important gap to understand the effectiveness, feasibility and barriers to, special care services.The overall aim of this systematic review is to synthesise global evidence on the evidence-based practices and improve disaster response.<br><br>METHODS: This systematic review utilized PubMed, Scopus, Web of Science, Embase, and grey literature from the time of inception of the different databases to January 2025, from which a total of 4465 records were identified. After a thorough, organized review of the identified records based on our exclusion criteria and inclusion criteria, a total of 31 articles were retained. The systematic review followed PRISMA 2020, and searched for studies on special care services in a pre-hospital disaster setting, and included primary research and review articles that described advanced interventions, and which had no time restrictions on date of publication. Articles that were waived from the cost of in-app purchasing were excluded due to limited resources and could limit the studies that were included. Quality assessment using STROBE, SANRA and checklists, along with the categories of findings using a thematic content analysis based on the dimensions of prehospital care.<br><br>RESULTS: Thematic analysis revealed six broad themes: Patient Care and Clinical Management, Operational Efficiency and Logistics, Personnel and Training, Technology and Equipment, System Coordination and Preparedness, and Ethical and Contextual Considerations. Advanced functions like REBOA, ultrasound and AI-related diagnostics improved survival and neurological outcomes, However, they were restricted due to limited resources, lack of training, and lack of coordination, particularly in low resource contexts.<br><br>CONCLUSIONS: The reviewed literature demonstrated that critical-care services such as Advanced Life Support (ALS), intubation, and ultrasound resulted in improved morbidity and mortality outcomes in disaster settings but were limited due to resource constraints, lack of training and inadequate coordination all the more pertinent to low-resource settings.<br><br>CLINICAL TRIAL NUMBER: Not applicable.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12245-025-01041-9.}, }
@article {pmid41103971, year = {2025}, author = {Arachchige, ASPM}, title = {Rethinking ALS: Current understanding and emerging therapeutic strategies.}, journal = {AIMS neuroscience}, volume = {12}, number = {3}, pages = {391-405}, pmid = {41103971}, issn = {2373-7972}, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive degeneration of the upper and lower motor neurons, which leads to muscle atrophy, spasticity, and ultimately respiratory failure. The etiology of ALS remains unclear, though a combination of genetic and environmental factors is suspected. Advances in understanding ALS pathophysiology, including the role of RNA metabolism, mitochondrial dysfunction, and glutamate toxicity, have paved the way for new research directions. While Riluzole offers limited survival benefits, there is no cure, and treatment remains mostly supportive. This article summarizes the current understanding of ALS in terms of its pathophysiology, epidemiology, risk factors, clinical presentation, and treatment strategies.}, }
@article {pmid41101301, year = {2025}, author = {Sasidharan, A and Somayaji, Y and Fernandes, R}, title = {Shifting Microglial Phenotypes: Targeting Disease-Associated Microglia in Neurodegeneration.}, journal = {ACS chemical neuroscience}, volume = {}, number = {}, pages = {}, doi = {10.1021/acschemneuro.5c00159}, pmid = {41101301}, issn = {1948-7193}, abstract = {Neurodegenerative disorders are marked by the gradual degeneration of neurons and deterioration of cognitive function. One key underlying factor in these diseases is neuroinflammation. An essential component of this process is microglia, which are the innate immune cells that maintain homeostasis in the brain. A common outcome of microglial dysregulation in neurodegenerative diseases is chronic neuroinflammation, which exacerbates neuronal damage and impairs synaptic function. This review focuses on the dual roles that disease-associated microglia (DAMs) play in neural inflammation and neuroprotection as well as their distinct transcriptional profile in neurodegenerative diseases. DAMs engage in phagocytosis to remove debris, in addition to releasing cytokines that promote inflammation. To create an effective medicine, it is imperative to comprehend these dual functions. The roles of DAMs in Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) are discussed, along with the mechanisms (such as the TREM2-APOE pathway) causing their activation. This review attempts to highlight the important aspects that could direct future investigations and treatment development by clarifying the interactions between DAMs and neurodegenerative diseases.}, }
@article {pmid41099730, year = {2025}, author = {Polu, PR and Mishra, S}, title = {Genetic convergence in brain aging and neurodegeneration: from cellular mechanisms to therapeutic targets.}, journal = {Journal of neurogenetics}, volume = {}, number = {}, pages = {1-20}, doi = {10.1080/01677063.2025.2571127}, pmid = {41099730}, issn = {1563-5260}, abstract = {The distinction between normal brain aging and neurodegeneration has traditionally been viewed as a binary classification, yet emerging evidence reveals a complex continuum of shared genetic mechanisms underlying both processes. This review synthesises current understanding of conserved molecular pathways that contribute to age-related neural decline across the spectrum from healthy aging to pathological neurodegeneration. We examine how fundamental cellular processes including protein quality control, mitochondrial dysfunction, inflammation, and synaptic maintenance are genetically regulated and become progressively dysregulated during aging. Key genetic pathways, such as insulin/IGF signalling, autophagy-lysosomal networks, and stress response mechanisms demonstrate remarkable conservation from model organisms to humans, suggesting evolutionary constraints on neural aging processes. The review highlights how genetic variants in these pathways can determine individual trajectories along the aging-neurodegeneration continuum, influencing susceptibility to diseases like Alzheimer's, Parkinson's, and ALS. We discuss evidence from comparative studies in C. elegans, Drosophila, rodents, and human populations that illuminate shared vulnerability genes and protective factors. Understanding these convergent mechanisms offers unprecedented opportunities for therapeutic intervention, as strategies targeting fundamental aging processes may simultaneously address multiple neurodegenerative conditions. This integrated perspective challenges traditional disease-centric approaches and supports the development of unified therapeutic strategies for promoting healthy brain aging while preventing neurodegeneration.}, }
@article {pmid41098540, year = {2025}, author = {Dafsari, HS and Schuler, J and Schober, E and Möller, B and Antebi, A and Fanto, M and Jungbluth, H}, title = {The space-time continuum in neurological disorders of the autophagosome-lysosome fusion machinery.}, journal = {Autophagy reports}, volume = {4}, number = {1}, pages = {2560903}, pmid = {41098540}, issn = {2769-4127}, abstract = {Autophagy is a highly conserved cellular pathway for the degradation and recycling of defective intracellular cargo and plays a vital role in the homeostasis of post-mitotic tissues, particularly the nervous system. Autophagosome-lysosome fusion represents the final critical step in macroautophagy with a tightly regulated process mediated by a complex molecular machinery of tethering vesicles for degradation. Since the first reports of human autophagy disorders, the scientific and clinical focus condensed on severe phenotypes with biallelic-truncating genotypes as monogenic models of near-complete autophagy perturbation. Recent reports suggest a much wider disease spectrum with defective autophagy, ranging from neurodevelopmental disorders to neurodegenerative phenotypes with later manifestation due to "milder" genotypes, including Alzheimer's disease (AD), Parkinson's disease (PD), and Amyotrophic Lateral Sclerosis-Frontotemporal Dementia (ALS-FTD). In addition, recent evidence identified molecular connections between physiological autophagy regulation during normal aging and pathophysiological hallmarks of aging-related disorders. These translational observations led to a more comprehensive understanding of autophagy at health and disease, in particular: 1) genetic location and allelism of pathogenic variants ("genomic space"); 2) protein-protein interaction in functional protein complexes ("proteomic space"); 3) metabolic autophagic flux with positive and negative regulators ("metabolomic space"); 4) age-related phenotypic progression over time. Here, we review the autophagosome-lysosome fusion machinery as a key structure both on the molecular level and with regards to the pathogenesis of the autophagy-related disease spectrum. We highlight the clinicopathological signature of disorders in the autophagosome-lysosome fusion machinery, in particular features warranting awareness from clinicians and geneticists to inform adequate diagnosis, surveillance, and patient guidance.}, }
@article {pmid41097145, year = {2025}, author = {Tuigunov, D and Sinyavskiy, Y and Nurgozhin, T and Zholdassova, Z and Smagul, G and Omarov, Y and Dolmatova, O and Yeshmanova, A and Omarova, I}, title = {Precision Nutrition and Gut-Brain Axis Modulation in the Prevention of Neurodegenerative Diseases.}, journal = {Nutrients}, volume = {17}, number = {19}, pages = {}, doi = {10.3390/nu17193068}, pmid = {41097145}, issn = {2072-6643}, support = {Grant No. AP23489983//This research is funded by the Science Committee of the Ministry of Science and Higher Education of the Republic of Kazakhstan/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/prevention &amp; control/microbiology ; *Gastrointestinal Microbiome/physiology ; *Brain ; *Precision Medicine/methods ; *Brain-Gut Axis/physiology ; Prebiotics/administration &amp; dosage ; Probiotics/administration &amp; dosage ; }, abstract = {In the recent years, the accelerating global demographic shift toward population aging has been accompanied by a marked increase in the prevalence of neurodegenerative disorders, notably Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. Among emerging approaches, dietary interventions targeting the gut-brain axis have garnered considerable attention, owing to their potential to modulate key pathogenic pathways underlying neurodegenerative processes. This review synthesizes current concepts in precision nutrition and elucidates neurohumoral, immune, and metabolic regulatory mechanisms mediated by the gut microbiota, including the roles of the vagus nerve, cytokines, short-chain fatty acids, vitamins, polyphenols, and microbial metabolites. Emerging evidence underscores that dysbiotic alterations contribute to compromised barrier integrity, the initiation and perpetuation of neuroinflammatory responses, pathological protein aggregations, and the progressive course of neurodegenerative diseases. Collectively, these insights highlight the gut microbiota as a pivotal target for the development of precision-based dietary strategies in the prevention and mitigation of neurodegenerative disorders. Particular attention is devoted to key bioactive components such as prebiotics, probiotics, psychobiotics, dietary fiber, omega-3 fatty acids, and polyphenols that critically participate in regulating the gut-brain axis. Contemporary evidence on the contribution of the gut microbiota to the pathogenesis of Alzheimer's disease, Parkinson's disease, and multiple sclerosis is systematically summarized. The review further discusses the prospects of applying nutrigenomics, chrononutrition, and metagenomic analysis to the development of personalized dietary strategies. The presented findings underscore the potential of integrating precision nutrition with targeted modulation of the gut-brain axis as a multifaceted approach to reducing the risk of neurodegenerative diseases and preserving cognitive health.}, }
@article {pmid41097004, year = {2025}, author = {Daponte, A and Koros, C and Skarlis, C and Siozios, D and Rentzos, M and Papageorgiou, SG and Anagnostouli, M}, title = {Neurofilament Biomarkers in Neurology: From Neuroinflammation to Neurodegeneration, Bridging Established and Novel Analytical Advances with Clinical Practice.}, journal = {International journal of molecular sciences}, volume = {26}, number = {19}, pages = {}, doi = {10.3390/ijms26199739}, pmid = {41097004}, issn = {1422-0067}, mesh = {Humans ; *Biomarkers/metabolism/blood ; *Neurofilament Proteins/metabolism/blood ; *Neurodegenerative Diseases/metabolism/diagnosis ; *Neuroinflammatory Diseases/metabolism/diagnosis ; Animals ; }, abstract = {Neuroaxonal damage underlies permanent disability in various neurological conditions, both neuroautoimmune and neurodegenerative. It is crucial to accurately quantify and monitor axonal injury using biomarkers to evaluate disease progression and treatment effectiveness and offer prognostic insights. Neurofilaments (NFs), and especially neurofilament light chain (NfL), show promise for this purpose, as their levels increase with neuroaxonal damage in both cerebrospinal fluid and blood, independent of specific causal pathways. Recent advances in ultrasensitive immunoassays enable the reliable detection of NFs in blood, transforming them from research tools into clinically applicable measures. In multiple sclerosis (MS), serum NfL correlates with disease activity, treatment response, and long-term disability, and may complement MRI in monitoring subclinical progression. In MS, NfL is primarily emerging as a marker of disease activity and treatment response; in amyotrophic lateral sclerosis (ALS), it has progressed further, being integrated into clinical trials as a pharmacodynamic endpoint and considered by regulatory agencies as a drug development tool. Additionally, NFs are increasingly being investigated in Alzheimer's disease, frontotemporal dementia, and other neurodegenerative disorders, though their disease specificity is limited. Ongoing challenges include older and novel assay harmonization, normative range interpretation, biological and analytical variability, and integration with other molecular and imaging biomarkers. This critical narrative review synthesizes the existing literature on NFs as diagnostic, prognostic, predictive, and pharmacodynamic biomarkers and discusses their role in therapeutic development and precision medicine in neuroautoimmune and neurodegenerative diseases.}, }
@article {pmid41096667, year = {2025}, author = {Skarlis, C and Angelopoulou, E and Rentzos, M and Papageorgiou, SG and Anagnostouli, M}, title = {Monoclonal Antibodies as Therapeutic Agents in Autoimmune and Neurodegenerative Diseases of the Central Nervous System: Current Evidence on Molecular Mechanisms and Future Directions.}, journal = {International journal of molecular sciences}, volume = {26}, number = {19}, pages = {}, doi = {10.3390/ijms26199398}, pmid = {41096667}, issn = {1422-0067}, mesh = {Humans ; *Antibodies, Monoclonal/therapeutic use/pharmacology ; *Neurodegenerative Diseases/drug therapy/immunology ; Animals ; *Central Nervous System Diseases/drug therapy/immunology ; Neuromyelitis Optica/drug therapy ; Central Nervous System/drug effects/immunology ; Multiple Sclerosis/drug therapy ; }, abstract = {Monoclonal antibodies (mAbs) have revolutionized the treatment landscape for neurological diseases, providing targeted, mechanism-based therapies for conditions ranging from autoimmune demyelinating disorders to neurodegenerative diseases. In multiple sclerosis (MS), mAbs against CD20, CD52, and α4-integrins offer disease-modifying efficacy by altering immune responses, depleting B cells, or blocking leukocyte migration into the central nervous system (CNS). Similarly, novel agents under investigation, such as frexalimab and foralumab, modulate T and B cell interactions and regulatory immunity. In neuromyelitis optica spectrum disorder (NMOSD), mAbs targeting IL-6, the complement cascade, and B cell lineage have demonstrated significant clinical benefit in preventing relapses and disability. In Alzheimer's disease (AD), several anti-amyloid mAbs have gained regulatory approval. Anti-tau and anti-α-synuclein antibodies, though promising, have shown limited efficacy to date in AD and parkinson's disease (PD), respectively. The evolving armamentarium of mAbs reflects a paradigm shift toward personalized neuroimmunology and neurodegeneration-targeted treatments, based on ongoing clarification of molecular and neuroinflammatory mechanisms. In this context, the present review summarizes current evidence on mAbs used in CNS disorders, with an emphasis on their pathophysiological targets, molecular mechanisms, clinical efficacy, and safety.}, }
@article {pmid41095520, year = {2025}, author = {Whelan, BM and Aldridge, D and Ruhle, J and Whitelock, P and Taubert, S and Collins, A and Kearney, E and Charania, S and Henderson, RD and Wallace, SJ and Mitchell, C and Stipancic, KL and Kuruvilla-Dugdale, M and Vogel, AP}, title = {To Treat or Not to Treat: A Scoping Review of Speech Treatment for Dysarthria in Amyotrophic Lateral Sclerosis (ALS).}, journal = {Healthcare (Basel, Switzerland)}, volume = {13}, number = {19}, pages = {}, doi = {10.3390/healthcare13192434}, pmid = {41095520}, issn = {2227-9032}, support = {N/A//University of Queensland, School of Health and Rehabilitation Sciences, New Staff Research Start-Up Fund/ ; }, abstract = {BACKGROUND: Speech loss is recognised as one of the most devastating outcomes for individuals with ALS, yet active speech intervention is rarely targeted in this population. Clinicians face significant challenges in managing dysarthria associated with ALS due to the rapidly progressive nature of the disease, historical concerns around intensive exercise accelerating decline, and an absence of direction on restorative and compensatory intervention strategies in current clinical care guidelines. This review evaluates the scope and quality of evidence for speech treatments in ALS to identify knowledge gaps and establish research priorities to guide clinical care.<br><br>METHODS: Studies were retrieved from six electronic databases (PubMed, CINAHL, Embase, Cochrane library, Web of Science, and PsycINFO).<br><br>RESULTS: Four studies met inclusion criteria. Treatment approaches included: music-based speech therapy; multisubsystem speech rehabilitation program, tongue strengthening and articulation training; and Lee Silverman Voice Treatment-LOUD[&#xae;] combined with additional voice and articulation therapy. Sample sizes were small, with all studies demonstrating notable methodological weaknesses. The limited evidence base, marked by conflicting results and methodological flaws, prevents any reliable conclusions about treatment effectiveness.<br><br>CONCLUSIONS: Despite the prevalence and impact of dysarthria in this population, evidence for speech treatment remains sparse, of generally low quality, and provides limited guidance for clinical practice. The changing perspective on exercise in ALS warrants rigorous investigation of tailored dysarthria interventions for this population that are minimally fatiguing and enhance speech by making use of residual physiologic support.}, }
@article {pmid41092899, year = {2025}, author = {Ruiz de Almodovar, C and Dupraz, S and Bonanomi, D}, title = {Neurovascular dynamics in the spinal cord from development to pathophysiology.}, journal = {Neuron}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.neuron.2025.09.017}, pmid = {41092899}, issn = {1097-4199}, abstract = {The vasculature is increasingly recognized as an active regulator of homeostasis and repair, beyond conventional roles in nutrient delivery. In the central nervous system, vascular cells adopt region-specific traits tailored to the distinct demands of the brain, retina, and spinal cord. Despite long-standing interest in the spinal cord as a model for neural development and injury, its vascular organization and properties remain understudied. The assumption that spinal cord and brain neurovascular systems are built and function in the same way has limited progress. Here, we challenge this view by examining specific properties underlying spinal cord vascular development, physiology, and pathology. We highlight unique angioarchitecture and homeostatic mechanisms, and discuss how neurovascular disruption contributes to spinal disorders and regenerative failure after injury. Identifying critical knowledge gaps, we aim to stimulate new research in spinal cord neurovascular biology, redefining its importance for health and disease.}, }
@article {pmid41092810, year = {2025}, author = {Lopez-Mateos, D and Harris, BJ and Hernández-González, A and Yarov-Yarovoy, V and Wulff, H}, title = {Recent advances in the pharmacology of voltage-gated ion channels.}, journal = {Pharmacological reviews}, volume = {77}, number = {6}, pages = {100090}, doi = {10.1016/j.pharmr.2025.100090}, pmid = {41092810}, issn = {1521-0081}, abstract = {Voltage-gated ion channels (VGICs) are critical regulators of membrane potential, cellular excitability, and calcium signaling in both excitable and nonexcitable tissues and constitute important drug targets for neurological, cardiovascular, and immunological diseases. This review describes recent progress in the pharmacology of voltage-gated Na[+], voltage-gated Ca[2+], and voltage-gated K[+] channels, highlighting clinical-stage compounds, emerging therapeutic modalities, and new strategies in VGIC drug discovery, emphasizing the increasingly central role of protein structures and artificial intelligence. Several compounds targeting VGICs have progressed to clinical trials for epilepsy, atrial fibrillation, psoriasis, and difficult-to-treat disorders, such as chronic pain, schizophrenia, major depression, and amyotrophic lateral sclerosis. The therapeutic landscape for VGIC-related disorders is expanding beyond traditional small molecules and antisense oligonucleotides and gene therapies targeting VGICs at the mRNA or gene level are currently in both early and late clinical trial stages for Dravet syndrome and developmental epileptic encephalopathy. The progression of such varied modalities suggests that the extensive efforts dedicated to elucidating VGIC biophysics and structure, coupled with rigorous target validation, are beginning to translate into therapeutic advancements. Furthermore, we discuss emerging discovery strategies, including the growing impact of VGIC structures, computational structural modeling, virtual screening of focused and ultralarge libraries, and artificial intelligence-driven redesign and de novo design of biologics. Although these approaches are poised to substantially accelerate the early stages of ion channel drug discovery, the clinical stages will continue to require careful selection of indications and thoughtful clinical trial design to fully realize the long-held potential of VGICs as drug targets. SIGNIFICANCE STATEMENT: Drug development for voltage-gated ion channels is widely considered to be challenging. This article reviews recent advances in the pharmacology of voltage-gated Na[+], voltage-gated Ca[2+], and voltage-gated K[+] channels by examining compounds currently in clinical trials, including emerging new therapeutic approaches such as antisense oligonucleotides and gene therapy. We then discuss noteworthy recent developments, including the increasing availability and impact of ion channel structures, structural modeling, virtual screening, and artificial intelligence-assisted protein design, which are likely to accelerate the early stages of ion channel drug discovery. Success of the later stages will continue to rely on rigorous target validation, and proper choices of clinical candidates and clinical trial design.}, }
@article {pmid41090732, year = {2025}, author = {Brocard, F and Dingu, N}, title = {Calpains at the Crossroads of Spinal Cord Physiology, Plasticity, and Pathology.}, journal = {Cells}, volume = {14}, number = {19}, pages = {}, pmid = {41090732}, issn = {2073-4409}, support = {ANR-24-CE16-1548//Agence National de la recherche/ ; ANR-21-CE17-0060//Agence National de la Recherche/ ; }, mesh = {*Calpain/metabolism ; Humans ; Animals ; *Spinal Cord/pathology/physiopathology/physiology/metabolism ; *Neuronal Plasticity/physiology ; }, abstract = {Calcium-dependent cysteine proteases, known as calpains, emerge as important regulators of spinal cord physiology, plasticity, and pathology. First characterized in the brain, they influence a wide range of processes in the spinal cord, maintaining neuronal homeostasis, shaping both synaptic and intrinsic plasticity, and modulating glial responses. When dysregulated, calpains contribute to the pathophysiology of traumatic and neurodegenerative spinal cord disorders, as well as to their associated motor and sensory complications, including spasticity and neuropathic pain. A recurring feature of these conditions is calpain-mediated proteolysis of ion channels, transporters, and cytoskeletal proteins, which promotes disinhibition and neuronal hyperexcitability. The resultant protein fragments are examined as prospective biomarkers for damage and disease progression. Meanwhile, promising strategies for neuroprotection and functional recovery in the clinic emerge as a result of innovative pharmacological and genetic approaches to modulate calpain activity. In this review, we present the current state of knowledge regarding the functions and regulation of calpains in the spinal cord and assess their translational potential as both therapeutic targets and effectors in spinal cord disorders.}, }
@article {pmid40762148, year = {2025}, author = {Mascias Cadavid, J and Mena Bravo, A and Barkhaus, P and Barnes, B and Benatar, M and Breevoort, S and Brown, A and Carter, GT and Crayle, J and Foucher, J and Heiman-Patterson, T and Hobson, E and Jackson, C and Jhooty, S and Mallon, E and Mcdermott, C and Pattee, G and Pierce, K and Pioro, E and Ratner, D and Rivner, M and Tito, E and Wicks, P and Bedlack, R}, title = {ALSUntangled #80: ISRIB (Integrated stress response InhiBitor).}, journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration}, volume = {26}, number = {7-8}, pages = {821-824}, doi = {10.1080/21678421.2025.2542919}, pmid = {40762148}, issn = {2167-9223}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/metabolism ; Humans ; Animals ; Stress Granules/drug effects/metabolism ; }, abstract = {ALSUntangled reviews alternative and off-label treatments for people living with amyotrophic lateral sclerosis (PALS). Here we assess ISRIB, a molecule that attenuates the integrated stress response (ISR). The ISR is an intracellular signaling network through which cells normally respond to stress, but in ALS it appears to be overactive, leading to the formation of "stress granules" which some but not all investigators believe can triggerapoptotic cell death. ISRIB can attenuate the formation of these stress granules while still allowing parts of protein synthesis to continue. Pre-clinical data demonstrate that ISRIB is beneficial in cell models of ALS. A small number of patients taking ISRIB in Spain report symptomatic improvements with little or no side effects, though we have not been able to independently verify these benefits. There are no clinical trials evaluating ISRIB in any condition and questions about its solubility and bioavailability have arisen. Currently, we do not have enough evidence to endorse the use of ISRIB for treating ALS. We support further research in disease models and clinical trials to study pharmacokinetics, safety and efficacy.}, }
@article {pmid41090725, year = {2025}, author = {Vishnumukkala, T and Che Mohd Nassir, CMN and Hein, ZM and Kalerammana Gopalakrishna, P and Karikalan, B and Alkatiri, A and Jagadeesan, S and Naik, VR and Thomas, W and Mohd Moklas, MA and Kamaruzzaman, MA}, title = {Glial Cells as Emerging Therapeutic Targets in Neurodegenerative Diseases: Mechanistic Insights and Translational Perspectives.}, journal = {Cells}, volume = {14}, number = {19}, pages = {}, doi = {10.3390/cells14191497}, pmid = {41090725}, issn = {2073-4409}, mesh = {Humans ; *Neurodegenerative Diseases/therapy/pathology ; *Neuroglia/metabolism/pathology/drug effects ; Animals ; *Translational Research, Biomedical ; Biomarkers/metabolism ; }, abstract = {Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease, multiple sclerosis, and amyotrophic lateral sclerosis share converging mechanisms of neuronal dysfunction, including protein aggregation, oxidative stress, and chronic neuroinflammation. Glial cells, once considered passive supporters, are now recognized as central drivers of these processes, offering both pathogenic triggers and therapeutic opportunities. Yet, despite compelling preclinical evidence, the translation of glial-targeted therapies into clinical success has been limited. This review provides a critical synthesis of current knowledge by examining therapeutic strategies through the lens of their translational challenges and failures. This narrative review highlights how interspecies variability of glial phenotypes, shifting neuroprotective versus neurotoxic states, limited biomarker stratification, and delivery barriers have constrained trials, such as anti-triggering receptor expressed on myeloid cells 2 (anti-TREM2) antibodies in AD and glial cell line-derived neurotrophic factor (GDNF) in PD. By analyzing these obstacles across major neurodegenerative disorders, this review argue that the next stage of glial medicine requires precision approaches that integrate stage-specific phenotyping, biomarker-guided patient selection, and innovative delivery platforms. Understanding not only what has been tried but why translation has stalled is essential to chart a roadmap for effective, disease-modifying glial therapies in the aging brain.}, }
@article {pmid41090678, year = {2025}, author = {Jing, W and Shan, Y and Wu, H and Li, T and Tang, H and Sun, Y and Napattharin, V and Loong, S and Qin, B and Pan, W}, title = {Integrative treatment of the motor neuron disease amyotrophic lateral sclerosis, efficacy of pharmacotherapy, traditional Chinese medicine and importance of respiratory support, life-style, and gastrostomy-assisted nutrition: A review.}, journal = {International journal of clinical pharmacology and therapeutics}, volume = {63 (Suppl. 1)}, number = {}, pages = {S14-S25}, pmid = {41090678}, issn = {0946-1965}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/etiology/physiopathology ; *Gastrostomy ; *Medicine, Chinese Traditional ; *Life Style ; *Integrative Medicine/methods ; Treatment Outcome ; }, abstract = {Currently, there are no effective treatments for amyotrophic lateral sclerosis (ALS), a chronic progressive neurodegenerative disease. Although the etiology of ALS is unknown, it is thought that factors such as diet, the environment, and lifestyle habits play a role. The pathogenesis of ALS includes alterations in glutamate neurotransmission, oxidative stress, mitochondrial dysfunction. Drugs such as riluzole, edaravone, dextromethorphan/quinidine combinations, and the administration of tofersen by injection are approved treatment options for ALS although a number of other agents are being examined in clinical trials. Despite these developments, the availability of effective treatment options is limited. This review summarizes the etiology and pathogenesis of ALS and describes treatments in detail as an integrative medicine approach and including traditional Chinese medicine together with the importance of the timing for interventions, precautions necessary for noninvasive ventilator and gastrostomy surgery, and precautions for dealing with respiratory issues with the overall aim of providing state-of-the-art clinical recommendations for the care and therapy of ALS patients.}, }
@article {pmid41088409, year = {2025}, author = {Ward, EL and Benowitz, L and Brunner, TM and Bu, G and Cayouette, M and Canto-Soler, V and Dá Mesquita, S and Di Polo, A and DiAntonio, A and Duan, X and Goldberg, JL and He, Z and Hu, Y and Liddelow, SA and La Torre, A and Margeta, M and Quintana, F and Shekhar, K and Stevens, B and Temple, S and Venkatesh, H and Welsbie, D and Flanagan, JG}, title = {Modeling neurodegeneration in the retina and strategies for developing pan-neurodegenerative therapies.}, journal = {Molecular neurodegeneration}, volume = {20}, number = {1}, pages = {108}, pmid = {41088409}, issn = {1750-1326}, mesh = {Humans ; *Neurodegenerative Diseases/therapy/pathology ; Animals ; *Glaucoma/therapy ; Disease Models, Animal ; *Retina/pathology ; }, abstract = {BACKGROUND: Glaucoma Research Foundation's third Catalyst for a Cure team (CFC3) was established in 2019 to uncover new therapies for glaucoma, a leading cause of blindness. In the 2021 meeting "Solving Neurodegeneration," (detailed in Mol Neurodegeneration 17(1), 2022) the team examined the failures of investigational monotherapies, issues with translatability, and other significant challenges faced when working with neurodegenerative disease models. They emphasized the need for novel, humanized models and proposed identifying commonalities across neurodegenerative diseases to support the creation of pan-neurodegenerative disease therapies. Since then, the fourth Catalyst for a Cure team (CFC4) was formed to explore commonalities between glaucoma and other neurodegenerative diseases. This review summarizes outcomes from the 2023 "Solving Neurodegeneration 2" meeting, a forum for CFC3 and CFC4 to share updates, problem solve, plan future research collaborations, and identify areas of unmet need or opportunity in glaucoma and the broader field of neurodegenerative disease research.<br><br>MAIN BODY: We summarize the recent progress in the field of neurodegenerative disease research and present the newest challenges and opportunities moving forward. While translatability and disease complexity continue to pose major challenges, important progress has been made in identifying neuroprotective targets and understanding neuron-glia-vascular cell interactions. New challenges involve improving our understanding of the disease microenvironment and timeline, identifying the optimal approach(es) to neuronal replacement, and finding the best drug combinations and synergies for neuroprotection. We propose solutions to common research questions, provide prescriptive recommendations for future studies, and detail methodologies, strategies, and approaches for addressing major challenges at the forefront of neurodegenerative disease research.<br><br>CONCLUSIONS: This review is intended to serve as a research framework, offering recommendations and approaches to validating neuroprotective targets, investigating rare cell types, performing cell-specific functional characterizations, leveraging novel adaptations of scRNAseq, and performing single-cell sorting and sequencing across neurodegenerative diseases and disease models. We focus on modeling neurodegeneration using glaucoma and other neurodegenerative pathologies to investigate the temporal and spatial dynamics of neurodegenerative disease pathogenesis, suggesting researchers aim to identify pan-neurodegenerative drug targets and drug combinations leverageable across neurodegenerative diseases.}, }
@article {pmid41084041, year = {2025}, author = {Hassan, YM and Wanas, A and Ali, AA and El-Sayed, WM}, title = {Integrating artificial intelligence with nanodiagnostics for early detection and precision management of neurodegenerative diseases.}, journal = {Journal of nanobiotechnology}, volume = {23}, number = {1}, pages = {668}, pmid = {41084041}, issn = {1477-3155}, abstract = {BACKGROUND: Neurodegenerative diseases—including Alzheimer’s, Parkinson’s, and amyotrophic lateral sclerosis (ALS)—as well as autoimmune disorders with neurodegenerative features such as multiple sclerosis (MS), present an escalating global challenge. Current diagnostics often detect pathology too late, and most treatments focus on symptom relief rather than disease modification. There is an urgent need for tools that enable early detection and precision-targeted intervention.<br><br>MAIN BODY: Nanotechnology offers unique advantages in this space, enabling early molecular detection, targeted drug delivery, and theranostic systems. Engineered nanocarriers, biosensors, and responsive nanodevices are being tailored to disease-specific features such as oxidative stress in AD or neuroinflammation in MS. Yet, issues like biocompatibility, clinical scalability, and long-term safety remain barriers to translation. Artificial intelligence (AI) enhances nanomedicine by improving biomarker sensitivity, stratifying patients, and enabling predictive disease modeling. From AI-guided nanoparticle design to closed-loop delivery systems and digital twin models, these technologies work synergistically to support real-time, personalized care. Still, critical challenges&#x2014;including algorithmic bias, lack of explainability, heterogeneous datasets, and limited regulatory clarity&#x2014;impede clinical integration. Additionally, high system complexity and cost risk excluding low-resource settings unless inclusive, scalable alternatives are pursued.<br><br>CONCLUSION: The convergence of AI and nanotechnology is reshaping neurodegenerative disease care, moving from reactive to proactive, personalized neurology. Realizing this promise requires cross-sector collaboration, ethical foresight, and translational rigor to ensure these innovations are safe, equitable, and accessible to all patients.<br><br>GRAPHICAL ABSTRACT: [Image: see text]}, }
@article {pmid41079430, year = {2025}, author = {Argelazi, RL and Graça, SC and Thomazoni, PV and Moura, CB and Gomes, AC and Kormanski, MK and de Almeida, SSC and Ferreira, YD and Santos, DH}, title = {TBK1 mutation and its role in frontotemporal dementia and amyotrophic lateral sclerosis in Brazilian families.}, journal = {Dementia &amp; neuropsychologia}, volume = {19}, number = {}, pages = {e20240227}, pmid = {41079430}, issn = {1980-5764}, abstract = {UNLABELLED: Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are progressive neurodegenerative diseases with unclear etiology. Mutations in the TBK1 gene are associated with an increased risk of both FTD and ALS, presenting a diverse phenotype that includes the behavioral variant of FTD, primary progressive aphasia, and pure ALS. This mutation is rare, and to date, only one case report on TBK1-related clinical manifestations has been published in Brazil.<br><br>OBJECTIVE: To investigate the association between TBK1 gene mutations and the clinical manifestations of FTD and ALS in a Brazilian family, documenting the clinical history and disease progression of three first-degree relatives. Additionally, to conduct a literature review to better understand the impact of this mutation and its implications for neurological practice.<br><br>METHODS: Clinical data were collected from three patients in the same family who were receiving care at Dom Pedro II Geriatric Hospital and Central Hospital of the Irmandade da Santa Casa de Misericordia de S&#xe3;o Paulo, including information on clinical symptoms, disease progression, and complementary exams - particularly genetic testing to detect and confirm the diagnosis. A detailed analysis of the existing literature on the disease was also conducted to better understand the implications of this mutation.<br><br>RESULTS: Three siblings affected by the TBK1 gene mutation were documented, with a unique family history suggesting that this genetic alteration has affected the lineage for several generations.<br><br>CONCLUSION: Although rare, frontotemporal dementia with accompanying motor deficits is of significant relevance to neurologists due to its poor prognosis and the potential familial impact on descendants.}, }
@article {pmid41073371, year = {2025}, author = {Liu, RY and Yin, KF and He, SY and Su, WM and Duan, QQ and Wen, XJ and Chen, T and Shen, C and Li, JR and Cao, B and Chen, YP}, title = {Viral infections and the risk of neurodegenerative diseases: a comprehensive meta-analysis and systematic review.}, journal = {Translational psychiatry}, volume = {15}, number = {1}, pages = {388}, pmid = {41073371}, issn = {2158-3188}, mesh = {Humans ; *Neurodegenerative Diseases/epidemiology/virology ; *Virus Diseases/epidemiology/complications ; *Amyotrophic Lateral Sclerosis/epidemiology/virology ; *Parkinson Disease/epidemiology/virology ; Risk Factors ; *Alzheimer Disease/epidemiology/virology ; }, abstract = {BACKGROUND: Viral infections have been implicated in the pathogenesis of neurodegenerative diseases (NDs); however, evidence linking specific viruses to Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) remains inconclusive. This study conducted a meta-analysis and systematic review to investigate these associations.<br><br>METHODS: Thorough searches were conducted across Embase, PubMed, Cochrane Library, Web of Science and Scopus until May 18, 2025, to identify observational studies investigating the relationship between viral infections and the risk of NDs, including AD, PD, and ALS. Meta-analyses were executed using a random-effects model with Stata MP18.0.<br><br>RESULTS: A total of 34,417 articles were identified, of which 73 met the eligibility criteria for inclusion in the meta-analysis, and 48 were included in the systematic review. The analysis demonstrated that infections with cytomegalovirus (CMV) (odds ratio [OR]&#x2009;=&#x2009;1.41; 95% confidence interval [CI]: 1.03, 1.93), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (OR&#x2009;=&#x2009;1.88; 95% CI: 1.53, 2.32), hepatitis C virus (HCV) (OR&#x2009;=&#x2009;1.39; 95% CI: 1.14, 1.69), and human herpesvirus (HHV) (OR&#x2009;=&#x2009;1.24; 95% CI: 1.02, 1.51) were associated with an increased risk of AD. Regarding PD, infections with hepatitis B virus (HBV) (OR&#x2009;=&#x2009;1.18; 95% CI: 1.04, 1.35) and HCV (OR&#x2009;=&#x2009;1.29; 95% CI: 1.18, 1.41) were identified as risk factors. Conversely, no significant correlation was found between any viral infection and the risk of ALS.<br><br>CONCLUSION: This meta-analysis supports the role of select viral infections in AD and PD pathogenesis. However, no association was found between viral infections and ALS, warranting further large, multicenter, and longitudinal studies to elucidate mechanisms and confirm causality.}, }
@article {pmid41063391, year = {2025}, author = {Inoue, K and Toyooka, K and Fujimura, H and Ueda, K and Kaido, M and Yamamoto, Y and Izumi, Y}, title = {Familial ALS With p. L127S (L126S) Variant of the Cu/Zn SOD1 Gene: A Report of Two New Cases and Literature Review.}, journal = {Neuropathology : official journal of the Japanese Society of Neuropathology}, volume = {45}, number = {6}, pages = {e70028}, pmid = {41063391}, issn = {1440-1789}, support = {25wm0625126s0301//Japan Agency for Medical Research and Development/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; Middle Aged ; Female ; *Superoxide Dismutase-1/genetics ; Male ; Adult ; Motor Neurons/pathology ; Inclusion Bodies/pathology ; }, abstract = {Herein, we report two autopsy cases of familial ALS with a p. L127S (L126S) SOD1 variant. Case 1 involved a 62-year-old woman who presented with lower-extremity muscle weakness with lower motor neuron signs. The patient developed bulbar palsy and died of respiratory failure 9 years after onset. Case 2 (the second son of Case 1) presented with lower-extremity muscle weakness at the age of 38 years, with upper and lower motor neuron signs and died of respiratory failure 8 years after onset. The pathological findings in both cases predominantly consisted of lower motor neuron loss and degeneration of the lateral and posterior funiculi. Numerous conglomerate hyaline inclusions (CHIs) were observed in the remaining motor neurons. Vacuole formation was observed inside the inclusions, sometimes with granular structures. Some inclusions were positive for ubiquitin, p62, and SOD1. Electron microscopy revealed that CHIs were composed of neurofilaments and expanded mitochondria. By literature review, ALS with p. L127S disclosed a male-dominant incidence rate, a variety of ages at onset, and low penetrance. The initial symptom was exclusively lower limb weakness. One-third of the patients only showed lower motor neuron signs and half did not present with bulbar symptoms. The neuropathological findings commonly observed in ALS with p. L127S variants were mainly the degeneration of lower motor neurons and the sensory system, including the posterior column, Clarke's nucleus, and the associated cerebellar system. The formation of intracytoplasmic hyaline inclusions was also a prominent feature. ALS with p. L127S variant should be included in the possible diagnosis of slowly progressive muscle weakness in the lower extremities, with or without family history or upper motor neuron signs. The loss of lower motor neurons and the accumulation of neurofilaments in the remaining neurons are key to the pathological diagnosis for ALS with p. L127S variant.}, }
@article {pmid41062721, year = {2025}, author = {Ramasubramanian, B and Ganguly, D and Rao, RP and Ramakrishna, S}, title = {Progress, pitfalls, and prospects in emerging materials for aluminum-sulfur batteries.}, journal = {Communications chemistry}, volume = {8}, number = {1}, pages = {301}, pmid = {41062721}, issn = {2399-3669}, abstract = {Aluminium-sulfur (Al-S) batteries have emerged as a promising post-lithium alternative owing to aluminium's abundance, safety, and high theoretical capacity. However, their practical implementation is impeded by key challenges such as sluggish Al[3+] redox kinetics, polysulfide shuttle effects, and volumetric changes of the electrodes during cycling. This review critically analysis recent advancements in host structural design engineering, new electrocatalysts, and electrolyte aimed at overcoming these limitations. Advanced host frameworks include 2D/3D porous structures, MXene-based multilayers, and single-atom doped materials that facilitate efficient sulfur confinement, enhance conductivity, and catalyse redox reactions. Embedded catalysts like Mo6S8 and CoS2 within nitrogen-doped carbons lower the decomposition barrier of Al2S3, promote stable Al-polysulfide conversion, and extend cycle life. Electrolyte optimization through ionic liquids, molten salts, and halide-modified systems further enhances ion mobility, suppresses passivation, and supports stable sulfur utilization. Emerging hybrid electrolytes combining high-donicity solvents with ionic or molten salt phases offer synergistic gains in redox kinetics and thermal stability. Density functional theory (DFT) guided designs elucidate key host-electrolyte-polysulfide interactions, revealing pathways for tailored material selection and performance enhancement. These integrated strategies pave the way for high-energy, long-lasting Al-S batteries that perform reliably at both room and elevated temperatures.}, }
@article {pmid41053519, year = {2025}, author = {Amiri, M and Afshary, H and Bezaatpour, A and Hatamikia, S and Wei, J and Boukherroub, R and Szunerits, S}, title = {A critical review on neurodegenerative biomarker diagnostics: where is the field heading to?.}, journal = {Analytical and bioanalytical chemistry}, volume = {}, number = {}, pages = {}, pmid = {41053519}, issn = {1618-2650}, abstract = {Neurodegenerative diseases (NDD), a collection of disorders with different underlying causes and clinical presentations, are recognized as a major area of concern of our society today. The most common NDD are Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and Huntington's disease, each one of them being characterized by the progressive degradation of nerve cells and accumulation of misfolded and aggregated proteins in the affected brain region. Diagnosing NDD is challenging, due to the heterogeneity of the disease and the overlap of symptoms. Yet, early detection and accurate diagnosis are crucial for effective NDD management. With the emergence of disease-modifying therapies for AD, monitoring disease progression and treatment success is becoming essential. The future of NND diagnostics is focusing on developing less invasive, cost-effective strategies that enable early NDD identification and detection with improved patient outcomes. The integration of biotechnology and nanotechnology is seen as crucial for advancing the analytical science aspect of NDD. The creation of these innovative tools and methodologies is on the verge of enabling new possibilities for clinical diagnostics, but is also faced with several hurdles that will be critically evaluated.}, }
@article {pmid40906311, year = {2025}, author = {Oubari, H and Berkane, Y and Jeljeli, M and Lellouch, AG and Smadja, DM}, title = {Engineering the Future of Stem Cells in Vascular Reconstruction: A Leap Towards Functional Endothelialized Tissue-Engineered Vascular Conduits.}, journal = {Stem cell reviews and reports}, volume = {21}, number = {8}, pages = {2796-2806}, pmid = {40906311}, issn = {2629-3277}, mesh = {Humans ; *Tissue Engineering/methods ; *Induced Pluripotent Stem Cells/cytology ; *Blood Vessel Prosthesis ; *Endothelial Cells/cytology ; Animals ; Tissue Scaffolds ; }, abstract = {The transition from reconstructive to regenerative strategies in vascular surgery has intensified the need for grafts that are biocompatible, growth-capable, and resistant to thrombosis. Addressing this challenge, Park et al. introduce a groundbreaking method for engineering fully biological, endothelialized tissue-engineered vascular conduits (TEVCs) using decellularized human umbilical arteries (dHUAs) coated with human induced pluripotent stem cell-derived endothelial cells (hiPSC-ECs). These constructs undergo shear stress training in bioreactors, mimicking physiological blood flow to enhance endothelial functionality and anti-thrombotic properties. Upon implantation in animal models, the grafts showed long-term patency, resistance to thrombosis, and progressive replacement of hiPSC-ECs by host endothelial cells, highlighting their regenerative and integrative potential. The study emphasizes the pivotal role of hemodynamic conditioning and key regulators such as KLF2 in promoting endothelial quiescence and vascular homeostasis. It further explores alternative strategies like endothelial colony-forming cells (ECFCs) and microfluidic systems for flow-induced maturation. Clinically, this approach offers a promising, scalable avenue for patient-specific, immune-compatible vascular grafts applicable in congenital heart disease, dialysis access, vascular grafts and coronary bypass. While challenges such as long-term durability and mechanical reinforcement remain, this research marks a transformative step toward functional, off-the-shelf vascular grafts. Park et al.'s work bridges biomimicry with regenerative medicine, paving the way for next-generation vascular therapies rooted in endothelial mechanobiology and personalized bioengineering.}, }
@article {pmid40304712, year = {2025}, author = {Freisem, D and Hoenigsperger, H and Catanese, A and Sparrer, KMJ}, title = {Inborn errors of canonical autophagy in neurodegenerative diseases.}, journal = {Human molecular genetics}, volume = {34}, number = {R1}, pages = {R23-R34}, doi = {10.1093/hmg/ddae179}, pmid = {40304712}, issn = {1460-2083}, support = {CA 2915/4-1//German Research Foundation/ ; CRC1506//German Research Foundation/ ; CRC1279//German Research Foundation/ ; SP 1600/7-1//German Research Foundation/ ; SP 1600/9-1//German Research Foundation/ ; }, mesh = {Humans ; *Autophagy/genetics ; *Neurodegenerative Diseases/genetics/pathology/metabolism ; Animals ; Mitophagy/genetics ; Parkinson Disease/genetics/pathology ; Mutation ; Proteostasis/genetics ; Amyotrophic Lateral Sclerosis/genetics/pathology ; }, abstract = {Neurodegenerative disorders (NDDs), characterized by a progressive loss of neurons and cognitive function, are a severe burden to human health and mental fitness worldwide. A hallmark of NDDs such as Alzheimer's disease, Huntington's disease, Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and prion diseases is disturbed cellular proteostasis, resulting in pathogenic deposition of aggregated protein species. Autophagy is a major cellular process maintaining proteostasis and integral to innate immune defenses that mediates lysosomal protein turnover. Defects in autophagy are thus frequently associated with NDDs. In this review, we discuss the interplay between NDDs associated proteins and autophagy and provide an overview over recent discoveries in inborn errors in canonical autophagy proteins that are associated with NDDs. While mutations in autophagy receptors seems to be associated mainly with the development of ALS, errors in mitophagy are mainly found to promote PD. Finally, we argue whether autophagy may impact progress and onset of the disease, as well as the potential of targeting autophagy as a therapeutic approach. Concludingly, understanding disorders due to inborn errors in autophagy-"autophagopathies"-will help to unravel underlying NDD pathomechanisms and provide unique insights into the neuroprotective role of autophagy, thus potentially paving the way for novel therapeutic interventions.}, }
@article {pmid41051689, year = {2025}, author = {Azam, HMH and Mumtaz, M and Rödiger, S and Schierack, P and Hussain, N and Aisha, A}, title = {MicroRNAs in neurodegenerative diseases: from molecular mechanisms to clinical biomarkers, detection methods and therapeutic strategies-advances and challenges.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {}, number = {}, pages = {}, pmid = {41051689}, issn = {1590-3478}, abstract = {Neurodegenerative diseases (NDDs) pose significant challenges in early detection and treatment due to their complex pathophysiology and heterogeneous clinical presentations. MicroRNAs (miRNAs), small noncoding RNAs that regulate gene expression, have emerged as promising diagnostic biomarkers and therapeutic targets in NDDs. Pathological examination of affected tissues reveals early synaptic dysfunction, protein misfolding, and neuroinflammation occur prior to overt clinical symptoms, highlighting the importance of sensitive diagnostics approaches in prodromal stages. This review summarizes for researchers on the role of miRNAs in NDDs by examining their diagnostic potential in biofluids such as blood and cerebrospinal fluid, and their therapeutic applicability through inhibition or replacement strategies. Literature from peer-reviewed databases was assessed with a focus on recent advances in molecular detection platforms, computational modeling of miRNA-mRNA interactions, and preclinical/clinical investigations.More than 2600 human miRNAs have been identified, collectively regulating over half of mammalian protein-coding genes. Quantitative methodologies, particularly reverse transcription quantitative PCR (RT-qPCR), enable reliable miRNA profiling, facilitating early diagnosis and prognosis of NDDs. Therapeutic strategies, including antagomirs, mimics, sponges and viral or non-viral delivery systems, show promise in modulating disease pathways. However, significant challenges remain, including variability in miRNA extraction and quantification protocols, off-target effects, delivery barriers across the blood brain barrier and limited reproducibility across studies. MiRNAs represent a class of molecular tools with potential to transform diagnostics and therapeutics in NDDs. Future research should prioritize methodological standardization, validation in large multicenter cohorts, and improved computational approaches to elucidate miRNA-mediated regulatory networks in NDDs. Replication studies and translational research are essential harnessing the the full clinical utility of miRNAs in the management of Alzheimer disease, Parkinson disease and other NDDs. Graphical Abstract.}, }
@article {pmid41050540, year = {2025}, author = {Bøgard, H and Green Knakkergaard, S and Simonÿ, C and Tang, LH and Christensen, JR and Dalhoff Pedersen, A and Luijk, A and Gundtoft Roikjær, S}, title = {Implementation of cross-sectoral rehabilitation in the Nordic countries: a scoping review.}, journal = {Frontiers in health services}, volume = {5}, number = {}, pages = {1662230}, pmid = {41050540}, issn = {2813-0146}, abstract = {INTRODUCTION: Rehabilitation needs are rising in the Nordic countries due to an aging population and declining health profiles. Nordic healthcare systems share common features, including universal access, organization, and substantial tax-based financing. Due to the organization of the healthcare system, patients often experience transitions between sectors as part of the rehabilitation program. This fragmented setup undermines the continuity and quality of rehabilitation, making implementation more difficult. To inform future implementation processes, this scoping review examines the factors that influence cross-sectoral rehabilitation in settings with comparable healthcare systems.<br><br>METHODS: This Scoping review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews. The search strategy aimed to identify published, peer-reviewed primary studies on interventions implemented in adult rehabilitation within Nordic countries. Data were charted following Levac et al.'s framework and analyzed using Elo &amp; Kyng&#xe4;s' content analysis to identify factors influencing implementation. Key study characteristics and implementation approaches were synthesized narratively and in tables.<br><br>RESULTS: Thirty-six papers were identified. Most studies described the implementation of rehabilitation transitioning from the secondary to the primary sector. A top-down implementation approach was predominantly reported and appears more facilitating than a bottom-up approach. Implementation of rehabilitation across sectors is influenced by an interplay of factors: (1) Organization &amp; Resources: alignment of context with intervention, involvement from front-line personnel, time &amp; resources, the workplace itself, and managers, and (2) Collaboration &amp; Communication, including knowledge and competence, attitudes, communication, patients, and families.<br><br>CONCLUSION: While this scoping review conveys that collaboration, communication, resources, and organization have a central role affecting the implementation of cross-sectoral rehabilitation, it further identifies knowledge gaps, such as the lack of the patients' perspective, the use of a framework or other systematic approach to ensure the success of the implementation.}, }
@article {pmid41047006, year = {2025}, author = {Stefano, GB and Büttiker, P and Weissenberger, S and Raboch, J and Anders, M}, title = {Semaglutide and the pathogenesis of progressive neurodegenerative disease: the central role of mitochondria.}, journal = {Frontiers in neuroendocrinology}, volume = {}, number = {}, pages = {101217}, doi = {10.1016/j.yfrne.2025.101217}, pmid = {41047006}, issn = {1095-6808}, abstract = {While mitochondria provide critical energy resources, mitochondrial dysfunction can lead to both metabolic and neurodegenerative disorders. Primary mitochondrial disorders (e.g., Leigh syndrome) are uniformly associated with profound neurodegeneration. Recent studies have also implicated mitochondrial dysfunction as a central feature of progressive neurodegenerative diseases, notably Alzheimer's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis, and Huntington's Disease. In addition to its profound impact on metabolic disease, the glucagon-like peptide-1 receptor agonist, semaglutide, has significant neuroprotective features and may limit the progression of one or more of these disorders. These observations might be explained at least in part by the impact of this drug on mitochondrial function and energy production. Collectively, these observations highlight disrupted energy homeostasis as a critical feature of neurodegenerative disease and suggest novel targets for the development of much-needed new neuropharmaceutical strategies.}, }
@article {pmid41046979, year = {2025}, author = {Puspita, L and Deline, M and Shim, JW}, title = {DUAL SMAD INHIBITION AS A VERSATILE PLATFORM IN HUMAN PLURIPOTENT STEM CELL-BASED NEUROSCIENCE AND REGENERATIVE MEDICINE.}, journal = {Molecules and cells}, volume = {}, number = {}, pages = {100284}, doi = {10.1016/j.mocell.2025.100284}, pmid = {41046979}, issn = {0219-1032}, abstract = {Dual SMAD inhibition is a robust and widely adopted protocol for directing human pluripotent stem cells (hPSCs) toward neuronal lineages by blocking transforming growth factor-beta and bone morphogenetic protein pathways. Suppressing TGF-β and BMP signaling enables efficient and reproducible induction of neuroectoderm, serving as the foundation for generating diverse brain region-specific neuronal subtypes. This review outlines the mechanistic basis and major achievements of the dual SMAD inhibition strategy, including its application in two recent clinical trials for Parkinson's disease, and its role in preclinical studies targeting conditions, such as spinal cord injury, retinal degeneration, and amyotrophic lateral sclerosis. In addition to its significant contribution to the generation of transplantation-ready grafts from hPSCs, the protocol serves as a valuable platform for disease modeling across various neurological and metabolic disorders. The key strengths include high efficiency, technical simplicity that enables precise control of cell fate using small molecules, versatility in both two- and three-dimensional culture systems, and reproducibility across various hPSC lines. This review also addresses key limitations, such as restricted gliogenic capacity and limited neural progenitor cell expansion. Future research should focus on incorporating emerging technologies to advance stem cell-based applications. Overall, dual SMAD inhibition represents a powerful and versatile platform for stem cell-based neuroscience and regenerative medicine.}, }
@article {pmid41042709, year = {2025}, author = {Hall, HK and Austin, E and Hutchinson, K and Cheek, C and Clay-Williams, R}, title = {A Systematic Review of Management of Cramping Pain in Patients with Amyotrophic Lateral Sclerosis.}, journal = {European neurology}, volume = {}, number = {}, pages = {1}, doi = {10.1159/000548820}, pmid = {41042709}, issn = {1421-9913}, abstract = {BACKGROUND/INTRODUCTION: Pain, particularly cramping, in people living with Amyotrophic Lateral Sclerosis (ALS) is often underrecognized and under-treated. Despite affecting over 70% of people living with ALS (plwALS), cramping pain remains inadequately managed due to its complex nature and the difficulties plwALS face in communicating their symptoms as the disease progresses. This systematic review explores both pharmacological and non-pharmacological treatments for cramping pain in ALS, aiming to assess and compare their efficacy.<br><br>METHODS: The systematic review was conducted following PRISMA guidelines and the protocol was registered with PROSPERO (ID CRD42024521649). A comprehensive search was performed across MEDLINE, Embase, Scopus, and Cochrane databases from inception until February 1, 2024, using specific search terms related to ALS and cramping.<br><br>RESULTS: The search resulted in the identification of 368 studies. After duplicates were removed, abstracts screened, and full texts reviewed, nine studies were included. Pharmacological interventions such as Mexiletine demonstrated significant reductions in cramp frequency and intensity in several trials, with varying doses showing distinct levels of effectiveness. Other medications like Dronabinol and Levetiracetam were also tested but showed limited efficacy in reducing cramp severity. Among non-pharmacological options, supervised exercise programs, particularly those incorporating stretching and functional mobility, were effective in reducing cramping pain intensity, while unsupervised home exercise programs did not show significant improvements.<br><br>CONCLUSION: The review demonstrates the scarcity of high-quality research on cramping pain management in ALS. Mexiletine emerged as the most promising pharmacological intervention, providing notable relief, while supervised exercise therapy demonstrated beneficial effects.}, }
@article {pmid41037122, year = {2025}, author = {Thakur, A and Sharma, R and Sharma, R and Devi, A}, title = {Neurodegeneration and aging: pathophysiology, diagnosis, and therapeutic targets.}, journal = {Inflammopharmacology}, volume = {}, number = {}, pages = {}, pmid = {41037122}, issn = {1568-5608}, abstract = {Aging is the greatest risk factor for AD, ALS, PD, FTD, and HD. Neurons in the brain experience many changes as people age, negatively affecting their structure and function. It examines the key processes behind brain aging, such as age-related death of cells, failure of the cells' powerhouses, oxidative stress, incorrect protein shapes, brain inflammation, difficulty in cleaning the brain, and deterioration of blood vessels, and shows their impact on neurodegeneration. With age, there are difficulties in brain-blood circulation, less synaptic change, and fewer new neurons, which make the disease even worse. Informed by human and animal trials, we see that mitochondria work less efficiently in aging brain cells, while oxidative damage to DNA increases doubly to triply. In addition, too much tau, amyloid-β, and α-synuclein building up is tied to declining mental abilities in the elderly. We further evaluate new tests that help with early detection and classification, for example, using biomarkers in cerebrospinal fluid (CSF), blood panels, detailed brain scans, and AI algorithms. It stresses that more aging-specific trials, better integration of multi-omics, and increased interest in research on the gut-brain axis are important. The communication between the aging of the body and the brain is also explained. This article covers the main cellular, molecular, and clinical issues linked to brain aging and highlights important future research areas needed to develop effective treatments for aging people.}, }
@article {pmid41032625, year = {2025}, author = {Rosenberg, GM and Murray, KA and Sawaya, MR and Jiang, YX and Geschwind, DH and Eisenberg, DS}, title = {Genetic and structural aspects of amyloid diseases.}, journal = {Science translational medicine}, volume = {17}, number = {818}, pages = {eadp3378}, doi = {10.1126/scitranslmed.adp3378}, pmid = {41032625}, issn = {1946-6242}, mesh = {Humans ; *Amyloidosis/genetics ; *Amyloid/chemistry/genetics/metabolism ; Mutation/genetics ; Animals ; }, abstract = {The conversion of proteins into insoluble fibrillar aggregates known as amyloid occurs in a wide variety of diseases, e.g., Alzheimer's disease, amyotrophic lateral sclerosis, systemic transthyretin amyloidosis, and multisystem atrophy. There are more than 60 disease-associated amyloid-forming proteins, and amyloid formation can occur sporadically or can be induced or accelerated by genetic mutations. This Review discusses structural mechanisms by which genetic changes promote amyloid formation and thereby influence disease outcomes. By dividing amyloid-forming proteins into six types according to the genetic mutations they carry and analyzing mutation-induced structural changes in amyloid fibrils, a better understanding of inheritance patterns of amyloid diseases (amyloidoses) can be obtained.}, }
@article {pmid40581671, year = {2025}, author = {Ono, S and Nakamura, M and Ikegami, T and Kajiyama, Y and Kume, K and Takahashi, Y and Takahashi, M and Mochizuki, H and Mizusawa, H and Kawakami, H and Yakushiji, Y}, title = {Spinocerebellar ataxia type 2 followed by amyotrophic lateral sclerosis due to a pure CAG repeat expansion in ATXN2: a case report and literature review.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {46}, number = {10}, pages = {5417-5421}, pmid = {40581671}, issn = {1590-3478}, mesh = {Humans ; Middle Aged ; *Amyotrophic Lateral Sclerosis/genetics/complications/diagnostic imaging ; Female ; *Ataxin-2/genetics ; *Spinocerebellar Ataxias/genetics/complications/diagnostic imaging ; *Trinucleotide Repeat Expansion/genetics ; Magnetic Resonance Imaging ; }, abstract = {BACKGROUND: Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant cerebellar ataxia caused by abnormal CAG expansions (≥ 34 repeats) in the ATXN2 gene (ATXN2), whereas intermediate CAG expansions (27-33 repeats) have been linked to amyotrophic lateral sclerosis (ALS).<br><br>CASE DESCRIPTION: A 53-year-old woman with longstanding cerebellar ataxia developed progressive upper limb weakness and muscle atrophy at the age of 51&#xa0;years. On neurological examination, she was found to have ataxic dysarthria, slow saccadic eye movements, tongue atrophy with fasciculations, muscle atrophy and weakness in both upper limbs, hyperreflexia with Babinski's sign, and limb and gait ataxia. Brain magnetic resonance imaging (MRI) showed brainstem and cerebellar atrophy. Genetic analysis identified an expanded CAG-repeat of 39/22 in ATXN2, and screening for other known ALS-related gene mutations was negative, leading to a diagnosis of both SCA2 and ALS associated with ATXN2.<br><br>CONCLUSIONS: SCA2 is typically associated with uninterrupted CAG-repeat expansions, whereas ALS-related ATXN2 expansions usually contain at least one CAA triplet. However, despite carrying an uninterrupted CAG-repeat expansion, this patient developed ALS. This case shows that ALS can emerge several decades after SCA2 onset, even in patients with pure CAG-repeats, underscoring the need for long-term monitoring in SCA2 patients. Further research is needed to clarify the roles of repeat length, CAA interruptions, and other factors in ATXN2-related ALS.}, }
@article {pmid41024175, year = {2025}, author = {Bamber, R and Carlton, J and McDermott, C and Stavroulakis, T}, title = {Understanding health-related quality of life of informal carers in amyotrophic lateral sclerosis: a scoping review and conceptual framework.}, journal = {Health and quality of life outcomes}, volume = {23}, number = {1}, pages = {90}, pmid = {41024175}, issn = {1477-7525}, support = {NIHR301648//National Institute for Health and Care Research/ ; NIHR301648//National Institute for Health and Care Research/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology/nursing ; *Quality of Life/psychology ; *Caregivers/psychology ; Patient Reported Outcome Measures ; }, abstract = {BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a rapidly progressive, life-limiting neurodegenerative disease. Informal carers provide extensive support, significantly impacting their health-related quality of life (HRQoL). Current HRQoL measurement using person-reported outcome measures (PROMs) in ALS carers lacks consistency and comprehensiveness, hindering robust assessment and synthesis. There is evident need for a comprehensive conceptual framework of HRQoL, to fully capture the multidimensional nature of caregiving in ALS. Such a framework is essential to inform research and clinical practice, ensuring relevant measurement and meaningful clinical discussions. This study aimed to develop this evidence-based framework.<br><br>METHODS: This study comprised two stages. Firstly, a scoping review was undertaken in March 2024 using Medline, Embase, and CINAHL to identify primary articles exploring HRQoL in ALS carers. Qualitative, mixed methods and quantitative articles using multi-item PROMs to assess HRQoL in informal ALS carers were included. Relevant themes and subthemes were extracted from articles and PROMs and mapped onto an existing conceptual framework for people with ALS (Quality of Life in ALS, QuALS), which covers physical, psychological, and social HRQoL domains in people with ALS. The Carer-QuALS framework was subsequently developed and refined using existing literature and consultation with ALS carers. PROMs within this review were then indexed against the finalised Carer-QuALS framework.<br><br>RESULTS: From 715 search results, 82 articles and 44 PROMs were eligible for inclusion. One new subtheme 'physical caring activities' emerged, while seven subthemes lacked support from the literature. In three structured consultation sessions, nine ALS carers, reviewed the draft Carer-QuALS framework (consisting of seven themes and 43 subthemes). Based on their input, one new subtheme 'privacy' was added, six subthemes were removed, and one was retained, despite lacking support from review literature. The final Carer-QuALS framework includes 37 subthemes: 8 physical, 6 social, and 23 psychological.<br><br>CONCLUSIONS: This review presents a comprehensive conceptual framework encompassing the multidimensional impact of ALS caregiving on the HRQoL of informal carers. The framework provides a resource that can be used by researchers, clinicians, and patient advocacy groups for multiple purposes (e.g., to support PROM selection to measure HRQoL, to guide future PROM development, and to facilitate discussions between informal carers and clinicians).}, }
@article {pmid41022359, year = {2025}, author = {Liu, C and Lai, FF and Zhang, T and Mao, KJ and Wan, HT and He, Y}, title = {Roles and therapeutic potential of PARP-1 in neurodegenerative diseases.}, journal = {Biochemical pharmacology}, volume = {}, number = {}, pages = {117373}, doi = {10.1016/j.bcp.2025.117373}, pmid = {41022359}, issn = {1873-2968}, abstract = {Poly(ADP-ribose) polymerase 1 (PARP-1) was first discovered in the 1960 s, and over the past few decades, there has been growing evidence that PARP-1 plays a key role in neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis. With DNA damage detection and repair as its main function, PARP-1 is activated by regulation in the early stages of neurodegenerative diseases, quickly and effectively repairs mild DNA damage, and protects nerve cells from death. However, as the disease progresses, severe DNA damage causes PARP-1 to overactivate, resulting in neuronal cell death, including apoptosis, necrosis, and parthanatos, further exacerbating the disease progression. PARP-1 is also involved in the pathological process of neurodegenerative diseases, such as pathological protein aggregation, neuroinflammation, mitochondrial dysfunction, autophagy disorder, and damage to the blood-brain barrier. According to a large number of studies, PARP-1 inhibition has shown great therapeutic potential for neurodegenerative diseases, and the development of PARP-1 inhibitors has received increasing attention. Here, we review the role of PARP-1 in the process of neurodegenerative diseases and summarize the latest research progress and application of PARP-1 inhibitors in neurodegenerative diseases.}, }
@article {pmid41019550, year = {2025}, author = {Chen, KQ and Cao, WJ and Liu, Z and Liu, RZ}, title = {Mini-review: Processed red meat intake and risk of neurodegenerative diseases.}, journal = {Frontiers in nutrition}, volume = {12}, number = {}, pages = {1663647}, pmid = {41019550}, issn = {2296-861X}, abstract = {Neurodegenerative diseases (NDDs) are a group of disorders characterized by the progressive loss of neurons in specific areas of the central nervous system. In recent years, more and more research has focused on the influence of diet on NDDs. As a common food, processed red meat is widely consumed worldwide. Many studies have shown that processed red meat may increase the risk of cancer, diabetes and cardiovascular disease. Unfortunately, it is unclear whether processed red meat affects NDDs. Therefore, we reviewed the existing literature on the role of processed meats in NDDs. We concluded that intake of processed meat may have an adverse effect on NDDs.}, }
@article {pmid41018945, year = {2025}, author = {Vucic, S and Shahrizaila, N and Kano, O and Menon, P and Agustini, S and Kulkantrakorn, K and Atchayaram, N and Lee, YC and Prado, MB and Ng, KWP and Chai, J and Son, B and Talman, P and Nghia, HTT and Tuan, LTQ and Shibuya, K and Izumi, Y and Atsuta, N and Henderson, RD and Cui, L and Liu, M and Ohnmar, O and Rabani, R and Hong, YH and Sung, JJ and Fan, D and Raykar, V and Kuwabara, S and Kim, SH and Sobue, G and Kiernan, MC}, title = {Pan-Asian consortium for treatment and research in ALS (PACTALS) guidelines for management of amyotrophic lateral sclerosis.}, journal = {The Lancet regional health. Western Pacific}, volume = {62}, number = {}, pages = {101684}, pmid = {41018945}, issn = {2666-6065}, abstract = {The Pan-Asian Consortium for Treatment and Research in ALS (PACTALS) guidelines were developed for the management of amyotrophic lateral sclerosis (ALS) patients living in the Asia-Pacific countries, taking into consideration the ethnic, racial and economic diversity of the region. The majority of patients reside in low-income (limited-resource setting) and middle-income countries. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was utilised for development of the PACTALS management guidelines. Nine broad research questions, divided into sections, were addressed. Evidence was derived from existing Cochrane reviews, systematic reviews, meta-analysis, and randomized controlled trials (RCT) along with consensus when evidence was limited. Recommendations were provided for diagnostic pathways, use of disease modifying therapies, appropriateness of multidisciplinary care models, management of respiratory dysfunction, communication and nutrition, addressing symptoms that affect the quality of life, managing cognitive, behavioural and emotional symptoms as well as appropriate implementation of palliative care services and addressing end-of-life issues. The PACTALS guidelines provide a much-needed framework for the management of ALS patients living in the Asia-Pacific region. The management guidelines will be updated as the treatment landscape evolves and evidence of novel management approaches becomes available.}, }
@article {pmid41017972, year = {2025}, author = {Feng, J and Hu, X and Liu, J and Wang, W and Chen, L and Pang, R and Zhang, A}, title = {Akkermansia muciniphila in neurological disorders: mechanisms and therapeutic potential via the gut-brain axis.}, journal = {Frontiers in neuroscience}, volume = {19}, number = {}, pages = {1650807}, pmid = {41017972}, issn = {1662-4548}, abstract = {In recent years, the role of Akkermansia muciniphila (A. muciniphila) in neurological diseases has attracted increasing attention. As a probiotic, A. muciniphila is closely associated with host health, metabolism, and immunity, demonstrating therapeutic potential in various conditions such as obesity, atherosclerosis, inflammatory bowel disease, diabetes, and liver disorders. In the context of neurological diseases, A. muciniphila significantly influences the host brain through the microbiota-gut-brain axis (MGBA). This review summarizes the roles and mechanisms of A. muciniphila and its active components (e.g., the outer membrane protein Amuc_1100, extracellular vesicles AmEVs, and short-chain fatty acids SCFAs) in various neurological disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), depression, cerebral palsy (CP), epilepsy (EP), autism spectrum disorder (ASD), and amyotrophic lateral sclerosis (ALS). It exerts protective effects by enhancing the intestinal barrier, regulating lipid metabolism, producing SCFAs, secreting neuroactive substances, and inhibiting neuroinflammation, thereby suggesting novel therapeutic avenues for neurological disorders. However, due to limited data from large-scale human clinical trials and the complexity of disease mechanisms and host-microbiota interactions, its clinical translation faces considerable challenges. Future efforts should focus on multicenter randomized controlled trials and in-depth mechanistic studies utilizing technologies such as metabolomics to facilitate evidence-based clinical application.}, }
@article {pmid41011076, year = {2025}, author = {Della Toffola, J and Ricci, E and Quagliotto, M and Manganotti, P and Benussi, A}, title = {Non-Invasive Brain Stimulation for Amyotrophic Lateral Sclerosis: Current Evidence and Future Perspectives.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {61}, number = {9}, pages = {}, pmid = {41011076}, issn = {1648-9144}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/physiopathology ; *Transcranial Magnetic Stimulation/methods/trends/standards ; *Transcranial Direct Current Stimulation/methods/trends/standards ; Brain/physiopathology ; }, abstract = {Background and Objectives: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting the upper and lower motor neurons, with a bleak prognosis and few treatment options. Non-invasive brain stimulation (NIBS) techniques, such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), represent emerging approaches aimed at modulating cortical hyperexcitability, a relevant pathogenetic mechanism in ALS. Materials and Methods: A systematic review of the literature was conducted following the PRISMA guidelines, exploring the Scopus and PubMed databases from April to June 2025 with terms related to ALS and NIBS. A total of 18 relevant studies were selected from the initial 708 articles, analysing stimulation protocols, clinical and neurophysiological outcomes, and associated biomarkers; their validity was assessed using the revised Cochrane risk-of-bias (RoB2) tool. Results: The selected studies were extremely heterogeneous, with NIBS techniques, including magnetic (rTMS, cTBS, tSMS) and electrical (tDCS) stimulation, showing variable effects. Low-frequency protocols (1 Hz rTMS) and cTBS showed a slight slowing of clinical progression, while prolonged home stimulation with tDCS and tSMS showed more significant improvements in terms of efficacy, tolerability, and adherence. The main limitations concern the heterogeneity of patients and protocols and the lack of standardised biomarkers, which is why the analysis remained at a descriptive level. The use of telemonitoring and caregiver training are essential to ensure safety and accessibility. Conclusions: NIBS represents a promising therapeutic approach for ALS, but further multicentre, standardised studies with prolonged follow-up are needed. Future strategies should include customisation of stimulation, combination with other therapies, and extension of application to pre-symptomatic phases.}, }
@article {pmid41009734, year = {2025}, author = {Genchi, G and Catalano, A and Carocci, A and Sinicropi, MS and Lauria, G}, title = {Copper, Cuproptosis, and Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {26}, number = {18}, pages = {}, doi = {10.3390/ijms26189173}, pmid = {41009734}, issn = {1422-0067}, mesh = {*Copper/metabolism/toxicity ; Humans ; *Neurodegenerative Diseases/metabolism/etiology/pathology ; Animals ; Homeostasis ; }, abstract = {Copper is a vital micronutrient for animals and plants acting as a crucial cofactor in the synthesis of numerous metabolic enzymes and contributing to mitochondrial respiration, metabolism, oxido-reductive reactions, signal transmission, and oxidative and nitrosative damage. In the cells, copper may exist in the Cu[+] and Cu[++] oxidation states and the interconversion between these two states may occur via various redox reactions regulating cellular respiration, energy metabolism, and cell growth. The human body maintains a low level of copper, and copper deficiency or copper excess may adversely affect cellular functions; therefore, regulation of copper levels within a narrow range is important for maintaining metabolic homeostasis. Recent studies identified a new copper-dependent form of cell death called cuproptosis. Cuproptosis occurs due to copper binding to lipoylated enzymes (for instance, pyruvate dehydrogenase and α-ketoglutarate dehydrogenase) in the tricarboxylic acid Krebs cycle. In recent years, extensive studies on copper homeostasis and copper-induced cell death in degenerative disorders, like Menkes, Wilson, Alzheimer, Parkinson's, Huntington's diseases, and Amyotrophic Lateral Sclerosis, have discussed the therapeutic potential of targeting cuproptosis. Copper contamination in the environment, which has increased in recent years due to the expansion of agricultural and industrial activities, is associated with a wide range of human health risks. Soil used for the cultivation of grapes has a long history of copper-based fungicide application (the Bordeaux mixture is rich in copper) resulting in copper accumulation at levels capable of causing toxicity in plants that co-inhabit the vineyards. Phytoremediation, which uses plants and biological solutions to remove toxic heavy metals and pesticides and other contaminants from soil and water, is an environmentally friendly and cost-effective technology used for the removal of copper. It requires plants to be tolerant of high levels of copper and capable of accumulating metal copper in plants' aerial organs and roots. This review aims at highlighting the importance of copper as an essential metal, as well as its involvement in cuproptosis and neurodegenerative diseases.}, }
@article {pmid41009457, year = {2025}, author = {Scognamiglio, A and Corvino, A and Caliendo, G and Fiorino, F and Perissutti, E and Santagada, V and Severino, B}, title = {Druggability of Sodium Calcium Exchanger (NCX): Challenges and Recent Development.}, journal = {International journal of molecular sciences}, volume = {26}, number = {18}, pages = {}, doi = {10.3390/ijms26188888}, pmid = {41009457}, issn = {1422-0067}, mesh = {*Sodium-Calcium Exchanger/metabolism/antagonists &amp; inhibitors/chemistry ; Humans ; Animals ; Protein Isoforms/metabolism ; Calcium/metabolism ; }, abstract = {Na[+]/Ca[2+] exchangers (NCXs) are membrane transporters crucial for calcium homeostasis in excitable tissues, particularly in the central nervous system. Growing evidence indicates that NCX dysfunction contributes to calcium overload and neuronal damage in several neurological conditions. Thus, pharmacological modulation of NCX isoforms (NCX1, NCX2, and NCX3) has emerged as a potential therapeutic strategy for disorders such as stroke, multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), and Parkinson's disease (PD). However, the identification of selective modulators directed at specific NCX isoforms, or even different splice variants, remains challenging and limits their clinical validation. This Review aims to provide an updated overview of small-molecule NCX modulators, described over the last two decades. Chemical structures, mechanisms of action, and isoform specificity are discussed, along with the most commonly used biological assays for their functional evaluation.}, }
@article {pmid41008559, year = {2025}, author = {Steffan, D and Pezzini, C and Esposito, M and Franco-Romero, A}, title = {Mitochondrial Aging in the CNS: Unravelling Implications for Neurological Health and Disease.}, journal = {Biomolecules}, volume = {15}, number = {9}, pages = {}, doi = {10.3390/biom15091252}, pmid = {41008559}, issn = {2218-273X}, mesh = {Humans ; *Mitochondria/metabolism/pathology/genetics ; *Neurodegenerative Diseases/metabolism/pathology/genetics ; *Aging/metabolism/pathology ; *Central Nervous System/metabolism/pathology ; Animals ; DNA, Mitochondrial/genetics/metabolism ; Oxidative Stress ; Reactive Oxygen Species/metabolism ; Mitophagy ; Mitochondrial Dynamics ; }, abstract = {Mitochondrial aging plays a central role in the functional decline of the central nervous system (CNS), with profound consequences for neurological health. As the brain is one of the most energy-demanding organs, neurons are particularly susceptible to mitochondrial dysfunction that arises with aging. Key features of mitochondrial aging include impaired mitochondrial dynamics, reduced mitophagy, increased production of reactive oxygen species (ROS), and accumulation of mitochondrial DNA (mtDNA) mutations. These alterations dramatically compromise neuronal bioenergetics, disrupt synaptic integrity, and promote oxidative stress and neuroinflammation, paving the path for the development of neurodegenerative diseases. This review also examines the complex mechanisms driving mitochondrial aging in the central nervous system (CNS), including the disruption of mitochondrial-organelle communication, and explores how mitochondrial dysfunction contributes to neurodegenerative diseases, such as Alzheimer's, Parkinson's, Huntington's, and amyotrophic lateral sclerosis. By synthesizing current evidence and identifying key knowledge gaps, we emphasize the urgent need for targeted strategies to restore mitochondrial function, maintain cognitive health, and delay or prevent age-related neurodegeneration.}, }
@article {pmid41008528, year = {2025}, author = {Tian, Z and Jin, F and Geng, Z and Xu, Z and Shao, Q and Liu, G and Ji, X and Liu, J}, title = {Unraveling the Mystery of Hemoglobin in Hypoxia-Accelerated Neurodegenerative Diseases.}, journal = {Biomolecules}, volume = {15}, number = {9}, pages = {}, doi = {10.3390/biom15091221}, pmid = {41008528}, issn = {2218-273X}, support = {20230484436//the Beijing Nova Program/ ; CX23YQ01//the Chinese Institutes for Medical Research, Beijing/ ; 22JCZXJ00190//Beijing-Tianjin-Heibei Basic Research Cooperation Project/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/pathology ; *Hemoglobins/metabolism ; *Hypoxia/metabolism/complications ; Animals ; Mitochondria/metabolism ; }, abstract = {Hypoxic stress is increasingly recognized as a convergent pathological factor in various age-related neurodegenerative diseases (NDDs), encompassing both acute events such as stroke and traumatic brain injury (TBI), and chronic disorders including Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS). Recent studies have revealed that hemoglobin (Hb), beyond its classical oxygen-transport function, exhibits unexpected expression and functional relevance within the central nervous system. Notably, both cerebral and circulating Hb appear to be dysregulated under hypoxic and aging conditions, potentially influencing disease onset and progression of these diseases. However, Hb's impact on neurodegeneration appears to be context-dependent: in acute NDDs, it may exert neuroprotective effects by stabilizing mitochondrial and iron homeostasis, whereas in chronic NDDs, aberrant Hb accumulation may contribute to toxic protein aggregation and neuronal dysfunction. This review provides an integrative overview of the emerging roles of Hb in hypoxia-related NDDs, highlighting both shared and distinct mechanisms across acute and chronic conditions. We further discuss potential therapeutic implications of targeting Hb-related pathways in NDDs and identify key gaps for future investigation.}, }
@article {pmid41008332, year = {2025}, author = {Bernetti, C and Cea, L and Buoso, A and Greco, F and Rossi, M and Pilato, F and Calandrelli, R and Di Gennaro, G and Di Lazzaro, V and Zobel, BB and Mallio, CA}, title = {A Comprehensive Overview of Subacute Combined Degeneration: MRI Diagnostic Challenges and Treatment Pathways.}, journal = {Brain sciences}, volume = {15}, number = {9}, pages = {}, doi = {10.3390/brainsci15090972}, pmid = {41008332}, issn = {2076-3425}, abstract = {Subacute combined degeneration (SCD) is a neurological disorder primarily caused by vitamin B12 deficiency. This condition leads to progressive demyelination and axonal damage, predominantly affecting the dorsal and lateral columns of the spinal cord. This review provides a comprehensive overview of SCD, detailing its complex etiology, pathophysiology, and clinical presentation. We highlight the critical role of magnetic resonance imaging (MRI) in the diagnostic process, discussing both the characteristic spinal cord findings and the more subtle intracranial abnormalities. Furthermore, we address the diagnostic challenges presented by conditions that mimic SCD in MRI, such as multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). We conclude by outlining current treatment pathways and identifying key areas for future research, including the use of advanced neuroimaging techniques and the potential for new therapeutic approaches. This updated synthesis aims to provide a clear framework for clinicians and researchers to better understand and manage SCD.}, }
@article {pmid41007730, year = {2025}, author = {Schreiner, TG and Menéndez-González, M and Schreiner, OD and Ciobanu, RC}, title = {Intrathecal Therapies for Neurodegenerative Diseases: A Review of Current Approaches and the Urgent Need for Advanced Delivery Systems.}, journal = {Biomedicines}, volume = {13}, number = {9}, pages = {}, doi = {10.3390/biomedicines13092167}, pmid = {41007730}, issn = {2227-9059}, abstract = {Neurodegenerative diseases (NDDs) pose an immense global health burden, and developing effective treatments is hindered by the blood-brain barrier (BBB). Intrathecal (IT) administration of therapeutics directly into the cerebrospinal fluid (CSF) bypasses the BBB, offering a promising avenue for antisense oligonucleotides (ASOs), gene therapies, antibodies, and stem cells for these disorders. This review synthesizes the current landscape of IT therapies for Alzheimer's disease, Parkinson's disease, Huntington's disease, and Amyotrophic Lateral Sclerosis based on the current literature and ClinicalTrials.gov. We highlight key trials and approaches, including the success of ASOs in spinal muscular atrophy and recent progress in other NDDs. However, the efficacy of these novel treatments is often constrained by the limitations of first-generation IT delivery systems, which struggle with uneven distribution, systemic leakage, and the demands of modern biologics. Drawing from recent analyses, we underscore the critical shortcomings of current devices and point out the innovations needed in shaping next-generation systems: subcutaneous access ports, CSF flow platforms, AI-driven adaptive dosing, nanoporous membranes, intrathecal pseudodelivery, and hydrogel scaffolds. We conclude by emphasizing the urgent need for these advanced IT drug delivery systems, alongside rigorous comparative assessments, cost-benefit analyses, and clear regulatory pathways to fully realize the potential of emerging CNS therapies and transform NDD management.}, }
@article {pmid41005573, year = {2025}, author = {Marlow, TR and Bowden, KM and Collins, MO and Shaw, PJ}, title = {The potential role of misfolded wild-type SOD1 protein in sporadic amyotrophic lateral sclerosis (ALS): a review of the evidence.}, journal = {Neurobiology of disease}, volume = {}, number = {}, pages = {107124}, doi = {10.1016/j.nbd.2025.107124}, pmid = {41005573}, issn = {1095-953X}, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterised by the selective loss of motor neurons in the motor cortex, brainstem and spinal cord. In 1993, the first ALS-linked gene mutations were identified in the Cu,Zn superoxide dismutase (SOD1) gene, which account for approximately 20 % of familial ALS cases. The mechanism of toxicity in this subset of patients is thought to arise from a gain-of-toxic function from the protein's propensity to misfold and aggregate into cytoplasmic inclusions. Immunohistochemical studies have shown that misfolded wildtype SOD1 (wtSOD1) is also detected in the motor neurons and glial cells of ALS patients without SOD1 mutations. It is proposed that disrupted, or aberrant, posttranslational modifications cause wtSOD1 to adopt a toxic conformation similar to that of the mutant protein. Subsequent mechanistic studies have shown that this misfolded wtSOD1 can disrupt cellular function and lead to motor neuron death through pathways similar to those observed in mutant SOD1-ALS. Given the limited neuroprotective treatments currently available that can effectively slow or reverse disease progression, targeting a pathogenic mechanism that features in both familial and sporadic ALS cases represents a promising therapeutic approach for a broader patient population. This review examines the growing body of evidence that supports or challenges the role of misfolded wtSOD1 in the pathophysiology of sporadic ALS and explores the potential implications of this mechanism in disease progression. Understanding how misfolded wtSOD1 contributes to disease pathogenesis provides new opportunities for developing more widely available treatments for this devastating disease.}, }
@article {pmid41004063, year = {2025}, author = {Dellarole, IL and Lombardo, A and Ciullini, A and Cazzaniga, FA and Domina, R and Bacınoğlu, MB and Moda, F}, title = {Seed Amplification Assays as Powerful Tools for Detecting Peripheral Biomarkers in Prion-Like Diseases.}, journal = {Sub-cellular biochemistry}, volume = {112}, number = {}, pages = {293-320}, pmid = {41004063}, issn = {0306-0225}, mesh = {Humans ; *Biomarkers/metabolism/blood/cerebrospinal fluid ; *Prion Diseases/diagnosis/metabolism ; *Prions/metabolism ; *Nucleic Acid Amplification Techniques/methods ; Neurodegenerative Diseases/diagnosis ; }, abstract = {Seed amplification assays (SAAs) are highly sensitive and advanced techniques originally developed for the study and diagnosis of prion diseases. Thanks to their remarkably high sensitivity and specificity, SAAs are now widely employed in both research and clinical settings for prion detection, especially in peripheral tissues of patients with prion disorders. Many neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies, frontotemporal dementia, and amyotrophic lateral sclerosis, show prion-like mechanisms involving the misfolding and self-propagation of pathological proteins. As a result, SAAs are being adapted and refined for clinical use to improve the diagnosis of these conditions. This includes detecting traces of pathological proteins in cerebrospinal fluid as well as in minimally or noninvasively collected samples, such as blood, urine, skin, and olfactory mucosa. This chapter offers an overview of the role of SAAs in the clinical diagnosis of neurodegenerative diseases.}, }
@article {pmid41002898, year = {2025}, author = {Truong, TT and Singh, AA and Bang, NV and Vu, NMH and Na, S and Choi, J and Oh, J and Mondal, S}, title = {Mitochondria-Associated Membrane Dysfunction in Neurodegeneration and Its Effects on Lipid Metabolism, Calcium Signaling, and Cell Fate.}, journal = {Membranes}, volume = {15}, number = {9}, pages = {}, doi = {10.3390/membranes15090263}, pmid = {41002898}, issn = {2077-0375}, support = {//This work was supported by a Research Grant of Pukyong National University (2023)/ ; }, abstract = {Mitochondria-associated membranes (MAMs) are essential for cellular homeostasis. MAMs are specialized contact sites located between the endoplasmic reticulum (ER) and mitochondria and control apoptotic pathways, lipid metabolism, autophagy initiation, and calcium signaling, processes critical to the survival and function of neurons. Although this area of membrane biology remains understudied, increasing evidence links MAM dysfunction to the etiology of major neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS). MAMs consist of a network of protein complexes that mediate molecular exchange and ER-mitochondria tethering. MAMs regulate lipid flow in the brain, including phosphatidylserine and cholesterol; disruption of this process causes membrane instability and impaired synaptic function. Inositol 1,4,5-trisphosphate receptor-voltage-dependent anion channel 1 (IP3R-VDAC1) interactions at MAMs maintain calcium homeostasis, which is required for mitochondria to produce ATP; dysregulation promotes oxidative stress and neuronal death. An effective therapeutic approach for altering neurodegenerative processes is to restore the functional integrity of MAMs. Improving cell-to-cell interactions and modulating MAM-associated proteins may contribute to the restoration of calcium homeostasis and lipid metabolism, both of which are key for neuronal protection. MAMs significantly contribute to the progression of neurodegenerative diseases, making them promising targets for future therapeutic research. This review emphasizes the increasing importance of MAMs in the study of neurodegeneration and their potential as novel targets for membrane-based therapeutic interventions.}, }
@article {pmid41002740, year = {2025}, author = {Bardhan, M and Anand, A and Javed, A and Chilo, MA and Khan, N and Garg, T and Surana, A and Huang, H and Samim, MM and Suresh, V and Khare, A and Menon, B and Kundu, T}, title = {Polymorphism of Melanocortin Receptor Genes-Association with Inflammatory Traits and Diseases.}, journal = {Diseases (Basel, Switzerland)}, volume = {13}, number = {9}, pages = {}, doi = {10.3390/diseases13090305}, pmid = {41002740}, issn = {2079-9721}, abstract = {Melanocortin receptors (MCRs) are responsible for various functions ranging from skin pigmentation, regulation of appetite, stress response and cognition, steroid synthesis, and energy balance to cellular regeneration and immunomodulation. The genetic polymorphism with tissue distribution ranging from the brain, limbic system, and adrenal cortex to neutrophils, monocytes, and macrophages is evident in MCRs. The mutations in MC1R, MC2R, MC3R, and MC4R genes are associated with risk of melanoma, familial glucocorticoid deficiency, obesity, and type 2 diabetes mellitus, respectively. Meanwhile, MC1R, MC2R, and MC5R genes are involved in the risk of major depressive disorder. Melanocortin receptors are involved in different inflammatory disorders, i.e., atopic dermatitis, autoimmune uveitis, sarcoidosis, respiratory diseases, multiple sclerosis, scleroderma, inflammatory bowel disease, amyotrophic lateral sclerosis, Alzheimer's disease, arthritis, and reperfusion injury. Several newer therapeutic agents related to MCRs have numerous advantages over the current anti-inflammatory drugs, demonstrating therapeutic relevance. Among them, α-MSH analogs play a role in atopic dermatitis and scleroderma, and MC1R agonist Dersimelagon has shown effectiveness in systemic sclerosis. The FDA has recently approved the repository corticotropin injection (RCI) to treat sarcoidosis. The FDA has also approved various melanocortin agonists, i.e., Bremelanotide, Afamelanotide, and Setmelanotide, for the treatment of hypoactive sexual desire disorder, Erythropoietic protoporphyria, and obesity, due to pro-opiomelanocortin and leptin receptor deficiency, respectively. Therefore, this review aims to summarize the function and genetic polymorphism of melanocortin receptors, regulatory pathways involving MCRs, and the existing evidence of the prime effect of MCRs on inflammatory responses via different mechanisms and their potential therapeutic use in inflammatory diseases.}, }
@article {pmid40999441, year = {2025}, author = {Abdi, K and Foroughi, Z and Najafi, Z and Afshari, M}, title = {Challenges and solutions to effective stewardship of rehabilitation services: a scoping review.}, journal = {BMC health services research}, volume = {25}, number = {1}, pages = {1211}, pmid = {40999441}, issn = {1472-6963}, support = {IR.USWR.REC.1402.099//University of Social Welfare and Rehabilitation Sciences/ ; }, mesh = {Humans ; *Rehabilitation/organization &amp; administration ; Iran ; *Delivery of Health Care/organization &amp; administration ; Health Policy ; }, abstract = {BACKGROUND AND AIM: Strong and effective stewardship is a fundamental function of health systems. However, rehabilitation services often receive insufficient attention due to the limited priority assigned to them by governments and health systems. In many countries-particularly low- and middle-income nations-this neglect has resulted in fragmented and poorly coordinated rehabilitation services across various sectors, with inconsistent service delivery influenced by the internal policies of individual institutions. This study investigates the broader barriers to rehabilitation services, analyzes their implications for stewardship, and proposes solutions to improve governance and system coordination.<br><br>METHOD: In this scoping review of studies conducted in Iran and globally, we identified factors and strategies for effective stewardship of rehabilitation services using Arksey and O'Malley's framework. Searches were performed in English databases (PubMed, Web of Science, and Scopus) and Persian databases (SID and Magiran), as well as the Google Scholar search engine, utilizing relevant English keywords and their Persian equivalents. Data were analyzed through a qualitative methodology employing directed content analysis. Additionally, Veillard et al.'s Health System Stewardship Framework was utilized to identify and analyze the challenges and solutions implemented in other countries.<br><br>FINDINGS: From a total of 38 published articles on rehabilitation services, six themes, eight sub-themes, 81 challenges, and 74 solutions were identified. The challenges included the ineffectiveness of the fragmented rehabilitation structure and stewardship, the absence of a comprehensive plan, and inadequate coordination and communication. Proposed solutions from these studies included establishing a central regulatory and governance body; developing rehabilitation services that recognize rehabilitation as a population-based strategy for health and well-being across a wide range of health conditions throughout the continuum of care and throughout life; and creating databases to track individuals with disabilities and the rehabilitation services provided to them.<br><br>CONCLUSION: Effective stewardship of integrated rehabilitation services necessitates service continuity, coordinated policymaking, and active stakeholder engagement. A cohesive governance structure, bolstered by a robust information system, is crucial for evidence-based decision-making. Aligning policies with operational plans fosters collaboration and improves service efficiency.}, }
@article {pmid40992439, year = {2025}, author = {Tien Vo, TT and Tsai, MH and Cheng, CY and Wang, YL and Lee, WJ and Lee, IT}, title = {The oral microbiome-redox-inflammation axis in neurodegeneration: mechanistic insights and therapeutic perspectives.}, journal = {Biochemical pharmacology}, volume = {242}, number = {Pt 3}, pages = {117362}, doi = {10.1016/j.bcp.2025.117362}, pmid = {40992439}, issn = {1873-2968}, abstract = {The oral microbiome is a highly diverse and metabolically active ecosystem that plays a pivotal role in maintaining oral and systemic homeostasis. Disruption of this balance, referred to as oral dysbiosis, has been increasingly implicated in the pathogenesis of neurodegenerative diseases (NDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Although the precise molecular mechanisms remain incompletely defined, accumulating evidence indicates that oxidative stress and redox signaling act as central mediators linking microbial imbalance to neuroinflammatory responses and progressive neuronal dysfunction. In this review, we critically synthesize interdisciplinary findings on the oral microbiome-brain axis, emphasizing redox-sensitive pathways that mediate communication between oral pathogens and the central nervous system. We discuss how reactive oxygen species (ROS), generated by microbial metabolites and pathogen-associated molecular patterns, activate various signaling cascades, thereby exacerbating neuroinflammation and glial activation. We further evaluate evidence that oral dysbiosis contributes to blood-brain barrier (BBB) disruption, peripheral immune priming, and chronic neuroimmune dysregulation. By integrating mechanistic, cellular, and clinical perspectives, we identify oxidative stress and redox signaling as critical biological bridges between oral dysbiosis and neurodegeneration. This framework highlights not only the translational potential of targeting redox pathways and the oral microbiome for preventive and therapeutic strategies but also the need for future research to clarify causal relationships and validate clinical applications.}, }
@article {pmid40795649, year = {2025}, author = {Rabbani, MG and Alif, SM and Zhou, Z and Ryan, J and Karim, MN}, title = {Association between higher serum uric acid levels and cognitive function: a systematic review and meta-analysis.}, journal = {The journals of gerontology. Series A, Biological sciences and medical sciences}, volume = {80}, number = {10}, pages = {}, doi = {10.1093/gerona/glaf174}, pmid = {40795649}, issn = {1758-535X}, mesh = {Humans ; *Uric Acid/blood ; *Cognition/physiology ; Male ; Female ; Cross-Sectional Studies ; Biomarkers/blood ; }, abstract = {BACKGROUND: Serum uric acid (SUA) levels may be associated with cognitive function, but findings have been inconsistent, potentially varying by cognitive domain and sex. We aimed to determine the association of SUA and different domains of cognitive function.<br><br>METHODS: Five electronic databases were searched to identify relevant peer-reviewed articles. Studies investigating the association between SUA levels and cognitive function were included. Standardized mean difference (SMD) was calculated, and separate meta-analyses were conducted for each of the domains. Risk of bias was assessed using the Newcastle-Ottawa Quality Assessment Scale. Between-study heterogeneity was investigated through subgroup analysis and a meta-regression model using study-level covariates.<br><br>RESULTS: Ten prospective cohort and 16 cross-sectional studies were eligible for inclusion, but only a subset of these studies was included in each meta-analysis. Pooled estimates from cross-sectional studies showed that higher SUA levels were significantly associated with better global cognition (n&#x2009;=&#x2009;6, SMD&#x2009;=&#x2009;2.27, 95% CI, 1.18-3.35), and learning and memory (n&#x2009;=&#x2009;4, SMD&#x2009;=&#x2009;1.49, 95% CI, 1.12-1.87). Sensitivity analysis, excluding the study conducted on amyotrophic lateral sclerosis patients, resulted in better performance estimates for executive function (n&#x2009;=&#x2009;4, SMD&#x2009;=&#x2009;0.51, 95% CI, 0.47-0.55) and language (n&#x2009;=&#x2009;2, SMD&#x2009;=&#x2009;0.75, 95% CI, 0.71-0.79). The pooled result from 2 prospective cohort studies found a positive relationship between SUA levels and attention (SMD&#x2009;=&#x2009;0.22, 95% CI, 0.07-0.36). Serum uric acid levels were associated with executive function and learning and memory in males, and with language in females.<br><br>CONCLUSIONS: Higher SUA levels were associated with better global cognitive performance executive function, learning and memory, attention and language. These findings highlight low SUA levels as a potentially useful biomarker for cognitive decline.}, }
@article {pmid40983949, year = {2025}, author = {Cheng, S and Xiao, B and Luo, Z}, title = {Glycosylation in neuroinflammation: mechanisms, implications, and therapeutic strategies for neurodegenerative diseases.}, journal = {Translational neurodegeneration}, volume = {14}, number = {1}, pages = {47}, pmid = {40983949}, issn = {2047-9158}, support = {2022YFC2503802//the National Key Research and Development Program of China/ ; z027001//The National Multidisciplinary Cooperative Diagnosis and Treatment Capacity Project for Major Diseases of Xiangya Hospital, Central South University/ ; 2021SK4001//the Innovative Construction Foundation of Hunan Province/ ; 2023JJ30924//the National Natural Science Foundation of Hunan province, China/ ; B202303076019//Scientific research project of Health Commission of Hunan Province/ ; }, mesh = {Humans ; Glycosylation ; *Neurodegenerative Diseases/metabolism/immunology/therapy ; Animals ; *Neuroinflammatory Diseases/metabolism ; Inflammation/metabolism ; Microglia/metabolism ; }, abstract = {Neuroinflammation is a key pathological mechanism underlying neurodegenerative diseases, and intricately interacts with protein glycosylation. Emerging evidence suggests that aberrant glycosylation disrupts immune homeostasis, activates microglia, and promotes the release of inflammatory mediators, thereby exacerbating neuroinflammatory responses. In addition, the inflammatory microenvironment can further dysregulate glycosylation patterns, creating a vicious cycle that amplifies disease pathology. Although the regulatory role of glycosylation in neuroinflammation associated with neurodegenerative diseases has been recognized, the precise molecular and cellular mechanisms remain incompletely understood. This review systematically examines the complex crosstalk between glycosylation and neuroinflammation, with a particular focus on the critical roles of glycosylation in key neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis. We explore how glycosylation abnormalities contribute to disease pathogenesis through effects on immune recognition, protein aggregation, and cellular functions. Understanding the molecular underpinnings of these diseases may pave the way for the development of therapeutic strategies targeting glycosylation pathways, ultimately improving clinical outcomes for patients.}, }
@article {pmid40981102, year = {2025}, author = {Juranek, JK and Kordas, B and Podlasz, P and Bossowska, A and Banach, M}, title = {Current Evidence on the Involvement of RAGE-Diaph1 Signaling in the Pathology and Treatment of Neurodegenerative Diseases-An Overview.}, journal = {Pathophysiology : the official journal of the International Society for Pathophysiology}, volume = {32}, number = {3}, pages = {}, pmid = {40981102}, issn = {1873-149X}, abstract = {Neurodegenerative diseases are a group of disorders characterized by the progressive deterioration of the structure and function of central nervous system neurons and include, among others, amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), Parkinson's (PD), Alzheimer's (AD), and Huntington's (HD) diseases. And while all these diseases seem to have different genetic and environmental components, growing evidence shows that they share common underlying pathological features such as increased neuroinflammation and excessive oxidative stress. RAGE, the receptor for advanced glycation end-products, is a signal transduction receptor, and its activation triggers an increase in proinflammatory molecules, oxidative stressors, and cytokines. Diaph1, protein diaphanous homolog 1, is an actin modulator and an intracellular ligand of RAGE. Studies demonstrated that RAGE and Diaph1 act together, and their downstream signaling pathways play a role in neurodegeneration. Here, based on current evidence and our own research, we provide an overview of the RAGE-Diaph1 signaling and discuss the therapeutic potential of targeted therapy aimed at RAGE-Diaph1 signaling inhibition in the prevention and treatment of neurodegenerative diseases.}, }
@article {pmid40977745, year = {2025}, author = {Wang, J and Li, Y and Xia, Y}, title = {C/EBPβ as a master regulator of inflammasome signaling in neurodegenerative diseases: mechanisms and therapeutic implications.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1656165}, pmid = {40977745}, issn = {1664-3224}, mesh = {Humans ; *Inflammasomes/metabolism/immunology ; *Neurodegenerative Diseases/metabolism/immunology/therapy/etiology ; Animals ; *Signal Transduction ; *CCAAT-Enhancer-Binding Protein-beta/metabolism/genetics ; }, abstract = {CCAAT/enhancer-binding protein beta (C/EBPβ), a key transcription factor, plays a central role in regulating inflammasome signaling in neurodegenerative diseases (NDs). This review synthesizes the mechanisms by which C/EBPβ modulates neuroinflammation and its potential as a therapeutic target. We conducted a comprehensive systematic review spanning January 1995 to June 2025, systematically querying Google Scholar and PubMed with the following keywords: neuroinflammation, inflammasome activation, C/EBPβ, therapeutic targeting, and neurodegenerative diseases. C/EBPβ exists in three isoforms-LAP1, LAP2, and LIP-each with distinct functions in inflammasome activation. In Alzheimer's disease (AD), C/EBPβ drives tau cleavage and Aβ pathology through the AEP axis and exacerbates neuroinflammation by upregulating APOE4. In Parkinson's disease (PD), C/EBPβ silencing reduces α-synuclein aggregation and dopaminergic neuron loss by suppressing the NLRP3 inflammasome. In Amyotrophic Lateral Sclerosis (ALS), C/EBPβ is hypothesized to contribute to TDP-43-associated inflammasome activation, though this requires further validation. In Multiple Sclerosis (MS), C/EBPβ may influence microglial activation and neuroinflammation, as shown in experimental autoimmune encephalomyelitis models. Modulators of the C/EBPβ-inflammasome axis include endogenous regulators like gut-derived metabolites and pharmacological interventions such as small-molecule inhibitors. Therapeutic strategies targeting C/EBPβ hold promise for mitigating neuroinflammation and neurodegeneration, though challenges remain in achieving isoform-specific targeting and blood-brain barrier penetration. Future directions include CRISPR-based editing and biomarker development for personalized therapies.}, }
@article {pmid40976462, year = {2025}, author = {Shi, M and Chu, F and Zhu, J}, title = {Stem cells therapy in neurodegenerative and neuroimmune diseases: current status of treatments and future prospects.}, journal = {Pharmacological research}, volume = {}, number = {}, pages = {107960}, doi = {10.1016/j.phrs.2025.107960}, pmid = {40976462}, issn = {1096-1186}, abstract = {Neurodegenerative and neuroimmune diseases, such as multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS) share a common pathologic hallmark i.e. loss of neurons in the central nervous system (CNS), despite diverse pathological manifestations. These diseases present major challenges to global health due to incurable or extremely difficult to treat, imposing a heavy burden on society and families. Stem cell therapy, as a novel promising approach for treating various neurological diseases, harnesses the regenerative potential of stem cells to repair damaged neural tissues and circuits, and has become the only hope for patients to recover their health or delay the deterioration of disease symptoms. In recent years, researchers have successfully generated neurons from multiple types of stem cells, and good curative effects have been achieved in their animal models and in clinical trials. This comprehensive review elaborates on the relevant content of stem cell biology, focuses on conducting an in-depth analysis of the current application status of various stem cells in major neurodegenerative and neuroimmune diseases including MS, AD, PD and ALS, kindling the hope for the development of stem cell-based cell therapies in neurological diseases.}, }
@article {pmid40972344, year = {2025}, author = {Del Moro, L and Brunetta, E and Gershwin, ME and Selmi, C}, title = {Microglia and myeloperoxidase in neuroinflammatory and neurodegenerative diseases.}, journal = {Current opinion in immunology}, volume = {97}, number = {}, pages = {102660}, doi = {10.1016/j.coi.2025.102660}, pmid = {40972344}, issn = {1879-0372}, abstract = {The dogma of an impenetrable blood-brain barrier (BBB) has given way to the view that resident immune cells within the central nervous system respond to a variety of blood-borne soluble factors, particularly cytokines, and play an important functional role. In particular, microglia cells contribute to the regulation of neuroinflammation, with both protective and pathological roles. Specific microglia activation states variably influence the progression of neuroinflammatory and neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis. Significant evidence indicates that gut microbiota-derived products regulate microglial function across the lifespan and influence the BBB. Myeloperoxidase (MPO) catalyzes the conversion of hydrogen peroxide and chloride ions into hypochlorous acid, a potent oxidant implicated in oxidative tissue damage and modulation of inflammatory signaling. Elevated MPO levels in the central nervous system have been correlated with human disease and the dysregulation of MPO activity in microglia is particularly detrimental, as it amplifies the oxidative stress, disrupts the BBB integrity, and potentiates the neuroinflammatory cascades through the activation of transcription factors like NF-κB. Targeting MPO activity through selective inhibitors or antioxidant strategies may attenuate microglial activation and reduce neuroinflammation, highlighting its potential as a therapeutic target, but the regulatory mechanisms governing MPO expression in microglia and its interplay with other inflammatory mediators remain poorly understood. New research efforts into the relationship between gut microbiota, microglia, MPO, and neuroinflammation are essential to unravel the complexities of neuropathology in a variety of conditions beyond neurodegenerative diseases.}, }
@article {pmid40969213, year = {2025}, author = {Ciechanover, A and Livneh, I}, title = {Protein quality control systems in neurodegeneration - culprits, mitigators, and solutions?.}, journal = {Frontiers in neurology}, volume = {16}, number = {}, pages = {1604076}, pmid = {40969213}, issn = {1664-2295}, abstract = {A key hallmark of neurodegenerative diseases (NDDs) is the formation of neurotoxic protein aggregates, which are considered to reflect inadequate protein quality control (PQC). In agreement with this fundamental pathophysiologic characteristic, the two main cellular systems responsible for cellular protein removal - the ubiquitin-proteasome system (UPS) and autophagy - have been extensively studied in the context of NDD. The involvement of these proteolytic machineries was interpreted in different ways - some pointed them as dysfunctional systems that may underlie pathogenesis, while others suggested they fulfill protective roles which delay the clinical presentation of these diseases. Perhaps not surprisingly, the growing body of knowledge concerning the different types of NDD portrays a more complex picture, and no distinct generalization can be made regarding the contribution of either the neurotoxic protein substrate(s) or proteolytic system(s) to the development of NDD. For instance, in Parkinson's disease, the toxic aggregation of α-synuclein, Parkinson's canonical culprit protein, can stem from seemingly unrelated events. Among them, alterations in α-synuclein itself, a mutation in Parkin - an E3 ubiquitin ligase targeting proteins and organelles to proteasomal and lysosomal degradation, respectively, as well as a mutation in LRRK2 - a kinase postulated to be linked with α-synuclein through their common removal by chaperone-mediated autophagy. Also, in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), the toxic aggregation of one protein - TDP-43 - can result from defects in other proteins, some of which are related to proteostasis, such as the shuttle protein Optineurin and the E3 ubiquitin ligase VCP. In contrast, ALS and FTLD demonstrate how common abnormalities leading to neurotoxic aggregate formation, may present clinically in profoundly different ways, from motor dysfunction to behavioral changes. In Alzheimer's Disease, the leading cause for dementia, rare cases were linked directly with PQC as they are caused by a mutation in one of the genes encoding ubiquitin itself, while the majority of cases were not directly linked to components of the two main proteolytic systems. All-in-all, the UPS and autophagy are heavily intertwined with NDD, either as part of the problem or as mitigating factors, and hopefully - as platforms for future therapeutics. In this review, we shall dissect NDDs from the perspective of protein turnover pathways, aiming to track both common and unique patterns of PQC failure in this group of diseases, which differ significantly from one another both in their clinical manifestations and affected anatomic regions, yet share the common trait of abnormal protein accumulation. We shall review some of the mechanistic understandings concerning protein aggregation in NDDs, describing the interactions of aggregated proteins with the UPS and autophagy, discuss recent controversies around the protein aggregates' hypothesis, and point to implications for developing therapeutic strategies.}, }
@article {pmid40962156, year = {2025}, author = {Yipeng, X and Guiqian, W and Qiaochu, Z and Tengjie, H and Yan, Z and Hai, H and Jing, Z}, title = {Molecular mechanisms by which mitochondrial dysfunction drives neuromuscular junction degeneration in amyotrophic lateral sclerosis.}, journal = {Neurobiology of disease}, volume = {}, number = {}, pages = {107103}, doi = {10.1016/j.nbd.2025.107103}, pmid = {40962156}, issn = {1095-953X}, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder marked by progressive degeneration of motor neurons and early deterioration of neuromuscular junctions (NMJs). Increasing evidence indicates that mitochondrial dysfunction plays a pivotal role in driving NMJ degeneration in ALS.<br><br>OBJECTIVE: This review aims to comprehensively summarize the molecular mechanisms by which mitochondrial defects contribute to NMJ instability, with a particular focus on bioenergetics, calcium homeostasis, oxidative stress, and impaired mitochondrial biogenesis.<br><br>CONCLUSION: Mitochondrial dysfunction is a core driver of NMJ degeneration in ALS. Targeting mitochondrial biogenesis and metabolism-particularly through the PGC-1&#x3b1; pathway-represents a promising strategy to preserve NMJ integrity and slow disease progression.}, }
@article {pmid40958782, year = {2025}, author = {Sun, LC and Li, WS and Chen, W and Zhao, DQ and Zhang, X and Li, CX and Ren, Z}, title = {Frontiers and Emerging Trends in Edaravone Research: A Bibliometric Analysis of Molecular Basis and Clinical Studies Using CiteSpace and VOSviewer.}, journal = {Journal of multidisciplinary healthcare}, volume = {18}, number = {}, pages = {5743-5758}, pmid = {40958782}, issn = {1178-2390}, abstract = {PURPOSE: Edaravone is a potent free-radical scavenger and antioxidant that has been widely investigated for its therapeutic potential in neurodegenerative diseases and oxidative stress-related conditions. Although previous studies have explored its molecular structure, pharmacological effects, and clinical applications, a comprehensive bibliometric analysis of its research trends and future directions remains lacking.<br><br>METHODS: This study employed bibliometric methods to analyze edaravone-related publications from 2000 to 2024, using the Web of Science Core Collection database. The analysis examined publication trends; contributions by countries, institutions, and authors; and keyword clustering. Data visualization tools, such as CiteSpace and VOSviewer, were utilized to identify research clusters and emerging trends in edaravone research.<br><br>RESULTS: The findings revealed a significant increase in edaravone-related publications, with China, Japan, and the United States as the leading contributors. Notable researchers, including Abe K and Yoshino H, have made substantial contributions to this field. Four major research clusters were identified: free radical scavenging, cerebral infarction, amyotrophic lateral sclerosis, and oxidative stress. Emerging trends suggest a growing interest in edaravone dexbornel for acute ischemic stroke treatment, as well as its potential applications in blood-brain barrier interactions and Alzheimer's disease.<br><br>CONCLUSION: This bibliometric analysis highlights the growing interest in edaravone and its potential clinical application, particularly in neuroprotection. While this study provides valuable insights into current research trends, future studies should incorporate a broader range of sources and languages to obtain a more comprehensive understanding of the impact and scope of edaravone.}, }
@article {pmid40958089, year = {2025}, author = {Zhang, M and Lin, Y and Wei, H and Ju, Q and Gao, T and Zhang, Y and Shen, L and Sun, C}, title = {The membrane receptor CD44: roles in neurodegenerative diseases.}, journal = {Expert opinion on therapeutic targets}, volume = {}, number = {}, pages = {}, doi = {10.1080/14728222.2025.2563243}, pmid = {40958089}, issn = {1744-7631}, abstract = {INTRODUCTION: With the increasing prevalence of aging populations, the incidence of neurodegenerative diseases continues to rise, posing a serious threat to human health and quality of life. Owing to the highly complex pathogenesis of these disorders, the identification of effective therapeutic targets remains a major challenge. CD44, a cell surface glycoprotein, plays a central role in regulating cell proliferation, survival, adhesion, and migration. Emerging evidence further indicates that CD44 contributes to NF-κB activation, thereby amplifying inflammatory responses.<br><br>AREAS COVERED: Given its central role in neuroinflammation, CD44 has attracted increasing attention as a potential therapeutic target for neurodegenerative diseases. This review explores the involvement of CD44 in amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), and Parkinson's disease (PD), with particular emphasis on its contributions to neuroinflammatory processes, neuronal survival, and pathological protein aggregation.<br><br>EXPERT OPINION: Chronic low-grade neuroinflammation is a major driver of neurodegenerative diseases, including ALS, AD, and PD. Growing evidence implicates CD44 as a key contributor to disease pathogenesis, with several studies reporting significantly elevated CD44 expression in affected patients. These findings highlight the role of CD44 in disease progression and suggest that targeting CD44-mediated inflammation may offer a promising therapeutic strategy for neurodegenerative disorders.}, }
@article {pmid40955309, year = {2025}, author = {Wang, L and Feng, L and Ning, B and Wang, Z and Dai, C and Li, M}, title = {Natural Products from Chinese Medicine Targeting NF-κB Signaling: Emerging Therapeutic Avenues for Neurodegenerative Diseases.}, journal = {Drug design, development and therapy}, volume = {19}, number = {}, pages = {8135-8159}, pmid = {40955309}, issn = {1177-8881}, mesh = {Humans ; *NF-kappa B/metabolism/antagonists &amp; inhibitors ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Biological Products/pharmacology/chemistry ; *Medicine, Chinese Traditional ; Signal Transduction/drug effects ; Animals ; *Drugs, Chinese Herbal/pharmacology/chemistry ; }, abstract = {This review summarizes recent advances in leveraging natural products from Chinese medicine to modulate the nuclear factor kappa B (NF-κB) signaling pathway for the prevention and treatment of neurodegenerative diseases (NDDs), focusing specifically on Alzheimer's disease (AD), Parkinson's disease (PD), and Amyotrophic lateral sclerosis (ALS). NF-κB proteins regulate cellular biological activity by binding to promoter regions in the nucleus and transcribing various protein-coding genes. Emerging evidence indicates that NF-κB plays a pivotal role in driving key hallmarks of NDD progression, including neuroinflammation, oxidative stress, mitochondrial dysfunction, and dysregulation of the cell cycle. Natural products from Chinese medicine exert modulatory effects on NF-κB signaling through diverse pharmacological mechanisms, ultimately improving cognitive and motor impairments in preclinical NDDs models. The pleiotropic nature of natural products derived from traditional Chinese medicine (TCM)-which operate through subunit-specific modulation of NF-κB-underscores their potential as next-generation therapeutics. Investigating the intricate regulation of NF-κB by natural products from Chinese medicine will not only enrich our understanding of the pathogenesis of NDDs but also establish a theoretical foundation for the development of new therapeutic drugs for NDDs, providing innovative strategies for prevention and treatment.}, }
@article {pmid40952592, year = {2025}, author = {Chen, C and Wang, GQ and Li, DD and Zhang, F}, title = {Microbiota-gut-brain axis in neurodegenerative diseases: molecular mechanisms and therapeutic targets.}, journal = {Molecular biomedicine}, volume = {6}, number = {1}, pages = {64}, pmid = {40952592}, issn = {2662-8651}, support = {No. 82160690//National Natural Science Foundation of China/ ; No. ZK [2021]-014//Science and Technology Foundation of Guizhou Province/ ; No. 2020-39//Collaborative Innovation Center of Chinese Ministry of Education/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/therapy/microbiology/metabolism/etiology ; *Gastrointestinal Microbiome ; *Brain/metabolism ; Animals ; Dysbiosis ; Probiotics/therapeutic use ; *Brain-Gut Axis ; }, abstract = {The microbiota-gut-brain axis (MGBA) is an intricate bidirectional communication network that links intestinal microbiota with the central nervous system (CNS) through immune, neural, endocrine, and metabolic pathways. Emerging evidence suggests that dysregulation of the MGBA plays pivotal roles in the onset and progression of neurodegenerative diseases. This review outlines the key molecular mechanisms by which gut microbes modulate neuroinflammation, blood-brain barrier integrity, protein misfolding, and neuronal homeostasis. We discuss how microbial metabolites, such as short-chain fatty acids, tryptophan derivatives, and bile acids, interact with host to influence CNS functions. Disease-specific features are described across Alzheimer's disease, Parkinson's disease, Multiple sclerosis, and Amyotrophic lateral sclerosis, emphasizing the distinct and overlapping pathways through which gut dysbiosis may contribute to pathogenesis. We further explore the translational potential of microbiota-targeted therapies, including probiotics, fecal microbiota transplantation, dietary interventions, and small-molecule modulators. While preclinical results are promising, clinical trials reveal considerable variability, highlighting the need for personalized approaches and robust biomarkers. Challenges remain in deciphering causal relationships, accounting for inter-individual variability, and ensuring reproducibility in therapeutic outcomes. Future research should integrate multi-omics strategies, longitudinal human cohorts, and mechanistic models to clarify the role of the MGBA in neurodegeneration. Collectively, understanding the MGBA provides a transformative perspective on neurodegenerative disease mechanisms and offers innovative therapeutic avenues that bridge neurology, microbiology, and precision medicine.}, }
@article {pmid40951906, year = {2025}, author = {Telec, W and Al-Saad, S and Karbowski, L and Kłosiewicz, T and Baszko, A}, title = {Postshock Pacing in Cardiac Arrest: A Concise Review.}, journal = {Emergency medicine international}, volume = {2025}, number = {}, pages = {9067144}, pmid = {40951906}, issn = {2090-2840}, abstract = {Following an administered shock in cardiac arrest, the heart commonly experiences a short phase of inability to efficiently perfuse. Despite being a commonly used feature in the ICD population, postshock pacing (PSP) is yet to be adequately explored for its utility in this pulseless phase. Notably, an overwhelming proportion of available data for transcutaneous pacing in spontaneous cardiac arrest stem from the 1980s and 1990s and revolve largely around nonshockable, as opposed to shockable rhythms. The lack of large-scale clinical trials assessing the efficacy of transcutaneous PSP and the considerable advancements in technology and training facilities since the 1990s indicates a need for reevaluation of current understanding of PSP and its applicability in cardiac arrest. Shedding light into the possible implications of transcutaneous PSP in emergency setting cardiac arrest may not only reshape the current protocols of ALS but also carry the potential of improving survival rates. This concise review serves as a summary of the existing knowledge on the subject of PSP and reveals further possible directions for the development of this therapy.}, }
@article {pmid40949612, year = {2025}, author = {Gao, L and Wang, J and Bi, Y}, title = {Nanotechnology for Neurodegenerative Diseases: Recent Progress in Brain-Targeted Delivery, Stimuli-Responsive Platforms, and Organelle-Specific Therapeutics.}, journal = {International journal of nanomedicine}, volume = {20}, number = {}, pages = {11015-11044}, pmid = {40949612}, issn = {1178-2013}, abstract = {Neurodegenerative diseases-including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis-are characterized by progressive neuronal loss and complex pathological mechanisms such as protein aggregation, mitochondrial dysfunction, and neuroinflammation. Conventional therapies offer limited efficacy due to the blood-brain barrier (BBB) and lack of targeted delivery. Nanotechnology has emerged as a transformative strategy for precise brain-targeted treatment. This review summarizes recent advances in nanoparticle-based drug delivery systems, including polymeric nanoparticles, liposomes, inorganic nanomaterials, and biomimetic carriers, highlighting their design features, BBB-penetration mechanisms, and disease-specific applications. Emphasis is placed on stimuli-responsive nanocarriers that react to pH, reactive oxygen species, or enzyme activity, enabling site-specific drug release. Additionally, organelle-targeting strategies-particularly those directed at mitochondria and lysosomes-are explored for their role in subcellular precision therapy. The integration of diagnostic and therapeutic modalities in theranostic nanoplatforms is also discussed. By consolidating preclinical progress and emerging technologies, this review offers insights into the future of nanomedicine in treating neurodegenerative diseases and lays the groundwork for clinical translation.}, }
@article {pmid40949164, year = {2025}, author = {Roczkowsky, A and Rachubinski, RA and Hobman, TC and Power, C}, title = {Peroxisomes as emerging clinical targets in neuroinflammatory diseases.}, journal = {Frontiers in molecular neuroscience}, volume = {18}, number = {}, pages = {1642590}, pmid = {40949164}, issn = {1662-5099}, abstract = {Peroxisomes are membrane-bounded organelles that contribute to a range of physiological functions in eukaryotic cells. In the central nervous system (CNS), peroxisomes are implicated in several vital homeostatic functions including, but not limited to, reactive oxygen species signaling and homeostasis; generation of critical myelin sheath components (including ether phospholipids); biosynthesis of neuroprotective docosahexaenoic acid; breakdown of neurotoxic metabolites (such as very-long chain fatty acids); and, intriguingly, glial activation and response to inflammatory stimuli. Indeed, peroxisomes play a critical role in modulating inflammatory responses and are key regulators of the mitochondrial antiviral signaling (MAVS) protein-mediated response to infections. The importance of peroxisomes in CNS physiology is exemplified by the peroxisome biogenesis disorders (PBDs), a spectrum of inherited disorders of peroxisome assembly and/or abundance, that are characterized in part by neurological manifestations ranging from severe cerebral malformations to vision and hearing loss, depending on the individual disorder. Recently, peroxisome dysfunction has been implicated in neurological diseases associated with neuroinflammation including Alzheimer's disease, amyotrophic lateral sclerosis, multiple sclerosis, and Parkinson's disease while also contributing to the pathogenesis of neurotropic viruses including SARS-CoV-2, Human Pegivirus, HIV-1 and Zika virus. In the present review, we examine the diverse roles that peroxisomes serve in CNS health before reviewing more recent studies investigating peroxisome dysfunction in inflammatory brain disorders and also highlight potential peroxisomal targets for diagnostic biomarkers and therapeutic interventions.}, }
@article {pmid40943341, year = {2025}, author = {Yang, EJ}, title = {The Emerging Role of the Brain-Gut Axis in Amyotrophic Lateral Sclerosis: Pathogenesis, Mechanisms, and Therapeutic Perspectives.}, journal = {International journal of molecular sciences}, volume = {26}, number = {17}, pages = {}, pmid = {40943341}, issn = {1422-0067}, support = {(KIOM) KSN2224011//KIOM/ ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive loss of motor neurons. Although genetic and environmental factors are established contributors, recent research has highlighted the critical role of the gut-brain axis (GBA) in ALS pathogenesis. The GBA is a bidirectional communication network involving neural, immune, and endocrine pathways that connect the gut microbiota with the central nervous system. Dysbiosis in ALS disrupts this axis, leading to increased intestinal permeability, neuroinflammation, and excitotoxicity. Notably, reductions in butyrate-producing bacteria, alterations in microbial metabolites, and enhanced NLRP3 inflammasome activation have been observed in patients with ALS. These changes may precede motor symptoms, suggesting a potential causative role. Interventions targeting the microbiome, such as dietary modulation, have shown promise in delaying disease onset and reducing inflammation. However, the clinical evidence remains limited. Given that gut dysbiosis may precede neurological symptoms, microbiota-targeted therapies offer a novel and potentially modifiable approach to ALS treatment. Understanding the role of GBA in ALS will open new avenues for early diagnosis and intervention. Further clinical trials are required to clarify the causal links and evaluate the efficacy of microbiome-based interventions. Understanding the brain-gut-microbiota axis in ALS could lead to new diagnostic biomarkers and therapeutic strategies.}, }
@article {pmid40905633, year = {2025}, author = {Verdés, S and Navarro, X and Bosch, A}, title = {Targeting Amyotrophic Lateral Sclerosis with Gene Therapy: From Silencing Genes to Enhancing Neuroprotection.}, journal = {Human gene therapy}, volume = {36}, number = {17-18}, pages = {1173-1198}, doi = {10.1177/10430342251372898}, pmid = {40905633}, issn = {1557-7422}, abstract = {Gene therapy is emerging as a transformative approach for treating amyotrophic lateral sclerosis (ALS), a progressive and fatal neurodegenerative disease. While gene replacement has shown a groundbreaking success in spinal muscular atrophy, the complexity of ALS-due to frequent gain-of-function mutations and a heterogeneous etiology-presents significant challenges. Importantly, approximately 90% of ALS cases are sporadic, with unknown genetic mutation, further complicating patient stratification and therapeutic targeting. As a result, gene therapy strategies must often address multiple pathological mechanisms simultaneously. So far, current gene therapy strategies aim to either suppress toxic gene expression or promote neuroprotection, predominantly via viral-mediated delivery systems. This review will provide an overview of emerging preclinical and clinical gene therapy approaches for ALS, focusing on two main strategies: gene silencing and neuroprotection. Gene silencing techniques, including antisense oligonucleotides (ASOs), viral-mediated RNA interference, and gene editing, have demonstrated efficacy in reducing mutant gene expression, particularly in SOD1 and C9orf72 models, although clinical translation has so far yielded limited success. The recent Food and Drug Administration's approval of the ASO therapy Qalsody for SOD1-ALS underscores the clinical potential of these approaches. Neuroprotective strategies aim to enhance motor neuron survival through delivery of trophic factors, often targeting both central and peripheral tissues to harness retrograde transport mechanisms. We will discuss the advantages and limitations of various delivery vectors, targeting specificity, timing of intervention, and translational challenges, alongside current clinical trial data. This review aims to synthesize how these approaches may converge to address the multifaceted nature of ALS and guide the development of next-generation therapeutics.}, }
@article {pmid40943213, year = {2025}, author = {Liu, D and Yu, S and Ji, B and Peng, Q and Gao, J and Zhang, J and Guo, Y and Hu, M}, title = {Molecular Mechanisms of Herbicide Resistance in Rapeseed: Current Status and Future Prospects for Resistant Germplasm Development.}, journal = {International journal of molecular sciences}, volume = {26}, number = {17}, pages = {}, doi = {10.3390/ijms26178292}, pmid = {40943213}, issn = {1422-0067}, support = {2023ZD0404203//Science and Technology Innovation 2030 Major Program/ ; 31901503//National Natural Science Foundation of China/ ; CARS-12//Agriculture Research System of China/ ; CX (23) 1001//Jiangsu Provincial Agricultural Science and Technology Independent Innovation Fund/ ; BE2021405//Jiangsu Province Key Research and Development Project/ ; }, abstract = {Rapeseed (Brassica napus) is a globally important oilseed crop whose yield and quality are frequently limited by weed competition. In recent years, there have been significant advances in our understanding of herbicide-resistance mechanisms in rapeseed and in the development of herbicide-resistant rapeseed germplasm. Here, we summarize the molecular mechanisms of resistance to three herbicides: glyphosate, glufosinate, and acetolactate synthase (ALS) inhibitors. We discuss progress in the identification of new resistance genes and the development of herbicide-resistant rapeseed germplasm, from the initial identification of natural mutants to artificial mutagenesis screening, introduction of exogenous resistance genes, and gene editing. In addition, we describe how synthetic biology and directed protein evolution will contribute to precision-breeding efforts in the near future. This is the first review to systematically integrate non-target resistance mechanisms and the potential applications of multi-omics and AI technologies for breeding of herbicide-resistant rapeseed, together with strategies for managing the risks associated with gene flow, the evolution of herbicide-resistant weeds, and the occurrence of volunteer plants resulting from deployment of herbicide-resistant rapeseed. By synthesizing current knowledge and future trends, this review provides guidance for safe, effective, and innovative approaches to the sustainable development of herbicide-resistant rapeseed.}, }
@article {pmid40943143, year = {2025}, author = {Calcagnile, M and Alifano, P and Damiano, F and Pontieri, P and Del Giudice, L}, title = {A Perspective on the Role of Mitochondrial Biomolecular Condensates (mtBCs) in Neurodegenerative Diseases and Evolutionary Links to Bacterial BCs.}, journal = {International journal of molecular sciences}, volume = {26}, number = {17}, pages = {}, doi = {10.3390/ijms26178216}, pmid = {40943143}, issn = {1422-0067}, support = {project 'NutrAge' (project nr. 7022)//CNR-DISBA/ ; FOE-2019 DBA.AD003.139//CNR/ ; }, abstract = {Biomolecular condensates (BCs), formed through liquid-liquid phase separation (LLPS), are membraneless compartments that dynamically regulate key cellular processes. Beyond their canonical roles in energy metabolism and apoptosis, Mitochondria harbor distinct BCs, including mitochondrial RNA granules (MRGs), nucleoids, and degradasomes, that coordinate RNA processing, genome maintenance, and protein homeostasis. These structures rely heavily on proteins with intrinsically disordered regions (IDRs), which facilitate the transient and multivalent interactions necessary for LLPS. In this review, we explore the composition and function of mitochondrial BCs and their emerging involvement in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis, and Huntington's disease. We provide computational evidence identifying IDR-containing proteins within the mitochondrial proteome and demonstrate their enrichment in BC-related functions. Many of these proteins are also implicated in mitochondrial stress responses, apoptosis, and pathways associated with neurodegeneration. Moreover, the evolutionary conservation of phase-separating proteins from bacteria to mitochondria underscores the ancient origin of LLPS-mediated compartmentalization. Comparative analysis reveals functional parallels between mitochondrial and prokaryotic IDPs, supporting the use of bacterial models to study mitochondrial condensates. Overall, this review underscores the critical role of mitochondrial BCs in health and disease and highlights the potential of targeting LLPS mechanisms in the development of therapeutic strategies.}, }
@article {pmid40940798, year = {2025}, author = {Li, L and Zheng, X and Ma, H and Zhu, M and Li, X and Sun, X and Feng, X}, title = {TREM2 in Neurodegenerative Diseases: Mechanisms and Therapeutic Potential.}, journal = {Cells}, volume = {14}, number = {17}, pages = {}, doi = {10.3390/cells14171387}, pmid = {40940798}, issn = {2073-4409}, abstract = {Neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), represent significant global health challenges, affecting millions and straining healthcare systems. These disorders involve progressive neuronal loss and cognitive decline, with incompletely elucidated underlying mechanisms. Chronic neuroinflammation is increasingly recognized as a critical contributor to disease progression. The brain's resident immune cells, microglia, are central to this inflammatory response. When overactivated, microglia and other immune cells, such as peripheral macrophages, can exacerbate inflammation and accelerate disease development. Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) is a transmembrane receptor of the immunoglobulin superfamily that demonstrates high expression on microglia in the central nervous system. TREM2 serves a vital role in regulating phagocytosis, synaptic pruning, and energy metabolism. This review examines the functions of TREM2 in neurodegenerative diseases and its potential as a therapeutic target, aiming to inform future treatment strategies.}, }
@article {pmid40940752, year = {2025}, author = {Lee, JH and Chang, W and Min, SS and Song, DY and Yoo, HI}, title = {Beyond Support Cells: Astrocytic Autophagy as a Central Regulator of CNS Homeostasis and Neurodegenerative Diseases.}, journal = {Cells}, volume = {14}, number = {17}, pages = {}, doi = {10.3390/cells14171342}, pmid = {40940752}, issn = {2073-4409}, support = {2023//Eulji University/ ; RS-2024-00438628//Korea Health Industry Development Institute/Republic of Korea ; }, abstract = {Autophagy is a fundamental catabolic pathway critical for maintaining cellular homeostasis in the central nervous system (CNS). While neuronal autophagy has been extensively studied, growing evidence highlights the crucial roles of astrocytic autophagy in CNS physiology and pathology. Astrocytes regulate metabolic support, redox balance, and neuroinflammatory responses. These functions are closely linked to autophagic activity. The disruption of astrocytic autophagy contributes to synaptic dysfunction, chronic inflammation, myelin impairment, and blood-brain barrier instability. Dysregulation of astrocytic autophagy has been implicated in the pathogenesis of multiple neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. This review summarizes the molecular mechanisms of autophagy in astrocytes and delineates its role in intercellular communication with neurons, microglia, oligodendrocytes, and endothelial cells. Furthermore, we will discuss current pharmacological approaches targeting astrocytic autophagy, with particular attention to repurposed agents such as rapamycin, lithium, and caloric restriction mimetics. Although promising in preclinical models, therapeutic translation is challenged by the complexity of autophagy's dual roles and cell-type specificity. A deeper understanding of astrocytic autophagy and its crosstalk with other CNS cell types may facilitate the development of targeted interventions for neurodegenerative diseases.}, }
@article {pmid40938039, year = {2025}, author = {Baroni, A and Moulton, C and Cristina, M and Sansone, L and Belli, M and Tasciotti, E}, title = {Nano- and Microplastics in the Brain: An Emerging Threat to Neural Health.}, journal = {Nanomaterials (Basel, Switzerland)}, volume = {15}, number = {17}, pages = {}, pmid = {40938039}, issn = {2079-4991}, support = {[Ricerca corrente]//Italian Ministry of Health/ ; }, abstract = {Nano- and microplastics (NMPs), with nanoplastics posing higher risks due to their smaller size and greater capacity for cellular and subcellular penetration, are being referred to as ubiquitous environmental neurotoxicants, due to their ability to pass through biological barriers, including the blood-brain barrier (BBB) and nasal olfactory epithelium, and to remain lodged in neural tissue. Upon uptake, such particles disturb neuronal homeostasis by multiple converging pathways, including oxidative stress, mitochondrial dysfunction, pathological protein aggregation, and chronic neuroinflammation, all closely involved with the molecular signatures of neurodegenerative disorders (Alzheimer's, Parkinson's, Amyotrophic Lateral Sclerosis-ALS). In addition to their neurotoxicity, recent findings suggest that NMPs could disturb synaptic communication and neuroplasticity, thereby compromising the brain's capacity to recover from an injury, a trauma, or neurodegeneration, thus impacting the progression of the disease, our ability to treat it and eventually the efficacy of rehabilitation approaches. Despite these findings, our understanding remains hampered by analytical issues, the scarcity of standard detection methods, and a total lack of longitudinal studies in humans. This review combines multidisciplinary evidence on brain-plastic interactions and calls for accelerated advances in our ability to monitor bioaccumulation in humans, and to integrate neurotoxicology paradigms in the assessment of this underappreciated but growing threat to brain health.}, }
@article {pmid40931498, year = {2025}, author = {Alemán-Villa, KM and Armienta-Rojas, DA and Camberos-Barraza, J and Rábago-Monzón, &#xc1;R and Camacho-Zamora, A and Osuna-Ramos, JF and Magaña-Gómez, JA and Guadrón-Llanos, AM and Calderón-Zamora, L and Norzagaray-Valenzuela, CD and Valdez-Flores, MA and Picos-Cárdenas, VJ and De la Herrán-Arita, AK}, title = {Neuroinflammation across the spectrum of neurodegenerative diseases: mechanisms and therapeutic frontiers.}, journal = {Neuroimmunomodulation}, volume = {}, number = {}, pages = {1-33}, doi = {10.1159/000548021}, pmid = {40931498}, issn = {1423-0216}, abstract = {Neuroinflammation has emerged as a central and dynamic component of the pathophysiology underlying a wide range of neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and multiple sclerosis. Far from being a secondary consequence of neuronal damage, inflammatory processes (mediated by microglia, astrocytes, peripheral immune cells, and associated molecular mediators) actively shape disease onset, progression, and symptomatology. This review synthesizes current knowledge on the cellular and molecular mechanisms that govern neuroinflammatory responses, emphasizing both shared and disease-specific pathways. We examine how innate and adaptive immune interactions contribute to neuronal vulnerability and neurodegenerative cascades, and explore the reciprocal communication between systemic and central immune compartments. Particular attention is given to emerging therapeutic strategies aimed at modulating neuroinflammation, including immunomodulatory drugs, glial-targeted interventions, and novel delivery platforms. By integrating findings across disciplines and disease models, we outline key translational challenges and propose future directions to harness neuroinflammation as a therapeutic target in the era of precision medicine. Ultimately, a deeper understanding of neuroimmune dynamics holds promise for redefining both the diagnosis and treatment of neurodegenerative disorders.}, }
@article {pmid40928564, year = {2025}, author = {Davidow, D and Paul, L and Jones, B and Hohlfeld, A and Rasenyalo, S and Dane, K and Shill, IJ and Hendricks, S}, title = {Player-Level Tackle Training Interventions in Tackle-Collision Sports: A Systematic Scoping Review.}, journal = {Sports medicine - open}, volume = {11}, number = {1}, pages = {103}, pmid = {40928564}, issn = {2199-1170}, abstract = {BACKGROUND: In tackle-collision sports, the tackle has the highest incidence, severity, and burden of injury. Head injuries and concussions during the tackle are a major concern within tackle-collision sports. To reduce concussion and head impact risk, evaluating optimal tackle techniques to inform tackle-related prevention strategies has been recommended. The purpose of this study was to perform a systematic scoping review of player-level tackle training intervention studies in all tackle-collision sports.<br><br>METHODS: The Arksey and O'Malley's five-stage scoping review process and Levac et al.'s framework were used, along with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews (PRISMA-ScR) checklist. The main inclusion criteria were that the study included an intervention aimed at improving a player's tackle abilities, and the intervention had to be delivered/implemented at the player-level in a training setting.<br><br>RESULTS: Thirteen studies were included in this review, seven studies in American Football (54%), followed by a combined cohort of rugby union and rugby league players (three studies; 23%), rugby union (two studies; 15%), and one study reported on a rugby league cohort (8%). Studies focused primarily on the tackler, with the intervention incorporating a form of instruction or feedback, delivered through video or an expert coach. Other interventions included an 8-week strength and power training programme, designing practice sessions based on baseline data, and helmetless training in American Football. All interventions demonstrated a favourable change in the outcome measured-which included tackler and ball-carrier kinematics based on motion capture video, tackler proficiency scoring, tackling task analysis, head impact frequencies by xPatch head-impact sensor technology, head impact kinematics using head-impact sensors (helmet or skin patches) and football tackle kinematics with motion capture systems or video.<br><br>CONCLUSION: This review shows that a range of studies have been undertaken focusing on player-level training interventions. The quality of studies were rated as 'good', and all studies showed improvements in outcome measures. Coaches and policy makers should ensure tackle technique is profiled alongside other player characteristics, and an evidence-based approach to improving player tackling is adopted, improving both performance and reducing injury risk.<br><br>KEY POINTS: Only 13 studies tested or implemented interventions at the player level in tackle-collision sports. The focus of the studies was primarily on the tackler, with the interventions incorporating a form of instruction or feedback, which was delivered through video or an expert coach. Other interventions included an 8-week strength and power training programme, designing practice sessions based on baseline data, and helmetless training in American Football. All interventions demonstrated a favourable change in the outcome measure and provide coaches and policymakers with tackle training insights.<br><br>REGISTRATION: The systematic scoping review was prospectively registered with OSF (registration number: https://doi.org/10.17605/OSF.IO/V3KZC).}, }
@article {pmid40924345, year = {2025}, author = {Kutlubaev, MA and Pervushina, EV and Kiernan, MC}, title = {The nature of fatigue in amyotrophic lateral sclerosis: a systematic review and meta-analysis.}, journal = {Acta neurologica Belgica}, volume = {}, number = {}, pages = {}, pmid = {40924345}, issn = {2240-2993}, abstract = {OBJECTIVES: Patients diagnosed with amyotrophic lateral sclerosis (ALS) typically describe symptoms of fatigue. Despite this frequency, the underlying mechanisms of fatigue are poorly understood, and are likely multifactorial. To help clarify mechanisms, the present systematic review was undertaken to determine the risk factors related to fatigue in ALS.<br><br>METHODS: A systematic review was conducted using PubMed and Google Scholar databases using key words. From a total of 40,014 articles, 18 articles were included in the final review, following PRISMA guidelines. Meta-regression and subgroup analyses were conducted to study the relationship between fatigue in ALS and different covariates.<br><br>RESULTS: Eighteen studies were included in the analysis. A number of factors were investigated, including age, sex, disease severity and duration, site of disease onset, neurophysiological parameters, and respiratory symptoms, depression and anxiety, sleep disorders, and pain. Combined analyses established that participants with ALS who reported fatigue had more severe disease, as confirmed by lower functional rating scores, than those who did not report fatigue. The remaining factors including depression, anxiety and pain, were not found to be related to the onset of fatigue in ALS. Overall, fatigue worsened quality of life in patients diagnosed with ALS.<br><br>DISCUSSION: Fatigue in ALS appears to be particularly associated with progressive neurological deficit and disability, linked to both central and peripheral neuromuscular mechanisms.}, }
@article {pmid40922888, year = {2025}, author = {Kademani, A and Avraam, C and Montenegro, D and Paloh, A and Somannagari, N and Gupta, A and Lafi, AW and Algaba, AE and Islam, R and Fahima, C and Siddiqui, HF}, title = {Exploring the Emerging Role of Stem Cell Therapy in Neurodegenerative Diseases and Spinal Cord Injury: A Narrative Review.}, journal = {Cureus}, volume = {17}, number = {8}, pages = {e89629}, pmid = {40922888}, issn = {2168-8184}, abstract = {Neurodegenerative diseases and spinal cord injuries (SCI) pose a significant burden on the healthcare system globally. Diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease precipitate cognitive, motor, and behavioral deficits. Parallelly, spinal cord injuries produce sensory and motor deficits, which are burdensome psychologically, socially, and economically. Current management strategies focus only on symptomatic relief, with no definitive cure. Stem cells have been explored for regenerative therapy. This review focuses on developments, limitations, and future potential of stem cell therapy. Stem cells affect the central nervous system via neuroprotective mechanisms, immunomodulatory effects, and mitigation of oxidative stress. The clinical implications of stem cell therapy in treating neurodegenerative diseases and SCI are debatable due to varied outcomes. Challenges related to sample size, long-term follow-up, and assessment of adverse effects should be mitigated in future research. Researchers are currently exploring optimal stem cell types along with various transplantation strategies. Biomaterials integrated with stem cells are a novel approach for treating neurodegenerative diseases and spinal cord injuries. Certain genetic modifications have shown improved results. Screening patients to ascertain better responses to therapy has proven to be a challenge. Other complications include graft vs. host reaction and degeneration of transplanted neurons due to pathogenesis and tumorigenesis. However, the majority of the potential stem cell therapeutic avenues are in the preclinical stage and are being tested on animal models. Guidelines pertaining to ethical concerns and regulatory frameworks need to be established to unfold the full potential of stem cell therapy in the clinical setting. Recent advances also show an increased need to formulate patient-specific approaches to treatment, ranging from stem cell selection to the technique of transplantation. Ongoing clinical trials can address the current challenges and leverage emerging technologies, leading to definitive treatments for neurodegenerative diseases and spinal cord injuries.}, }
@article {pmid40922457, year = {2025}, author = {Eroglu, E and Harmanci, N}, title = {Emerging Molecular Targets in Neurodegenerative Disorders: New Avenues for Therapeutic Intervention.}, journal = {Basic &amp; clinical pharmacology &amp; toxicology}, volume = {137}, number = {4}, pages = {e70107}, doi = {10.1111/bcpt.70107}, pmid = {40922457}, issn = {1742-7843}, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/physiopathology/metabolism/genetics ; Animals ; *Molecular Targeted Therapy ; Autophagy/drug effects ; Drug Development ; }, abstract = {Neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis and frontotemporal dementia represent a significant global health burden with limited therapeutic options. Current treatments are primarily symptomatic and fail to modify disease progression, emphasizing the urgent need for novel, mechanism-based interventions. Recent advances in molecular neuroscience have identified several non-classical pathogenic pathways, including neuroinflammation, mitochondrial dysfunction, impaired autophagy and proteostasis, synaptic degeneration and non-coding RNA dysregulation. In this focused review, we highlight emerging molecular targets such as TREM2, NLRP3, mTOR, TFEB, PINK1 and SIRT3, which offer promising avenues for therapeutic intervention. We also address challenges in target validation and translational drug development, while proposing future research directions that may facilitate the design of more effective treatments. A deeper understanding of these molecular mechanisms is essential for developing disease-modifying strategies to combat neurodegeneration.}, }
@article {pmid39708835, year = {2025}, author = {Davalos, L and Kushlaf, H}, title = {Advances in Disease-Modifying Therapeutics for Chronic Neuromuscular Disorders.}, journal = {Seminars in respiratory and critical care medicine}, volume = {46}, number = {3}, pages = {250-258}, doi = {10.1055/a-2463-3385}, pmid = {39708835}, issn = {1098-9048}, mesh = {Humans ; *Neuromuscular Diseases/drug therapy/physiopathology/therapy ; Chronic Disease ; Myasthenia Gravis/drug therapy ; }, abstract = {Neuromuscular disorders can cause respiratory impairment by affecting the muscle fibers, neuromuscular junction, or innervation of respiratory muscles, leading to significant morbidity and mortality. Over the past few years, new disease-modifying therapies have been developed and made available for treating different neuromuscular disorders. Some of these therapies have remarkable effectiveness, resulting in the prevention and reduction of respiratory complications. For myasthenia gravis (MG), efgartigimod, ravulizumab, rozanolixizumab, and zilucoplan have been Food and Drug Administration (FDA)-approved for the treatment of acetylcholine receptor (AChR) antibody-positive generalized MG in the past 2 years. Rozanolixiumab is also approved for treating MG caused by muscle-specific tyrosine kinase (MuSK) antibodies. The new MG therapeutics target the complement system or block the neonatal fragment crystallizable (Fc) receptors (FcRn), leading to significant clinical improvement. For spinal muscular atrophy (SMA), nusinersen (intrathecal route) and risdiplam (oral route) modify the splicing of the SMN2 gene, increasing the production of normal survival motor neuron (SMN) protein. Onasemnogene abeparvovec is a gene replacement therapy that encodes a functional SMN protein. All SMA medications, particularly onasemnogene abeparvovec, have led to clinically meaningful improvement. For late-onset Pompe disease (LOPD), avalglucosidase alfa has shown a greater improvement in respiratory function, ambulation, and functional outcomes in comparison to alglucosidase alfa, and cipaglucosidase alfa combined with miglustat has shown improvement in respiratory and motor function in a cohort of enzyme replacement therapy-experienced LOPD patients. Amyotrophic lateral sclerosis (ALS) remains a challenge. The two most recent FDA-approved medications, namely sodium phenylbutyrate and tofersen, may slow down the disease by a few months in a selected population but do not stop the progression of the disease.}, }
@article {pmid40920272, year = {2025}, author = {Ku, JB and Pak, RJ and Ku, SS and Holland, RD and Kim, HS}, title = {Clinical Efficacy of Stem Cell Therapy in Neurotraumatic and Neurodegenerative Conditions: A Comparative Review.}, journal = {Tissue engineering and regenerative medicine}, volume = {}, number = {}, pages = {}, pmid = {40920272}, issn = {2212-5469}, abstract = {BACKGROUND: Neurotraumatic conditions, such as spinal cord injury, brain injury, and neurodegenerative conditions, such as amyotrophic lateral sclerosis, pose a challenge to the field of rehabilitation for its complexity and nuances in management. For decades, the use of cell therapy in treatment of neurorehabilitation conditions have been explored to complement the current, mainstay treatment options; however, a consensus for standardization of the cell therapy and its efficacy has not been reached in the medical community. This study aims to provide a comparative review on the very topic of cell therapy use in neurorehabilitation conditions in an attempt to bridge the gap in knowledge.<br><br>METHODS: Studies were searched from the PubMed database published from 2014 to 2024 employing the terms including but not exclusive to "spinal cord injury," "brain injury," "amyotrophic lateral sclerosis," "regenerative medicine," "cell therapy," and "stem cell." Following the PRISMA 2020 statement, the studies were screened, included, and excluded. Thirty three studies were identified and selected for this review.<br><br>RESULTS: Countless researchers investigated the efficacy of various stem cell products for the treatment of numerous neurotraumatic conditions, such as spinal cord injury, traumatic brain injury, and neurodegenerative conditions such as amyotrophic lateral sclerosis. The recent decade of studies suggest that in neurotraumatic conditions, bone-marrow-derived and neural stem cells can be effective, and in neurodegenerative conditions, such as ALS, mesenchymal and neural stem cells can be efficacious.<br><br>CONCLUSION: Emerging data from the latest research is encouraging to the patients suffering from neurotraumatic and neurodegenerative conditions, which present themselves as a need for further studies with improved standardization in study design, including cell source specification, differentiation and culture method, and outcome measures to ensure a wide applicability.}, }
@article {pmid40917070, year = {2025}, author = {Xie, J and Xu, J and Tian, Z and Liang, J and Tang, H}, title = {Extended Insights Into Advancing Multi-Omics and Prognostic Methods for Cancer Prognosis Forecasting.}, journal = {Frontiers in bioscience (Landmark edition)}, volume = {30}, number = {8}, pages = {44091}, doi = {10.31083/FBL44091}, pmid = {40917070}, issn = {2768-6698}, mesh = {Humans ; Prognosis ; *Lung Neoplasms/genetics/pathology/therapy/diagnosis ; *Biomarkers, Tumor/genetics ; *Adenocarcinoma of Lung/genetics/pathology ; Genomics/methods ; Gene Expression Regulation, Neoplastic ; *Neoplasms/genetics ; Multiomics ; }, abstract = {Zhang et al.'s recent article utilizes comprehensive single-cell data to identify differences in tumor cell populations, highlighting the CKS1B+ malignant cell subcluster as a potential target for immunotherapy. It develops a prognostic and immunotherapeutic signature (PIS) based on this subcluster, demonstrating good performance in predicting lung adenocarcinoma (LUAD) prognosis. The study also validates the role of PSMB7 in LUAD progression. However, there are areas for improvement. There is a lack of clarity regarding the relationship between the CKS1B+ malignant cell subcluster and the PIS, particularly in terms of why PSMB7 was selected for functional studies. The sequencing data are retrospectively obtained from public databases and lack prospective clinical validation. It is suggested to collect LUAD patient tissues for RT-qPCR and RNA-seq analysis and seek external multi-center validations. Additionally, integrating emerging multi-omics methods is recommended to further validate the findings. Despite these limitations, the study represents progress in understanding LUAD and treatment strategies, and continuous evaluation and refinement of multi-omics and machine learning methods are expected for future research and clinical practice.}, }
@article {pmid40855953, year = {2025}, author = {Logroscino, G and Giannoni-Luza, S and Urso, D and Hamdi, N}, title = {Heterogeneity of frequencies of motor neuron disease across ethnicities and geographical areas: focus on Arabic countries in the Mediterranean area.}, journal = {Current opinion in neurology}, volume = {38}, number = {5}, pages = {588-595}, doi = {10.1097/WCO.0000000000001415}, pmid = {40855953}, issn = {1473-6551}, mesh = {Humans ; Mediterranean Region/epidemiology ; *Amyotrophic Lateral Sclerosis/epidemiology/ethnology/genetics ; Prevalence ; Incidence ; *Motor Neuron Disease/epidemiology/ethnology ; Registries ; Egypt/epidemiology ; Ethnicity ; }, abstract = {PURPOSE OF REVIEW: Although amyotrophic lateral sclerosis (ALS) epidemiology has been increasingly characterized in many regions, data from Arabic countries remain limited. This review aims to summarize the current knowledge on the burden of ALS in Arabic Mediterranean countries, with a particular focus on Egypt.<br><br>RECENT FINDINGS: ALS exhibits significant geographic and ethnic variability in terms of incidence, phenotype, and genetic background. Data from the Global Burden of Disease Study 2021 show that Egypt has one of the lowest age-standardized rates of ALS incidence, prevalence, and mortality in the Mediterranean basin. During the past three decades, Egypt has seen a notable decline in ALS-related Disability-Adjusted Life Years and deaths, in contrast to neighboring countries. A national registry has recently been initiated to enhance epidemiological surveillance in the country.<br><br>SUMMARY: ALS in Arabic Mediterranean countries presents a distinct epidemiological profile. These differences likely reflect a combination of genetic, demographic, and healthcare-related factors. Strengthening national registries and promoting regional collaborations will be crucial for gaining a deeper understanding of the determinants of ALS in these underrepresented populations.}, }
@article {pmid40832750, year = {2025}, author = {Erdi-Krausz, G and Shaw, PJ}, title = {Antisense oligonucleotide therapy in amyotrophic lateral sclerosis.}, journal = {Current opinion in neurology}, volume = {38}, number = {5}, pages = {574-580}, doi = {10.1097/WCO.0000000000001413}, pmid = {40832750}, issn = {1473-6551}, mesh = {*Amyotrophic Lateral Sclerosis/genetics/therapy/drug therapy ; Humans ; *Oligonucleotides, Antisense/therapeutic use ; Animals ; C9orf72 Protein ; Superoxide Dismutase-1 ; *Genetic Therapy/methods ; Superoxide Dismutase/genetics ; DNA-Binding Proteins/genetics ; }, abstract = {PURPOSE OF REVIEW: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with few treatment options available. The approval of tofersen, an antisense oligonucleotide, for SOD1 -ALS by the FDA and EMA may herald a new era of treatment in these patients.<br><br>RECENT FINDINGS: So far, trials against the most common genetic form of ALS, C9orf72 , have been unsuccessful, but new preclinical data may show a promising new direction to take. Clinical trials targeting other, more rare genetic mutations associated with familial ALS are currently underway. Other research assessing the use of ASOs to target aberrant splicing associated with sporadic forms of ALS has also produced promising results in preclinical models, using patient-derived induced cellular models and animal models. These therapies are focussed largely on alleviating and reversing TDP-43 pathology, opening up the possibility of not only arresting disease progression, but reversing neurodegeneration.<br><br>SUMMARY: ASO therapies have made some promising steps towards treating familial ALS, particularly SOD1 . Ongoing early clinical/preclinical phase research is underway to utilise this technology in other genetic mutations linked with ALS, as well as in sporadic cases.}, }
@article {pmid40832743, year = {2025}, author = {Verde, F}, title = {Neurochemical biomarkers of amyotrophic lateral sclerosis: recent developments.}, journal = {Current opinion in neurology}, volume = {38}, number = {5}, pages = {614-619}, doi = {10.1097/WCO.0000000000001411}, pmid = {40832743}, issn = {1473-6551}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/metabolism/cerebrospinal fluid/blood ; *Biomarkers/blood/cerebrospinal fluid/metabolism ; *Neurofilament Proteins/cerebrospinal fluid/blood/metabolism ; DNA-Binding Proteins/blood ; tau Proteins/blood ; }, abstract = {REVIEW PURPOSE: To provide an overview of the recent developments in the field of neurochemical biomarkers of amyotrophic lateral sclerosis (ALS).<br><br>RECENT FINDINGS: Neurofilaments, especially NFL, have been confirmed to be good biomarkers for ALS. NFL may be diagnostically useful but its main role is as prognostic and pharmacodynamic biomarker. Inflammatory biomarkers, especially the chitinases, might also serve as pharmacodynamic biomarkers in treatment trials targeting neuroinflammation. GFAP could reflect cognitive-behavioural impairment. CSF dipeptides are diagnostic biomarkers for ALS caused by the C9ORF72 exanucleotide repeat expansion and may be used to confirm target engagement by experimental drugs. Levels of TDP-43 (virtually the ideal biomarker for ALS) in CSF and plasma have not been demonstrated to be consistently altered in ALS. However, promising advancements have been achieved in seed amplification assays for the protein, in its quantification in plasma extracellular vesicles, and in the measurement of CSF levels of a protein reflecting splicing dysfunction of TDP-43. Finally, blood phosphorylated tau has emerged as an ALS biomarker linked to lower motor neuron (or muscle) pathology.<br><br>SUMMARY: NFL is still the best neurochemical biomarker for ALS. However, substantial advances have been recently made, especially regarding detection of TDP-43 and blood phosphorylated tau.}, }
@article {pmid40832740, year = {2025}, author = {Lang, C}, title = {Sleep alterations in amyotrophic lateral sclerosis.}, journal = {Current opinion in neurology}, volume = {38}, number = {5}, pages = {606-613}, doi = {10.1097/WCO.0000000000001424}, pmid = {40832740}, issn = {1473-6551}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/physiopathology ; *Sleep Wake Disorders/etiology/physiopathology ; }, abstract = {PURPOSE OF REVIEW: This review summarizes recent evidence on sleep disturbances in amyotrophic lateral sclerosis (ALS), emphasizing their role as intrinsic features of the disease process rather than consequence of motor decline.<br><br>RECENT FINDINGS: Emerging data suggest that sleep disturbances such as sleep fragmentation, rapid eye movement sleep (REM) and non rapid eye movement sleep (NREM) alterations and circadian changes often precede classic motor symptoms. Structural and functional hypothalamic changes have been observed in early ALS, suggesting a direct role in sleep-wake dysregulation. In addition, impaired glymphatic clearance during sleep may contribute to neurodegeneration by impairing the removal of protein waste. Polysomnographic studies and cohort data support the presence of prodromal sleep abnormalities in both symptomatic patients and gene mutation carriers. Noninvasive ventilation has shown benefits not only in respiratory management but also in improving sleep quality and overall prognosis.<br><br>SUMMARY: Sleep alterations in ALS are increasingly recognized as early indicators and potential modulators of disease progression. The hypothalamus and the glymphatic system emerge as key contributors to these disturbances, highlighting sleep as a therapeutic target. Understanding the role of sleep in ALS pathophysiology may aid in earlier diagnosis and novel intervention strategies aimed at modifying disease course.}, }
@article {pmid40772655, year = {2025}, author = {He, J and Fan, D}, title = {Amyotrophic lateral sclerosis in Mainland China: clinical translational challenges and opportunities.}, journal = {Current opinion in neurology}, volume = {38}, number = {5}, pages = {596-605}, pmid = {40772655}, issn = {1473-6551}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology/therapy/diagnosis ; China/epidemiology ; *Translational Research, Biomedical ; Biomarkers ; }, abstract = {PURPOSE OF REVIEW: Amyotrophic lateral sclerosis (ALS) imposes a growing medical and socioeconomic burden in China. This review synthesizes recent advances in understanding ALS epidemiology, biomarker discovery, therapeutic innovations, and policy frameworks in China. It highlights the urgency of addressing challenges, including fragmented healthcare resources, translational medicine gaps, and regional inequities, while emphasizing China's unique contributions to global ALS research.<br><br>RECENT FINDINGS: Chinese ALS cohorts exhibit distinct epidemiological profiles, including a younger mean age of onset and prolonged median survival. Policy initiatives, such as ALS inclusion in rare disease registries and insurance reforms, aim to reduce financial burdens of patients. Multimodal biomarker exploration has advanced integrated diagnostic models combining neurofilament light chain (NfL) and clinical data platforms. Neuroimaging and electrophysiological studies reveal glymphatic dysfunction, white matter degeneration, and neuromuscular junction abnormalities, with novel links to hepatic metabolism. Genomic analyses identify population-specific variants. Therapeutic innovations in China include not only biopharmaceuticals, but also integrative traditional Chinese medicine (TCM) approaches.<br><br>SUMMARY: China's ALS landscape is transitioning towards precision medicine through biomarker-guided diagnostics and multidisciplinary care models. Key priorities include establishing a national ALS registry, standardizing biomarker validation, and expanding clinical trials to bridge translational medicine gaps.}, }
@article {pmid40772638, year = {2025}, author = {Menge, S and Decker, L and Freischmidt, A}, title = {Genetics of ALS - genes and modifier.}, journal = {Current opinion in neurology}, volume = {38}, number = {5}, pages = {568-573}, pmid = {40772638}, issn = {1473-6551}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *Genetic Predisposition to Disease/genetics ; Mitochondria/genetics ; }, abstract = {PURPOSE OF REVIEW: Amyotrophic lateral sclerosis (ALS) is a complex genetic disorder, and the pace of discoveries is very rapid. This review aims at briefly summarizing our current knowledge, and at discussing the progress of the last two years.<br><br>RECENT FINDINGS: Common variation in numerous genes and variants in some nuclear-encoded mitochondrial genes were linked to an increased or modified risk of ALS, respectively. Mitochondrial function, i.e. specific mitochondrial haplotypes and loss-of-function variants in mitochondria-related genes, was identified as potent modifier of ALS survival, but not risk. Pioneering analyses of copy number variations in ALS-related genes revealed an increased load in ALS, but causality is unclear. A rare hyperactive variant of ER stress associated transcription factor CREB3 was linked to both substantially decreased ALS risk and slower disease progression. Furthermore, variants in IGFBP7 were linked to rare "ALS reversals", but existence of such phenotypes is controversial.<br><br>SUMMARY: Common variation increasing ALS risk contributes to our understanding of sporadic ALS, and novel structural variants have the potential to at least partly explain the missing heritability in ALS. Identification of mitochondrial function and ER stress signaling as potent disease modifiers provide valuable starting points for therapeutic approaches beyond targeting single causative genes.}, }
@article {pmid40767546, year = {2025}, author = {Dupuis, L and Robertson, J}, title = {Is amyotrophic lateral sclerosis less severe in mice than in humans?.}, journal = {Current opinion in neurology}, volume = {38}, number = {5}, pages = {581-587}, pmid = {40767546}, issn = {1473-6551}, mesh = {*Amyotrophic Lateral Sclerosis/genetics/physiopathology/pathology ; Animals ; Humans ; *Disease Models, Animal ; Mice ; Gene Knock-In Techniques ; Mice, Transgenic ; }, abstract = {PURPOSE OF REVIEW: We review here novel knock-in models of amyotrophic lateral sclerosis (ALS).<br><br>RECENT FINDINGS: Knock-in mouse models of various familial forms of ALS generally display a mild motor phenotype, with limited progression, that do not recapitulate the full-blown clinical picture of ALS.<br><br>SUMMARY: ALS is a devastating neurodegenerative disease in humans. Typically manifesting in the fifth or sixth decade of life, ALS leads to progressive motor dysfunction and death, usually within 2-5&#x200a;years from symptom onset. A subset of ALS cases are dominantly inherited. Over the last 30&#x200a;years, multiple mouse models of ALS have been generated, and recent advances in mouse genome editing techniques have enabled the generation of mouse strains carrying orthologous mutations in endogenous genes that mirror those causing familial forms of ALS. Intriguingly, many of these knock-in mouse models develop much milder phenotypes than patients with ALS carrying the same mutations. A full-blown ALS clinical phenotype seems to be only elicited upon overexpression of mutant genes beyond the endogenous levels. Here, we review these novel models and argue that these models could represent how ALS manifests in the mouse species. We also evaluate how these models could be used for characterizing mechanisms and preclinical drug evaluation.}, }
@article {pmid40916690, year = {2025}, author = {Sharma, S and Gupta, M and Sharma, S}, title = {Exploring Thiophene-Based Pharmacophores as Emerging Therapeutics for Neurodegenerative Disorders.}, journal = {Critical reviews in analytical chemistry}, volume = {}, number = {}, pages = {1-29}, doi = {10.1080/10408347.2025.2554239}, pmid = {40916690}, issn = {1547-6510}, abstract = {Neurodegenerative disorders (NDD) i.e., dementia of the Alzheimer's type, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis are a rising worldwide epidemic driven by aging populations and characterized by progressive neuronal impairment. In the face of symptomatic therapies, disease-modifying treatments are beyond reach, for many years, at least, owing to the multifactorial origin, including protein aggregation, oxidative stress, neuroinflammation, and neurotransmitter dysregulation. Here, we point out thiophene, a five-membered heterocyclic sulfur-containing scaffold, as an underinvestigated but highly versatile pharmacophore with great potential in therapeutics of NDD. Here, we provide a systematic review of thiophene derivatives identified between 2006 and 2024, highlighting that these compounds are capable of modulating the aggregation of amyloid-β, inhibiting acetylcholinesterase, alleviating oxidative stress, inhibiting the toxicity of α-synuclein, and restoring neurotransmitter homeostasis. Specific emphasis is placed on their structural malleability, blood-brain barrier penetrability, and multi-targeting, which collectively present advantages over traditional heterocyclic templates. Progress in the areas of structure-activity relationship (SAR)-motivated design, synthetic methods, molecular docking, and preclinical assessment is reviewed, leading to the establishment of lead thiophene scaffolds with micro or nanomolar-range activity. This review also provides future directions, such as the requirement of pharmacokinetic improvement, target verification, and translational research to bridge preclinical discoveries with clinical utility. This article collectively places thiophene derivatives as an innovative chemical platform for the design of next-generation drugs for neurodegenerative diseases.}, }
@article {pmid40914405, year = {2025}, author = {Wang, J and Li, X and Yang, F and Guo, P and Ren, C and Duan, Z and Bi, M and Kong, Y and Zhang, Y and Lu, J}, title = {Exploration of endoplasmic reticulum stress-related gene markers in amyotrophic lateral sclerosis: a comprehensive analysis of bioinformatics and machine learning.}, journal = {Analytical biochemistry}, volume = {}, number = {}, pages = {115969}, doi = {10.1016/j.ab.2025.115969}, pmid = {40914405}, issn = {1096-0309}, abstract = {This study aimed to investigate potential biomarkers related to Endoplasmic reticulum (ER) stress in Amyotrophic lateral sclerosis (ALS) through a comprehensive bioinformatic approach. The gene expression profiles of ALS patients and healthy controls were downloaded from the Gene Expression Omnibus (GEO) database. ER stress-related genes were collected from the MSigDB databases and document literature. The "limma" R package was employed to detect the differentially expressed ER stress-related genes (DE-ERSGs). Three methods of machine learning were applied to select the hub DE-ERSGs. ROC curves were conducted to evaluate model performance. An external dataset was chosen to evaluate the diagnostic capability of hub genes. The CIBERSORT algorithm was used to evaluate the immune cell infiltration characteristics. Additionally, we constructed a systematic ceRNA regulatory network using Cytoscape software and predicted the possible drug candidates using the Enrichr platform. Molecular docking analysis was used to further validate the binding ability of the candidate drug molecules to the hub genes. Six hub DE-ERSGs (ABCA1, CKAP4, TOR1AIP1, MMP9, EDC4, and ALPP) were identified, and the related models performed well. These hub genes were concentrated in multiple pathways and related to various immune cells. Drugs such as nitroglycerin, diazepam, FENRETINIDE, and edaravone exhibited good binding affinity to the hub genes, indicating that they may be promising drugs for the management of ALS. This study revealed the essential role of ER stress in the pathogenesis of ALS from an integrative perspective, providing guidance for the development of new therapeutic targets and diagnostic strategies.}, }
@article {pmid40909873, year = {2025}, author = {Wang, X and Dong, B and Gan, Q and Li, J and Wu, P and Guan, Y and Wang, J}, title = {Unraveling the Vicious Cycle: Oxidative Stress and Neurotoxicity in Neurodegenerative Diseases.}, journal = {FASEB bioAdvances}, volume = {7}, number = {8}, pages = {e70041}, pmid = {40909873}, issn = {2573-9832}, abstract = {Oxidative stress is characterized by an imbalance between the production and elimination of free radicals, where the rate of free radical generation surpasses the rate of their removal. This imbalance can lead to tissue and organ damage, contributing to the pathogenesis of various diseases. The nervous system, due to its high oxygen consumption, is particularly susceptible to oxidative stress. Numerous neurotoxins can induce neurotoxicity through oxidative stress, thereby contributing to the onset of neurodegenerative diseases, such as Parkinson's disease, Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis. Furthermore, neurotoxicity can exacerbate oxidative stress by disrupting mitochondrial metabolism and impairing the activity of antioxidant enzymes, thereby intensifying neurotoxic effects. This review examines the mechanisms underlying the interaction between oxidative stress and neurotoxicity and explores strategies to mitigate neurotoxicity by reducing oxidative stress, with the aim of informing future clinical approaches for the treatment of neurodegenerative diseases.}, }
@article {pmid40908745, year = {2025}, author = {Pask, S and Okwuosa, C and Mohamed, A and Price, R and Young, J and Curtis, T and Henderson, S and Winter-Luke, I and Sunny, A and Chambers, RL and Greenley, S and Johansson, T and Bone, AE and Barclay, S and Higginson, IJ and Sleeman, KE and Murtagh, FE}, title = {Models, components and outcomes of palliative and end-of-life care provided to adults living at home: A systematic umbrella review of reviews.}, journal = {Palliative medicine}, volume = {}, number = {}, pages = {2692163251362567}, doi = {10.1177/02692163251362567}, pmid = {40908745}, issn = {1477-030X}, abstract = {BACKGROUND: There is growing demand for home-based palliative care because of patient preference, and increased number of deaths. Optimal models for community-based palliative and end-of-life care are unknown.<br><br>AIM: To identify, synthesise and describe review-level evidence to better understand models of palliative and end-of-life care for adults living at home, and examine components of these models and their association with outcomes.<br><br>DESIGN: Systematic umbrella review, using key concepts established a priori from Firth et al. and Brereton et al.''s model descriptions. Quality assessment used AMSTAR-2 or equivalent.<br><br>DATA SOURCES: MEDLINE, EMBASE, CINAHL, Cochrane Database, Epistemonikos (inception - 2024), supplemented by CareSearch, PROSPERO and citation searches.<br><br>RESULTS: From 6683 initial papers, n&#x2009;=&#x2009;66 reviews were included. Seven models of care were identified; by setting (in-home, outpatient); type of professionals (specialist, integrated, non-specialist); or mode (telehealth, education/training). Components included: holistic person-centred assessment, skilled professionals, access to medicines/care/equipment, patient/family support, advance care planning, integration of services, virtual/remote technology and education. We categorised outcomes into: (i) patient outcomes, (ii) family/informal caregiver outcomes, (iii) professional outcomes and iv) service utilisation/cost outcomes. The 'in-home palliative care' model was most researched with good evidence of positive benefit. Specialist and integrated models of care were next most researched, with evidence of improved patient and service utilisation outcomes. Cost-effectiveness evidence was lacking.<br><br>CONCLUSION: This meta-level evidence supports provision of in-home palliative care, with most review level evidence showing positive effect on patient outcomes. There was also evidence to support specialist palliative care and integration of primary palliative care with specialist support.}, }
@article {pmid40907612, year = {2025}, author = {Kumar, AP and Puthussery, DT}, title = {Regulation of PPAR-γ coactivator-1α and its implication in mitochondrial function and neurodegenerative diseases.}, journal = {Ageing research reviews}, volume = {112}, number = {}, pages = {102887}, doi = {10.1016/j.arr.2025.102887}, pmid = {40907612}, issn = {1872-9649}, abstract = {Peroxisome proliferator-activated receptor (PPAR)-γ coactivator (PGC)-1α, interacts with numerous transcription factors implicated in a wide spectrum of biological responses. It has been identified as a key player in the transcriptional regulation of many mitochondrial components. The activity of PGC1-α is regulated at multiple levels, such as gene expression, transcriptional, post-transcriptional, and post-translational modification. The purpose of this review is to highlight the data supporting PGC1-α-mediated regulation by transcriptional and post-translational modification. We summarize the mechanisms involved in PGC1-α regulation by phosphorylation (AMPK, p38 MAPK, Akt, and GSK3β), acetylation (GCN5, p300, and SRCC), and ubiquitination (E3-ubiquitin ligase). Moreover, the review focuses on the multidomain structure of PGC1-α, its expression in the brain, and the importance of PGC1-α-mediated mitochondrial functions. Mitochondrial dysfunction and impaired energy metabolism are key characteristics of neurodegenerative diseases like Alzheimer's, Huntington's, Parkinson's, amyotrophic lateral sclerosis, and multiple sclerosis. It is associated with reduced PGC1-α expression or activity, resulting in an imbalance in the maintenance of mitochondrial dynamics. In this backdrop, we additionally provide a comprehensive overview of the implication of PGC1-α in the pathogenesis of neurodegenerative disease. Overall, PGC1-α acts as a potential target for therapies to reduce mitochondrial dysfunction associated with neurodegenerative diseases and aid in neuroprotection.}, }
@article {pmid40906916, year = {2025}, author = {Kakoty, V and Kang, JH and Lee, OH and Oh, DH and Ko, YT}, title = {Grueneberg Ganglion: An Unexplored Site for Intranasal Drug Delivery in Alzheimer's Disease.}, journal = {ACS chemical neuroscience}, volume = {}, number = {}, pages = {}, doi = {10.1021/acschemneuro.5c00376}, pmid = {40906916}, issn = {1948-7193}, abstract = {Neurological disorders such as Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Multiple Sclerosis, and Amyotrophic Lateral Sclerosis pose significant challenges for treatment. Reasons for the difficulty in finding cures for these conditions include complications in early diagnosis, progressive and irreversible neuronal damage, and the presence of the blood-brain barrier (BBB), which hinders the delivery of drugs to the affected areas of the brain. Intranasal (INL) drug administration has increasingly gained popularity among researchers for targeting neurological conditions, because of its ability to bypass the BBB. However, chronic INL administration leads to nasal mucosa irritation. Additionally, rapid mucociliary clearance, a lack of targeted drug delivery, increased enzymatic degradation, and tight junctions that obstruct drug transport limit the clinical applicability of the INL route. To overcome these challenges, a unique region in the rodent nose, known as the Grueneberg Ganglion (GG), can be considered to be a novel site for INL drug administration. GG is a small structure housed under the snout cartilage of the nasal septum, approximately 1.5 mm from the nasal opening in mice. It is directly connected to the main olfactory bulb through axons. This Perspective aims to expand knowledge on why GG may be a viable option for INL delivery to combat neurological conditions. For better understanding, we have explained the INL administration in GG, using Alzheimer's Disease and INL insulin therapy as a role model for the current review.}, }
@article {pmid40905723, year = {2025}, author = {Peng, C and Maiuri, T and Truant, R}, title = {Tipping the PARylation scale: Dysregulation of PAR signaling in Huntington and neurodegenerative diseases.}, journal = {Journal of Huntington's disease}, volume = {}, number = {}, pages = {18796397251372667}, doi = {10.1177/18796397251372667}, pmid = {40905723}, issn = {1879-6400}, abstract = {Poly(ADP-ribosyl)ation (PARylation), a crucial post-translational modification, is catalyzed by ADP-ribosyltransferases (ARTs) and has significant implications in various cellular processes, including DNA damage response, cell signaling, and immune processes. Aberrant PAR signaling is implicated in numerous neurodegenerative diseases, including Alzheimer, Parkinson, amyotrophic lateral sclerosis, and cerebellar ataxia, where increased PAR levels and PARP1 activity are commonly observed. However, Huntington disease exhibits a unique characteristic: reduced PAR levels and impaired PARP1 activity even in prodromal phase. This finding challenges the prevailing understanding of PAR's role in neurodegeneration and suggests that dysregulation of PAR signaling, whether through overactivation or suppression, can lead to neuronal dysfunction. Herein, we discuss how this balance may impact neurodegenerative diseases, and possible connections between PAR signaling and emerging modifiers of disease onset identified by HD genome-wide association studies (GWAS).}, }
@article {pmid40905501, year = {2025}, author = {Huang, Y and Wan, Y and Chen, J and Qin, M and Wang, J and Liang, H}, title = {Knowledge mapping of biomarkers in amyotrophic lateral sclerosis: a comprehensive bibliometric and visual analysis.}, journal = {Neurodegenerative disease management}, volume = {}, number = {}, pages = {1-17}, doi = {10.1080/17582024.2025.2554525}, pmid = {40905501}, issn = {1758-2032}, abstract = {BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a severe neurodegenerative disease, and there is currently an urgent need to identify valuable biomarkers to accelerate diagnosis, optimize treatment and prognosis.<br><br>METHODS: To conduct a bibliometric analysis of publications related to "ALS biomarker" over the past 20&#x2009;years, utilizing the subject search feature of the Web of Science Core Collection along with CiteSpace, VOSviewer, and Bibliometrix.<br><br>RESULTS: This review presents a 20-year bibliometric analysis of ALS biomarker research (2004-2024), analyzing 2535 publications showing rising trends. The United States led contributions, with Turner, Martin R as the most productive/cited author. Key research hotspots included cerebrospinal fluid, tdp-43, clinical trial, and neuroinflammation. Topics such as neurofilament light chain, machine learning, and exosomes could potentially represent the cutting edge of future research.<br><br>CONCLUSION: In summary, this study uses bibliometric analysis of ALS biomarker research to provide a forward-looking perspective on its future limitations and potential.}, }
@article {pmid40904199, year = {2025}, author = {Isik, S and Osman, S and Yeman-Kiyak, B and Shamshir, SRM and Sanchez, NME}, title = {Advances in Neurodegenerative Disease Therapy: Stem Cell Clinical Trials and Promise of Engineered Exosomes.}, journal = {CNS neuroscience &amp; therapeutics}, volume = {31}, number = {9}, pages = {e70577}, pmid = {40904199}, issn = {1755-5949}, mesh = {Humans ; *Exosomes/transplantation/metabolism ; *Neurodegenerative Diseases/therapy ; Animals ; *Stem Cell Transplantation/methods/trends ; *Clinical Trials as Topic/methods ; }, abstract = {AIM: This review provides a systematic evaluation of 94 stem cell clinical trials to treat neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease.<br><br>METHODS: Data were collected from using relevant search terms, focusing exclusively on stem cell therapy. Of the 8000+ participants in these trials, nearly 70% were enrolled in AD-related studies. Only three Phase 3 studies were conducted, and most trials were in the early phases (Phases 1 and 2). Mesenchymal stem cells, neural stem cells, induced pluripotent stem cells, and embryonic stem cells are used the most to treat neurodegenerative diseases. This review also explores the emerging fields of preclinical and clinical investigations of stem cell-derived exosome-based therapies for neurodegenerative diseases.<br><br>RESULTS: Exosomes can cross the blood-brain barrier to deliver therapeutic molecules directly to the brain, offering a less invasive alternative to stem cell transplantation. Mesenchymal stem cell-derived exosomes, in particular, have demonstrated significant potential in preclinical models by reducing neuroinflammation, oxidative stress, and promoting neuronal regeneration. Additionally, recent advances in exosome engineering, including surface modifications, therapeutic agent loading, and transgenic modifications, have improved targeting, stability, blood-brain barrier delivery, and neural cell interactions, enabling targeted and effective treatment. Exosome-based therapies are in the preliminary phases of clinical investigation, with only three clinical trials.<br><br>CONCLUSION: Given the increasing interest in exosome therapy, clinical investigations are expected to increase. This growth will be driven by ongoing advancements in exosome technology, a deeper understanding of their therapeutic potential, and escalating demand for innovative treatment strategies for neurodegenerative diseases.}, }
@article {pmid40903341, year = {2025}, author = {Vedula, P and Ishizuka, K and Hayashida, A and Sueo, K and Sawa, A}, title = {Stress-induced nuclear GAPDH: Scientific update and clinical application.}, journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics}, volume = {}, number = {}, pages = {e00725}, doi = {10.1016/j.neurot.2025.e00725}, pmid = {40903341}, issn = {1878-7479}, abstract = {Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is known as a moonlighting protein beyond its original glycolytic function. Stress-induced nuclear translocation of GAPDH has been reproducibly reported, which results in variety types of cellular responses, including cell death and dysfunction. Blocking this stress-induced cascade has been regarded as a target of drug discovery and development for human disease conditions, particularly for neurological and psychiatric diseases. There are promising small compounds that can block this cascade in cell and animal models. Nevertheless, the clinical trials for Parkinson's disease and amyotrophic lateral sclerosis with one of these compounds Omigapil were unsuccessful. Including these failure cases, this review article discussed the scientific frontline of GAPDH, particularly stress-induced nuclear GAPDH, and its potential for clinical applications.}, }
@article {pmid40901987, year = {2025}, author = {Sun, Z and Li, C and Leitner, D and Wu, M and Zhang, J and Wisniewski, T and Ge, Y}, title = {Age-related Vascular Alterations in the Choroid Plexus: Novel Insights from Pathophysiology and Imaging Studies.}, journal = {Aging and disease}, volume = {}, number = {}, pages = {}, doi = {10.14336/AD.2025.0735}, pmid = {40901987}, issn = {2152-5250}, abstract = {The choroid plexus (ChP), a highly vascularized brain structure responsible for cerebrospinal fluid (CSF) production, undergoes significant age-related changes that may contribute to neurodegenerative diseases involving disrupted immune regulation, fluid homeostasis and waste clearance. Compared to other brain regions, vascular research on the ChP remains limited despite its critical role as a central interface between the blood and CSF. This review focuses on age-related vascular and structural alterations in the ChP from both histopathological and neuroimaging perspectives, and explores their impact on CSF dynamics, immune regulation, and the integrity of the blood-CSF barrier (BCSFB). Rather than shrinking, the aging ChP often enlarges due to dystrophic changes, as shown in volumetric MRI studies. Histological studies reveal epithelial degeneration, basement membrane thickening, and stromal fibrosis in the normal aging process. In dementia such as Alzheimer's disease (AD), proteomic studies have identified upregulation of AD- and immune-related proteins, along with downregulation of proteins linked to CSF clearance and metabolic support. Emerging high-resolution contrast-enhanced MRI techniques now allow in vivo visualization of microvascular changes within the ChP, shedding light on its normal and abnormal aging processes. Understanding these alterations is critical, as they may influence the onset and progression of various neurological diseases such as AD, Parkinson's disease (PD), normal pressure hydrocephalus, and amyotrophic lateral sclerosis (ALS). The recent advancements and challenges described in this study underscore the need for deeper investigation into ChP aging to inform future diagnostic and therapeutic strategies of neurodegenerative diseases.}, }
@article {pmid40900744, year = {2025}, author = {Mani, S and Wasnik, S and Shandilya, C and Srivastava, V and Khan, S and Singh, KK}, title = {Pathogenic synergy: dysfunctional mitochondria and neuroinflammation in neurodegenerative diseases associated with aging.}, journal = {Frontiers in aging}, volume = {6}, number = {}, pages = {1615764}, pmid = {40900744}, issn = {2673-6217}, abstract = {The term "neurodegenerative diseases" (NDDs) refers to a range of aging-associated conditions, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Unique clinical symptoms and underlying pathological mechanisms distinguish each of these illnesses. Although these conditions vary, they share chronic neuroinflammation as a defining characteristic. Protein aggregation and mitochondrial dysfunction are believed to play a role in initiating the neuroinflammatory response and, subsequently, the development and course of these illnesses. Apart from providing energy to the cells, mitochondria are involved in the immunoinflammatory response associated with neurological disorders such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, and epilepsy. This involvement is attributed to controlling processes such as inflammasome activation and cell death. Under inflammatory conditions, the underlying regulatory mechanisms for these aging-associated disorders may include calcium homeostasis imbalance, mitochondrial oxidative stress, mitochondrial dynamics, and epigenetics. Various NDDs are linked to neuroinflammation and mitochondrial dysfunction. The linkages between these occurrences are becoming more apparent, but the etiology of these pathologic lesions is yet to be elucidated. This review examines the role of neuroinflammation and mitochondrial dysfunction in the growth and course of NDDs, emphasizing the possibility of identifying novel therapeutic targets to address aging-related neurodegenerative processes and retard the progression of these illnesses.}, }
@article {pmid40897992, year = {2025}, author = {Quigley, SE and Quigg, KH and Goutman, SA}, title = {Genetic and Mechanistic Insights Inform Amyotrophic Lateral Sclerosis Treatment and Symptomatic Management: Current and Emerging Therapeutics and Clinical Trial Design Considerations.}, journal = {CNS drugs}, volume = {}, number = {}, pages = {}, pmid = {40897992}, issn = {1179-1934}, support = {R01NS120926/NH/NIH HHS/United States ; R01NS127188/NH/NIH HHS/United States ; R01TS000344/ACL/ACL HHS/United States ; R01TS000327//Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry/ ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting both upper and lower motor neurons. ALS is classically characterized by painless progressive weakness, causing impaired function of limbs, speech, swallowing, and respiratory function. The disease is fatal within 2-4 years, often the result of respiratory failure. The pathologic hallmark for a majority of ALS cases is aberrant cytoplasmic accumulations of the nuclear protein TAR-DNA binding protein (TDP-43). A total of 10-15% of ALS can be attributed to a single gene mutation, known as genetic or "familial" ALS, while the remainder of cases are termed nongenetic or "sporadic" although heritability has been measured in up to 37% in this population. Complex interactions between genetics, environment, and physiologic susceptibility are thought to contribute to disease. Management is primarily supportive in nature, though there are several approved treatments worldwide. This review details the mechanisms and evidence of approved disease-modifying treatments, relevant measures to track disease burden and progression used in clinical trials, and approaches to pharmacologic management of common symptoms in ALS. As there is not currently a cure for ALS, research into the complex pathophysiologic and genetic alterations contributing to disease is of great interest. This review further discusses the current understanding of genetic etiologies and altered physiology leading to disease, such as neuroinflammation, integrated stress response, aberrant proteostasis and mitochondrial dysfunction, among others. The translation of preclinical discoveries into current investigational therapeutics, novel therapeutic categories such as antisense oligonucleotides and stem cell transplantation, as well as future horizons harnessing the power of artificial intelligence in drug development and clinical trials are discussed.}, }
@article {pmid40895800, year = {2025}, author = {D'Arrigo, C and Labbate, S and Galante, D}, title = {Boosting the Therapeutic Potential of Extracellular Vesicles Derived From Mesenchymal Stem Cells via Advanced Preconditioning for Neurodegenerative Disorders.}, journal = {Stem cells international}, volume = {2025}, number = {}, pages = {2616653}, pmid = {40895800}, issn = {1687-966X}, abstract = {Acute and chronic neurodegenerative conditions (NDs) are major causes of disability and mortality worldwide. Acute NDs encompass conditions such as stroke, traumatic brain injury (TBI), and spinal cord injury (SCI). On the other hand, chronic NDs include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS). Currently, no definitive cure exists for these diseases, and available therapies focus primarily on slowing the progression of symptoms. Mesenchymal stem cells (MSCs), due to their multilineage differentiation capacity, immunomodulatory abilities, and regenerative properties, have gained attention in regenerative medicine. In recent years, extracellular vesicles (EVs) derived from MSCs have shown great promise as a cell-free therapeutic approach, eliminating the risks associated with direct MSCs use, such as tumorigenicity and poor cell survival after transplantation. EVs have emerged as powerful mediators of intercellular communication and tissue repair, exhibiting immunomodulatory, anti-inflammatory, and proregenerative properties. However, limitations such as low EVs yield and reduced efficacy due to MSCs replicative senescence restrict their therapeutic potential. Preconditioning strategies, including hypoxia, 3D cultures, and biochemical priming, have been explored in other fields to enhance EVs properties, yet their specific application to NDs remains under-reported. This review aims to address this gap by analyzing the preconditioning methods used to boost the therapeutic potential of MSCs-derived EVs for neurodegenerative diseases. These preconditioning strategies may enhance EVs yield, functional cargo, and targeted therapeutic efficacy for treating acute and chronic NDs.}, }
@article {pmid40891578, year = {2025}, author = {Toyota, S}, title = {Expanding Chemistry of Expanded Helicenes.}, journal = {Chemistry (Weinheim an der Bergstrasse, Germany)}, volume = {}, number = {}, pages = {e02193}, doi = {10.1002/chem.202502193}, pmid = {40891578}, issn = {1521-3765}, support = {23K26637//Japan Society for the Promotion of Science/ ; 20H02721//Japan Society for the Promotion of Science/ ; 23H01944//Japan Society for the Promotion of Science/ ; }, abstract = {Expanded helicenes are interesting compounds created by modifying the original helicene structure through the incorporation of linearly fused benzene rings, enlarging the helical diameter. Motivated by Tilley et al.'s report of a key expanded helicene structure in 2017, several research groups have synthesized such nonplanar aromatic compounds, aiming to explore their impressive structures, properties, and chiroptical performance. This review highlights recent advances in the expanded helicene chemistry through experimental and theoretical studies. The shape and length of helical structures depend on the number and combination of angularly and linearly fused benzene rings. Helical structures are classified using notations, and specific compounds corresponding to each structural form, namely, hexagonal, triangular, rhombic, or others, are introduced herein. As an extension of the molecular design, examples of nonhexagonal and heteroaromatic ring-embedded expanded helicenes are presented. Specifically, this review focuses on how the diameters, lengths, and turn numbers of helical structures depend on dynamic processes involving helical inversion and chiroptical properties (circular dichroism (CD) and circularly polarized luminescence (CPL)). The characteristics and perspectives of this molecular design are also discussed.}, }
@article {pmid40891506, year = {2025}, author = {Pir, GJ and Buddenkotte, J and Alam, MA and Own, A and Eck, RJ and Kraemer, BC and Mandelkow, E and Steinhoff, M}, title = {TDP-43 proteinopathies and neurodegeneration: insights from Caenorhabditis elegans models.}, journal = {The FEBS journal}, volume = {}, number = {}, pages = {}, doi = {10.1111/febs.70239}, pmid = {40891506}, issn = {1742-4658}, support = {11S-0117 180326//Qatar National Research Fund/ ; //Katharina Hardt Foundation/ ; F99AG088436/NH/NIH HHS/United States ; //Cure Alzheimer's Fund/ ; }, abstract = {TDP-linked proteinopathies, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and limbic-predominant age-related TDP-43 encephalopathy (LATE), are characterised by pathogenic deposits containing transactive response DNA-binding protein 43 (TDP-43) in the brain and spinal cord of patients. These hallmark pathological features are associated with widespread neuronal dysfunction and progressive neurodegeneration. TDP-43's role as an essential RNA/DNA-binding protein in RNA metabolism and gene expression regulation is clear, but deciphering the intricate pathophysiological mechanisms underpinning TDP-43-mediated neurodegeneration is paramount for developing effective therapies and novel diagnostic tools for early detection before frank neuronal loss occurs. The nematode Caenorhabditis elegans, with highly conserved TDP-43 orthologue TDP-1, serves as a powerful genetic model to investigate the molecular underpinnings of TDP-43 proteinopathies. Here, we provide a brief overview of the structural and functional characteristics of TDP-43 and TDP-1, highlighting their conserved roles in RNA metabolism, stress responses, and neurodegeneration. We then delve into the pathobiology of TDP-43, drawing insights from C. elegans models expressing either monogenic TDP-43 variants or bigenic combinations with ALS-associated risk genes, and discuss how these models have advanced our understanding of the pathomechanisms of TDP-43 proteinopathies. By employing its simplicity and genetic manipulability, we discuss how these models have helped identify chemical and genetic suppressors of TDP-43-induced phenotypes, including small molecules like Pimozide and the probiotic Lacticaseibacillus rhamnosus HA-114, now in clinical trials. This review underscores the translational value of C. elegans in unraveling the biochemical pathways and interactions in TDP-43 proteinopathies that perturb cellular physiology, potentially facilitating mechanism-based therapy development.}, }
@article {pmid40887101, year = {2025}, author = {Guillot, SJ and Luppi, PH and Dupuis, L and Bolborea, M}, title = {Sleep in neurodegenerative diseases: A focus on melatonin, melanin-concentrating hormone and orexin.}, journal = {Journal of neuroendocrinology}, volume = {}, number = {}, pages = {e70085}, doi = {10.1111/jne.70085}, pmid = {40887101}, issn = {1365-2826}, support = {ANR-16-CE16-0015//Agence Nationale de la Recherche/ ; ANR-16-CE92-0031//Agence Nationale de la Recherche/ ; ANR-19-CE17-0016//Agence Nationale de la Recherche/ ; ANR-20-CE17-0008//Agence Nationale de la Recherche/ ; ANR-24-CE37-4064//Agence Nationale de la Recherche/ ; //TargetALS/ ; //Fondation Thierry Latran/ ; //Association Francaise de Recherche sur la scl&#xe9;rose lat&#xe9;rale amyotrophique/ ; //Radala Foundation for ALS Research/ ; //ARSLA/ ; //University of Starsbourg fundation/ ; //Fondation Bettencourt Schueller/ ; DEQ20180339179//Fondation pour la Recherche M&#xe9;dicale/ ; //Axa Research Funds/ ; }, abstract = {Sleep and circadian rest-activity rhythm alterations are recognised as inherent clinical features of various neurodegenerative diseases. Traditionally viewed as secondary manifestations of neurodegeneration, recent studies have revealed that disruptions in circadian rhythm and sleep-wake cycles can precede clinical symptoms and significantly contribute to the underlying pathophysiological progression. In this review, we summarise recent research on the impact of sleep and circadian rhythm alterations in ageing and major neurodegenerative diseases, including Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis, and frontotemporal dementia, highlighting the roles of melatonin, orexin, and melanin-concentrating hormone (MCH) systems as key regulators at the intersection of sleep and neurodegeneration. We argue that sleep and circadian alterations may serve as early biomarkers and therapeutic targets for these diseases.}, }
@article {pmid40885478, year = {2025}, author = {Hafiz, B and Aldahlawi, A and Ashqar, A and Hamzah, A and Alotaibi, Y and Bajunaid, K and Baeesa, S}, title = {Outcomes of Surgical Versus Endovascular Treatment of Spinal Dural Arteriovenous Fistula: A Systematic Review and Meta-Analysis.}, journal = {World neurosurgery}, volume = {}, number = {}, pages = {124420}, doi = {10.1016/j.wneu.2025.124420}, pmid = {40885478}, issn = {1878-8769}, abstract = {BACKGROUND: Spinal dural arteriovenous fistulas (SDAVFs) are the most prevalent type of spinal vascular malformation and can lead to progressive neurological impairments if left untreated. Endovascular embolization and microsurgical resection are treatment options, although the optimal treatment method remains a subject of debate.<br><br>OBJECTIVE: A comprehensive systematic review and meta-analysis to compare the endovascular and microsurgical treatment outcomes of SDAVFs.<br><br>METHODS: An exhaustive literature search was conducted in the PubMed, Embase, Scopus, and Web of Science databases, encompassing publications from 2014 to 2024. A total of 522 patients from seven studies (417 surgical and 105 endovascular) met the inclusion criteria. Information on post-treatment complications, recurrence/failure rates, and functional improvement as assessed by the Aminoff-Logue Scale (ALS) or modified ALS (mALS) was extracted. I[2] statistics were used to evaluate heterogeneity, and random-effects models were used to compute risk ratios (RRs) and odds ratios (ORs).<br><br>RESULTS: Compared to endovascular intervention, surgical treatment was linked to significantly lower rates of recurrence or treatment failure (RR: 0.19; 95% CI: 0.09-0.39; p < 0.001), especially in long-term follow-up and thoracic-level studies. With greater ALS/mALS gains and a higher percentage of patients achieving full or partial recovery, functional improvement favored surgery. Although complication types varied, complication rates were similar across modalities (OR: 0.84; 95% CI: 0.48-1.49). Asymmetry in funnel plots indicated possible publication bias in favor of successful surgical outcomes.<br><br>CONCLUSION: For SDAVFs, surgical ligation provides better long-term results than endovascular embolization in terms of neurological recovery and recurrence prevention. Even though both procedures are usually safe, surgery is the recommended first-line course of action due to the higher failure and recurrence rates linked to embolization, especially in patients with operable anatomy and progressive symptoms.}, }
@article {pmid40858858, year = {2025}, author = {Loo, YS and Yusoh, NA and Yap, K and Ng, CS}, title = {Programmable self-replicating JEV nanotherapeutics redefine RNA delivery in ALS.}, journal = {Communications biology}, volume = {8}, number = {1}, pages = {1282}, pmid = {40858858}, issn = {2399-3642}, support = {PM010CNI000148//International Brain Research Organization (IBRO)/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/therapy/genetics ; Humans ; Animals ; *Encephalitis Virus, Japanese/genetics/physiology ; *Oligonucleotides, Antisense/administration &amp; dosage/genetics ; *Genetic Therapy/methods ; MicroRNAs/genetics ; Virus Replication ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron degeneration, leading to paralysis and respiratory failure. Current therapies offer limited benefits, highlighting the need for novel therapeutic strategies. Antisense oligonucleotides (ASO) and CRISPR/Cas9 gene editing hold promise, but their effective delivery to the central nervous system (CNS) remains a significant challenge. Here, a potential approach involves utilizing engineered Japanese encephalitis virus (JEV) as a self-replicating nanocarrier for targeted ASO delivery to motor neurons. By leveraging JEV's natural neurotropism and "Trojan horse" mechanism of immune cell-mediated CNS entry, this strategy overcomes the blood-brain and blood-spinal cord barriers (BBB/BSCB). Incorporation of ASO sequences within the JEV genome facilitates co-packaging and sustained therapeutic delivery, while microRNA (miRNA)-mediated attenuation may enhance safety and CNS specificity. This theoretical framework offers a potential paradigm shift in CNS gene therapy for ALS and other neurodegenerative diseases by enabling efficient, targeted, and sustained ASO delivery. However, experimental validation remains critical to assess its safety and therapeutic efficacy.}, }
@article {pmid40884740, year = {2025}, author = {Kalasa Anil Kumar, AP and Subair, S and Basthikoppa Shivamurthy, P and Ummar, S and Rajeev, AC and Raju, R}, title = {Decoding ATXN2 Phosphocode: Structural Insights and Therapeutic Opportunities in Disease.}, journal = {The protein journal}, volume = {}, number = {}, pages = {}, pmid = {40884740}, issn = {1875-8355}, abstract = {Ataxin-2 (ATXN2), a key RNA-binding protein, regulates RNA metabolism, stress granule formation, and neuronal homeostasis, with dysregulated phosphorylation contributing to Spinocerebellar Ataxia type 2 (SCA2), amyotrophic lateral sclerosis (ALS), and cancer. This review integrates structural biology, phosphoproteomics, and interactome analyses to map six critical phosphosites (S772, T741, S624, S684, S784, S889) within ATXN2's intrinsically disordered regions. Modulated by kinases GSK3β and CDK13 and phosphatases like INPP5F, these sites orchestrate interactions with RNA-binding partners (e.g., ATXN2L, FXR2, STAU2) and co-regulated proteins (e.g., TP53BP1, NUP153), driving pathogenesis through disrupted autophagy, nucleocytoplasmic transport, and stress granule dynamics. We propose targeted therapies, including GSK3β inhibitors for ALS, antisense oligonucleotides for SCA2, and MTOR modulators for cancer, to restore ATXN2 function. By elucidating phosphocode of ATXN2, this work highlights novel avenues for precision medicine in neurodegenerative and oncogenic diseases.}, }
@article {pmid40883656, year = {2025}, author = {García-Parra, B and Guiu, JM and Povedano, M and Modamio, P}, title = {Geographic distribution of amyotrophic lateral sclerosis-related genes: a systematic review.}, journal = {Neurodegenerative disease management}, volume = {}, number = {}, pages = {1-7}, doi = {10.1080/17582024.2025.2554382}, pmid = {40883656}, issn = {1758-2032}, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a rare motor neuron disease. There is no effective treatment, but disease-modifying therapies do exist. Objective. To identify the geographical distribution of ALS-related genes.<br><br>METHODS: A systematic review was conducted according to the PRISMA 2020 guidelines in PubMed and Web of Science. Inclusion criteria: patients with ALS, no age or gender restriction, English and Spanish languages, studies published until 31 July 2025.<br><br>RESULTS: Thirty-eight results were obtained, 32 were selected, 19 articles were assessed for eligibility, and 8 articles were included from databases. Three articles recommended by clinical experts were added, so 11 results were reviewed. This research showed that published articles on the geographic distribution of ALS-related genes are limited, particularly for underrepresented regions such as Africa.<br><br>CONCLUSION: The findings demonstrate the need for intensified international research to improve knowledge of the genetic epidemiology of ALS.}, }
@article {pmid40871062, year = {2025}, author = {Yang, HM}, title = {Overcoming the Blood-Brain Barrier: Advanced Strategies in Targeted Drug Delivery for Neurodegenerative Diseases.}, journal = {Pharmaceutics}, volume = {17}, number = {8}, pages = {}, pmid = {40871062}, issn = {1999-4923}, support = {03-2025-0200//Seoul National University Hospital/ ; }, abstract = {The increasing global health crisis of neurodegenerative diseases such as Alzheimer's, Parkinson's, amyotrophic lateral sclerosis, and Huntington's disease is worsening because of a rapidly increasing aging population. Disease-modifying therapies continue to face development challenges due to the blood-brain barrier (BBB), which prevents more than 98% of small molecules and all biologics from entering the central nervous system. The therapeutic landscape for neurodegenerative diseases has recently undergone transformation through advances in targeted drug delivery that include ligand-decorated nanoparticles, bispecific antibody shuttles, focused ultrasound-mediated BBB modulation, intranasal exosomes, and mRNA lipid nanoparticles. This review provides an analysis of the molecular pathways that cause major neurodegenerative diseases, discusses the physiological and physicochemical barriers to drug delivery to the brain, and reviews the most recent drug targeting strategies including receptor-mediated transcytosis, cell-based "Trojan horse" approaches, gene-editing vectors, and spatiotemporally controlled physical methods. The review also critically evaluates the limitations such as immunogenicity, scalability, and clinical translation challenges, proposing potential solutions to enhance therapeutic efficacy. The recent clinical trials are assessed in detail, and current and future trends are discussed, including artificial intelligence (AI)-based carrier engineering, combination therapy, and precision neuro-nanomedicine. The successful translation of these innovations into effective treatments for patients with neurodegenerative diseases will require essential interdisciplinary collaboration between neuroscientists, pharmaceutics experts, clinicians, and regulators.}, }
@article {pmid40870005, year = {2025}, author = {Jeong, J and Kim, J and Kim, MS}, title = {Dual Nature of Mitochondrial Integrated Stress Response: Molecular Switches from Protection to Pathology.}, journal = {Genes}, volume = {16}, number = {8}, pages = {}, pmid = {40870005}, issn = {2073-4425}, mesh = {Humans ; *Mitochondria/metabolism/pathology/genetics ; *Stress, Physiological ; Animals ; *Amyotrophic Lateral Sclerosis/metabolism/drug therapy/pathology/genetics ; }, abstract = {BACKGROUND: The mitochondrial integrated stress response (ISR) represents a fundamental cellular adaptation mechanism with dual protective and pathological roles. We critically analyzed current literature on ISR mechanisms, focusing on recent paradigm shifts including the 2020 discovery of the OMA1-DELE1-HRI axis, emerging controversies over context-dependent activation patterns, and the January 2025 clinical trial failures that have reshaped the therapeutic landscape.<br><br>METHODS: We reviewed recent literature (2020-2025) examining ISR mechanisms, clinical trials, and therapeutic developments through comprehensive database searches.<br><br>RESULTS: The field has evolved from simple linear pathway models to recognition of complex, context-dependent networks. Recent findings reveal that ISR activation mechanisms vary dramatically based on cellular metabolic state, with distinct pathways operating in proliferating versus differentiated cells. The "dark microglia" phenotype in neurodegeneration and DR5-mediated apoptotic switches exemplify pathological ISR manifestations, while adaptive responses include metabolic reprogramming and quality control enhancement.<br><br>CONCLUSIONS: The 2025 failures of DNL343 and ABBV-CLS-7262 in ALS trials underscore the need for precision medicine approaches that account for context-dependent ISR functions, temporal dynamics, and disease-specific mechanisms.}, }
@article {pmid40869392, year = {2025}, author = {Șerban, M and Toader, C and Covache-Busuioc, RA}, title = {Blueprint of Collapse: Precision Biomarkers, Molecular Cascades, and the Engineered Decline of Fast-Progressing ALS.}, journal = {International journal of molecular sciences}, volume = {26}, number = {16}, pages = {}, pmid = {40869392}, issn = {1422-0067}, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology/diagnosis ; Humans ; *Biomarkers/metabolism ; Disease Progression ; Animals ; Mitochondria/metabolism ; Precision Medicine ; Neurofilament Proteins/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is still a heterogeneous neurodegenerative disorder that can be identified clinically and biologically, without a strong set of biomarkers that can adequately measure its fast rate of progression and molecular heterogeneity. In this review, we intend to consolidate the most relevant and timely advances in ALS biomarker discovery, in order to begin to bring molecular, imaging, genetic, and digital areas together for potential integration into a precision medicine approach to ALS. Our goal is to begin to display how several biomarkers in development (e.g., neurofilament light chain (NfL), phosphorylated neurofilament heavy chain (pNfH), TDP-43 aggregates, mitochondrial stress markers, inflammatory markers, etc.) are changing our understanding of ALS and ALS dynamics. We will attempt to provide a framework for thinking about biomarkers in a systematic way where our candidates are not signals alone but part of a tethered pathophysiological cascade. We are particularly interested in the fast progressor phenotype, a devastating and under-characterized subset of ALS due to a rapid axonal degeneration, early respiratory failure, and very short life span. We will try to highlight the salient molecular features of this ALS subtype, including SOD1 A5V toxicity, C9orf72 repeats, FUS variants, mitochondrial collapse, and impaired autophagy mechanisms, and relate these features to measurable blood and CSF (biomarkers) and imaging platforms. We will elaborate on several interesting tools, for example, single-cell transcriptomics, CSF exosomal cargo analysis, MRI techniques, and wearable sensor outputs that are developing into high-resolution windows of disease progression and onset. Instead of providing a static catalog, we plan on providing a conceptual roadmap to integrate biomarker panels that will allow for earlier diagnosis, real-time disease monitoring, and adaptive therapeutic trial design. We hope this synthesis will make a meaningful contribution to the shift from observational neurology to proactive biologically informed clinical care in ALS. Although there are still considerable obstacles to overcome, the intersection of a precise molecular or genetic association approach, digital phenotyping, and systems-level understandings may ultimately redefine how we monitor, care for, and treat this challenging neurodegenerative disease.}, }
@article {pmid40869205, year = {2025}, author = {Lewandowski, D and Konieczny, M and Różycka, A and Chrzanowski, K and Owecki, W and Kalinowski, J and Stepura, M and Jagodziński, P and Dorszewska, J}, title = {Cathepsins in Neurological Diseases.}, journal = {International journal of molecular sciences}, volume = {26}, number = {16}, pages = {}, pmid = {40869205}, issn = {1422-0067}, mesh = {Humans ; *Cathepsins/metabolism ; Animals ; *Nervous System Diseases/metabolism/pathology ; Lysosomes/metabolism ; Biomarkers/metabolism ; }, abstract = {Cathepsins, a family of lysosomal proteases, play critical roles in maintaining cellular homeostasis through protein degradation and modulation of immune responses. In the central nervous system (CNS), their functions extend beyond classical proteolysis, influencing neuroinflammation, synaptic remodeling, and neurodegeneration. Emerging evidence underscores the crucial role of microglial cathepsins in the pathophysiology of several neurological disorders. This review synthesizes current knowledge on the involvement of cathepsins in a spectrum of CNS diseases, including Parkinson's disease, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, epilepsy, Huntington's disease, and ischemic stroke. We highlight how specific cathepsins contribute to disease progression by modulating key pathological processes such as α-synuclein and amyloid-β clearance, tau degradation, lysosomal dysfunction, neuroinflammation, and demyelination. Notably, several cathepsins demonstrate both neuroprotective and pathogenic roles depending on disease context and expression levels. Additionally, the balance between cathepsins and their endogenous inhibitors, such as cystatins, emerges as a critical factor in CNS pathology. While cathepsins represent promising biomarkers and therapeutic targets, significant gaps remain in our understanding of their mechanistic roles across diseases. Future studies focusing on their regulation, substrate specificity, and interplay with genetic and epigenetic factors may yield novel strategies for early diagnosis and disease-modifying treatments in neurology.}, }
@article {pmid40868276, year = {2025}, author = {Voicu, V and Toader, C and Șerban, M and Covache-Busuioc, RA and Ciurea, AV}, title = {Systemic Neurodegeneration and Brain Aging: Multi-Omics Disintegration, Proteostatic Collapse, and Network Failure Across the CNS.}, journal = {Biomedicines}, volume = {13}, number = {8}, pages = {}, pmid = {40868276}, issn = {2227-9059}, abstract = {Neurodegeneration is increasingly recognized not as a linear trajectory of protein accumulation, but as a multidimensional collapse of biological organization-spanning intracellular signaling, transcriptional identity, proteostatic integrity, organelle communication, and network-level computation. This review intends to synthesize emerging frameworks that reposition neurodegenerative diseases (ND) as progressive breakdowns of interpretive cellular logic, rather than mere terminal consequences of protein aggregation or synaptic attrition. The discussion aims to provide a detailed mapping of how critical signaling pathways-including PI3K-AKT-mTOR, MAPK, Wnt/β-catenin, and integrated stress response cascades-undergo spatial and temporal disintegration. Special attention is directed toward the roles of RNA-binding proteins (e.g., TDP-43, FUS, ELAVL2), m6A epitranscriptomic modifiers (METTL3, YTHDF1, IGF2BP1), and non-canonical post-translational modifications (SUMOylation, crotonylation) in disrupting translation fidelity, proteostasis, and subcellular targeting. At the organelle level, the review seeks to highlight how the failure of ribosome-associated quality control (RQC), autophagosome-lysosome fusion machinery (STX17, SNAP29), and mitochondrial import/export systems (TIM/TOM complexes) generates cumulative stress and impairs neuronal triage. These dysfunctions are compounded by mitochondrial protease overload (LONP1, CLPP), UPR maladaptation, and phase-transitioned stress granules that sequester nucleocytoplasmic transport proteins and ribosomal subunits, especially in ALS and FTD contexts. Synaptic disassembly is treated not only as a downstream event, but as an early tipping point, driven by impaired PSD scaffolding, aberrant endosomal recycling (Rab5, Rab11), complement-mediated pruning (C1q/C3-CR3 axis), and excitatory-inhibitory imbalance linked to parvalbumin interneuron decay. Using insights from single-cell and spatial transcriptomics, the review illustrates how regional vulnerability to proteostatic and metabolic stress converges with signaling noise to produce entropic attractor collapse within core networks such as the DMN, SN, and FPCN. By framing neurodegeneration as an active loss of cellular and network "meaning-making"-a collapse of coordinated signal interpretation, triage prioritization, and adaptive response-the review aims to support a more integrative conceptual model. In this context, therapeutic direction may shift from damage containment toward restoring high-dimensional neuronal agency, via strategies that include the following elements: reprogrammable proteome-targeting agents (e.g., PROTACs), engineered autophagy adaptors, CRISPR-based BDNF enhancers, mitochondrial gatekeeping stabilizers, and glial-exosome neuroengineering. This synthesis intends to offer a translational scaffold for viewing neurodegeneration as not only a disorder of accumulation but as a systems-level failure of cellular reasoning-a perspective that may inform future efforts in resilience-based intervention and precision neurorestoration.}, }
@article {pmid40868211, year = {2025}, author = {Flor, J and Silveira, AT and Martins, IA and Otero, LB and Silva, FM and Vizuete, AFK and Wink, MR and Rigatto, K}, title = {Biological Actions of Alamandine: A Scoping Review.}, journal = {Biomedicines}, volume = {13}, number = {8}, pages = {}, pmid = {40868211}, issn = {2227-9059}, abstract = {Objective: This scoping review aims to comprehensively map the existing literature on the mechanisms of action of Alamandine (ALA), a peptide within the renin-angiotensin system, and its effects across various physiological systems. Materials and Methods: Utilizing the Joanna Briggs Institute methodology, a thorough search of databases including PubMed, Embase, Scopus, and Web of Science was conducted up to 30 January 2025. The review focused on identifying studies that explore the biological and therapeutic roles of ALA in different contexts, incorporating in vivo, in vitro, and in silico research. Results: A total of 590 records were initially identified, with 25 meeting the eligibility criteria for inclusion in this review. China emerged as the leading contributor to the research in this area, with a significant focus on the cardiovascular system. The studies revealed that ALA exhibits a range of beneficial effects, including anti-inflammatory, vasodilatory, antifibrotic, and antiapoptotic actions. These effects are primarily mediated through the inhibition of the mitogen-activated protein kinase (MAPK) signaling pathway and modulation of the nitric oxide pathway. The review also highlighted AL's potential in mitigating oxidative stress and its implications in treating cardiovascular diseases, fibrosis, and cancer. Conclusions: The findings suggest that ALA holds significant therapeutic potential, offering antihypertensive, anti-inflammatory, antifibrotic, and anticancer benefits without notable adverse effects, warranting further research to explore its full potential and mechanism of action.}, }
@article {pmid40876427, year = {2025}, author = {Ibrahim, SI and Zaher, DM and Hersi, FA and Hamouda, AO and Al Hindawi, MA and Omar, HA}, title = {Repurposing edaravone in oncology: Bridging antioxidant defense and immune modulation.}, journal = {International immunopharmacology}, volume = {164}, number = {}, pages = {115413}, doi = {10.1016/j.intimp.2025.115413}, pmid = {40876427}, issn = {1878-1705}, abstract = {Edaravone, a synthetic free radical scavenger originally approved for neurological disorders such as stroke and amyotrophic lateral sclerosis (ALS), is gaining attention for its emerging potential role in cancer. Beyond its well-established antioxidant properties, edaravone demonstrates significant anti-inflammatory and immunomodulatory activities, including the inhibition of key pathways such as NF-κB, JAK2/STAT3, and TLR4/IL-6, suggesting potential to modulate immune responses within the tumor microenvironment. This review discusses how edaravone disrupts oncogenic signaling, induces cell cycle arrest, and enhances apoptosis, particularly in cancer stem cells and therapy-resistant models. It also examines edaravone's dual role in combination therapies, where it may improve the cytotoxicity of chemotherapeutic and radiotherapeutic agents while simultaneously protecting normal tissues from treatment-induced toxicities. By linking mechanistic insights with therapeutic outcomes, this review highlights the rationale for repurposing edaravone as a potential adjuvant in cancer therapy. Although clinical data are currently limited, preliminary findings are encouraging and warrant further investigation into edaravone's potential use in cancer treatment regimens.}, }
@article {pmid40866928, year = {2025}, author = {Tsang, VSK and Malaspina, A and Henson, SM}, title = {The metabolic intersection between immunosenescence and neuroinflammation in amyotrophic lateral sclerosis.}, journal = {Journal of inflammation (London, England)}, volume = {22}, number = {1}, pages = {36}, pmid = {40866928}, issn = {1476-9255}, support = {BBX009610/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive loss of motor neurons. Although it is traditionally viewed as a neuron-centric disease, neurodegeneration is increasingly linked to immunosenescence and age-related immune dysfunction, but the mechanisms connecting immune ageing to neurodegeneration remain poorly understood. In this review, we explore how metabolic reprogramming, especially the loss of metabolic plasticity in senescent immune cells, drives neuroinflammation in ALS. Senescent immune cells, including microglia and T cells, exhibit mitochondrial dysfunction, redox imbalance, impaired autophagy, and altered nutrient-sensing pathways that impair their homeostatic and reparative capacities. These cells adopt a metabolically demanding pro-inflammatory phenotype, sustaining an inflammatory secretome while promoting glial activation and neuronal damage. Finally, we discuss how targeting immunometabolic pathways may offer new therapeutic opportunities to restore immune balance, mitigate neuroinflammation, and potentially slow ALS progression. Understanding the metabolic basis of immune ageing is essential for developing effective, age-tailored interventions for ALS.}, }
@article {pmid40863128, year = {2025}, author = {Pawłowska, M and Kruszka, J and Porzych, M and Garbarek, J and Nuszkiewicz, J}, title = {Ketogenic Metabolism in Neurodegenerative Diseases: Mechanisms of Action and Therapeutic Potential.}, journal = {Metabolites}, volume = {15}, number = {8}, pages = {}, pmid = {40863128}, issn = {2218-1989}, abstract = {Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, are characterized by progressive neuronal loss and share key pathological features such as oxidative stress, mitochondrial dysfunction, and chronic neuroinflammation. Recent research has highlighted the potential of ketogenic metabolism, particularly the use of ketone bodies like β-hydroxybutyrate, as a therapeutic approach targeting these shared mechanisms. This review provides a comprehensive synthesis of current knowledge on the neuroprotective effects of ketogenic interventions, including both dietary strategies and exogenous ketone supplementation. We discuss how ketone bodies improve mitochondrial function, reduce reactive oxygen species, modulate inflammatory pathways, and influence neurotransmission and synaptic plasticity. Additionally, we examine experimental and clinical evidence supporting the application of ketogenic therapies in neurodegenerative diseases, highlighting disease-specific findings, benefits, and limitations. While preclinical data are robust and suggest meaningful therapeutic potential, clinical studies remain limited and heterogeneous, with challenges related to adherence, safety, and patient selection. The review also addresses the translational relevance of ketogenic strategies, considering their feasibility, combination with other therapies, and the need for personalized approaches based on genetic and metabolic profiles. By critically evaluating existing data, this article aims to clarify the mechanisms through which ketogenic metabolism may exert neuroprotective effects and to outline future directions for research and clinical application in the context of neurodegenerative disorders.}, }
@article {pmid40859959, year = {2025}, author = {Mao, S and Qiao, R and Wang, Q and Shen, L and Li, D and Huo, X and Wang, J and Liu, K and Chen, W and Zhu, T and Zhang, B and Leng, S and Bai, Y}, title = {Activity and Heterogeneity of Astrocytes in Neurological Diseases: Molecular Mechanisms and Therapeutic Targets.}, journal = {MedComm}, volume = {6}, number = {9}, pages = {e70329}, pmid = {40859959}, issn = {2688-2663}, abstract = {Astrocytes, the most prevalent glial cells in the central nervous system (CNS), play crucial roles in maintaining CNS homeostasis and responding to various pathological stimuli. They play key roles in neural development, neurotransmission, neuroinflammation, metabolic support, and tissue repair. Recent advancements in single-cell sequencing have revealed the remarkable heterogeneity of astrocytes, with distinct subpopulations differentially contributing to disease progression in neurological disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, ischemic stroke, intracerebral hemorrhage, and multiple sclerosis. In addition, they play an important role in various behavioral neuropsychiatric disorders. This review highlights the dual roles of astrocytes in disease progression, driven by their diverse molecular profiles and functions. It outlines the key molecular mechanisms underlying astrocyte heterogeneity and their impact on neuroinflammation, neuronal support, and ionic balance regulation. Additionally, the review discusses potential therapeutic strategies targeting astrocytes to modulate these processes, aiming to improve treatment outcomes in neurological diseases. By elucidating the specific roles of astrocyte subsets in disease, this review seeks to advance the development of precision medicine for astrocyte-related neurological disorders.}, }
@article {pmid40856865, year = {2025}, author = {Shandilya, C and Mani, S}, title = {Rho kinase isoforms in neurodegeneration: from cellular functions to therapeutic targets.}, journal = {Molecular biology reports}, volume = {52}, number = {1}, pages = {846}, pmid = {40856865}, issn = {1573-4978}, mesh = {Humans ; *rho-Associated Kinases/metabolism/antagonists &amp; inhibitors/genetics ; *Neurodegenerative Diseases/metabolism/drug therapy ; Mitochondria/metabolism ; Animals ; Mitophagy ; Neurons/metabolism ; Protein Isoforms/metabolism ; Signal Transduction ; Reactive Oxygen Species/metabolism ; Mitochondrial Dynamics ; Isoenzymes/metabolism ; Oxidative Stress ; }, abstract = {Mitochondria serve as an important cellular organelle for maintaining neurotransmission and synaptic plasticity in neuronal cells by playing a key role in ATP generation, maintaining calcium homeostasis, and regulating the levels of reactive oxygen species (ROS), etc. The regulation of the dynamic nature of mitochondria, including their fission, fusion, and removal of damaged mitochondria by mitophagy, is also very important for neuronal health. Abnormalities in mitochondrial processes, including but not limited to fission, fusion, and mitophagy, are known to be associated with numerous neurodegenerative diseases (NDDs), such as Parkinson's disease (PD), Alzheimer's disease (AD), Amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD). In the recent past, the Rho kinase (ROCK) isoforms, particularly ROCK1 and ROCK2, have gained a lot of attention in NDDs, mainly for their role in regulating the dynamics of the mitochondria, mitophagy, and other cell signalling pathways. By adding phosphate groups to Drp1, ROCK1 is crucial in supporting excessive mitochondrial fission, causing the death of neuronal cells. On the other hand, ROCK2 inhibits Parkin-dependent mitophagy by inhibiting the PTEN protein, the activator of Parkin-dependent mitophagy. This impaired mitochondrial quality control via reduced mitophagic flux leads to oxidative stress and neuronal degeneration, the central pathological feature of NDDs. The inhibition of ROCK isoforms has shown great promise in neuroprotective effects, controlling the dynamics of mitochondria in neuronal cells, lowering inflammation, and improving motor and cognitive functions in preclinical models of different NDDs, indicating ROCK isoforms as an attractive therapeutic target in different NDDs. This review aims to highlight the therapeutic significance of targeting ROCK isoforms in different NDDs.}, }
@article {pmid40849485, year = {2025}, author = {Helal, MM and AbouShawareb, H and Abbas, OH and Haddad, R and Zain, Y and Osman, ASA and Hassan, AK}, title = {GLP-1 receptor agonists in Parkinson's disease: an updated comprehensive systematic review with meta-analysis.}, journal = {Diabetology &amp; metabolic syndrome}, volume = {17}, number = {1}, pages = {352}, pmid = {40849485}, issn = {1758-5996}, abstract = {Previous studies have demonstrated an increased risk of developing Parkinson's disease (PD) in patients with type 2 diabetes mellitus (T2DM), as well as more severe and rapid motor and non-motor deterioration in diabetic PD patients compared to their non-diabetic counterparts. Additional research has suggested that diabetic subjects treated with glucagon-like peptide-1 (GLP-1) receptor agonists exhibit a reduced incidence of PD compared to those receiving other anti-diabetic medications. GLP-1 receptor agonists are FDA-approved therapies for T2DM, and recent studies have explored their potential as repurposed treatments for neurodegenerative diseases, including PD, AD, and ALS, as well as cerebrovascular disorders. This systematic review aims to assess the available literature on the efficacy and safety profiles of GLP-1 receptor agonists in PD management. A comprehensive search of PubMed, Scopus, CENTRAL, Web of Science, Embase, and ClinicalTrials.gov was conducted to identify relevant studies. The primary outcomes of this review include motor impairment in PD, as assessed by MDS-UPDRS Part III, as well as motor complications (Part IV) and motor experiences of daily living (Part II), and the incidence of gastrointestinal and systemic side effects. Meta-analysis showed that GLP-1 receptor agonists significantly improved motor function, as reflected by MDS-UPDRS Part III scores in the ON state (mean difference = - 2.88; p = 0.01; I[2] = 30%), although they were associated with a higher incidence of adverse events across all safety outcomes. Findings and conclusions of this review will contribute to a clearer understanding of the therapeutic potential of GLP-1 receptor agonists in PD, guiding future clinical research and treatment strategies.}, }
@article {pmid40848858, year = {2025}, author = {Chen, X and Ma, Y and Liu, H and Wang, Y}, title = {Multifunctional regulation and treatment of ubiquitin specific protease 10.}, journal = {Biochemical pharmacology}, volume = {242}, number = {Pt 1}, pages = {117251}, doi = {10.1016/j.bcp.2025.117251}, pmid = {40848858}, issn = {1873-2968}, abstract = {USP10 is a critical deubiquitinating enzyme within the ubiquitin-specific protease family, playing multifaceted roles in cellular physiology and disease pathogenesis. Structurally composed of a G3BP1-interacting motif, a N-terminal domain (mediating most protein interactions), and a catalytic USP domain (residues 415-795, catalytic triad C424-H736-D751), USP10 regulates diverse cellular pathways by stabilizing key proteins through deubiquitination. It exhibits context-dependent functional duality, particularly in cancer: USP10 promotes tumorigenesis in various cancers (e.g., glioblastoma, esophageal, pancreatic, breast cancers) by stabilizing oncoproteins like CCND1, YAP1, HDAC7, and RUNX1, enhancing proliferation, metastasis, and immune evasion. Conversely, it suppresses tumors (e.g., NSCLC, CRC, thyroid cancer) by stabilizing tumor suppressors like p53, PTEN, and Axin1, inhibiting pathways such as Wnt/β-catenin. Beyond oncology, USP10 contributes to neurodegenerative diseases (neuroprotective in PD/ALS, neurotoxic in AD via Tau stabilization), viral immunity (inhibits SARS-CoV-2 infection), inflammatory responses, male reproduction, and metabolic/cardiovascular disorders. Its regulatory mechanisms include phosphorylation (e.g., by AMPK, AKT, ATM) controlling subcellular localization and activity, and ubiquitination via USP13. USP10's therapeutic significance drives inhibitor development (Spautin-1, D1, Wu-5, P22077, Parthenolide), though cross-reactivity within the USP family due to conserved catalytic domains remains a challenge. Novel strategies like PROTACs and engineered ubiquitin variants (UbVs) offer promise for future selective targeting of USP10 dysregulation in diverse diseases. A comprehensive understanding of its structure and context-specific functions is essential for exploiting its full therapeutic potential.}, }
@article {pmid40840854, year = {2025}, author = {Fernàndez-Bernal, A and Mota, N and Pamplona, R and Area-Gómez, E and Portero-Otin, M}, title = {Mission cholesterol: Uncovering its hidden role in ALS neurodegeneration.}, journal = {Biochimica et biophysica acta. Molecular basis of disease}, volume = {1871}, number = {8}, pages = {168021}, doi = {10.1016/j.bbadis.2025.168021}, pmid = {40840854}, issn = {1879-260X}, abstract = {Cholesterol is a central determinant of membrane architecture, signaling, and cellular homeostasis in the central nervous system (CNS). While historically viewed as a structural component, emerging evidence highlights its dynamic regulatory role in neuronal function, particularly through its compartmentalized synthesis, trafficking, and turnover. This review examines the complex landscape of cholesterol metabolism in the CNS, emphasizing the cooperative roles of astrocytes and neurons, the partitioning of biosynthetic pathways, and the barriers that distinguish brain cholesterol pools from peripheral sources. We focus on mitochondria-associated endoplasmic reticulum membranes (MAMs) as key regulatory platforms for cholesterol sensing, esterification, and signaling, underscoring their emerging role in neurodegenerative diseases. Disruptions in MAM integrity, lipid raft composition, and transcriptional regulation of cholesterol-handling genes have been linked to pathologies such as amyotrophic lateral sclerosis (ALS), particularly through the actions of TDP-43. By consolidating recent findings from lipidomics, cell biology, and disease models, we propose that cholesterol dyshomeostasis constitutes a shared mechanistic axis across diverse neurodegenerative conditions. Understanding this axis offers novel insights into the metabolic vulnerability of neurons and highlights cholesterol metabolism as a promising target for therapeutic intervention.}, }
@article {pmid40839108, year = {2025}, author = {Mukherjea, N and Khandelwal, A and Saluja, R and Kalra, N}, title = {The Role of the human microbiome in neurodegenerative diseases: A Perspective.}, journal = {Current genetics}, volume = {71}, number = {1}, pages = {17}, pmid = {40839108}, issn = {1432-0983}, mesh = {Humans ; *Neurodegenerative Diseases/microbiology ; *Microbiota ; Parkinson Disease/microbiology ; *Gastrointestinal Microbiome ; Alzheimer Disease/microbiology ; Inflammasomes ; Inflammation/microbiology ; }, abstract = {Advances in diagnostics, therapeutics, and large-scale clinical studies have significantly expanded our understanding how human health is shaped by the microorganisms that colonize the body since birth. This article explores the rapidly evolving field of human microbiome research, focusing upon how microbial communities influence neurological health and contribute to the development of neurodegenerative diseases (NDs). Multiple factors, including age, lifestyle, and immunological memory, are recognized as major determinants of an individual's microbiome composition, which in turn can influence the onset and the progression of disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. These conditions have been linked to mechanisms including the aggregation of pathogenic proteins (e.g., amyloid-β and α-synuclein), inflammation driven by activation of the Toll-like receptor (TLR) signaling pathway, the NLRP3 inflammasome, as well as the modulatory effect of microbial metabolites such as short-chain fatty acids (SCFAs) and lipopolysaccharides (LPS). The article also highlights ongoing research and emerging strategies aimed at leveraging the human microbiome for better diagnosis, and management of NDs.}, }
@article {pmid40838713, year = {2025}, author = {Noor, SM and Reddy, DH and Srikanth, Y and Viswanadh, MK and Dumala, N and Chakravarthy, G and Nalluri, BN and Naryanarao, A and Duguluri, S and Yadagiri, G and Prasanna, VS and Sundaram, S and Gujjari, L and Ramakrishna, K}, title = {Morin hydrate: a comprehensive review on therapeutic potential in treating neurological diseases.}, journal = {Nutritional neuroscience}, volume = {}, number = {}, pages = {1-25}, doi = {10.1080/1028415X.2025.2544605}, pmid = {40838713}, issn = {1476-8305}, abstract = {Background: Morin hydrate is a polyphenolic flavonoid present in various vegetables, fruits, nuts, and sea products. It has been reported to offer multiple protective effects against a range of diseases, including cancer, cardiovascular, liver, neurological, metabolic, and renal disorders.Objective: This review highlights the molecular mechanisms and therapeutic potential of Morin in neurological diseases, including Parkinson's disease, Alzheimer's disease, traumatic brain injury, neuropathic pain, stroke, Huntington's disease, multiple sclerosis, amyotrophic lateral sclerosis, depression, anxiety, sleep, encephalopathy, schizophrenia, and psychosis, etc.Methods: The research and review articles were collected from the Pubmed, Scopus, Web of Science, and Google Scholar databases using 'Morin' and the above-mentioned neurological diseases as keywords.Results: The neuroprotective effects of Morin are primarily attributed to its ability to mitigate oxidative stress, inflammation, excitotoxicity, calcium dysregulation, mitochondrial dysfunction, neurotransmitter alterations, protein modifications, and enzymatic inhibition.Conclusion: Despite its promising pharmacological profile, the clinical adaptation of Morin for combating neurological diseases requires further validation through comprehensive preclinical and clinical investigations.}, }
@article {pmid40837865, year = {2025}, author = {Khan, H and Riaz, H and Ahmed, A and Kiyani, MM and Jawad, SM and Ud Din Shah, SS and Abualait, T and Al-Hussain, F and Li, HT and Bashir, S}, title = {CRISPR/Cas9 a genomic engineering technology for treatment in ALS mouse models.}, journal = {Regenerative therapy}, volume = {30}, number = {}, pages = {575-583}, pmid = {40837865}, issn = {2352-3204}, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a complex neurodegenerative disorder characterized by the death of motor neurons in the spinal cord and brain regions, leading to a reduced survival rate in patients. Nearly 20 gene mutations are associated with ALS, with SOD1, FUS, TARDBP, and C9orf72 mutations being more common. Ninety percent of ALS cases are related to sporadic ALS, while the remaining 10 % are associated with familial ALS. CRISPR/Cas9, a genome engineering technology known as clustered regularly interspaced short palindromic repeats/CRISPR-associated system 9, has the potential for gene editing and for studying the underlying mechanisms of ALS in mouse models. This technique enables neuroscientists to reverse mutations found in ALS mouse models, providing new hope for understanding the complexities of ALS. Additionally, this tool can create mutations to probe the functional changes of genetic diseases. Using CRISPR/Cas9 with an in vivo delivery method involving adeno-associated vectors, it is possible to silence mutations in the SOD1-linked ALS mouse model. Some limitations related to CRISPR/Cas9 have been discussed in previous studies and need to be addressed before clinical trials can proceed. In this review-based study, we summarise the latest research on CRISPR/Cas9 genome editing for ALS in mouse models and discuss its limitations and future prospects as well.}, }
@article {pmid40835551, year = {2025}, author = {Rajsic, S and Treml, B and Breitkopf, R and Lederer, W}, title = {Ethical Considerations for Patients Requiring Extracorporeal Cardiopulmonary Resuscitation.}, journal = {Journal of cardiothoracic and vascular anesthesia}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.jvca.2025.07.032}, pmid = {40835551}, issn = {1532-8422}, abstract = {Immediate recognition of cardiac arrest and the initiation of cardiopulmonary resuscitation (CPR) can significantly improve survival chances. The use of extracorporeal membrane oxygenation during CPR (eCPR) could further enhance survival rates. Current evidence supports the implementation of eCPR as a part of the Advanced Life Support protocol, which may positively affect survival and long-term neurological outcomes and provide additional time for diagnosing and treating the underlying cause of cardiac arrest. Based on the patient's potential for recovery and neurological outcome, multidisciplinary teams can pursue weaning of the patient from mechanical support or withdrawal of care in the case of an unfavorable outcome. These decisions should align with the patient's values, prognosis, and ethical guidelines. A healthcare system that actively promotes eCPR as a standardized part of every Advanced Life Support protocol may face challenges, such as an increased number of patients requiring constant care in long-term care facilities. This could potentially lead to a reduced quality of life and create burdens on patients, families, the healthcare system, and society. Furthermore, in cases of potential organ donation, the principles of beneficence and autonomy may place healthcare providers in significant ethical dilemmas. Given the potential for eCPR to become a standard of care for eligible patients, this work focuses on the ethical and social implications, as well as the impact on the healthcare system.}, }
@article {pmid40831763, year = {2025}, author = {B S, P and Talwar, P}, title = {Influence of palmitoylation in axonal transport mechanisms in neurodegenerative diseases.}, journal = {Frontiers in cellular neuroscience}, volume = {19}, number = {}, pages = {1613379}, pmid = {40831763}, issn = {1662-5102}, abstract = {Progressive functional loss and death of neurons are characteristics of neurodegenerative diseases such as Alzheimer's disease (AD), Amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). These diseases are often linked with disruptions in axonal transport and synaptic functions. Accumulation of misfolded proteins is observed as a commonly shared pathology for these diseases, where aberrant accumulation of amyloid beta (Aβ), tau, α-synuclein (α-syn) and TAR DNA-binding protein 43 (TDP-43), are found in AD, PD and ALS, respectively. These accumulations are observed to be involved in disrupting axonal transport and compromising neuronal survival. Axonal transport is an essential process where proper functioning of the transport mechanism is important for maintaining neuronal hemostasis by transporting of proteins, organelles and neurotransmitter complexes. This review explores the role of palmitoylation in regulating neuronal axonal transport and their impact on other neuronal functions along with neurodegeneration mechanisms. Palmitoylation is a reversible lipid modification, which is widely studied second to phosphorylation. Enzymes like palmitoyl acyltransferases and acyl-protein thioesterases are responsible for attachment and detachment of palmitic acid causing palmitoylation and depalmitoylation of neuronal proteins. In axonal transport, palmitoylation influences the localization and functioning of the proteins, which connectively plays a role in synaptic stability by interacting with synaptic scaffolding proteins and neurotransmission receptors.}, }
@article {pmid40829685, year = {2025}, author = {Wang, Y and Zhou, Y and Tian, H and Li, Q and Chen, Y and Wang, L and Yin, Z and Zhou, J and Liang, F}, title = {NF-κB signalling pathway in neurodegenerative diseases: Acupuncture as a potential therapeutic approach.}, journal = {Brain research}, volume = {1865}, number = {}, pages = {149893}, doi = {10.1016/j.brainres.2025.149893}, pmid = {40829685}, issn = {1872-6240}, abstract = {The NF-κB signaling pathway plays a crucial role in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, particularly through its role in the regulation neuroinflammation, oxidative stress, protein misfolding, and apoptosis. Emerging evidence suggests that acupuncture modulates the NF-κB pathway, thus offering therapeutic potential by mitigating neuroinflammation, reducing oxidative stress, and protecting mitochondrial function. Specifically, acupuncture inhibits NF-κB activation, downregulates pro-inflammatory mediators like TNF-α and IL-6, and mitigates neurotoxicity and apoptosis. These effects are substantiated in animal models of Alzheimer's and Parkinson's diseases, with preliminary evidence in amyotrophic lateral sclerosis models. However, current studies largely rely on preclinical models with limited acupoint selection, short observation periods, and a lack of standardized protocols, posing challenges for translation to clinical settings. Future research should prioritize well-designed clinical trials, expand acupoint combinations, and explore synergistic effects with conventional therapies, aiming to maximize acupuncture's therapeutic efficacy in neurodegenerative diseases.}, }
@article {pmid40828270, year = {2025}, author = {Harerimana, A and Pillay, JD and Mchunu, G}, title = {The pitfalls of "toughing it out": mapping stoic attitudes in cancer patients. A scoping review.}, journal = {Medicine, health care, and philosophy}, volume = {}, number = {}, pages = {}, pmid = {40828270}, issn = {1572-8633}, abstract = {Stoicism (with an upper-case 'S') as a life philosophy promotes resilience, self-control and rational acceptance of adversity. In contrast, lower-case stoicism, including pseudo-stoicism or stoic attitudes-characterised by emotional suppression and the silent endurance of pain or hardship-has been linked to adverse health outcomes among cancer patients. Thus, further research is needed to understand the drawbacks of stoic attitudes in cancer patients. This scoping review aims to map stoic attitudes in cancer patients, particularly in relation to potential health consequences. The review adhered to Levac et al.'s framework for scoping reviews. A systematic search was conducted from five electronic databases: CINAHL, Emcare, Medline Ovid, Scopus, and Web of Science. Manual searches were conducted using Google and Google Scholar. A total of 955 records were identified, 526 were screened (title and abstracts), and 450 were excluded. After reviewing 76 full-text articles, 12 studies satisfied the inclusion criteria for data extraction and thematic analysis, consisting of five qualitative and seven quantitative studies. A time frame of 10 years was considered, ranging from 2014 to 2024. This scoping review revealed that pseudo-stoic attitudes in cancer patients often lead to emotional suppression, reduced social support, delayed help-seeking and poor management of symptoms such as pain. These attitudes were linked to poorer psychological outcomes and underreporting of symptoms, especially among older males and rural cancer patients. Studies found that stoic traits were sometimes associated with persistence and treatment adherence among cancer patients. Pseudo-stoicism hinders emotional expression and delays help-seeking, leading to adverse health outcomes; however, stoic attitudes are also associated with adaptive qualities, such as psychological endurance and a commitment to care. Therefore, it is vital to promote balanced coping strategies that honour resilience while encouraging open emotional engagement among cancer patients.}, }
@article {pmid40822241, year = {2025}, author = {Tan, X and Gao, N}, title = {The emerging role of cellular senescence in amyotrophic lateral sclerosis.}, journal = {Frontiers in neuroscience}, volume = {19}, number = {}, pages = {1599492}, pmid = {40822241}, issn = {1662-4548}, abstract = {Cellular senescence is a state of permanent cell cycle arrest and is considered a key contributor to aging and age-related diseases, including amyotrophic lateral sclerosis (ALS). The physiological processes of aging lead to a variety of molecular and cellular phenotypes, and evidence of overlap between ALS and aging-related biomarkers suggests that cell type-specific senescence may be a critical factor in ALS. Senescent microglial cells, astrocytes, and neurons have been detected in ALS patients and animal models. However, while accumulating evidence suggests a potential link between cellular senescence and ALS, this connection remains not yet conclusively established. Importantly, how senescent cells may contribute to the neuropathophysiology of ALS remains largely unknown. Additionally, the growing popularity of anti-aging therapies has highlighted the potential of senescent cell clearance as a promising strategy for treating age-related diseases, including ALS. This review provides an overview of cellular senescence, discusses recent advances in understanding how senescence in different cell types influences ALS pathogenesis, and explores the potential role of anti-senescence therapies in ALS treatment.}, }
@article {pmid40821767, year = {2025}, author = {Zhao, S and Fu, D and Lin, Y and Sun, X and Wang, X and Wu, X and Zhang, X}, title = {The role of the microbiome on immune homeostasis of the host nervous system.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1609960}, pmid = {40821767}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Homeostasis/immunology ; Animals ; *Central Nervous System/immunology ; Nervous System Diseases/immunology/microbiology ; }, abstract = {The gut microbiota is often termed the "second genome" of the human body. It has been shown to be one of the most significant environmental factors (non-genetic) influencing the onset, progression, and prognosis of various neurological and psychiatric disorders through its interactions with the host immune, nervous, and endocrine systems. Changes in the function and composition of the gut microbiota are strongly associated with amyotrophic lateral sclerosis, autism spectrum disorder, depression, Parkinson's disease, and Alzheimer's disease. This review summarizes the research regarding the associations and regulatory mechanisms between the gut microbiota and the central nervous system in order to explore the role of the gut microbiota in maintaining neural homeostasis.}, }
@article {pmid40821656, year = {2025}, author = {Sanghai, N and Tranmer, GK}, title = {Use of Proteomics to Explore Biomarkers of Amyotrophic Lateral Sclerosis (ALS): Proof of Principle from Humanized SOD1 Mouse to Human ALS.}, journal = {ACS pharmacology &amp; translational science}, volume = {8}, number = {8}, pages = {2415-2430}, pmid = {40821656}, issn = {2575-9108}, abstract = {Amyotrophic lateral sclerosis (ALS) is a rare motor neurodegenerative disease affecting multiple cellular proteins during the progression of the disease. ALS was first discovered by Charcot in 1869, and since then, scientists have been unable to identify a singular cause of the disease. Further, there are no effective treatments available to cure ALS. The benchmark discovery of humanized preclinical SOD1 mouse models, which recapitulates the clinical and pathological phenotypes of human ALS, gives hope to medicinal chemists and neuroscientists around the globe that a suitable drug-like molecule can be discovered and translated into human beings as a means to slow down the progression of the disease. However, little success has been achieved until now in terms of finding an effective treatment for heterogenic and incurable ALS. One area marked for improvement is the use of semiquantitative, antibody-based targeted Western blotting (WB) experiments, which lack the power to analyze multiple cellular events within the entire dysregulated proteomic system. With the inconsistency of WB experiments, unexpected cellular pathways go undiscovered, and hence, loss of translation with no target engagement is seen from preclinical to human clinical ALS. Recent advancements in discovery-based quantitative proteomics have many advantages over WB. These innovative techniques could help solve the inherent problem in WB and their inability to discover multiple altered proteins with the added capability of longitudinal analysis in preclinical SOD1 models, further validating the findings in human ALS. Herein, we applied a holistic approach to summarize various reports on the use of proteomics in ALS from the published literature, and importantly, we found that using a discovery-based proteomics approach in SOD1 preclinical ALS models has revealed a more diverse and global picture of pathological proteins that affect multiple pathways during different stages of disease progression. Furthermore, we found that the proteomic profiling of the humanized SOD1 mouse model provided a proof of principle for translating the diverse pathological biomarker proteins identified in clinical human ALS cases. Moreover, we believe that advancements in the proteomics approach toward ALS biomarkers could bridge the gap between preclinical and clinical studies, enabling scientists worldwide to discover novel biomarkers and treatments that modify the progression of ALS.}, }
@article {pmid40819701, year = {2025}, author = {Haslam, AX and Blandón, MDMT and Castro, ASR}, title = {Ocular manifestations in Dengue Fever: A Systematic Review and Meta-Analysis.}, journal = {American journal of ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajo.2025.08.021}, pmid = {40819701}, issn = {1879-1891}, abstract = {TOPIC: Ocular manifestations in dengue fever remain underrecognized despite reports of vision-threatening complications. This systematic review and meta-analysis aimed to determine the pooled prevalence of ocular manifestations in dengue patients, characterizing their spectrum, frequency, and clinical significance.<br><br>CLINICAL RELEVANCE: Dengue fever affects millions globally, predominantly in tropical regions. While systemic complications are well documented, ophthalmic involvement remains poorly defined, with variable prevalence estimates and unclear risk factors. Early recognition is crucial for timely intervention, particularly in endemic areas where clinical suspicion is low.<br><br>METHODS: A comprehensive search was conducted in PubMed, CINAHL, and LILACS. Eligible studies included observational studies reporting the prevalence of ocular manifestations in dengue patients. Risk of bias was assessed using Hoy et al.'s tool for prevalence studies. Pooled prevalence estimates were calculated using a random-effects model, and heterogeneity was assessed using I[2] statistics.<br><br>RESULTS: A total of 32 studies, including 11,426 patients, were included. The pooled prevalence of ocular manifestations, calculated from 16 studies, was 0.32 (95% CI: 0.22-0.45, I[2]&#x202f;=&#x202f;91.8%). Retro-ocular pain had a pooled prevalence of 0.20 (95% CI: 0.10-0.37, I[2]&#x202f;=&#x202f;99.6%), while blurred vision was reported in 0.11 (95% CI: 0.05-0.23, I[2]&#x202f;=&#x202f;92.8%). Among structural manifestations, subconjunctival hemorrhage had a prevalence of 0.18 (95% CI: 0.10-0.30, I[2]&#x202f;=&#x202f;94.1%), retinal hemorrhage 0.08 (95% CI: 0.05-0.12, I[2]&#x202f;=&#x202f;77.8%), maculopathy 0.04 (95% CI: 0.02-0.08, I[2]&#x202f;=&#x202f;91.6%), and uveitis 0.05 (95% CI: 0.01-0.24, I[2]&#x202f;=&#x202f;97.4%). Significant heterogeneity was observed across studies, likely due to differences in diagnostic criteria, study populations, and disease severity.<br><br>CONCLUSION: This study highlights a substantial prevalence of ocular manifestations in dengue patients, emphasizing the need for increased clinical awareness, particularly in endemic regions. Given the heterogeneity in reported prevalence, future research should focus on prospective, standardized ophthalmologic assessments to improve early diagnosis and management.}, }
@article {pmid40817956, year = {2025}, author = {Mannan, A and Sharma, A and Singh, TG}, title = {Boosting Brain Clean-Up: Can Targeting UPS Genes Offer Neuroprotection?.}, journal = {Molecular neurobiology}, volume = {}, number = {}, pages = {}, pmid = {40817956}, issn = {1559-1182}, abstract = {The ubiquitin-proteasome system (UPS) plays a critical role in protein homeostasis within eukaryotic cells. This review article examines the UPS's role in neuronal morphology and neurodegeneration through systematic analysis of current research. In neurodegenerative disorders (NDDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), UPS dysfunction contributes significantly to pathogenesis through accumulation of ubiquitinated misfolded proteins, disruption of cellular proteostasis, impaired substrate ubiquitination, and proteasomal deterioration. The UPS maintains normal central nervous system (CNS) function by regulating protein degradation. When this system fails, cellular proteostasis becomes compromised, accelerating neurodegeneration. Recent research has identified potential interventions for UPS activation through genetic modification and synthetic compounds. This review assesses how specific UPS components could serve as pharmacological targets for treating NDDs. By modulating UPS-mediated genes and pathways, novel therapeutic strategies may emerge for conditions including AD, PD, HD), and ALS. Current evidence suggests the UPS represents a promising therapeutic target for addressing the fundamental protein homeostasis disruptions underlying these devastating neurological conditions. Targeting this system could potentially slow disease progression by restoring proper protein degradation mechanisms and preventing toxic protein accumulation characteristic of NDDs.}, }
@article {pmid40817431, year = {2025}, author = {SyBing, AB and Chen, H and Wang, DD}, title = {Re-Evaluation of Fixed Dosing Versus Body Size-Based Dosing Approaches for Large Molecule Therapeutics in Adults.}, journal = {Clinical pharmacology and therapeutics}, volume = {}, number = {}, pages = {}, doi = {10.1002/cpt.70015}, pmid = {40817431}, issn = {1532-6535}, abstract = {Wang et al.[1] (2009) and Zhang et al.[2] (2011) recommended a fixed dosing approach for large molecule therapeutics for first-in-human (FIH) trials, based on the finding that the majority of α values (body size effect on clearance) were < 0.5 across 12 monoclonal antibodies (mAbs) and 18 therapeutic proteins (TPs) and peptides, and fixed dosing provides advantages such as convenience, reduced medical errors, and cost-effectiveness. They also recommended that the approved dosing approach should be determined by α and the therapeutic window. This review aims to re-evaluate these recommendations using a larger dataset (N = 143) of diverse molecules. Results showed 62% (78/126) of non-ADC drugs were approved with fixed dosing, and 58% (28/48) of non-ADC drugs approved with body size-based dosing had an α < 0.7 where fixed dosing would be appropriate. Therefore, only the remaining 16% (20/126) of non-ADC drugs required body size-based dosing. In addition, the FIH dosing approach had significant implications on the approved dosing approach with 68% (90/133) of drugs using the same dosing approach in FIH and approval. Lastly, of non-ADC drugs evaluated, 56% (71/126) demonstrated a relationship between α and the approved dosing approach. When α did not explain the approved dosing approach, lack of clinically meaningful differences in exposure (49%, 27/55) was the most common justification. These findings confirm Wang et al.'s and Zhang et al.'s previous conclusions, continuing to support their recommendations. Based on these insights, a decision tree is proposed for selecting the appropriate dosing approach at each stage of drug development.}, }
@article {pmid40813983, year = {2025}, author = {Wang, YT and Li, Q and Liu, JC and Chen, C and Ding, HX and Zha, X and Zhang, K}, title = {Cystatin F-a key player in central nervous system disease.}, journal = {Journal of neuroinflammation}, volume = {22}, number = {1}, pages = {203}, pmid = {40813983}, issn = {1742-2094}, support = {81901005//National Natural Science Foundation of China/ ; 81571046//National Natural Science Foundation of China/ ; 2022-MS-203//Natural Science Foundation of Liaoning Province/ ; JYTMS20230122//Basic Scientific Research Project of the Education Department of Liaoning Province/ ; LJKZ0755//Educational Department of Liaoning province/ ; 2023JH2/20200116//Department of Science &amp; Technology of Liaoning province/ ; }, mesh = {Humans ; *Central Nervous System Diseases/metabolism ; Animals ; *Cystatins/metabolism ; Biomarkers, Tumor ; }, abstract = {Cystatin F is an endogenous cysteine protease inhibitor that belongs to the type II cystatin family. It has several unique characteristic structures that determine some of its specific functions. Cystatin F is expressed predominantly in peripheral immune cells and in the microglia of the central nervous system (CNS). Under physiological conditions, the expression of cystatin F in the CNS is minimal. However, emerging evidence suggests that it is significantly upregulated in several CNS diseases. Intriguingly, the role of cystatin F differs across disease contexts-serving a neuroprotective function while promoting pathological progression. Moreover, its function may shift across different pathological stages within the same disorder, reflecting a multifaceted pathophysiology. Cystatin F primarily acts by modulating neuroinflammation, clearing debris, and orchestrating immune responses via its selective expression in disease-associated microglia. As a vital player in CNS diseases, various intervention strategies targeting cystatin F have been proposed, including receptor-interacting protein kinase 1 pathway inhibition, miRNA targeting, mRNA stabilization, necroptosis inhibition, transcriptional regulation and upstream pathway modulation. Several approaches have yielded encouraging results in preclinical models, underscoring the therapeutic potential of modulating cystatin F activity. This review provides a comprehensive overview of the structural features, biological functions, and diverse roles of cystatin F in CNS diseases, including Alzheimer's disease, multiple sclerosis, Parkinson's disease, amyotrophic lateral sclerosis, stroke, Aicardi-Goutières syndrome, prion disease, and glioblastoma. Recent advances in therapeutic interventions focusing on cystatin F have been critically assessed, and key challenges related to clinical translation are outlined, offering new perspectives on therapeutic directions.}, }
@article {pmid40810164, year = {2025}, author = {Alo, B and Lamers, C}, title = {Crossing Barriers: Advancements in Macromolecular Therapeutics for Neurodegenerative Diseases and Strategies to Overcome the Blood-Brain Barrier.}, journal = {ACS pharmacology &amp; translational science}, volume = {8}, number = {8}, pages = {2353-2383}, pmid = {40810164}, issn = {2575-9108}, abstract = {Neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, present considerable challenges for our societies and health systems due to their progressive nature, the demographic shift toward older populations, and limited treatment options. Recent advances in macromolecular therapeutics, including antibodies, peptides, and proteins, offer novel therapeutic modalities for a broad range of diseases. Their high potency and specificity hold promise for disease-modifying therapies to combat neurodegenerative diseases. However, the blood-brain barrier poses a significant challenge for the effective delivery of these large molecules to the central nervous system. This review discusses the physiological role of the blood-brain barrier and its influence on restricting the exposure of macromolecules in the brain. Furthermore, emerging strategies for enhancing blood-brain barrier permeability to macromolecules are highlighted. This review summarizes modifications designed to utilize receptor-mediated uptake, adsorptive-mediated transcytosis, carrier-mediated transport, and nanoparticle-based delivery systems to overcome the blood-brain barrier. Additionally, we emphasize the importance of testing macromolecular therapeutics for their blood-brain barrier permeability and review the methods for such in vitro and in vivo testing. Finally, we shed light on therapeutics in preclinical and clinical development for neurodegenerative diseases and their challenges.}, }
@article {pmid40807333, year = {2025}, author = {Godela, A and Rogacz, D and Pawłowska, B and Biczak, R}, title = {Natural Neuroinflammatory Modulators: Therapeutic Potential of Fungi-Derived Compounds in Selected Neurodegenerative Diseases.}, journal = {Molecules (Basel, Switzerland)}, volume = {30}, number = {15}, pages = {}, pmid = {40807333}, issn = {1420-3049}, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy ; *Fungi/chemistry ; *Biological Products/therapeutic use/pharmacology/chemistry ; Animals ; }, abstract = {Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis remain incurable. Current therapeutic strategies primarily focus on slowing disease progression, alleviating symptoms, and improving patients' quality of life, including the management of comorbid conditions. Over the past few decades, the incidence of diagnosed neurodegenerative disorders has risen significantly. As the number of affected individuals continues to grow, so does the urgent need for effective treatments that can halt or mitigate the progression of these diseases. Among the most promising therapeutic resources are bioactive compounds derived from fungi. The high quality of proteins, polysaccharides, unsaturated fatty acids, triterpenoids, sterols, and secondary metabolites found in fungi have attracted growing interest from researchers across multiple disciplines. One intensively studied direction involves the use of naturally occurring fungi-derived nutraceuticals in the treatment of various diseases, including neurodegenerative conditions. This article provides an overview of recent findings on fungal compounds-such as phenolic compounds, carbohydrates, peptides and proteins, and lipids-that may have potential applications in the treatment of neurodegenerative diseases and the alleviation of their symptoms.}, }
@article {pmid40806770, year = {2025}, author = {Sharbafshaaer, M and Pepe, R and Notariale, R and Canale, F and Tessitore, A and Tedeschi, G and Trojsi, F}, title = {Neuroaxonal Degeneration as a Converging Mechanism in Motor Neuron Diseases (MNDs): Molecular Insights into RNA Dysregulation and Emerging Therapeutic Targets.}, journal = {International journal of molecular sciences}, volume = {26}, number = {15}, pages = {}, pmid = {40806770}, issn = {1422-0067}, support = {PERMEALS PNRR-MAD-2022-12375731//Italian Ministry of Health/ ; }, mesh = {Humans ; *Motor Neuron Disease/genetics/metabolism/pathology/therapy ; Animals ; *RNA/genetics/metabolism ; *Axons/pathology/metabolism ; *Nerve Degeneration/genetics/pathology ; Molecular Targeted Therapy ; }, abstract = {Motor Neuron Diseases (MNDs) such as Amyotrophic Lateral Sclerosis (ALS), Primary Lateral Sclerosis (PLS), Hereditary Spastic Paraplegia (HSP), Spinal Muscular Atrophy with Respiratory Distress Type 1 (SMARD1), Multisystem Proteinopathy (MSP), Spinal and Bulbar Muscular Atrophy (SBMA), and ALS associated to Frontotemporal Dementia (ALS-FTD), have traditionally been studied as distinct entities, each one with unique genetic and clinical characteristics. However, emerging research reveals that these seemingly disparate conditions converge on shared molecular mechanisms that drive progressive neuroaxonal degeneration. This narrative review addresses a critical gap in the field by synthesizing the most recent findings into a comprehensive, cross-disease mechanisms framework. By integrating insights into RNA dysregulation, protein misfolding, mitochondrial dysfunction, DNA damage, kinase signaling, axonal transport failure, and immune activation, we highlight how these converging pathways create a common pathogenic landscape across MNDs. Importantly, this perspective not only reframes MNDs as interconnected neurodegenerative models but also identifies shared therapeutic targets and emerging strategies, including antisense oligonucleotides, autophagy modulators, kinase inhibitors, and immunotherapies that transcend individual disease boundaries. The diagnostic and prognostic potential of Neurofilament Light Chain (NfL) biomarkers is also emphasized. By shifting focus from gene-specific to mechanism-based approaches, this paper offers a much-needed roadmap for advancing both research and clinical management in MNDs, paving the way for cross-disease therapeutic innovations.}, }
@article {pmid40806624, year = {2025}, author = {Șerban, M and Toader, C and Covache-Busuioc, RA}, title = {The Redox Revolution in Brain Medicine: Targeting Oxidative Stress with AI, Multi-Omics and Mitochondrial Therapies for the Precision Eradication of Neurodegeneration.}, journal = {International journal of molecular sciences}, volume = {26}, number = {15}, pages = {}, pmid = {40806624}, issn = {1422-0067}, mesh = {Humans ; *Oxidative Stress/drug effects ; *Mitochondria/metabolism/drug effects ; *Neurodegenerative Diseases/metabolism/therapy/drug therapy ; *Artificial Intelligence ; Oxidation-Reduction ; Antioxidants/therapeutic use/pharmacology ; Biomarkers/metabolism ; *Precision Medicine/methods ; Animals ; Reactive Oxygen Species/metabolism ; Brain/metabolism ; Multiomics ; }, abstract = {Oxidative stress is a defining and pervasive driver of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). As a molecular accelerant, reactive oxygen species (ROS) and reactive nitrogen species (RNS) compromise mitochondrial function, amplify lipid peroxidation, induce protein misfolding, and promote chronic neuroinflammation, creating a positive feedback loop of neuronal damage and cognitive decline. Despite its centrality in promoting disease progression, attempts to neutralize oxidative stress with monotherapeutic antioxidants have largely failed owing to the multifactorial redox imbalance affecting each patient and their corresponding variation. We are now at the threshold of precision redox medicine, driven by advances in syndromic multi-omics integration, Artificial Intelligence biomarker identification, and the precision of patient-specific therapeutic interventions. This paper will aim to reveal a mechanistically deep assessment of oxidative stress and its contribution to diseases of neurodegeneration, with an emphasis on oxidatively modified proteins (e.g., carbonylated tau, nitrated α-synuclein), lipid peroxidation biomarkers (F2-isoprostanes, 4-HNE), and DNA damage (8-OHdG) as significant biomarkers of disease progression. We will critically examine the majority of clinical trial studies investigating mitochondria-targeted antioxidants (e.g., MitoQ, SS-31), Nrf2 activators (e.g., dimethyl fumarate, sulforaphane), and epigenetic reprogramming schemes aiming to re-establish antioxidant defenses and repair redox damage at the molecular level of biology. Emerging solutions that involve nanoparticles (e.g., antioxidant delivery systems) and CRISPR (e.g., correction of mutations in SOD1 and GPx1) have the potential to transform therapeutic approaches to treatment for these diseases by cutting the time required to realize meaningful impacts and meaningful treatment. This paper will argue that with the connection between molecular biology and progress in clinical hyperbole, dynamic multi-targeted interventions will define the treatment of neurodegenerative diseases in the transition from disease amelioration to disease modification or perhaps reversal. With these innovations at our doorstep, the future offers remarkable possibilities in translating network-based biomarker discovery, AI-powered patient stratification, and adaptive combination therapies into individualized/long-lasting neuroprotection. The question is no longer if we will neutralize oxidative stress; it is how likely we will achieve success in the new frontier of neurodegenerative disease therapies.}, }
@article {pmid40806469, year = {2025}, author = {Wang, J and Shen, Y and Liao, P and Yang, B and Jiang, R}, title = {Roles of Ion Channels in Oligodendrocyte Precursor Cells: From Physiology to Pathology.}, journal = {International journal of molecular sciences}, volume = {26}, number = {15}, pages = {}, pmid = {40806469}, issn = {1422-0067}, support = {82401445//National Natural Science Foundation of China/ ; 82271249//National Natural Science Foundation of China/ ; 2024M752251//China Postdoctoral Science Foundation/ ; 2024NSFSC1636//Sichuan Science and Technology Program/ ; 2024HXBH013//Post doctor Research Fund of West China Hospital of Sichuan University/ ; ZYYC23002//1-3-5 Project for Disciplines of Excellence of West China Hospital of Sichuan University/ ; GZC20241141//Postdoctoral Fellowship Program of CPSF/ ; }, mesh = {Humans ; *Ion Channels/metabolism ; Animals ; *Oligodendrocyte Precursor Cells/metabolism/pathology ; Oligodendroglia/metabolism ; Cell Differentiation ; }, abstract = {Oligodendrocyte precursor cells (OPCs) are a distinct and dynamic glial population that retain proliferative and migratory capacities throughout life. While traditionally recognized for differentiating into oligodendrocytes (OLs) and generating myelin to support rapid nerve conduction, OPCs are now increasingly appreciated for their diverse and non-canonical roles in the central nervous system (CNS), including direct interactions with neurons. A notable feature of OPCs is their expression of diverse ion channels that orchestrate essential cellular functions, including proliferation, migration, and differentiation. Given their widespread distribution across the CNS, OPCs are increasingly recognized as active contributors to the development and progression of various neurological disorders. This review aims to present a detailed summary of the physiological and pathological functions of ion channels in OPCs, emphasizing their contribution to CNS dysfunction. We further highlight recent advances suggesting that ion channels in OPCs may serve as promising therapeutic targets across a broad range of disorders, including, but not limited to, multiple sclerosis (MS), spinal cord injury, amyotrophic lateral sclerosis (ALS), psychiatric disorders, Alzheimer's disease (AD), and neuropathic pain (NP). Finally, we discuss emerging therapeutic strategies targeting OPC ion channel function, offering insights into potential future directions in the treatment of CNS diseases.}, }
@article {pmid40806377, year = {2025}, author = {Ghosh, M and Bayat, AH and Pearse, DD}, title = {Small Extracellular Vesicles in Neurodegenerative Disease: Emerging Roles in Pathogenesis, Biomarker Discovery, and Therapy.}, journal = {International journal of molecular sciences}, volume = {26}, number = {15}, pages = {}, pmid = {40806377}, issn = {1422-0067}, mesh = {Humans ; *Extracellular Vesicles/metabolism ; *Biomarkers/metabolism ; *Neurodegenerative Diseases/therapy/metabolism/diagnosis/pathology/etiology ; Animals ; }, abstract = {Neurodegenerative diseases (NDDs) such as Alzheimer's, Parkinson's, ALS, and Huntington's pose a growing global challenge due to their complex pathobiology and aging demographics. Once considered as cellular debris, small extracellular vesicles (sEVs) are now recognized as active mediators of intercellular signaling in NDD progression. These nanovesicles (~30-150 nm), capable of crossing the blood-brain barrier, carry pathological proteins, RNAs, and lipids, facilitating the spread of toxic species like Aβ, tau, TDP-43, and α-synuclein. sEVs are increasingly recognized as valuable diagnostic tools, outperforming traditional CSF biomarkers in early detection and disease monitoring. On the therapeutic front, engineered sEVs offer a promising platform for CNS-targeted delivery of siRNAs, CRISPR tools, and neuroprotective agents, demonstrating efficacy in preclinical models. However, translational hurdles persist, including standardization, scalability, and regulatory alignment. Promising solutions are emerging, such as CRISPR-based barcoding, which enables high-resolution tracking of vesicle biodistribution; AI-guided analytics to enhance quality control; and coordinated regulatory efforts by the FDA, EMA, and ISEV aimed at unifying identity and purity criteria under forthcoming Minimal Information for Studies of Extracellular Vesicles (MISEV) guidelines. This review critically examines the mechanistic roles, diagnostic potential, and therapeutic applications of sEVs in NDDs, and outlines key strategies for clinical translation.}, }
@article {pmid40806339, year = {2025}, author = {Sonkodi, B}, title = {The Microbiota-Gut-Brain Axis in Light of the Brain Axes and Dysbiosis Where Piezo2 Is the Critical Initiating Player.}, journal = {International journal of molecular sciences}, volume = {26}, number = {15}, pages = {}, pmid = {40806339}, issn = {1422-0067}, mesh = {Humans ; *Ion Channels/metabolism ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis/metabolism/microbiology ; Animals ; *Brain/metabolism ; Alzheimer Disease/metabolism ; Hippocampus/metabolism ; Circadian Rhythm ; }, abstract = {The current opinion paper puts into perspective how altered microbiota transplanted from Alzheimer's patients initiates the impairment of the microbiota-gut-brain axis of a healthy recipient, leading to impaired cognition primarily arising from the hippocampus, dysfunctional adult hippocampal neurogenesis, dysregulated systemic inflammation, long-term spatial memory impairment, or chronic pain with hippocampal involvement. This altered microbiota may induce acquired Piezo2 channelopathy on enterochromaffin cells, which, in turn, impairs the ultrafast long-range proton-based oscillatory synchronization to the hippocampus. Therefore, an intact microbiota-gut-brain axis could be responsible for the synchronization of ultradian and circadian rhythms, with the assistance of rhythmic bacteria within microbiota, to circadian regulation, and hippocampal learning and memory formation. Hippocampal ultradian clock encoding is proposed to be through a Piezo2-initiated proton-signaled manner via VGLUT3 allosteric transmission at a distance. Furthermore, this paper posits that these unaccounted-for ultrafast proton-based long-range oscillatory synchronizing ultradian axes may exist not only within the brain but also between the periphery and the brain in an analogous way, like in the case of this depicted microbiota-gut-brain axis. Accordingly, the irreversible Piezo2 channelopathy-induced loss of the Piezo2-initiated ultradian prefrontal-hippocampal axis leads to Alzheimer's disease pathophysiology onset. Moreover, the same irreversible microdamage-induced loss of the Piezo2-initiated ultradian muscle spindle-hippocampal and cerebellum-hippocampal axes may lead to amyotrophic lateral sclerosis and Parkinson's disease initiation, respectively.}, }
@article {pmid40802439, year = {2025}, author = {Sousa, ES and Silva, LACD and Paiva, RM and Soares, KD and Azevedo, IC and Santos, VEP}, title = {Transitional Care for Patients with Amyotrophic Lateral Sclerosis to the Home: A Scoping Review.}, journal = {Revista brasileira de enfermagem}, volume = {78}, number = {3}, pages = {e20240297}, pmid = {40802439}, issn = {1984-0446}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/complications ; *Transitional Care/standards/trends ; *Home Care Services/trends/standards ; }, abstract = {OBJECTIVES: to map the care required for the transition of patients with Amyotrophic Lateral Sclerosis to the home environment.<br><br>METHODS: a scoping review was conducted following the JBI guidelines. The search for publications on the topic was carried out in databases such as PubMed and Web of Science between February and May 2023. Full-text studies that addressed the research objective were included. Letters to the editor, editorials, and opinion articles were excluded.<br><br>RESULTS: the final sample consisted of seven articles. Regarding care, the studies highlighted assistance with basic life needs, care planning, protocol development, the use of telehealth, and communication between healthcare services.<br><br>CONCLUSIONS: the care required for the transition of individuals with Amyotrophic Lateral Sclerosis to the home environment ranges from assistance with basic human needs to the coordination with other healthcare services. Altogether, these actions contribute to a safe and effective transitional process.}, }
@article {pmid40801981, year = {2025}, author = {Goleij, P and Amini, A and Sanaye, PM and Heidari, MM and Tabari, MAK and Aschner, M and Larsen, DS and Khan, H and Daglia, M}, title = {The IL-12 family cytokines in neurodegenerative diseases: dual roles in neurotoxicity and neuroprotection.}, journal = {Inflammopharmacology}, volume = {}, number = {}, pages = {}, pmid = {40801981}, issn = {1568-5608}, abstract = {Neurodegenerative diseases (NDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS) are characterized by progressive neuronal loss and chronic neuroinflammation. Increasing evidence highlights the interleukin-12 (IL-12) cytokine family-including IL-12, IL-23, IL-27, and IL-35-as central regulators of immune responses in the central nervous system (CNS). IL-12 and IL-23 predominantly promote pro-inflammatory pathways by driving Th1/Th17 activity, microglial activation, and neurotoxicity, whereas IL-27 and IL-35 exert anti-inflammatory and neuroprotective effects through IL-10 induction and expansion of regulatory immune subsets. This review synthesizes disease-specific expression patterns and experimental findings, underscoring the dual pathogenic and protective roles of these cytokines. Therapeutic strategies targeting IL-12 family signaling have shown promise in preclinical and clinical contexts. In AD, blockade of IL-12/IL-23 reduced amyloid burden and improved cognition, while agents such as tadalafil and bergapten enhanced IL-27-mediated neuroprotection via PI3K/Akt, Wnt/β-catenin, and cGMP/PKG pathways. In MS, approaches including p40 blockade (ustekinumab, ABT-874), interferon-β therapy, hematopoietic stem cell transplantation, and B-cell depletion (ocrelizumab) variably suppressed IL-12/IL-23 and augmented IL-27/IL-35, influencing relapse rates and progression. Natural compounds such as curcumin, berberine, and vitamin D further highlight metabolic and dietary opportunities for cytokine modulation. In PD, combinatorial regimens combining herbal formulations with anti-inflammatory agents dampened IL-12-driven macrophage activation and supported dopaminergic neuron survival. Taken together, IL-12 family cytokines emerge as both biomarkers and therapeutic targets in NDs. However, context-dependent activity, blood-brain barrier constraints, and incomplete understanding-particularly of IL-35-pose translational challenges warranting further investigation.}, }
@article {pmid40801430, year = {2025}, author = {Foster-Powell, A and Rostami-Hodjegan, A and Meno-Tetang, G and Mager, DE and Ogungbenro, K}, title = {Mathematical Modeling of Neuroinflammation in Neurodegenerative Diseases.}, journal = {CPT: pharmacometrics &amp; systems pharmacology}, volume = {}, number = {}, pages = {}, doi = {10.1002/psp4.70064}, pmid = {40801430}, issn = {2163-8306}, support = {BB/W509930/1//Biotechnology and Biosciences Research Council (BBSRC) Industrial CASE studentship in collaboration with AstraZeneca (AZ), UK/ ; }, abstract = {Age-related neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD) and Parkinson's disease (PD) are an increasing public health concern. Whereas the pathology of these diseases is complex, chronic central inflammation, or neuroinflammation, is commonly observed across many neurodegenerative diseases. Despite a huge wealth of resources and promising preclinical testing, effective disease-modifying therapies do not exist. This failure is owing to a combination of poor biological understanding of this response, unsuitable animal models, and poor scaling from pathway up to clinical levels. In order to address these challenges, systems-level mathematical models may be utilized. Here, we provide a background on neuroinflammation and summarize available mathematical models of this response. Models described by ordinary, partial, and delay differential equations, and Boolean logic are introduced and discussed. The results as discussed in this review suggest logic-based modeling as a formalism capable of managing the challenges associated with the modeling of CNS diseases.}, }
@article {pmid40799366, year = {2025}, author = {Gao, B and Wang, L and Gong, J and Zhu, Z and Liu, Q and Yuan, H and Wang, H}, title = {The interplay between physical exercise and autophagy signaling in brain health, neurodegenerative diseases and aging.}, journal = {Frontiers in aging neuroscience}, volume = {17}, number = {}, pages = {1579208}, pmid = {40799366}, issn = {1663-4365}, abstract = {Brain health is increasingly recognized as a critical component of overall wellbeing, particularly concerning neurodegenerative diseases, which are characterized by the progressive degeneration of the nervous system. Conditions such as Alzheimer's disease (AD) and Parkinson's disease, together with less common disorders, resembling Amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD), significantly impact cognitive and physical health, affecting over 50 million individuals worldwide. This review explores the multifaceted relationship between brain health and neurodegeneration, emphasizing the roles of biological, environmental, and lifestyle factors. Notably, physical activity has been identified as a potent intervention that enhances neuroplasticity and metabolic resilience while mitigating the effects of neurodegeneration. Research indicates that exercise activates autophagy, which is crucial for clearing neurotoxic aggregates like amyloid-beta and α-synuclein, thereby promoting neuronal health. Additionally, exercise stimulates the production of neurotrophic factors such as BDNF and GDNF, which are essential for neuronal survival and function. Despite the promising findings regarding exercise as a preventive and therapeutic strategy for neurodegenerative diseases, further investigation into the underlying mechanisms is necessary to optimize these interventions. This review aims to elucidate the complex interactions between exercise, autophagy, and brain health to provide insights into effective strategies for combating neurodegeneration.}, }
@article {pmid40794238, year = {2025}, author = {Jellinger, KA}, title = {Comorbid pathologies and their impact on progressive supranuclear palsy: current view.}, journal = {Journal of neural transmission (Vienna, Austria : 1996)}, volume = {}, number = {}, pages = {}, pmid = {40794238}, issn = {1435-1463}, support = {Society for the Promotion of Research in Experimental Neurology, Vienna, Austria//Society for the Promotion of Research in Experimental Neurology, Vienna, Austria/ ; }, abstract = {Progressive supranuclear palsy, a four-repeat tauopathy, is clinically characterized by early postural instability and falls, vertical supranuclear palsy, levodopa poorly-responsive parkinsonism, pseudobulbar palsy, and cognitive impairment. It is morphologically featured by accumulation of hyperphosphorylated tau protein in neurons and glia predominantly in the basal ganglia, brainstem tegmentum and frontal cortex, associated with degeneration of the extrapyramidal system and cortical atrophy. Isolated PSP neuropathology is uncommon, with nearly 70% showing co-neuropathologies including Alzheimer-type, Lewy body, TDP-43 pathologies, argyrophilic grains, and other tauopathies and neurodegenerative disorders (Parkinson disease, amyotrophic lateral sclerosis). The most common comorbid conditions are hypertension, cardiovascular and cerebrovascular diseases, diabetes mellitus, polyneuropathies, muscular and urological disorders. Due the increased prevalence of comorbidities and their eminent impact on the progress and outcome of the disease, clinical trials should account for them in their design and selection. However, currently little is known about co-pathologies in these patients. In view of the eminent burden of comorbidities and resulting therapeutic consequences, the frequency of the different co-pathologies in PSP and their clinical impact will be discussed. It should provide insight into their pathogenic backgrounds as a basis for adequate treatment procedures to improve the quality of life of patients with this fatal disease.}, }
@article {pmid40787733, year = {2025}, author = {Raaphorst, J and Gullick, NJ and Shokraneh, F and Brassington, R and Min, M and Ali, SS and Gordon, PA}, title = {Non-targeted immunosuppressive and immunomodulatory therapies for idiopathic inflammatory myopathies.}, journal = {The Cochrane database of systematic reviews}, volume = {8}, number = {8}, pages = {CD015855}, pmid = {40787733}, issn = {1469-493X}, mesh = {Humans ; *Myositis/drug therapy ; *Immunosuppressive Agents/therapeutic use/adverse effects ; Randomized Controlled Trials as Topic ; Dermatomyositis/drug therapy ; *Immunomodulating Agents/therapeutic use/adverse effects ; Bias ; Child ; Adult ; Polymyositis/drug therapy ; }, abstract = {BACKGROUND: Idiopathic inflammatory myopathies (IIM) are autoimmune-mediated inflammatory disorders of skeletal muscles with non-muscle involvement in some people, which carry significant morbidity and mortality. Treatment of IIM represents an area of unmet need. This review is an update of a review previously published in 2012, as new and promising data on non-targeted treatments have emerged.<br><br>OBJECTIVES: To assess the effects (benefits and harms) of non-targeted immunosuppressant and immunomodulatory treatments for IIM: dermatomyositis (DM, including juvenile dermatomyositis, jDM), immune-mediated necrotising myopathy (IMNM), anti-synthetase syndrome (ASS), overlap-myositis (OM) and polymyositis (PM). We also included cancer-related myositis and amyopathic dermatomyositis.<br><br>SEARCH METHODS: On 3 February 2023, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, Embase, MEDLINE, ClinicalTrials.gov and WHO ICTRP. We intended to check references and citations, and contact experts to identify additional studies, but lacked the resources.<br><br>SELECTION CRITERIA: We included all randomised controlled trials (RCTs) or quasi-RCTs involving participants (adults and children) with IIM according to defined criteria. We included non-targeted immunosuppressants and immunomodulatory treatments alone or in combination, compared with a placebo, no treatment or another non-targeted immunosuppressant or immunomodulatory treatment. Our two primary outcomes were improvement of function or disability and improvement of muscle strength compared with baseline. By preference, we used the Health Assessment Questionnaire Disability Index (HAQ-DI) for disability and the Manual Muscle Test-8 (MMT8) score (adults or children) for muscle strength. Other outcomes were achievement of definitions of improvement (DOI) (the International Myositis Assessment and Clinical Studies (IMACS) Group or the more recent total improvement scores (TIS); for children, we reported achievement of improvement defined by the Paediatric Rheumatology International Trials Organisation (PRINTO)), cumulative corticosteroid dose, change in skin disease activity, serious adverse event and withdrawals for lack of benefit or adverse events.<br><br>DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. To assess the risk of bias, we used the domain-based Cochrane risk of bias tool (RoB 1). We used fixed-effect models and, when needed, random-effects models for meta-analysis. We created summary of findings tables for any comparison for which data were available but prioritised comparisons of the following with placebo, no treatment or standard care: immunoglobulin, azathioprine and methotrexate. We included other comparisons as additional tables. We assessed the certainty of evidence using the GRADE approach.<br><br>MAIN RESULTS: We identified 16 studies (789 participants). The risk of bias in all but one study was high or unclear. Intravenous immunoglobulin (IVIg), compared to placebo, probably improves disability and muscle strength in participants with refractory IIM (standardised mean difference (SMD) 0.86, 95% confidence interval (CI) 0.51 to 1.21 (disability) and 0.78, 95% CI 0.43 to 1.13 (muscle strength); 3 RCTs, 136 participants; both moderate-certainty evidence). IVIg has a higher response rate based on American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria than placebo (risk ratio (RR) 1.80, 95% CI 1.26 to 2.56; 1 RCT, 95 participants; moderate-certainty evidence). IVIg, compared to placebo, improves skin symptoms (Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) total activity score 0 to 100; higher worse) in people with refractory DM (mean difference (MD) -8.20, 95% CI -11.91 to -4.49; 1 RCT, 95 participants; moderate-certainty evidence). There may be more serious adverse events with IVIg than with placebo (RR 1.91, 95% CI 0.50 to 7.30; 2 RCTs, 144 participants; very low-certainty evidence), but little or no difference between IVIg and placebo in withdrawals for either lack of benefit or adverse events (RR 1.02, 95% CI 0.24 to 4.33; 3 RCTs, 154 participants; very low-certainty evidence). For azathioprine versus placebo, one study showed little or no effect of azathioprine on improvement in muscle strength, but the evidence was very uncertain (RR 1.33, 95% CI 0.43 to 4.13; 1 RCT; 16 participants; very low-certainty evidence). The evidence was also very uncertain for cumulative steroid dose (MD 12.06 mg/kg, 95% CI -6.09 to 30.21; 1 RCT, 16 participants; very low-certainty evidence). This early study did not assess IMACS DOI or CDASI or measure function or disability. Serious adverse events and withdrawals for either lack of benefit or adverse events were not systematically reported. For methotrexate, there may be little or no improvement in adults with DM or PM in function (Amyotrophic Lateral Sclerosis Functional Rating Scale 0 to 40, higher better) (MD 1.24, 95% CI -1.60 to 4.08; 1 RCT, 27 participants; very low-certainty evidence), muscle strength (MMT scale 0 to 80, higher better) (MD -5.68, 95% CI -12.94 to 1.58; 1 RCT, 27 participants; very low-certainty evidence), achievement of IMACS DOI (RR 1.01, 95% CI 0.74 to 1.39; 1 RCT, 27 participants; very low-certainty evidence). Cumulative steroid dose was measured, but the data could not be analysed, and change in CDASI was not measured. In children with new-onset jDM on a background therapy of prednisone, a higher proportion may achieve minimal improvement according to the PRINTO criteria with methotrexate than with placebo (RR 1.40, 95% CI 1.01 to 1.96; 1 RCT, 93 participants; low-certainty evidence). Serious adverse events may occur slightly more frequently with methotrexate (RR 1.48, 95% CI 0.54 to 4.07; 2 RCTs, 124 participants; low-certainty evidence). There may be fewer withdrawals for lack of benefit or adverse events with methotrexate (RR 0.62, 95% CI 0.37 to 1.05; 3 RCTs, 151 participants; low-certainty evidence).<br><br>AUTHORS' CONCLUSIONS: Our review shows improvement in disability, muscle strength and skin symptoms following IVIg in people with refractory DM (for PM, these data are not reliable; other subtypes have not been investigated in RCTs). The improvements related to IVIg in DM may be clinically meaningful, but the absence of established minimal clinically important differences (MCIDs) for both disability and muscle strength in IIM does not facilitate interpretation. For the other agents, the small number of trials of immunosuppressive and immunomodulatory therapies is inadequate to decide whether these agents are beneficial in IIM (excluding IBM). Our review shows room for improvement in the conduct and reporting of clinical trials in IIM, as well as the need to further investigate MCIDs for important outcome measures in IIM.}, }
@article {pmid40787603, year = {2025}, author = {Fonseca, I and Rueda, M and Cabanzo, C}, title = {The effect of dance interventions on well-being dimensions in older adults: a systematic review.}, journal = {Frontiers in sports and active living}, volume = {7}, number = {}, pages = {1594754}, pmid = {40787603}, issn = {2624-9367}, abstract = {BACKGROUND: Dance is increasingly recognized as a strategy that can support healthy aging. It incorporates physical, emotional, cognitive, and social engagement, which makes it particularly relevant for older populations. However, the effects of dance on multidimensional well-being have not yet been thoroughly synthesized.<br><br>OBJECTIVES: Systematically review empirical studies examining the effects of dance-based interventions on physical, emotional, cognitive, and social dimensions of well-being in older adults. We considered studies that assessed one or more of these dimensions as indicators of well-being.<br><br>DATA SOURCES: Studies were identified through database searches in Scopus, Web of Science, and SportDiscus conducted between October and November 2024.<br><br>Included studies were qualitative or quantitative empirical research published in peer-reviewed journals. Participants were adults aged 60 and older or identified as older adults. Interventions involved dance-based activities. Comparators included no intervention or alternative physical or recreational programs. The outcomes addressed at least one domain of well-being.<br><br>SYNTHESIS METHODS: This review followed the PRISMA 2020 guidelines. Eligibility criteria were defined using the PICOS framework. Study quality was assessed using Law et al.'s (1998) 16-item checklist. Due to methodological heterogeneity, a narrative synthesis was performed.<br><br>LIMITATIONS AND CONCLUSIONS: Although the results suggest that dance is a promising, low-cost intervention for promoting multidimensional well-being in older adults, several limitations should be noted. Many studies had small sample sizes or did not report effect sizes or randomization. Furthermore, some studies assessed only one or two dimensions of well-being rather than a multidimensional profile. This limits the scope of conclusions that can be drawn about integrated well-being. Future research should prioritize more rigorous designs, standardize multidimensional outcome measures, and assess long-term integrative effects to better inform health promotion policies.}, }
@article {pmid40784657, year = {2025}, author = {Babcock, KJ and Abdolmohammadi, B and McKee, AC}, title = {Recent Advances in Chronic Traumatic Encephalopathy.}, journal = {The American journal of pathology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajpath.2025.07.008}, pmid = {40784657}, issn = {1525-2191}, abstract = {Exposure to repeated head impacts (RHIs), such as those experienced in contact sports or military service, can lead to the development of chronic traumatic encephalopathy (CTE), a neurodegenerative tauopathy. CTE cannot be diagnosed during life, only by post-mortem neuropathologic examination. The pathognomonic lesion of CTE consists of a perivascular accumulation of hyperphosphorylated tau as neurofibrillary tangles and dotlike neurites, preferentially at the depths of cortical sulci. The biomechanics of RHI involve acceleration, deceleration, and rotational forces that distort brain tissue and strain fragile structures, such as blood vessels and axons, especially in the crevices of the brain, where these forces are localized. CTE is unique from other tauopathies in its molecular structure, pattern, and regional distribution of tau. Studies in American football, rugby, and ice hockey players demonstrate a dose-response relationship between years of exposure to sport and increased CTE risk and severity. The clinical symptoms associated with CTE are classified as traumatic encephalopathy syndrome. Exposure to RHI also increases the deposition of other pathologic proteins, including β-amyloid, α-synuclein, and transactive response DNA-binding protein (TDP-43), raising the risk for other neurodegenerations, such as Alzheimer disease, Lewy body disease, frontotemporal lobar degeneration, and amyotrophic lateral sclerosis.}, }
@article {pmid40782358, year = {2025}, author = {St Clair-Sullivan, N and Brighton, LJ and Jha, P and Bone, AE and Sudirman, NA and Maddocks, M and Bayly, J}, title = {Assistive technologies for people with advanced disease and in palliative care: a scoping review.}, journal = {Disability and rehabilitation. Assistive technology}, volume = {}, number = {}, pages = {1-17}, doi = {10.1080/17483107.2025.2536175}, pmid = {40782358}, issn = {1748-3115}, abstract = {Population ageing, multi-morbidity and associated disability is shifting global demand for health and care services. Innovative solutions are required to meet the evolving needs of people with advanced disease, support independent functioning and quality of life. This scoping review aimed to map and examine evidence on the role of assistive technology in adults with advanced disease and those receiving palliative care. A systematic search of Medline, Embase, PsychINFO and Cinahl, was conducted from inception to 31[st] July 2024 for studies investigating use of assistive technologies in people with advanced disease or receiving palliative care. Titles and abstracts were independently screened before full texts retrieved for eligibility review, data extraction, synthesis and descriptive analysis. 23/811 screened papers met eligibility criteria. Participants included ALS/MND (n13/23); palliative care (n4/23); cancer (n2/23); dementia (n2/23); Parkinson's (n1/23) and frailty (n1/23). Studies evaluated assistive technologies supporting ten functional domains; most frequently to support communication and information management (n13/23), least frequently orthoses and prosthesis, and domestic activities and participation in domestic life (n1/23). Outcomes of assistive technology use related to functioning, quality of life, dignity in end-of-life care and health service use. Implications for individual users, device design and delivery are discussed. This review highlights potential benefits of assistive technologies and gaps in research on their use for adults with advanced disease or receiving palliative care. Empirical evidence is limited and focuses on communication enhancing high-tech devices. Future research should explore assistive technology's impact over time on health outcomes, alongside strategies to integrate provision in care.}, }
@article {pmid40779613, year = {2025}, author = {Chaouch, A and Crook, A and Douglas, AGL and McDermott, CJ and Al-Chalabi, A and McNeill, A and Bedford, J and Howard, J and MacLeod, R}, title = {The use of genetic testing in amyotrophic lateral sclerosis (ALS): a practical approach.}, journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration}, volume = {}, number = {}, pages = {1-7}, doi = {10.1080/21678421.2025.2539895}, pmid = {40779613}, issn = {2167-9223}, abstract = {Amyotrophic lateral sclerosis (ALS) is a rare and fatal neurodegenerative disease thought to be precipitated by genetic, environment and lifestyle factors. In the UK, whole genome sequencing has become available to all people living with ALS, regardless of their family history or age of onset of disease. However, there is currently no formal guidance on how to deliver genetic counseling and testing in busy mainstream clinics. This article offers practical suggestions to clinicians who may wish or need to discuss genomic testing. As more clinical trials and targeted gene therapies develop, it is likely that conversations will evolve, reflecting the dynamic nature of this important and complex field.}, }
@article {pmid40779080, year = {2025}, author = {Huo, X and Wang, L and Ma, J and Wu, Z and Wang, K}, title = {Bibliometric analysis of publication trends in meningioma research (1992 - 2023).}, journal = {Neurosurgical review}, volume = {48}, number = {1}, pages = {595}, pmid = {40779080}, issn = {1437-2320}, support = {2024-4-2048//Capital's Funds for Health Improvement and Research/ ; 2022YFE0112500//National Natural Science Foundation of China/ ; 62027813//National Natural Science Foundation of China,China/ ; YGLX202518//Beijing Hospitals Authority Clinical medicine Development of special funding support/ ; }, mesh = {*Meningioma ; *Bibliometrics ; Humans ; *Meningeal Neoplasms ; *Biomedical Research ; }, abstract = {The purpose of this study was providing an overview of meningioma research and its current situation. We conducted a bibliometric study of 14,027 articles and reviews on meningioma between January, 1992 to June, 2023 with the bibliometrix tool and VOSviewer. The distribution of authorship and collaboration patterns among countries, institutions, publications, and authors were analyzed. Core sources was analyzed with Bradford's law and author productivity was analyzed with Lotka's Law. The current situation and key areas were assessed through co-occurrence analysis. The number of publications has steadily increased over the years. The United States and University California San Francisco made the most contribution country and institution, respectively. Among the cited authors, Zhang J. emerged as the leading contributor while Perry A. was the most productive. Black P.M. had the highest h-index and Nassiri F. ranked first among the m-index. The most frequently cited study was Louis D.N. et al.'s 2016 publication in Acta Neuropathologica, titled "The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary." The journals with the most published articles and most cited publications were World Neurosurgery and Journal of Neurosurgery, respectively. According to keyword analysis, treatment option, chemotherapy, NF2 gene and estrogen receptor, and progesterone receptor are becoming more popular. This study provided a comprehensive overview of meningioma research, as well as potential future research fields, such as the chemotherapy and NF2 gene.}, }
@article {pmid40778304, year = {2025}, author = {Zhang, K and Wen, M and Nan, X and Zhao, S and Li, H and Ai, Y and Zhu, H}, title = {NMDA receptors in neurodegenerative diseases: mechanisms and emerging therapeutic strategies.}, journal = {Frontiers in aging neuroscience}, volume = {17}, number = {}, pages = {1604378}, pmid = {40778304}, issn = {1663-4365}, abstract = {NMDA receptors (NMDARs) are widely distributed throughout the central nervous system (CNS) and play pivotal roles in normal physiological processes such as synaptic plasticity, learning, and memory. Substantial evidence indicates that NMDAR dysfunction, particularly excessive calcium influx, critically contributes to the pathogenesis of major neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). Dysregulated glutamatergic signaling synergizes with pathological protein aggregation (e.g., Aβ, α-synuclein, mutant huntingtin) to drive neuronal loss. We systematically delineate NMDAR-related mechanisms underlying neurodegeneration, highlighting spatial-specific roles (e.g., synaptic NMDAR-mediated neuroprotection versus extrasynaptic NMDAR-mediated excitotoxicity) and crosstalk with mitochondrial dysfunction and oxidative stress. We critically evaluate current therapeutic strategies targeting NMDARs, including subunit-selective modulators, downstream effector modulation, and glutamate transporter modulation designed to restore NMDAR homeostasis. Consequently, NMDARs and their modulators represent promising therapeutic targets for these refractory conditions. This review comprehensively summarizes current research on the involvement of NMDARs and the glutamatergic system in neurodegenerative diseases. Furthermore, we discuss the clinical application of NMDAR-targeting agents and explore emerging therapeutic strategies focused on modulating NMDAR-related pathways. This article aims to provide a reference for elucidating the molecular mechanisms underlying these neurodegenerative disorders and to highlight potential avenues for future drug development.}, }
@article {pmid40775702, year = {2025}, author = {Seckin, M and Tiwana, R and Fry, D and Bailey, C}, title = {Key themes and approaches in palliative and end-of-life care education for the general public: a systematic review.}, journal = {BMC palliative care}, volume = {24}, number = {1}, pages = {219}, pmid = {40775702}, issn = {1472-684X}, support = {2683473//NHS England/ ; 2683473//NHS England/ ; 2683473//NHS England/ ; 2683473//NHS England/ ; }, mesh = {Humans ; *Terminal Care/methods/standards ; *Palliative Care/methods/standards ; }, abstract = {BACKGROUND: Families, friends, and communities play a vital role in supporting individuals facing declining health, caregiving duties, loss, or grief, especially with the growing desire to die at home. The general public can significantly impact end-of-life care and offer essential support mechanisms. This review aimed to explore and identify key educational components related to palliative and end-of-life care for citizens, volunteers, and the general public.<br><br>METHODS: A mixed-method systematic review was conducted, incorporating four electronic databases (MEDLINE, PsycINFO, CINAHL, and the Cochrane Library) and grey literature searches, and quality was assessed using Hawker et al.'s (2002) critical appraisal checklists.<br><br>RESULTS: Twenty studies published between 2011 and 2023 were included, covering topics in palliative, end-of-life care, and bereavement education. These studies involved a total of 10,307 participants and identified 16 different educational programmes for the public, volunteers, and lay caregivers. The analysis revealed six main themes: foundational concepts and philosophies, communication and decision-making, planning and preparation, symptom management, end-of-life care practices, and caregiving support.<br><br>CONCLUSIONS: This review highlights the importance of training programmes to improve community involvement in caregiving and enhance the quality of care for individuals with life-limiting conditions. Expanding access to such educational resources can empower more people to contribute confidently to end-of-life care in their communities.<br><br>PROSPERO-ID: CRD42024533124.}, }
@article {pmid40774708, year = {2025}, author = {Brown, KR and Quinton, ML and Tidmarsh, G and Cumming, J}, title = {Athletes' access to, attitudes towards and experiences of help-seeking for mental health: a scoping review.}, journal = {BMJ open}, volume = {15}, number = {8}, pages = {e097492}, pmid = {40774708}, issn = {2044-6055}, mesh = {Humans ; *Athletes/psychology ; *Patient Acceptance of Health Care/psychology ; *Mental Health ; *Mental Disorders/therapy/psychology ; *Help-Seeking Behavior ; *Mental Health Services ; *Health Services Accessibility ; }, abstract = {OBJECTIVES: Athletes have been found to experience a similar prevalence of mental health issues to non-athletes. However, they are subjected to a greater array of barriers to help-seeking for mental health, including sport-specific factors. This scoping review synthesised the literature on athletes' access to, attitudes towards and experiences of help-seeking for mental health from formal (mental health professionals such as psychiatrists) and semiformal sources (those who are not mental health professionals but are a service provider such as a coach).<br><br>DESIGN: The Joanna Briggs Institute framework and recommendations were used alongside the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Protocols checklist for scoping reviews. This scoping review was predominantly informed by Arksey and O'Malley's framework for scoping reviews, supplemented by Levac et al's additional recommendations. Rickwood and colleagues' help-seeking frameworks informed the research question, inclusion/exclusion criteria and analysis.<br><br>DATA SOURCES: The search terms and synonyms of "athlete" AND "mental health" AND "help-seeking" were searched in PsychINFO, Embase, MEDLINE, APA PsychArticles Full Text, Web of Science Core Collection, Scopus, Sport Discus, CINAHL and Proquest (Education Database, Health &amp; Medical Collection, Nursing &amp; Allied Health database, Psychology Database, Public Health Database, Education Collection, and Medicine &amp; Education). These searches were conducted at three time points between April 2022 and 2024.<br><br>ELIGIBILITY CRITERIA: The inclusion and exclusion criteria were initially predetermined and specified in the protocol paper published in BMJ Open. Primary research articles, interventions and systematic reviews that referred to semiformal and formal sources of support were included.<br><br>DATA EXTRACTION AND SYNTHESIS: The lead reviewer (KRB) screened all titles and abstracts, and full texts, and extracted data from all included studies. A second reviewer was involved in screening and extracting 20%-30% of studies at each stage. Findings were synthesised descriptively (eg, study population, data collection method and location of studies) and by content (eg, access, attitudes and experiences, sources of support, use of theory and the validity of quantitative measures used).<br><br>RESULTS: After screening 4954 titles and abstracts and 275 full texts in Covidence, 104 papers were included in the review. This comprised of 87 primary research articles, 13 interventions and 4 systematic reviews. Most of the primary articles and interventions were published in the USA (50%). 49.4% of the primary articles used quantitative methods, 34.5% used qualitative methods and 16.1% used mixed methods. Attitudes towards mental health help-seeking were investigated in 78.8% of the included studies, experiences of help-seeking in 53.8% and access to sources of support in 31.7% of studies. Of the primary articles and interventions, formal sources were investigated in 55% of studies, semiformal sources in 2% and both in 26% of studies.<br><br>CONCLUSIONS: This scoping review of 104 papers showed the benefit of using help-seeking frameworks to shape and analyse a review. Analysing the results using these frameworks provided a novel contribution to the literature, showing where the athlete help-seeking literature base is currently focused and identified gaps for further research. For example, there is a need for further research on athletes in less developed nations, more qualitative and mixed methods studies, and further research on athletes' access to mental health support and their interactions with semiformal sources. The results have applied implications in public health and sport by highlighting the different factors that impact athlete help-seeking, and therefore areas where they require support.}, }
@article {pmid40757018, year = {2025}, author = {Kato, N and Suzuki, R and Kaneko, H and Horimoto, Y}, title = {Effects of telerehabilitation on physical function and activities of daily living in patients with amyotrophic lateral sclerosis: a scoping review.}, journal = {Journal of physical therapy science}, volume = {37}, number = {8}, pages = {427-434}, pmid = {40757018}, issn = {0915-5287}, abstract = {[Purpose] This study aimed to clarify the effects of telerehabilitation on physical function and activities of daily living in patients with amyotrophic lateral sclerosis through a literature review. [Participants and Methods] We conducted a scoping review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Extension for Scoping Reviews reporting guidelines. The PubMed, Scopus, Web of Science, and ProQuest databases were searched. Study design, type of interventions, telerehabilitation methods, adherence, effectiveness, adverse events, and patient satisfaction were extracted from the selected literature. [Results] Four case-series and one case-control study were identified. The interventions included respiratory muscle training (two studies), aerobic exercise, stretching, and comprehensive physical therapy (one study each). Various modalities were used, including videoconferencing, on-demand instructional videos, and real-time monitoring of vital signs using wearable devices. No serious adverse events were reported in any study. The dropout rate was 0-21%, and the compliance rate was 90%, indicating high adherence. Improvements in respiratory function and ADL were observed following respiratory rehabilitation. Patient satisfaction with telerehabilitation was high. [Conclusion] Telerehabilitation may improve adherence, respiratory function, and activities of daily living in patients with amyotrophic lateral sclerosis. However, its effects on other aspects of physical function remain unclear. Further high-quality studies are needed to establish evidence-based practices.}, }
@article {pmid40754996, year = {2025}, author = {Stam, R}, title = {Low frequency magnetic field exposure and neurodegenerative disease: systematic review of animal studies.}, journal = {Electromagnetic biology and medicine}, volume = {}, number = {}, pages = {1-15}, doi = {10.1080/15368378.2025.2540435}, pmid = {40754996}, issn = {1536-8386}, abstract = {Epidemiological studies have found an association between occupational exposure to low frequency magnetic fields and the occurrence of motor neuron disease and Alzheimer's disease. No association has been found for Parkinson's disease and the evidence for multiple sclerosis is insufficient. Animal models studying the effects of low frequency magnetic fields on neurodegenerative disease induction or progression could provide more evidence on causation and the underlying mechanisms. A systematic search and review was conducted of peer-reviewed research articles involving animal experiments on the effects of low frequency magnetic field exposure on behavioural and neuroanatomical outcomes relevant for neurodegenerative diseases in humans. Firstly, experimental studies in naive animals do not support a causal relationship between exposure to low frequency magnetic fields and the induction of neuropathology relevant for Alzheimer's disease, but the number of studies relevant for motor neuron disease, multiple sclerosis and Parkinson's disease is too limited to draw conclusions. Secondly, experimental studies in existing animal models for neurodegenerative disease support a therapeutic (beneficial) effect of low frequency magnetic field treatment on behavioural and neuroanatomical abnormalities relevant for dementia (including Alzheimer's disease), multiple sclerosis and Parkinson's disease and no effect on disease progression in models relevant for motor neuron disease.}, }
@article {pmid40747386, year = {2025}, author = {Arnold, WD and Castoro, R and Saxena, S}, title = {Innovations In Physical Medicine and Rehabilitation: Advances in the Diagnosis, Treatment, and Care of Amyotrophic Lateral Sclerosis.}, journal = {Missouri medicine}, volume = {122}, number = {3}, pages = {199-205}, pmid = {40747386}, issn = {0026-6620}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/therapy/rehabilitation ; *Physical and Rehabilitation Medicine/trends/methods ; Quality of Life ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease that causes loss of upper and lower motor neurons, leading to muscle weakness and ultimately death. This review highlights recent advancements in Neuromuscular Medicine and Physical Medicine and Rehabilitation (PM&amp;R), emphasizing innovations in the diagnosis, treatment, and care delivery for ALS. The field of PM&amp;R emphasizes a multidisciplinary, patient-centered approach, incorporating advanced diagnostic tools, therapeutic strategies, adaptive equipment, and telerehabilitation to optimize function. Neuromuscular PM&amp;R physicians play a key role in managing symptoms and maximizing functional independence. Current disease-modifying therapies include riluzole and edaravone which provide only modest benefits, but emerging gene therapies like tofersen for SOD1-related ALS offer promise for targeted treatment for genetic forms of ALS. Future advancements in regenerative therapies, biotechnologies, and digital health integration hold the potential to improve care and enhance the quality of life and functional independence of individuals living with ALS.}, }
@article {pmid40744389, year = {2025}, author = {Nelson, VK and Begum, MY and Suryadevara, PR and Madhuri Kallam, SD and Panda, SP and Bodapati, A and Sanga, V and Bishoyi, AK and Ballal, S and Monsi, M and Walia, C and Prasad, GVS and Abomughaid, MM and Shukla, S and Chauhan, P and Jha, NK}, title = {Natural bioactive compounds as modulators of autophagy: A herbal approach to the management of neurodegenerative diseases.}, journal = {European journal of pharmacology}, volume = {1005}, number = {}, pages = {178003}, doi = {10.1016/j.ejphar.2025.178003}, pmid = {40744389}, issn = {1879-0712}, abstract = {Neurodegenerative diseases (NDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), Polyglutamine (polyQ), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) disease are a significant health concern that affects millions of people every year worldwide. The main pathological hallmark of various NDs is the formation of misfolded protein aggregation and accumulation of inclusion bodies. These protein aggregates are mainly responsible for producing toxic effects and initiating neuronal cell death, ultimately promoting various NDs. On the other hand, the patients suffering from these kinds of diseases live in impaired conditions, imposing a substantial financial burden on the family. However, the current treatment strategies can only offer temporary relief from the disease symptoms and can't reverse the disease completely. Hence, there is an urgent need for specific and novel drug treatment that can significantly eradicate NDs. Ubiquitin proteasome system (UPS) and autophagy are the two essential intracellular defensive mechanisms that are involved in clearing the protein aggregates, pathogens, and damaged organelles from the cytoplasm and maintaining protein homeostasis. Nevertheless, UPS is inefficient in removing some kinds of organelles and aggregating-prone proteins, specifically in neuronal and glial cells. Under this kind of circumstance, the autophagy mechanism plays a vital role in eliminating the accumulated protein aggregates and other toxic elements from the cytoplasm of the neuronal cells that initiate oxidative stress. However, in NDs, the autophagy function is impaired, and the protein aggregates can't be eliminated effectively. Hence, forced up-regulation of autophagy function by applying various external agents could be a potential therapeutic strategy to control NDs like AD, PD, HD, and ALS. In this review, we focused on different kinds of plant-derived compounds that induce autophagy. We also discussed the role of these plant-derived autophagy modulators in various NDs. In this way, the current review will be a standalone reference to the researchers working in this area.}, }
@article {pmid40741338, year = {2025}, author = {Marek, A and Brož, B and Kriegelstein, M and Nováková, G and Hojcsková, J and Blechová, M and Žáková, L and Jiráček, J and Maletínská, L}, title = {Late-stage labeling of diverse peptides and proteins with iodine-125.}, journal = {Journal of pharmaceutical analysis}, volume = {15}, number = {7}, pages = {101198}, pmid = {40741338}, issn = {2214-0883}, abstract = {The preparation of specifically iodine-125 ([125]I)-labeled peptides of high purity and specific activity represents a key tool for the detailed characterization of their binding properties in interaction with their binding partners. Early synthetic methods for the incorporation of iodine faced challenges such as harsh reaction conditions, the use of strong oxidants and low reproducibility. Herein, we review well-established radiolabeling strategies available to incorporate radionuclide into a protein of interest, and our long-term experience with a mild, simple and generally applicable technique of [125]I late-stage-labeling of biomolecules using the Pierce iodination reagent for the direct solid-phase oxidation of radioactive iodide. General recommendations, tips, and details of optimized chromatographic conditions to isolate pure, specifically [125]I-mono-labeled biomolecules are illustrated on a diverse series of (poly)peptides, ranging up to 7.6 kDa and 67 amino acids (aa). These series include peptides that contain at least one tyrosine or histidine residue, along with those featuring disulfide crosslinking or lipophilic derivatization. This mild and straightforward late-stage-labeling technique is easily applicable to longer and more sensitive proteins, as demonstrated in the cases of the insulin-like growth factor binding protein-3 (IGF-BP-3) (29 kDa and 264 aa) and the acid-labile subunit (ALS) (93 kDa and 578 aa).}, }
@article {pmid40739673, year = {2025}, author = {Zheng, X and Yuan, W and Li, L and Ma, H and Zhu, M and Li, X and Feng, X}, title = {Targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) to tackle central nervous system diseases: role as a promising approach.}, journal = {European journal of medical research}, volume = {30}, number = {1}, pages = {690}, pmid = {40739673}, issn = {2047-783X}, mesh = {Humans ; *Proprotein Convertase 9/metabolism/genetics ; *PCSK9 Inhibitors/therapeutic use ; *Central Nervous System Diseases/drug therapy/metabolism ; Animals ; }, abstract = {Atherosclerosis-associated disease (ASD) represents a complex pathological condition, characterized by the formation of atherosclerotic plaques within the arterial walls, encompassing cholesterol depositions, which is primarily attributed to elevated levels of low-density lipoprotein-cholesterol (LDL-C). A log-linear association between the absolute magnitude of LDL-C exposure and ASD risk has been widely studied. High levels of LDL-C have been acknowledged as the predominant culprit. The previous research findings have demonstrated that PCSK9 inhibitors (PCSK9i) can remarkably diminish the risk of ASD. The current research has primarily focused on the relevance of PCSK9 to the cardiovascular system and lipid metabolism; however, an increasing body of evidence shows that PCSK9 is pivotal in pathogenic processes in other organ systems. Yet, PCSK9's impact on the brain is complex and not fully clarified, although several recent studies emphasize a putative role of its impact on various neurodegenerative disorders. Among neurological disorders, not only stroke but neurogenesis, neural cell differentiation, central LDL receptor metabolism, neural cell apoptosis, neuroinflammation, alcohol use disorder (AUD), amyotrophic lateral sclerosis(ALS), and Alzheimer's Disease (AD) are related to PCSK9. PCSK9 expression in brain is low but greatly upregulated in neurological disorders. Therefore, PCSK9 is a promising pathway for the treatment of central nervous diseases. This review comprehensively describes evidence from the previous research on the effects of PCSK9i on the central nervous system, with a focus on the clinical potential of PCSK9i. We anticipate that this review will generate data that will help biomedical researchers or clinical workers develop treatments for the neurological diseases based on PCSK9i.}, }
@article {pmid40738791, year = {2025}, author = {Roy, A and Dawson, VL and Dawson, TM}, title = {From metabolism to mind: The expanding role of the GLP-1 receptor in neurotherapeutics.}, journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics}, volume = {}, number = {}, pages = {e00712}, doi = {10.1016/j.neurot.2025.e00712}, pmid = {40738791}, issn = {1878-7479}, abstract = {GLP-1 receptor agonists (GLP-1RAs), initially approved for diabetes and obesity, are now under investigation for neuroprotective effects in a range of neurological disorders. These agents, whose receptors are widely expressed in brain regions involved in cognition and metabolism, modulate neurotransmitter release and promote neurogenesis. While preclinical studies consistently demonstrate benefits in models of Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis (ALS), clinical trial outcomes have been variable, largely owing to heterogeneity in study populations and trial design. Newer agents, such as NLY01 and tirzepatide, are under development to enhance central nervous system penetration and efficacy. Although GLP-1RAs are generally safe in metabolic conditions, their use in neurological diseases requires careful monitoring and patient selection. Future directions include developing reliable biomarkers, implementing precision medicine strategies, and exploring the use of combination therapies to maximize therapeutic potential.}, }
@article {pmid40732891, year = {2025}, author = {Hein, ZM and Arbain, MFF and Kumar, S and Mehat, MZ and Hamid, HA and Che Ramli, MD and Che Mohd Nassir, CMN}, title = {Intermittent Fasting as a Neuroprotective Strategy: Gut-Brain Axis Modulation and Metabolic Reprogramming in Neurodegenerative Disorders.}, journal = {Nutrients}, volume = {17}, number = {14}, pages = {}, pmid = {40732891}, issn = {2072-6643}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/therapy ; *Fasting/physiology ; Gastrointestinal Microbiome/physiology ; Animals ; *Brain/metabolism ; *Brain-Gut Axis/physiology ; *Neuroprotection ; Energy Metabolism ; Brain-Derived Neurotrophic Factor/metabolism ; Metabolic Reprogramming ; Intermittent Fasting ; }, abstract = {Intermittent fasting (IF) is emerging as a heterogeneous neurometabolic intervention with the possibility of changing the course of neurodegenerative diseases. Through the modulation of the gut-brain axis (GBA), cellular bioenergetics (or metabolic) reprogramming, and involvement in preserved stress adaptation pathways, IF influences a range of physiological mechanisms, including mitobiogenesis, autophagy, circadian rhythm alignment, and neuroinflammation. This review critically synthesises current preclinical and early clinical evidence illustrating IF's capability to supplement synaptic plasticity and integrity, reduce toxic proteins (proteotoxic) burden, and rehabilitate glial and immune homeostasis across models of Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. The key players behind these effects are bioactive metabolites such as short-chain fatty acids (SCFA) and β-hydroxybutyrate (BHB), and molecular mediators such as brain-derived neurotrophic factor (BDNF). We feature the therapeutic pertinence of IF-induced changes in gut microbiota composition, immune response, and mitochondrial dynamics, and we discuss emerging approaches for merging IF into precision medicine frameworks. Crucial challenges include individual variability, protocol optimisation, safety in cognitively vulnerable populations, and the need for biomarker-guided, ethically grounded clinical trials. Finally, we propose IF as a scalable and flexible intervention that, when personalised and integrated with other modalities, may reframe neurodegeneration from a model of irreversible decline to one of modifiable resilience.}, }
@article {pmid40726565, year = {2025}, author = {Dukic, S and Govaarts, R and Hillebrand, A and de Visser, M and Seeck, M and McMackin, R}, title = {Novel approaches to EEG and MEG in motor neurone disease: IFCN Handbook Chapter.}, journal = {Clinical neurophysiology practice}, volume = {10}, number = {}, pages = {301-315}, pmid = {40726565}, issn = {2467-981X}, abstract = {Motor neurone diseases (MNDs) are increasingly being acknowledged as network disorders, with cortical dysfunction and degeneration extending beyond the motor cortex. Measures of this broader cortical pathophysiology are providing promising candidates in the search for diagnostic and prognostic biomarkers of the MNDs. Electroencephalography (EEG) and magnetoencephalography (MEG) offer a direct view of neural network activity by detecting changes in electromagnetic fields of the brain. Measurements based on EEG/MEG have often been overlooked in the search for MND biomarkers, largely due to their limited spatial resolution and the perceived challenges associated with noise in these signals. However, with recent developments in sensor technology and source reconstruction algorithms, alongside substantial improvement in pipelines that address noise, EEG/MEG-based measures can now be readily employed for spatiotemporally-precise, economical and non-invasive characterisation of cortical network pathophysiology in MNDs. Here, we provide an overview of how EEG/MEG signals have been employed to quantify neural network function in MND. We outline the advantages and limitations of these measurements, discuss the most clinically promising EEG/MEG studies of MNDs to date, and highlight future directions warranted to harness the full potential of these technologies for understanding and assessing MNDs.}, }
@article {pmid40725930, year = {2025}, author = {He, Y and Ming, W and Tan, Y and Wang, Y and Wang, M and Li, H and Jiao, Z and Hou, Y}, title = {The effectiveness of cognitive behavioral therapy in patients with motor neuron disease: A systematic review.}, journal = {Medicine}, volume = {104}, number = {30}, pages = {e43597}, pmid = {40725930}, issn = {1536-5964}, mesh = {Humans ; *Cognitive Behavioral Therapy/methods ; *Motor Neuron Disease/psychology/therapy ; Quality of Life ; Caregivers/psychology ; Anxiety/therapy/etiology ; Depression/therapy/etiology ; Treatment Outcome ; }, abstract = {BACKGROUND: Motor neuron disease (MND) is a neurodegenerative disorder that causes progressive loss of motor function. With limited disease-modifying drug therapies, cognitive behavioral therapy (CBT) has emerged as a key nonpharmacological intervention. This systematic review evaluated CBT's therapeutic potential across clinical domains to inform psychosocial care of patients with MND.<br><br>METHODS: Comprehensive searches were performed in PubMed, Web of Science, Cochrane Library, and Embase, from inception until February 2025. Two researchers independently screened the literature, extracted data, assessed study quality, and resolved disagreements via consensus or third-party consultation.<br><br>RESULTS: Five studies involving 561 patients were included. Compared with conventional care, CBT significantly improves patients' quality of life and psychological flexibility. However, the effects on caregiver burden and physical health were not statistically significant. CBT modalities included acceptance and commitment therapy, dialectical behavior therapy, rational-emotive behavior therapy, mindfulness cognitive therapy, and metacognitive training. Traditional CBT demonstrated superior efficacy in reducing anxiety and depression compared to acceptance and commitment therapy.<br><br>CONCLUSION: CBT effectively enhances psychological flexibility and quality of life and reduces anxiety and depression in patients with MND. The standardization of outcome measures requires improvement. High-quality randomized controlled trials are needed to further assess CBT's impact of CBT on caregiver burden and patients' physical health.}, }
@article {pmid40725270, year = {2025}, author = {Tahri, A and Niccolai, E and Amedei, A}, title = {Neurosteroids, Microbiota, and Neuroinflammation: Mechanistic Insights and Therapeutic Perspectives.}, journal = {International journal of molecular sciences}, volume = {26}, number = {14}, pages = {}, pmid = {40725270}, issn = {1422-0067}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Neuroinflammatory Diseases/metabolism/microbiology/therapy ; Animals ; *Neurosteroids/metabolism ; *Neurodegenerative Diseases/metabolism/microbiology ; Brain/metabolism ; Inflammation ; }, abstract = {The gut-brain axis (GBA) represents a complex bidirectional communication network that links the gut microbiota (GM) and the central nervous system (CNS). Recent research has revealed that neurosteroids (NSs) play crucial roles in modulating neuroinflammatory responses and promoting neuroprotection. Meanwhile, GM alterations have been associated with various neuroinflammatory and neurodegenerative conditions, such as multiple sclerosis, Alzheimer's disease, and amyotrophic lateral sclerosis. This review aims to provide a comprehensive overview of the intricate interactions between NS, GM, and neuroinflammation. We discuss how NS and metabolites can influence neuroinflammatory pathways through immune, metabolic, and neuronal mechanisms. Additionally, we explore how GM modulation can impact neurosteroidogenesis, highlighting potential therapeutic strategies that include probiotics, neuroactive metabolites, and targeted interventions. Understanding these interactions may pave the way for innovative treatment approaches for neuroinflammatory and neurodegenerative diseases, promoting a more integrated view of brain health and disease management.}, }
@article {pmid40724820, year = {2025}, author = {Tomaszewska-Zaremba, D and Gajewska, A and Misztal, T}, title = {Anti-Inflammatory Effects of Cannabinoids in Therapy of Neurodegenerative Disorders and Inflammatory Diseases of the CNS.}, journal = {International journal of molecular sciences}, volume = {26}, number = {14}, pages = {}, pmid = {40724820}, issn = {1422-0067}, mesh = {Humans ; *Cannabinoids/therapeutic use/pharmacology ; *Neurodegenerative Diseases/drug therapy ; *Anti-Inflammatory Agents/therapeutic use/pharmacology ; Animals ; *Inflammation/drug therapy ; Central Nervous System/drug effects ; *Central Nervous System Diseases/drug therapy ; }, abstract = {Many neurodegenerative diseases are associated with immune system disorders, while neurodegenerative processes often occur in inflammatory conditions of the Central Nervous System (CNS). Cannabinoids exhibit significant therapeutic potential due to their dual ability to modulate both neural and immune functions. These compounds have a broad spectrum of action, allowing them to target multiple pathological mechanisms underlying neurodegenerative and inflammatory CNS diseases. The present review outlines the therapeutic potential of cannabinoids, with a focus on their anti-inflammatory properties, in the treatment of neurodegenerative conditions, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease, as well as inflammatory CNS disorders like multiple sclerosis and HIV-associated dementia.}, }
@article {pmid40722307, year = {2025}, author = {Ghaderi, S and Mohammadi, S and Fatehi, F}, title = {Magnetic Resonance Neuroimaging in Amyotrophic Lateral Sclerosis: A Comprehensive Umbrella Review of 18 Studies.}, journal = {Brain sciences}, volume = {15}, number = {7}, pages = {}, pmid = {40722307}, issn = {2076-3425}, abstract = {Background/Objectives: Despite extensive research, the underlying causes of amyotrophic lateral sclerosis (ALS) remain unclear. This umbrella review aims to synthesize a vast body of evidence from advanced magnetic resonance imaging (MRI) studies of ALS, encompassing a wide range of neuroimaging techniques and patient cohorts. Methods: Following the PRISMA guidelines, we conducted an extensive search of four databases (PubMed, Scopus, Web of Science, and Embase) for articles published until 3 December 2024. Data extraction and quality assessment were independently performed using the AMSTAR2 tool. Results: This review included 18 studies that incorporated data from over 29,000 ALS patients. Structural MRI consistently showed gray matter atrophy in the motor and extra-motor regions, with significant white matter (WM) atrophy in the corticospinal tract and corpus callosum. Magnetic resonance spectroscopy revealed metabolic disruptions, including reduced N-acetylaspartate and elevated choline levels. Functional MRI studies have demonstrated altered brain activation patterns and functional connectivity, reflecting compensatory mechanisms and neurodegeneration. fMRI also demonstrated disrupted motor network connectivity and alterations in the default mode network. Diffusion MRI highlighted microstructural changes, particularly reduced fractional anisotropy in the WM tracts. Susceptibility-weighted imaging and quantitative susceptibility mapping revealed iron accumulation in the motor cortex and non-motor regions. Perfusion MRI indicated hypoperfusion in regions associated with cognitive impairment. Conclusions: Multiparametric MRI consistently highlights widespread structural, functional, and metabolic changes in ALS, reflecting neurodegeneration and compensatory mechanisms.}, }
@article {pmid40717894, year = {2025}, author = {Yu, M and Ma, H and Lai, X and Wu, J and Shen, M and Yan, J}, title = {Stem cell extracellular vesicles: a new dawn for anti-inflammatory treatment of neurodegenerative diseases.}, journal = {Frontiers in aging neuroscience}, volume = {17}, number = {}, pages = {1592578}, pmid = {40717894}, issn = {1663-4365}, abstract = {Mesenchymal stem cell-derived extracellular vesicles, as carriers for intercellular communication, are rich in bioactive substances such as proteins and nucleic acids, and show unique potential in the treatment of neurodegenerative diseases. Their vesicular structure, with a diameter of 30-150 nm, can penetrate the blood-brain barrier and modulate the activity of microglia and astrocytes by delivering functional molecules. This process inhibits the release of pro-inflammatory factors and enhances the expression of anti-inflammatory mediators, thereby alleviating neuroinflammation in the pathological process of neurodegenerative diseases. As natural drug carriers, extracellular vesicles can improve the targeted delivery efficiency of therapeutic molecules. However, their specific anti-inflammatory mechanisms remain not fully understood and require further exploration. This article discusses the anti-inflammatory effects in the context of neurodegenerative diseases and provides a summary and outlook on the anti-inflammatory actions associated with extracellular vesicles from past research.}, }
@article {pmid40717876, year = {2025}, author = {Castillo-Bustamante, M and Anderson, C and Gutierrez, VA}, title = {The Use of Posturography in Vestibular Evaluation of Neurodegenerative Disorders: Diagnostic and Rehabilitative Impacts.}, journal = {Cureus}, volume = {17}, number = {7}, pages = {e88752}, pmid = {40717876}, issn = {2168-8184}, abstract = {Neurodegenerative disorders, such as Parkinson's disease, multiple sclerosis, Alzheimer's disease, and amyotrophic lateral sclerosis, frequently present with vestibular dysfunction and balance disturbances, significantly impacting patients' quality of life and increasing the risk of falls. Vestibular impairments in these conditions can manifest as dizziness, unsteadiness, and difficulty maintaining postural control, further complicating the motor and cognitive deficits typical of these diseases. As a result, the assessment and management of balance dysfunction in neurodegenerative disorders have become crucial components of care. Posturography, an objective method for evaluating postural stability and balance control, has emerged as a valuable tool in the vestibular evaluation of patients with neurodegenerative conditions. By providing precise, quantitative measurements of balance deficits, posturography allows for a detailed analysis of postural control mechanisms that may be compromised due to vestibular involvement. This technique not only aids in diagnosing vestibular dysfunction but also plays a key role in developing targeted rehabilitation strategies. When integrated into vestibular rehabilitation (VR) programs, posturography can guide individualized therapy aimed at mitigating fall risk, improving functional mobility, and enhancing patients' overall quality of life. VR exercises, tailored to address specific balance deficits identified through posturographic analysis, can be particularly beneficial in promoting compensatory mechanisms and optimizing patients' functional abilities. This review highlights the significance of posturography as both a diagnostic and therapeutic tool in managing vestibular impairments associated with neurodegenerative diseases, offering the potential for improved outcomes through more personalized and effective rehabilitation interventions.}, }
@article {pmid40717814, year = {2025}, author = {Righes, G and Semenzato, L and Koutsikos, K and Zanato, V and Pinton, P and Giorgi, C and Patergnani, S}, title = {The role of autophagy in the pathogenesis and treatment of multiple sclerosis.}, journal = {Autophagy reports}, volume = {4}, number = {1}, pages = {2529196}, pmid = {40717814}, issn = {2769-4127}, abstract = {Autophagy is a crucial cellular process responsible for the degradation and recycling of damaged or unnecessary components, maintaining cellular homeostasis and protecting against stress. Dysregulation of autophagy has been implicated in a variety of neurodegenerative diseases, including multiple sclerosis, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease. Various types of autophagy exist, each with distinct mechanisms, such as macroautophagy, mitophagy, lipophagy, and chaperone-mediated autophagy. These processes are essential for the removal of toxic substrates like protein aggregates and dysfunctional mitochondria, which are vital for neuronal health. In neurodegenerative diseases, the impairment of these clearance mechanisms leads to the accumulation of harmful substances, which accelerate disease progression. Modulating autophagy has emerged as a promising therapeutic strategy, with ongoing studies investigating molecules that can either stimulate or regulate this process. However, despite its potential, significant challenges remain in translating preclinical findings into clinically effective treatments. In this review, we will explore the different types of autophagy, their roles in neurodegenerative diseases, and the therapeutic potential associated with modulating these processes.}, }
@article {pmid40713843, year = {2025}, author = {Burg, T and Van Den Bosch, L}, title = {Glycerophospholipids in ALS: insights into disease mechanisms and clinical implication.}, journal = {Molecular neurodegeneration}, volume = {20}, number = {1}, pages = {85}, pmid = {40713843}, issn = {1750-1326}, support = {#00099187//Fondation Thierry Latran/ ; ABMM//ABMM/ ; ALS Liga Belgi&#xeb; (A cure for ALS)//ALS Liga Belgi&#xeb; (A cure for ALS)/ ; 12AIK24N//FWO/ ; G0C1620N//FWO/ ; G088523N//FWO/ ; G026924N//FWO/ ; C14/22/132//Onderzoeksraad, KU Leuven/ ; IDN/22/ 012//Onderzoeksraad, KU Leuven/ ; Muscular Dystrophy Association//Muscular Dystrophy Association/ ; Target ALS//Target ALS/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/pathology ; Humans ; *Glycerophospholipids/metabolism ; Animals ; Lipid Metabolism/physiology ; Motor Neurons/metabolism/pathology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease affecting the adult motor system, with no effective treatments available. Despite extensive research efforts, the exact pathological cascade leading to progressive motor neuron degeneration remains elusive. Recent evidence highlights significant modifications in lipid metabolism during ALS progression, even before the onset of motor symptoms. Glycerophospholipids, the primary components of cellular membranes, are frequently altered in ALS patients and models. These lipids not only play a structural role in membranes, but also contribute to cellular metabolism, signaling pathways, and cell type-specific processes such as neuronal transmission and muscle contraction. In this review, we discuss glycerophospholipid physiological functions in the motor system and review recent studies demonstrating their alterations and the possible underlying pathological mechanisms in ALS. Furthermore, we discuss challenges emerging from studying lipid alterations in neurodegeneration and evaluate the therapeutic potential of glycerophospholipids.}, }
@article {pmid40712472, year = {2025}, author = {Yousef, AM and Cantor-Cutiva, LC and Hunter, EJ}, title = {Mapping 74 years in acoustic analysis of voice disorders: A bibliometric review and future research directions.}, journal = {Journal of communication disorders}, volume = {117}, number = {}, pages = {106555}, pmid = {40712472}, issn = {1873-7994}, support = {R01 DC012315/DC/NIDCD NIH HHS/United States ; }, abstract = {PURPOSE: This paper conducts a bibliometric analysis to identify and examine the strengths, gaps, and trends in research on acoustic voice assessment for voice disorders.<br><br>METHODS: A bibliometric analysis was performed on journal articles about voice disorders and acoustic voice assessment in English, Spanish, and Portuguese using seven indexed databases. The analyzed bibliometric parameters included publication year, authors, institutions, countries, journals, subject areas, and keywords. VOSviewer software was used for keyword co-occurrence analysis and authorships network analysis. The initial search yielded 6532 publications, with 1253 relevant papers after screening (1951-2024).<br><br>RESULTS: Publications in acoustic voice assessment had 74 years of exponential growth (25 % published after 2021). The publishing journals covered 80 categories and subjects. Artificial Intelligence, though recent, was among the top journal subjects. Health conditions like dementia, Alzheimer's, Amyotrophic lateral sclerosis, and depression were underassessed compared to Parkinson's. The literature focused on four separate themes: physiology of voice-affecting conditions; speech acoustics for evaluating dysphonia; speech production measurements for treating voice disorders; machine learning integration for voice disorder assessment.<br><br>CONCLUSIONS: Taking a wide view of acoustic voice assessment demonstrated research strengths and gaps-highlighting where it is used and not used-and the co-occurrence of various voice assessment topics. These insights reveal future opportunities to implement acoustic voice assessment.}, }
@article {pmid40710301, year = {2025}, author = {Pasqualucci, E and Angeletti, D and Rosso, P and Fico, E and Zoccali, F and Tirassa, P and De Virgilio, A and de Vincentiis, M and Severini, C}, title = {Management of Dysarthria in Amyotrophic Lateral Sclerosis.}, journal = {Cells}, volume = {14}, number = {14}, pages = {}, pmid = {40710301}, issn = {2073-4409}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/therapy/physiopathology ; *Dysarthria/therapy/diagnosis/etiology/physiopathology/complications ; Quality of Life ; }, abstract = {Amyotrophic lateral sclerosis (ALS) stands as the leading neurodegenerative disorder affecting the motor system. One of the hallmarks of ALS, especially its bulbar form, is dysarthria, which significantly impairs the quality of life of ALS patients. This review provides a comprehensive overview of the current knowledge on the clinical manifestations, diagnostic differentiation, underlying mechanisms, diagnostic tools, and therapeutic strategies for the treatment of dysarthria in ALS. We update on the most promising digital speech biomarkers of ALS that are critical for early and differential diagnosis. Advances in artificial intelligence and digital speech processing have transformed the analysis of speech patterns, and offer the opportunity to start therapy early to improve vocal function, as speech rate appears to decline significantly before the diagnosis of ALS is confirmed. In addition, we discuss the impact of interventions that can improve vocal function and quality of life for patients, such as compensatory speech techniques, surgical options, improving lung function and respiratory muscle strength, and percutaneous dilated tracheostomy, possibly with adjunctive therapies to treat respiratory insufficiency, and finally assistive devices for alternative communication.}, }
@article {pmid40709766, year = {2025}, author = {Albrecht, I and Gilissen, J and Robijn, L and Pype, P and Deliens, L and Chambaere, K}, title = {What determines quality in palliative sedation? A scoping review identifying elements contributing to palliative sedation quality.}, journal = {Palliative medicine}, volume = {39}, number = {8}, pages = {849-870}, doi = {10.1177/02692163251351534}, pmid = {40709766}, issn = {1477-030X}, mesh = {Humans ; *Palliative Care/standards/methods ; *Quality of Health Care/standards ; *Hypnotics and Sedatives/therapeutic use ; *Terminal Care/standards ; Female ; Male ; }, abstract = {BACKGROUND: Palliative sedation involves using sedatives to reduce consciousness until death. Though common in end-of-life care, it remains complex and controversial, with unclear quality parameters and limited guidance for improvement. A comprehensive overview of elements that reflect quality in palliative sedation is currently missing.<br><br>AIM: To identify quality reflecting elements for palliative sedation reported in peer-reviewed, indexed and gray literature.<br><br>DESIGN: Scoping review using Levac et al.'s methodological framework, including systematic searching, screening and narrative synthesis.<br><br>DATA SOURCES: Academic databases with indexed sources (MEDLINE, EMBASE, CENTRAL, CINAHL, PsycINFO) and databases also containing gray literature (MEDNAR, Web of Science) were searched between February and December 2023 for sources with primary data published after 2009, without restrictions on population or study design.<br><br>RESULTS: Among the 60 sources analyzed, 157 elements reflecting palliative sedation quality were identified and thematized into 22 themes and four overarching domains: (1) process elements of decision-making such as indication, proximity to death, timing, patient involvement, proactiveness, patient support, family involvement, artificial nutrition and hydration; (2) process elements of performance, such as level of sedation, medication use, monitoring, duration, care continuation, family support; (3) outcome elements covering patient comfort, family well-being, family satisfaction, professionals' well-being and satisfaction; (4) process elements of collaboration and documentation.<br><br>CONCLUSION: This scoping review found a broad range of elements reflecting palliative sedation quality - beyond clinical performance, sedation outcomes or patient level elements alone. These insights can inform the development of a core set of indicators to support quality monitoring in palliative sedation.}, }
@article {pmid40709087, year = {2025}, author = {Wang, G and Zhou, X and Pang, X and Ma, K and Li, L and Song, Y and Hou, D and Wang, X}, title = {Pharmacological effects, molecular mechanisms and strategies to improve bioavailability of curcumin in the treatment of neurodegenerative diseases.}, journal = {Frontiers in pharmacology}, volume = {16}, number = {}, pages = {1625821}, pmid = {40709087}, issn = {1663-9812}, abstract = {With the global population aging, the incidence of neurodegenerative diseases (NDs), such as Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis, has been progressively increasing. However, effective therapeutic strategies and clinical drugs for these disorders remain scarce. Curcumin, a natural polyphenolic compound primarily derived from the herbaceous plant Curcuma longa L., has been proposed as a promising candidate for ND treatment based on the excellent antioxidant, anti-inflammatory and neuroprotective properties. Its pharmacological activities encompass scavenging reactive oxygen species, mitigating toxic protein aggregation and cytotoxicity, repairing mitochondrial dysfunction, and inhibiting excessive neuronal apoptosis. Compared with synthetic drugs, curcumin demonstrates a more favorable safety profile with fewer side effects. Nevertheless, its clinical application is substantially hindered by poor bioavailability, which stems from low aqueous solubility, inefficient intestinal absorption, and rapid metabolism and systemic elimination. Conventional administration methods often fail to achieve effective concentrations in vivo. Further clinical trials are also required to validate the therapeutic efficacy and potential adverse effects in human subjects. This article systematically reviews the pathogenesis of NDs and the knowledge on curcumin including pharmacological effects, neuroprotective mechanisms, functions across specific NDs and advanced strategies to enhance the bioavailability, with the aim of promoting the development and clinical translation of curcumin-based therapeutics for NDs.}, }
@article {pmid40702789, year = {2025}, author = {Zota, I and Calogeropoulou, T and Chanoumidou, K and Charalampopoulos, I and Gravanis, A}, title = {Synthetic microneurotrophins: Neurotrophin receptors for therapeutics of neurodegenerative diseases.}, journal = {British journal of pharmacology}, volume = {182}, number = {19}, pages = {4466-4489}, doi = {10.1111/bph.70143}, pmid = {40702789}, issn = {1476-5381}, support = {Dinnesmin//FP7 Health/ ; //European Regional Development Fund of the European Union and Greek/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/metabolism ; Animals ; *Dehydroepiandrosterone/analogs &amp; derivatives/pharmacology/therapeutic use ; *Neuroprotective Agents/pharmacology/therapeutic use ; *Receptors, Nerve Growth Factor/metabolism ; Nerve Growth Factors ; Blood-Brain Barrier/metabolism ; }, abstract = {Neurodegenerative disorders are characterised by the chronic progressive degeneration of specific neuronal subtypes, neuroinflammation, myelin damage and synaptic loss. Despite their growing incidence, advancements in effective treatments remain limited, because of lack of knowledge for the aetiology of the diverse pathophysiology to design systematic therapies. Several studies highlight the role of neurotrophic factors (NTFs) as potential neuroprotective, regenerative therapies for these disorders. Although NTFs hold protective and regenerative potential for chronic neuroinflammatory and neurodegenerative conditions, major hurdles impair their clinical use, such as optimising the dosage of NTFs, minimising the invasiveness of delivery methods, overcoming blood-brain-barrier (BBB) impermeability and managing side effects. In the last two decades our group have synthesised and screened a large chemical library of steroidal analogues of dehydroepiandrosterone (DHEA), an endogenous steroid hormone, for their ability to mimic neurotrophin neuroprotective and neurogenic actions. Interestingly, DHEA was shown to interact with all neurotrophin receptors, acting most probably as an ancestral neurotrophin early in evolution. However, its chronic pharmacological use is questioned by its action as a major precursor of steroidogenesis. This review highlights the findings of numerous preclinical studies on these synthetic, non-toxic, BBB permeable DHEA derivatives, named microneurotrophins (MNTs), deprived of endocrine actions, activators of specific neurotrophin receptors. The multimodal actions of MNTs against neuronal death and activation of microglia, in addition to their beneficial effects in synaptogenesis and neurogenesis, place them as interesting lead molecules in the armamentarium of therapeutics for neurodegeneration.}, }
@article {pmid40702300, year = {2025}, author = {AlJuhani, AA and Desoky, RM and Binshalhoub, AA and Alzahrani, MJ and Alraythi, MS and Alzahrani, FF}, title = {Advances in postmortem interval estimation: A systematic review of machine learning and metabolomics across various tissue types.}, journal = {Forensic science, medicine, and pathology}, volume = {}, number = {}, pages = {}, pmid = {40702300}, issn = {1556-2891}, abstract = {BACKGROUND: Traditional postmortem interval (PMI) estimation methods rely on observable changes such as rigor mortis, livor mortis, and algor mortis but are often affected by environmental factors. Metabolomics, combined with techniques like nuclear magnetic resonance (NMR) and mass spectrometry, improves accuracy by identifying biochemical changes postmortem. Machine learning methods such as Principal Component Analysis (PCA), Partial Least Squares (PLS), and Support Vector Machines (SVMs), enhance PMI predictions by analyzing metabolite data. This review aims to summarize advances in using machine learning for PMI estimation and identify the optimal combination of tissue samples and algorithms for accurate predictions.<br><br>METHODS: We retrieved relevant articles up to September 2024 from PubMed, Scopus, Web of Science, IEEE, and Cochrane Library. Data were extracted from eligible studies by two independent reviewers. This included the number and species of subjects, tissue sample used, PMI range in the study, metabolic profiling technique, machine learning algorithms, potential PMI markers, and model performance.<br><br>RESULTS: We compared machine learning models for PMI estimation across various tissues. Zhang et al. (2022) had the best performance with a random forest (RF) model using cardiac blood, achieving a mean absolute error (MAE) of 1.067&#xa0;h by selecting key metabolites. Wu et al. (2017) followed with an orthogonal signal-corrected PLS model (R[2]&#x2009;>&#x2009;0.99, MAE 1.18-2.37&#xa0;h). Lu et al. (2022) achieved 93% accuracy with a multi-organ stacking model. Other promising models include Zhang et al.'s (2017) nu-SVM on pericardial fluid (RMSE&#x2009;=&#x2009;2.38&#xa0;h) and Sato et al.'s (2015) PLS model on cardiac blood (MAE&#x2009;=&#x2009;5.73&#xa0;h).<br><br>CONCLUSION: Cardiac blood is best for short PMIs with random forest models, while skeletal muscle and stacking models excel for longer PMIs. Future studies should refine and validate these findings as well as extend the findings to human subjects.}, }
@article {pmid40702249, year = {2025}, author = {Sulthana, N and Mittal, P and Goyal, A and Ballal, S and Maharana, L and Rana, AJ and Khan, Y and Goyal, K and Mishra, R and Ali, H and Gupta, G and Hussain, MS}, title = {Targeting ASK1 signaling in neurodegeneration: molecular insights and therapeutic promise.}, journal = {Apoptosis : an international journal on programmed cell death}, volume = {}, number = {}, pages = {}, pmid = {40702249}, issn = {1573-675X}, abstract = {Apoptosis signal-regulating kinase 1 (ASK1), a redox-sensitive member of the mitogen-activated protein kinase kinase kinase (MAP3K) family, is a master regulator of neuronal apoptosis as well as neuroinflammation in neurodegenerative disorders (NDs). Under oxidative and endoplasmic reticulum stress conditions, ASK1 sets off a series of pathways, ultimately leading to impairment of cellular functions and the cell's demise. The comprehensive review focuses on the diverse contributions of ASK1 to neurodegeneration driven by Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). Human and animal evidence links dysregulated ASK1 signaling is related to amyloid deposition, tau hyperphosphorylation, neuroinflammation, abnormal protein folding, and subsequent neurodegeneration. ASK1 plays a role in tau hyperphosphorylation and amyloid-beta-induced neurotoxicity in AD. ASK1-mediated apoptosis of dopaminergic neurons caused by oxidative stress and aggregation of α-synuclein contributes to PD. Furthermore, ASK1 activation is associated with motor neuron degeneration in ALS related to endoplasmic reticulum stress caused by mutant SOD1. Moreover, the pathogenesis of HD involves the activation of ASK1 by the cellular stress caused by mutant huntingtin protein. ASK1 signaling potentiates inflammatory signals in MS because it is involved in demyelination and neuronal injury. Nonetheless, obstacles persist such as developing brain-targeted therapies, reducing adverse systemic effects, and defining disease-stage-specific functions of ASK1. This review aims to comprehensively examine the role of ASK1 signaling in major NDs, discuss its upstream and downstream regulatory mechanisms, and evaluate the current and emerging therapeutic strategies targeting ASK1.}, }
@article {pmid40699743, year = {2025}, author = {Wang, S and Pan, L and Sun, C and Ma, C and Pan, H}, title = {Balancing Microglial Density and Activation in Central Nervous System Development and Disease.}, journal = {Current issues in molecular biology}, volume = {47}, number = {5}, pages = {}, pmid = {40699743}, issn = {1467-3045}, support = {32260194 to S.Wang, and 82071245 and 82360238 to H.Pan//National Natural Science Foundation of China/ ; 20224BAB206038 to S.Wang, 20224BAB206042 to C.Sun, and 20202ACB215003 and 20232ACB205008 to H.Pan//Natural Science Foundation of Jiangxi Province/ ; }, abstract = {Microglia, the resident immune cells of the central nervous system, play multifaceted roles in both health and disease. During development, they regulate neurogenesis and refine neural circuits through synaptic pruning. In adulthood, microglia maintain homeostasis and dynamically respond to pathological insults, where they contribute to responding to neuroinflammatory challenges. This review summarizes microglial contributions to neurodevelopment and also outlines their function across various neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, highlighting both protective and detrimental effects. Finally, recent advances in microglial-targeted therapies and lifestyle-based interventions are highlighted, underscoring the translational potential of modulating microglial states. Elucidating the dual roles of microglia in development and disease could guide the design of therapeutic strategies aimed at enhancing neuroprotection while minimizing neurotoxicity.}, }
@article {pmid40699658, year = {2025}, author = {Brezic, N and Gligorevic, S and Sic, A and Knezevic, NN}, title = {Protein Misfolding and Aggregation as a Mechanistic Link Between Chronic Pain and Neurodegenerative Diseases.}, journal = {Current issues in molecular biology}, volume = {47}, number = {4}, pages = {}, pmid = {40699658}, issn = {1467-3045}, abstract = {Chronic pain, defined by persistent pain beyond normal healing time, is a pervasive and debilitating condition affecting up to 30-50% of adults globally. In parallel, neurodegenerative diseases (NDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) are characterized by progressive neuronal loss and cognitive or motor decline, often underpinned by pathological protein misfolding and aggregation. Emerging evidence suggests a potential mechanistic link between chronic pain and NDs, with persistent pain contributing to neuroinflammatory states and protein homeostasis disturbances that mirror processes in neurodegeneration. This review explores the hypothesis that protein misfolding and aggregation serve as a mechanistic bridge between chronic pain and neurodegeneration. We systematically examine molecular pathways of protein misfolding, proteostasis dysfunction in chronic pain, and shared neuroimmune mechanisms, highlighting prion-like propagation of misfolded proteins, chronic neuroinflammation, and oxidative stress as common denominators. We further discuss evidence from experimental models and clinical studies linking chronic pain to accelerated neurodegenerative pathology-including tau accumulation, amyloid dysregulation, and microglial activation-and consider how these insights open avenues for novel therapeutics. Targeting protein aggregation, enhancing chaperone function, modulating the unfolded protein response (UPR), and attenuating glial activation are explored as potential strategies to mitigate chronic pain and possibly slow neurodegeneration. Understanding this intersection not only elucidates chronic pain's role in cognitive decline but also suggests that interventions addressing proteostasis and inflammation could yield dual benefits in pain management and neurodegenerative disease modification.}, }
@article {pmid40694206, year = {2025}, author = {Mahto, K and Kuwar, OK and Maloo, A and Kalia, N}, title = {Therapeutic potential of luteolin in neurodegenerative disorders: targeting Nrf2, NFĸB, MAPK, and JAK-STAT pathways to combat neuroinflammation and apoptosis.}, journal = {Inflammopharmacology}, volume = {}, number = {}, pages = {}, pmid = {40694206}, issn = {1568-5608}, abstract = {Neurodegenerative diseases, including Alzheimer's, Parkinson's, Huntington's disease, Multiple sclerosis and Amyotrophic Lateral Sclerosis, are characterized by progressive neuronal loss, oxidative stress, chronic neuroinflammation, mitochondrial dysfunction, and apoptosis. The Nrf2/ARE, IĸB/NFĸB, MAPK/AP-1, and JAK-STAT signaling pathways play a pivotal role in these pathological processes, making them promising therapeutic targets. Luteolin, a naturally occurring flavonoid, has demonstrated potent antioxidant, anti-inflammatory, and neuroprotective properties by modulating these interconnected pathways. Activation of Nrf2/ARE signaling by luteolin enhances cellular antioxidant defences, while its inhibition of NFĸB, MAPK/AP-1, and JAK-STAT pathways suppresses neuroinflammation and apoptotic signalling, thereby mitigating neuronal damage. Emerging evidences suggest that luteolin effectively reduces neurotoxic effects by regulating inflammatory cytokine production, stabilizing mitochondrial function, and maintaining redox homeostasis. Its ability to interfere with crosstalk between these signaling pathways highlights its potential as a multi-targeted neuroprotective agent. Preclinical studies have provided strong evidence supporting luteolin's role in mitigating neurodegeneration, suggesting its applicability in neurodegenerative disease management. These findings underscore the therapeutic potential of luteolin in neurodegenerative diseases by targeting multiple pathological mechanisms. However, further investigations are needed to fully elucidate its molecular mechanisms and optimize its therapeutic benefits.}, }
@article {pmid40694109, year = {2025}, author = {Levy, G and Schizas, C}, title = {Use and misuse of the sedimentation sign in lumbar spine stenosis.}, journal = {European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society}, volume = {}, number = {}, pages = {}, pmid = {40694109}, issn = {1432-0932}, abstract = {PURPOSE: The nerve root sedimentation sign (SedSign), introduced in 2010, is a radiological marker for lumbar spinal stenosis (LSS) on MRI. Despite widespread adoption, methodological inconsistencies in its application across studies have raised concerns about validity. This systematic review evaluated the accuracy of SedSign definitions and their impact on conclusions in published research.<br><br>METHODS: PubMed and Google Scholar were searched for articles utilising the SedSign. Definitions and illustrations were independently assessed by two authors against Barz et al.'s original criteria, classified as accurate, inaccurate, or absent. Study conclusions regarding SedSign's clinical and radiological utility were categorised as positive or negative. Journal metrics were analysed for correlation with reported accuracy.<br><br>RESULTS: Only 14 out of 31 studies applied the SedSign definition correctly. Of the 21 studies endorsing its utility, 10 used inaccurate definitions. Notably, 3 of 5 studies dismissing its value also misapplied the criteria. Inaccurate reporting showed no significant association with journal metrics.<br><br>CONCLUSION: Frequent misapplication of the SedSign in the literature may impact the reliability of research on lumbar spinal stenosis-even in high-impact journals. These findings expose a critical need for stricter adherence to validated radiological criteria and more vigilant peer review. Professional societies may play a key role in the future by developing comprehensive open-access guidelines to support researchers and reviewers in the standardized application of gradings and classifications, thereby enhancing consistency across studies. Ensuring methodological rigour is essential to minimise misleading conclusions with potential clinical implications.}, }
@article {pmid40688669, year = {2025}, author = {Zhu, RK and Shi, J and Zhou, HJ and Ge, L and Yin, WH and Zeng, H and Wang, XW}, title = {Biological applications of graphene-based nanomaterials in neurodegenerative diseases.}, journal = {Materials today. Bio}, volume = {33}, number = {}, pages = {102064}, pmid = {40688669}, issn = {2590-0064}, abstract = {Neurodegenerative diseases (NDDs) have become a major challenge in global public health due to neurotoxicity caused by progressive neuronal degeneration and abnormal protein aggregation, which has attracted widespread attention. Graphene-based nanomaterials provide innovative solutions for the early diagnosis and precise treatment of NDDs by virtue of their ultra-high conductivity, large specific surface area and multifunctional properties. In this paper, we systematically discuss the key applications of these materials in the diagnosis and treatment of NDDs, and deeply analyze the technological breakthroughs and clinical translation challenges. The core of this paper is to illustrate that graphene-based nanomaterials are expected to reshape the paradigm of NDDs diagnosis and treatment through cross-scale technological innovations, promoting the synergistic development of early diagnosis, personalized treatment and real-time monitoring, and providing a transformative strategy for overcoming NDDs.}, }
@article {pmid40685330, year = {2025}, author = {Far, BF and Akbari, M and Habibi, MA and Katavand, M and Nasseri, S}, title = {CRISPR Technology in Disease Management: An Updated Review of Clinical Translation and Therapeutic Potential.}, journal = {Cell proliferation}, volume = {}, number = {}, pages = {e70099}, doi = {10.1111/cpr.70099}, pmid = {40685330}, issn = {1365-2184}, abstract = {CRISPR-Cas9 technology has rapidly advanced as a transformative genome-editing platform, facilitating precise genetic modifications and expanding therapeutic opportunities across various diseases. This review explores recent developments and clinical translations of CRISPR applications in oncology, genetic and neurological disorders, infectious diseases, immunotherapy, diagnostics, and epigenome editing. CRISPR has notably progressed in oncology, where it enables the identification of novel cancer drivers, elucidation of resistance mechanisms, and improvement of immunotherapies through engineered T cells, including PD-1 knockout CAR-T cells. Clinical trials employing CRISPR-edited cells are demonstrating promising results in hematologic malignancies and solid tumours. In genetic disorders, such as hemoglobinopathies and muscular dystrophies, CRISPR-Cas9 alongside advanced editors like base and prime editors show significant potential for correcting pathogenic mutations. This potential was affirmed with the FDA's first approval of a CRISPR-based therapy, Casgevy, for sickle cell disease in 2023. Neurological disorders, including Alzheimer's, ALS, and Huntington's disease, are increasingly targeted by CRISPR approaches for disease modelling and potential therapeutic intervention. In infectious diseases, CRISPR-based diagnostics such as SHERLOCK and DETECTR provide rapid, sensitive nucleic acid detection, particularly valuable in pathogen outbreaks like SARS-CoV-2. Therapeutically, CRISPR systems target viral and bacterial genomes, offering novel treatment modalities. Additionally, CRISPR-mediated epigenome editing enables precise regulation of gene expression, expanding therapeutic possibilities. Despite these advances, significant challenges remain, including off-target effects, delivery methodologies, immune responses, and long-term genomic safety concerns. Future improvements in editor precision, innovative delivery platforms, and enhanced safety assessments will be essential to fully integrate CRISPR-based interventions into standard clinical practice, significantly advancing personalised medicine.}, }
@article {pmid40683546, year = {2025}, author = {Mehboodi, M and Namdari, MP and Abdollahi, Z and Mobarezi, Z and Kiani, M and Chamani, F and Khanbabaie, H and Rabiei, S and Maleki, MH and Sanati, H and Shahedin, GJ and Isaei, E}, title = {The relationship between increased levels of microbiota-derived lipopolysaccharide in obesity and the pathophysiology of neurodegenerative diseases.}, journal = {Microbial pathogenesis}, volume = {207}, number = {}, pages = {107905}, doi = {10.1016/j.micpath.2025.107905}, pmid = {40683546}, issn = {1096-1208}, mesh = {Humans ; *Lipopolysaccharides/metabolism ; *Obesity/microbiology/complications ; *Neurodegenerative Diseases/physiopathology/microbiology/etiology ; *Gastrointestinal Microbiome/physiology ; Animals ; Inflammation ; Blood-Brain Barrier ; Oxidative Stress ; }, abstract = {Lipopolysaccharide (LPS), a potent pro-inflammatory endotoxin derived from the outer membrane of Gram-negative bacteria, has been identified as a crucial link between obesity-related systemic inflammation and the onset of neurodegenerative diseases. Modifications in gut microbiota associated with obesity disrupt the integrity of the intestinal barrier, resulting in increased permeability and heightened levels of circulating LPS a phenomenon known as metabolic endotoxemia. The elevated presence of LPS promotes persistent low-grade inflammation and oxidative stress, both of which are critical contributors to neurodegeneration. This review aims to explore the biological pathways through which LPS influences the development and advancement of neurodegenerative diseases, including Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS). The role of LPS in exacerbating neuroinflammation through the activation of microglia and the impairment of the blood-brain barrier (BBB) is thoroughly examined. Moreover, the review delves into the interrelated effects of obesity-related systemic inflammation, insulin resistance, and mitochondrial dysfunction in enhancing LPS-driven neurodegenerative mechanisms. Special emphasis is placed on the common pathological characteristics present in these disorders, such as protein misfolding, neuronal apoptosis, and disrupted synaptic function, which may be exacerbated by LPS-related processes. By clarifying the relationships between obesity, LPS, and neurodegenerative diseases, this review underscores potential therapeutic approaches aimed at modulating gut microbiota, improving intestinal barrier function, and mitigating systemic inflammation to prevent or decelerate the progression of these debilitating disorders.}, }
@article {pmid40682794, year = {2025}, author = {Sheikh Saleh, D and Mraer, L and Fatima, H and Gubari, H and Alsayed, MA and Hassan, FE}, title = {Decoding the Dialogue: Immunity and central nervous system interactions in neurodegenerative diseases.}, journal = {The Egyptian journal of immunology}, volume = {32}, number = {3}, pages = {20-31}, doi = {10.55133/eji.320303}, pmid = {40682794}, issn = {1110-4902}, mesh = {Humans ; *Neurodegenerative Diseases/immunology ; *Central Nervous System/immunology ; Animals ; Immunity, Innate ; *Neuroimmunomodulation ; Microglia/immunology ; Astrocytes/immunology ; Blood-Brain Barrier/immunology ; }, abstract = {This review article aims to discuss neuroimmune interactions by emphasizing the role of central and peripheral immunities in central nervous system (CNS) protection and function, as well as how abnormalities in this relationship may be implicated in the genesis of neurodegenerative diseases (NDDs). Immune elements that play roles within the CNS both during stable and infectious states are described. Innate CNS immunity is explored as a distinct entity comprised of the brain blood barrier, CNS parenchyma, and resident immune cells-microglia and astrocytes, whose roles in antigen recognition and clearance and neuromodulation are further enumerated. Due to the inability of the CNS to independently initiate an adaptive immune response, the necessary recruitment and regulation of elements from the peripheral immune system (PIS) are described in a process that, in chief, utilizes resident antigen-presenting cells to prime naïve T-cells, which later enter the CNS through areas of access to the cerebrospinal fluid. The previous modes of interaction especially enable microglia, astrocytes, and T-cells to play part in neurodevelopment and plasticity, and the proposed mechanisms by which they participate in synaptic pruning, neurogenesis, and memory are examined. In addition to its protective role, the PIS has also been shown to play a regulatory role in the CNS, where it drives responses that optimize immune function, such as fever and sickness behavior. Due to the high level of involvement of the immune system within the CNS, dysregulations of the immune system are thought to be implicated in numerous NDD pathogeneses, where neuroinflammation both causes and is caused by immune reactions. Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis are particularly discussed.}, }
@article {pmid40681220, year = {2025}, author = {Abd El-Aziz, MK and Wadan, AS and Albahttiti, ATI and Moradikor, N}, title = {Emotional stress and cardiovascular health: Impacts on neurodegenerative disease progression.}, journal = {Progress in brain research}, volume = {294}, number = {}, pages = {101-133}, doi = {10.1016/bs.pbr.2025.04.004}, pmid = {40681220}, issn = {1875-7855}, mesh = {Humans ; *Stress, Psychological/physiopathology/complications/metabolism ; *Neurodegenerative Diseases/physiopathology/metabolism ; *Cardiovascular Diseases/physiopathology/metabolism ; Disease Progression ; Hypothalamo-Hypophyseal System/physiopathology/metabolism ; Pituitary-Adrenal System/physiopathology/metabolism ; }, abstract = {Stress is an inevitable part of people's lives and is considered to have a severe impact on health, especially in the case of cardiovascular diseases and neurodegenerative diseases. This chapter aims to reveal the links between emotional stress, cardiovascular health, and neurodegenerative disease progression. Chronic stress is therefore recognized as a significant cause of cardiovascular diseases mainly because of the effects it has on the hypothalamic-pituitary-adrenal (HPA) axis and the (SNS) sympathetic which neurodegenerative nervous are diseases system such (as ALS) through inflammation of Alzheimer's mechanisms and disease, vascular such as Parkinson's functions. The mechanisms of work also establish the crosstalk between CVD and NDD, demonstrating that they share genetic, molecular, and systemic associations. It is essential to know these pathways to design interventions that will help prevent or lessen the effects of stress on health and thus enhance patient care.}, }
@article {pmid40675338, year = {2025}, author = {Shtilbans, A}, title = {Combination Supplement Therapy: A New Frontier in Treatment of Neurodegenerative Diseases.}, journal = {The Journal of nutrition}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tjnut.2025.07.004}, pmid = {40675338}, issn = {1541-6100}, abstract = {This review highlights the importance and potential beneficial effects of dietary supplements, including taurine, tauroursodeoxycholic acid (TUDCA), curcumin, coenzyme Q10, creatine, and N-acetylcysteine, in the management of neurodegenerative diseases. Studies in preclinical models have consistently shown significant potential of these supplements in mitigating neurodegenerative pathology. Through a range of mechanisms targeting different molecular pathways, these supplements demonstrate therapeutic outcomes in preclinical models of conditions such as Parkinson disease, Alzheimer disease, amyotrophic lateral sclerosis, and Huntington disease. This review discusses published data on each of these supplements in the context of neurodegenerative diseases. It also discusses a combination therapy concept and proposes a strategy to formulate an optimal blend of these supplements. This combination approach will target key processes, including mitochondrial dysfunction, protein misfolding, neuroinflammation, and oxidative stress responsible for neurodegenerative conditions. Additionally, this review examines various models used for both the initial screening and subsequent assessment of candidate supplement combinations.}, }
@article {pmid40673975, year = {2025}, author = {Giorgi, A and Heckman, CJ and Perreault, MC}, title = {Spinally Projecting Serotonergic Neurons in Motor Network Modulation.}, journal = {Journal of neurophysiology}, volume = {}, number = {}, pages = {}, doi = {10.1152/jn.00139.2025}, pmid = {40673975}, issn = {1522-1598}, support = {20153//National Science Foundation (NSF)/ ; }, abstract = {Spinally projecting serotonergic (5-HTsp) neurons represent a heterogeneous population of neurons in the brainstem whose relevance in the control of movement has largely been inferred. Numerous studies across a variety of species have suggested that 5-HTsp neurons exert a widespread influence on spinal sensorimotor networks, operating at multiple levels (primary afferents, interneurons, and motoneurons) through various serotonin receptor subtypes. However, despite the anatomical and neurochemical complexity of the 5-HTsp system, most supporting evidence has largely been derived from indirect approaches (e.g., exogenous application of 5-HT and agonists/antagonists of 5-HT receptors). Direct demonstrations of specific anatomical and functional connectivity have been limited, occasionally yielding apparent discrepant results. Consequently, as the primary provider of serotonin to the spinal cord, the exact contributions of the 5-HTsp neurons remain to be fully elucidated. For this mini-review, we sifted through the literature of the last six decades, starting after the characterization of the brainstem raphe nuclei and monoaminergic systems [1-3], to provide a clearer picture of what is currently known of the anatomy and influences of the different populations of 5-HTsp neurons on sensorimotor circuits and motor behaviors. We focused on studies reporting direct manipulation of brainstem 5-HTsp neurons, excluding those targeting 5-HT neurotransmission by exogenous application of 5-HT. This emphasis aims to highlight the urgency of resolving how 5-HTsp neuron subpopulations differentiate anatomically and functionally, so that they can be integrated as dedicated components in current models of supraspinal control of movement and motor diseases such as Parkinson's and amyotrophic lateral sclerosis. Along the way, we point out gaps in knowledge that may be filled using newly available research tools.}, }
@article {pmid40664112, year = {2025}, author = {Sahoo, BR and Bardwell, JC}, title = {Protein and RNA chaperones.}, journal = {Molecular aspects of medicine}, volume = {104}, number = {}, pages = {101384}, doi = {10.1016/j.mam.2025.101384}, pmid = {40664112}, issn = {1872-9452}, mesh = {Humans ; *Molecular Chaperones/metabolism/chemistry ; *RNA/metabolism/chemistry ; G-Quadruplexes ; Animals ; Protein Folding ; Protein Aggregates ; *RNA-Binding Proteins/metabolism/chemistry ; Amyotrophic Lateral Sclerosis/metabolism ; }, abstract = {Cells preserve macromolecular homeostasis by utilizing molecular chaperones that prevent aggregation or promote correct folding of protein and RNA. Here we discuss non-traditional proteinaceous chaperones like RNA-binding chaperones that work by modulating RNA structure, preventing aberrant interactions, and regulating intracellular granule dynamics. We also discuss the chaperone functions of other macromolecules such as nucleic acids, and in particular G-quadruplexes, which are very effective at preventing protein aggregation and accelerating protein folding. These chaperones are particularly important in G-quadruplex linked amyloid aggregation and repeat-expansion diseases such as Parkinson's disease and amyotrophic lateral sclerosis, where RNA aggregation and misfolded protein accumulation co-occur. By comparing protein and non-protein chaperone systems, we highlight the principles that underlie chaperone action across molecular classes.}, }
@article {pmid40663766, year = {2025}, author = {Matthews, AM and Whiteley, AM}, title = {UBQLN2 in neurodegenerative disease: mechanistic insights and emerging therapeutic potential.}, journal = {Biochemical Society transactions}, volume = {53}, number = {4}, pages = {823-833}, pmid = {40663766}, issn = {1470-8752}, support = {R01 NS131660/NS/NINDS NIH HHS/United States ; T32 GM142607/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; Autophagy-Related Proteins/genetics/metabolism ; *Adaptor Proteins, Signal Transducing/genetics/metabolism ; *Neurodegenerative Diseases/metabolism/genetics/therapy ; Animals ; Amyotrophic Lateral Sclerosis/genetics/metabolism ; Autophagy ; Mutation ; Mitochondria/metabolism ; Frontotemporal Dementia/genetics/metabolism ; *Cell Cycle Proteins/genetics/metabolism ; }, abstract = {Ubiquilins (UBQLNs) regulate cellular protein turnover by shuttling proteins, or 'clients', to the proteasome or autophagy pathways for degradation. Of the five different UBQLN genes in humans, UBQLN2 is the most highly expressed in the nervous system and muscle tissue and has been linked to multiple neurodegenerative diseases. In particular, point mutations of UBQLN2 cause an X-linked, dominant form of amyotrophic lateral sclerosis (ALS), ALS with frontotemporal dementia (ALS/FTD), or FTD. Failed protein degradation is a hallmark of many neurodegenerative diseases, including ALS and FTD; however, it is not clear exactly how ALS/FTD-associated UBQLN2 mutations contribute to pathogenesis. Recent studies have revealed the complexity of UBQLN2 biology and allow deeper understanding as to how UBQLN2 dysfunction may contribute to neurodegenerative disease. UBQLN2 is necessary for mitochondrial protein degradation and for regulating mitochondrial turnover, both of which are essential for motor neurons and have been implicated in the pathogenesis of ALS. Stress granule (SG) formation and regulation are also affected by UBQLN2 mutations, and their dysregulation may contribute to the toxic protein aggregation and SG changes observed in neurodegenerative disease. Finally, there are compelling links connecting UBQLN2 dysfunction with changes to downstream neuronal morphology, function, and behavior. This review will detail the emerging consensus on how UBQLN2 protects against neurodegenerative disease and will provide insights into potential therapeutic approaches.}, }
@article {pmid40661315, year = {2025}, author = {Anjum, F and Bakhuraysah, M and Alsharif, A and Mohammad, T and Shamsi, A and Hassan, MI}, title = {Emerging biomarkers in amyotrophic lateral sclerosis: from pathogenesis to clinical applications.}, journal = {Frontiers in molecular biosciences}, volume = {12}, number = {}, pages = {1608853}, pmid = {40661315}, issn = {2296-889X}, abstract = {Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative condition marked by the gradual loss of motor neurons in the brain and spinal cord. As the most common adult-onset motor neuron disease, ALS manifests through gradually worsening muscle weakness that ultimately progresses to complete paralysis. The disease presents in both sporadic and familial forms. Diagnosis is often delayed until substantial and irreversible motor neuron damage has already occurred. Clinical outcomes in ALS have only been defined through large-scale clinical trials with lengthy follow-up periods due to the disease's inherent heterogeneity and the absence of disease-specific biomarkers. Current biomarker detection methods, such as invasive cerebrospinal fluid (CSF) analysis or advanced imaging, are impractical for routine use, particularly in late-stage ALS. Several blood-based biomarkers have shown promise, including neurofilament levels, cryptic RNA-derived peptides, and immune-mediated changes, which may enable non-invasive monitoring. Nevertheless, the development of these methods is hindered by technical challenges, such as blood matrix interference and low analyte abundance. Among the emerging biomarkers, neurofilament light chain (NfL) appears to be the most promising, as its concentrations change in line with disease progression and distinguish clinically relevant groups. NfL facilitates patient stratification based on clinical progression rates (e.g., rapid vs slow progressors), while cryptic exon-derived peptides, such as UNC13A-derived peptides, enable genetic stratification by identifying molecular subtypes linked to TDP-43 pathology (e.g., C9orf72 vs sporadic ALS). These biomarkers hold promise to optimize clinical trial design through enriched cohort selection and accelerating therapeutic translation by monitoring target engagement. In this review, we have summarized recent developments in ALS biomarker studies, focusing on neurofilaments in each biofluid, transcriptomic signatures, and neuroinflammatory biomarkers, emphasizing technical challenges surrounding reproducibility in measurement. Finally, we discussed the potential integration of these biomarkers into clinical practice to advance drug development through precision medicine, thereby enabling shorter and more targeted clinical trials.}, }
@article {pmid40658257, year = {2025}, author = {Fasano, A and Vacchiano, V and Bonan, L and McMackin, R and Nasseroleslami, B and Hardiman, O and Liguori, R}, title = {Neurophysiological biomarkers of networks impairment in amyotrophic lateral sclerosis.}, journal = {Journal of neurology}, volume = {272}, number = {8}, pages = {507}, pmid = {40658257}, issn = {1432-1459}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnosis ; Biomarkers ; Transcranial Magnetic Stimulation ; *Nerve Net/physiopathology ; Electroencephalography ; Electromyography ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a heterogeneous disease involving motor system as well as cognitive domains. There is an urgent need for objective biomarkers that can subcategorize subjects into homogeneous groups based on disease pathobiology.In this review, we discuss novel neurophysiological techniques that provide detailed, multiscale and multidimensional insights into ALS networks impairment, spanning from the micro-columnar architecture of the motor cortex to motor and cognitive networks. Specifically, Transcranial Magnetic Stimulation (TMS) paradigms can be used to evaluate the status of excitatory and inhibitory networks within the layers of the motor cortex. Abnormalities in functional connectivity between the two motor areas, as well as within the frontal-temporal and frontal parietal networks, can be characterized using novel source-localization analysis of high-density electroencephalography (EEG). TMS and EEG techniques provide data that correlate with both motor and cognitive impairment. Furthermore, cortico-muscular coherence analysis can be used to assess functional dysregulation within the entire motor system, and novel surface electromyography (EMG) techniques, such as motor unit number estimation, motor unit number index, and nerve excitability testing studies provide useful insights into axonal loss and membrane ion channel dysfunctions in lower motor neurons.The integrated analysis of these biomarkers provides valuable insights into the clinical and biologic heterogeneity of the disease, aiding the intelligent design of next generation precision-based therapeutics.}, }
@article {pmid40657896, year = {2025}, author = {Dogra, SR and Bhonsle, J and Sharma, A}, title = {MicroRNA Dysregulation in Neurodegeneration: Role, Biomarker Potential and Therapeutics.}, journal = {The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques}, volume = {}, number = {}, pages = {1-12}, doi = {10.1017/cjn.2025.10361}, pmid = {40657896}, issn = {0317-1671}, abstract = {Neurodegenerative diseases (NDDs) are a group of complex disorders marked by pathophysiological mechanisms involving protein aggregation, mitochondrial dysfunction, oxidative stress and neuroinflammation. Irrespective of extensive research advances, NDDs have become a serious global concern and persist as a major therapeutic challenge. In recent years, microRNAs (miRNAs), a class of small non-coding RNAs, have established a pivotal role in combating NDDs. The altered expression of miRNAs is reported to be associated with the progression of various NDDs. This review aims to discuss miRNA biogenesis; dysregulation in NDDs, specifically Alzheimer's disease, Parkinson's disease (PD) and amyotrophic lateral sclerosis; their potential as biomarkers; and promising therapeutic targets. Additionally, there are various emerging technologies discussed that are advanced approaches to enhance miRNA-based diagnostics and therapeutics.}, }
@article {pmid40652712, year = {2025}, author = {Brüge, A and Ponimaskin, E and Labus, J}, title = {Targeting the serotonergic system in the treatment of neurodegenerative diseases-emerging therapies and unmet challenges.}, journal = {Pharmacological reviews}, volume = {77}, number = {5}, pages = {100071}, doi = {10.1016/j.pharmr.2025.100071}, pmid = {40652712}, issn = {1521-0081}, abstract = {More than 65 million people worldwide experience neurodegenerative diseases, such as Alzheimer disease, frontotemporal dementia, Parkinson disease, and amyotrophic lateral sclerosis. As the risk of developing these diseases increases with age, increasing life expectancy will further accelerate their prevalence. Despite major advances in the understanding of the molecular mechanisms of neurodegeneration, no curative therapy is available to date. Neurodegenerative diseases are known to be associated with alterations in serotonergic neurotransmission, which might critically contribute to the pathogenesis of these diseases. Therefore, targeting the serotonergic system appears to be a promising therapeutic approach. In this review, we provide a comprehensive overview of pathological changes in serotonergic neurotransmission in different neurodegenerative diseases and discuss novel treatment strategies based on targeted modulation of the serotonergic system. We primarily focus on the therapeutic approaches modulating serotonin homeostasis, its biosynthesis, and the modulation of defined serotonin receptors. SIGNIFICANCE STATEMENT: A common feature of multiple neurodegenerative diseases is dysregulation of the serotonergic system at the cellular, molecular, and genetic levels that strongly contributes to specific pathological phenotypes. Targeting these alterations represents a suitable therapeutic strategy to combat disease-relevant pathomechanisms, slow down disease progression, and overcome pathological consequences.}, }
@article {pmid40651187, year = {2025}, author = {Chang, J and Teo, AH and Shaw, TB and Dupuis, L and Ngo, ST and Steyn, FJ}, title = {Deciphering hypothalamic pathology in ALS: insights into non-motor symptoms and disease progression.}, journal = {EBioMedicine}, volume = {118}, number = {}, pages = {105845}, pmid = {40651187}, issn = {2352-3964}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology/metabolism/etiology/physiopathology/diagnosis ; *Hypothalamus/pathology/metabolism/diagnostic imaging/physiopathology ; Disease Progression ; Animals ; Biomarkers ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with highly heterogeneous clinical presentations. Among the non-motor features increasingly recognised as clinically relevant is the dysregulation of energy balance, with weight loss-particularly due to fat mass loss-emerging as a significant modifier of disease risk, progression, and survival. In this context, the hypothalamus-a key regulator of homeostatic and metabolic processes-has gained attention for its potential role in ALS pathophysiology. This Review synthesises emerging evidence of hypothalamic involvement in ALS, including neuronal loss, proteinopathy, and volume loss observed through histological and neuroimaging studies. We critically examine current imaging approaches and their technical limitations and explore neuroendocrine dysfunction across the hypothalamic-pituitary axes. Collectively, these findings suggest that hypothalamic dysfunction may contribute to clinically relevant metabolic, sleep, behavioural, and cognitive changes in ALS, adding to our understanding of ALS as a multisystem disease. Continued investigation of the hypothalamus may reveal novel biomarkers, inform risk stratification, and identify therapeutic opportunities to address disease heterogeneity and improve clinical outcomes.}, }
@article {pmid40650046, year = {2025}, author = {Cattaneo, M and Giagnorio, E and Lauria, G and Marcuzzo, S}, title = {Therapeutic Approaches for C9ORF72-Related ALS: Current Strategies and Future Horizons.}, journal = {International journal of molecular sciences}, volume = {26}, number = {13}, pages = {}, pmid = {40650046}, issn = {1422-0067}, support = {//Italian Ministry of Health (RRC)/ ; T4-AN-09 prog. ZRPOS2//CALabria HUB per Ricerca Innovativa ed Avanzata- CALHUB.RIA "Creazione di Hub delle Sci-enze della Vita"/ ; prog. ZRA124//AriSLA foundation, "Bulb-Omics"/ ; PNRR-MCNT2-2023-12377336//the European Union - Next Generation EU - NRRP M6C2 - Investment 2.1 Enhancement and strengthening of biomedical research in the NHS,/ ; }, mesh = {Humans ; *C9orf72 Protein/genetics/metabolism ; *Amyotrophic Lateral Sclerosis/genetics/therapy/metabolism/pathology ; Animals ; DNA Repeat Expansion ; Gene Editing ; Genetic Therapy/methods ; Mutation ; Oligonucleotides, Antisense/therapeutic use ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of upper and lower motor neurons. One of its major genetic causes is C9ORF72, where mutations lead to hexanucleotide repeat expansions in the C9ORF72 gene. These expansions drive disease progression through mechanisms, including the formation of toxic RNAs and the accumulation of damaged proteins such as dipeptide repeats (DPRs). This review highlights these pathogenic mechanisms, focusing on RNA foci formation and the accumulation of toxic DPRs, which contribute to neuronal damage. It also discusses promising targeted therapies, including small molecules and biological drugs, designed to counteract these specific molecular events. Small molecules such as G-quadruplex stabilizers, proteasome and autophagy modulators, and RNase-targeting chimeras show potential in reducing RNA foci and DPR accumulation. Furthermore, targeting enzymes involved in repeat-associated non-AUG (RAN) translation and nucleocytoplasmic transport, which are crucial for disease pathogenesis, opens new therapeutic avenues. Even some anti-viral drugs show encouraging results in preclinical studies. Biological drugs, such as antisense oligonucleotides and gene-editing technologies like CRISPR-Cas, were explored for their potential to specifically target C9ORF72 mutations and modify the disease's molecular foundations. While preclinical and early clinical data show promise, challenges remain in optimizing delivery methods, ensuring long-term safety, and improving efficacy. This review concludes by emphasizing the importance of continued research and the potential for these therapies to alter the disease trajectory and improve patient outcomes.}, }
@article {pmid40649976, year = {2025}, author = {Jiménez-García, AM and Tortorella, ME and Nishimura, AL and Arias, N}, title = {The Differential Effects of Genetic Mutations in ALS and FTD Genes on Behavioural and Cognitive Changes: A Systematic Review and Meta-Analysis.}, journal = {International journal of molecular sciences}, volume = {26}, number = {13}, pages = {}, pmid = {40649976}, issn = {1422-0067}, support = {PID2023-151715OB-IOO//Ministry of Science and Innovation/ ; PLEC2022-009464//European Union NextGeneration EU/PRTR/ ; CPP2022-009646//European Union NextGeneration EU/PRTR/ ; }, mesh = {Humans ; *Frontotemporal Dementia/genetics/psychology ; *Amyotrophic Lateral Sclerosis/genetics/psychology ; *Mutation ; *Cognition ; tau Proteins/genetics ; C9orf72 Protein/genetics ; Progranulins/genetics ; Superoxide Dismutase-1/genetics ; Endosomal Sorting Complexes Required for Transport/genetics ; RNA-Binding Protein FUS/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are linked by shared genetic mutations and overlapping clinical features, forming a clinical spectrum. This systematic review and meta-analysis analysed 97 studies, including 3212 patients with key ALS/FTD gene mutations, to identify gene-specific behavioural profiles. Chromosome 9 open reading frame 72 (C9orf72) mutations were strongly associated with psychotic symptoms and aggression, while superoxide dismutase 1 (SOD1) mutations had minimal cognitive effects. Progranulin (PGRN) mutations correlated with apathy and hallucinations, microtubule-associated protein tau (MAPT) mutations with disinhibition, and charged multivesicular body protein 2B (CHMP2B) with social impairments. Fused in sarcoma (FUS) mutations caused early sleep disturbances, TANK-binding kinase 1 (TBK1) led to disinhibition, and presenilin 1 and 2 (PSEN1/2) was linked to severe aggression. Prodromal cognitive changes in PGRN, MAPT, and CHMP2B mutations suggested early disease onset. Despite overlapping symptoms and clinical heterogeneity, understanding gene-specific patterns could inform tailored care strategies to enhance the quality of life for ALS and FTD patients. This study calls for refined guidelines integrating genetic behavioural profiles to improve patient and family support.}, }
@article {pmid40649921, year = {2025}, author = {Neumann, S and Heumann, R}, title = {Is the Voltage-Dependent Anion Channel a Major Player in Neurodegenerative Diseases?.}, journal = {International journal of molecular sciences}, volume = {26}, number = {13}, pages = {}, pmid = {40649921}, issn = {1422-0067}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/pathology ; *Voltage-Dependent Anion Channels/metabolism/genetics ; Animals ; Mitochondria/metabolism ; }, abstract = {The family of voltage-dependent anion channels (VDACs) comprises three isoforms (VDAC-1, VDAC-2, VDAC-3). VDACs have been extensively described as localised in the outer mitochondrial membrane where they are involved in the exchange of ions, metabolites, and ATP/ADP between mitochondria and cytosol. The VDAC interacts with disease-specific proteins and thus regulates the mitochondrial function and controls the cellular energy resources, explaining its involvement in cell death and apoptosis. In addition, VDAC-1 and -2 can also be found at other cellular locations such as in the sarcoplasmic reticulum, in the endoplasmic reticulum, as well as in the plasma membrane. Through single-channel pore regulation, oligomerisation, or changed expression levels the VDAC is involved in different neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis, Huntington's disease, and others. Here, we critically summarise current discussions about the VDAC as a common key player for these diseases. We suggest that the VDAC acts as a transmembrane multifunctional regulatory protein which might serve as a pharmacological target for the development of novel drugs against neurodegenerative diseases such as the application of recombinant antibody technology.}, }
@article {pmid40649859, year = {2025}, author = {Tomczak, J and Kapsa, A and Boczek, T}, title = {Adenylyl Cyclases as Therapeutic Targets in Neuroregeneration.}, journal = {International journal of molecular sciences}, volume = {26}, number = {13}, pages = {}, pmid = {40649859}, issn = {1422-0067}, support = {2020/39/D/NZ4/01250//National Science Center/ ; }, mesh = {Humans ; *Adenylyl Cyclases/metabolism ; Animals ; *Nerve Regeneration/drug effects ; Signal Transduction/drug effects ; Cyclic AMP/metabolism ; *Neurodegenerative Diseases/drug therapy/metabolism ; Neuronal Plasticity ; }, abstract = {Adenylyl cyclases (ACs) are key regulators of cyclic adenosine monophosphate (cAMP) signaling-a pathway critical for neuroregeneration, synaptic plasticity, and neuronal survival. In both the central and peripheral nervous systems, injury-induced activation of ACs promotes axonal outgrowth and functional recovery through the stimulation of protein kinase A (PKA), exchange proteins directly activated by cAMP (Epac), and cAMP-response element-binding protein (CREB). Among the various AC isoforms, calcium-sensitive AC1, AC8, and AC5, as well as bicarbonate-responsive soluble AC (sAC), have emerged as crucial mediators of neuroplasticity and axon regeneration. These isoforms coordinate diverse cellular responses-including gene transcription, cytoskeletal remodeling, and neurotransmitter release-to metabolic, synaptic, and injury-related signals. Dysregulation of AC activity has been implicated in the pathophysiology of neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis, as well as in chronic pain syndromes. Pharmacological modulation of cAMP levels through AC activation, phosphodiesterase (PDE) inhibition, or pituitary adenylyl cyclase-activating polypeptide (PACAP) receptor signaling has shown therapeutic promise in preclinical models by enhancing neurogenesis, remyelination, and synaptic repair. Conversely, targeted inhibition of specific AC isoforms, particularly AC1, has demonstrated efficacy in reducing maladaptive plasticity and neuropathic pain. This review highlights the diverse roles of ACs in neuronal function and injury response and discusses emerging strategies for their therapeutic targeting.}, }
@article {pmid40648551, year = {2025}, author = {Al-Ajlouni, YA and Al Ta'ani, O and Zweig, SA and Bak, M and Tanashat, M and Gabr, A and Khamis, Z and Al-Bitar, F and Islam, M}, title = {Assessing the Therapeutic Role of Rehabilitation Programs in Chemotherapy-Induced Peripheral Neuropathy (CIPN)-A Scoping Review.}, journal = {Healthcare (Basel, Switzerland)}, volume = {13}, number = {13}, pages = {}, pmid = {40648551}, issn = {2227-9032}, abstract = {Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common, debilitating side effect of cancer treatment. Characterized by symptoms like pain, numbness, and muscle weakness, CIPN significantly impacts patients' quality of life. Current management strategies vary, with limited consensus on effective treatments. This scoping review aims to explore comprehensive rehabilitation interventions for CIPN, focusing on enhancing patient well-being and functional abilities. Methods: A scoping review, guided by Arksey and O'Malley's framework and Levac et al.'s refinements, was conducted to assess rehabilitation programs for CIPN. Searches across six databases were performed, with inclusion and exclusion criteria focusing on studies with physical rehabilitation interventions. Data were charted, detailing interventions, demographics, and outcomes. Results were synthesized descriptively and presented narratively with tables. Results: The review included 24 studies covering diverse cancer types and treatments, involving a total of 1167 participants. Various interventions for CIPN were assessed, and results were thematically categorized according to exercise category. Physical modalities like ultrasound and exercise showed promise in symptom relief for colorectal and breast cancer patients. No distinct advantage was found in the timing of exercise interventions. Complementary therapies such as acupuncture and yoga demonstrated effectiveness in managing CIPN symptoms. Conclusions: This review highlights the effectiveness of diverse physical and complementary interventions in managing CIPN, advocating for their integration into standard protocols. It emphasizes the need for holistic, patient-centered approaches that combine exercises, physical therapy, and complementary therapies to improve patient outcomes. These findings set a direction for future research and clinical practices focused on comprehensive and personalized CIPN management strategies.}, }
@article {pmid40646945, year = {2025}, author = {Davì, F and Iaconis, A and Cordaro, M and Di Paola, R and Fusco, R}, title = {Nutraceutical Strategies for Targeting Mitochondrial Dysfunction in Neurodegenerative Diseases.}, journal = {Foods (Basel, Switzerland)}, volume = {14}, number = {13}, pages = {}, pmid = {40646945}, issn = {2304-8158}, abstract = {In neurons, mitochondria generate energy through ATP production, thereby sustaining the high energy demands of the central nervous system (CNS). Mitochondrial dysfunction within the CNS was implicated in the pathogenesis and progression of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis, often involving altered mitochondrial dynamics like fragmentation and functional impairment. Accordingly, mitochondrial targeting represents an alternative therapeutic strategy for the treatment of these disorders. Current standard drug treatments present limitations due to adverse effects associated with their chronic use. Therefore, in recent years, nutraceuticals, natural compounds exhibiting diverse biological activities, have garnered significant attention for their potential to treat these diseases. It has been shown that these compounds represent safe and easily available sources for the development of innovative therapeutics, and by modulating mitochondrial function, nutraceuticals offer a promising approach to address neurodegenerative pathologies. We referred to approximately 200 articles published between 2020 and 2025, identified through a focused search across PubMed, Google Scholar, and Scopus using keywords such as "nutraceutical," "mitochondrial dysfunction," and "neurodegenerative diseases. The purpose of this review is to examine how mitochondrial dysfunction contributes to the genesis and progression of neurodegenerative diseases. Also, we discuss recent advances in mitochondrial targeting using nutraceuticals, focusing on their mechanisms of action related to mitochondrial biogenesis, fusion, fission, bioenergetics, oxidative stress, calcium homeostasis, membrane potential, and mitochondrial DNA stability.}, }
@article {pmid40641139, year = {2025}, author = {Sun, Y and Wei, K and Liao, X and Wang, J and Gao, L and Pang, B}, title = {Lipid metabolism in microglia: Emerging mechanisms and therapeutic opportunities for neurodegenerative diseases (Review).}, journal = {International journal of molecular medicine}, volume = {56}, number = {3}, pages = {}, pmid = {40641139}, issn = {1791-244X}, mesh = {*Microglia/metabolism/pathology ; Humans ; *Lipid Metabolism ; Animals ; *Neurodegenerative Diseases/metabolism/pathology/therapy ; }, abstract = {Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis, are characterized by progressive neuronal loss and neuroinflammation, with microglial dysfunction emerging as a central driver of pathogenesis. Microglia, the central nervous system‑resident immune cells, exhibit dual pro‑inflammatory and anti‑inflammatory phenotypes, dynamically regulated by lipid metabolic reprogramming. Chronic activation of M1 microglia exacerbates neuronal damage, while M2 microglia promote tissue repair via phagocytic clearance and neurotrophic factor secretion. Lipid dysregulation‑marked by ceramide accumulation, cholesterol esterification defects and oxidized lipid‑driven neuroinflammation‑critically modulates microglial polarization. Mechanistic studies reveal that mitochondrial dysfunction, lysosomal stress and ferroptosis intersect with lipid metabolic pathways to amplify neurotoxicity. Therapeutic strategies targeting lipid homeostasis, such as TREM2 agonism, demonstrate efficacy in preclinical models by restoring microglial function and mitigating pathology. This review synthesizes emerging evidence linking microglial lipid metabolism to NDD progression, highlighting novel biomarkers and therapeutic avenues to disrupt the lipid‑neuroinflammation axis in neurodegeneration.}, }
@article {pmid40640916, year = {2025}, author = {Lemarchant, S and Engelhardt, B and Cicchetti, F and Bix, GJ and Janus, A and Godfrin, Y and Blasco, H and Campbell, M and de Rus Jacquet, A}, title = {Restoring brain barriers: an innovative approach for treating neurological disorders.}, journal = {Fluids and barriers of the CNS}, volume = {22}, number = {1}, pages = {72}, pmid = {40640916}, issn = {2045-8118}, mesh = {Humans ; *Blood-Brain Barrier/drug effects/physiopathology/pathology/metabolism ; *Nervous System Diseases/drug therapy/therapy/pathology ; Animals ; }, abstract = {The complex etiology of neurological disorders is a major challenge to the identification of therapeutic candidates. Tackling brain vascular dysfunction is gaining attention from the scientific community, neurologists and pharmaceutical companies, as a novel disease-modifying strategy. Here, we provide evidence that at least 41% of neurological diseases and related conditions/injuries display a co-pathology of blood-brain and blood-spinal cord barrier alterations and dysfunctions, and we discuss why this figure may represent only a fraction of a larger phenomenon. We further provide clinical evidence that barrier status may contribute to pathological and functional outcomes in patients. Finally, we discuss drug candidates under development to repair brain barriers.}, }
@article {pmid40640892, year = {2025}, author = {Noh, MY and Kwon, HS and Kwon, MS and Nahm, M and Jin, HK and Bae, JS and Kim, SH}, title = {Biomarkers and therapeutic strategies targeting microglia in neurodegenerative diseases: current status and future directions.}, journal = {Molecular neurodegeneration}, volume = {20}, number = {1}, pages = {82}, pmid = {40640892}, issn = {1750-1326}, support = {RS-2024-00348451//Korea Dementia Research Center/ ; }, mesh = {Humans ; *Microglia/metabolism ; *Neurodegenerative Diseases/metabolism/therapy ; *Biomarkers/metabolism ; Animals ; }, abstract = {Recent advances in our understanding of non-cell-autonomous mechanisms in neurodegenerative diseases (NDDs) have highlighted microglial dysfunction as a core driver of disease progression. Conditions such as Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and frontotemporal dementia (FTD) share features of impaired microglial phagocytosis, chronic neuroinflammation, and metabolic dysregulation. These insights have prompted new therapeutic strategies targeting microglial function and emphasized the need for reliable biomarkers to monitor disease progression and treatment response. Well-established therapeutic targets, such as triggering receptor expressed on myeloid cells 2 (TREM2), progranulin (PGRN), and sortilin (SORT1), along with emerging candidates including LILRB4, P2Y6R, TAM receptors, and neuroinflammation-related markers, are discussed alongside novel blood, cerebrospinal fluid (CSF), and imaging biomarkers. Despite notable progress, many of these biomarkers remain restricted to preclinical studies and face translational challenges due to species-specific differences, lack of standardization, and clinical heterogeneity. Emerging technologies-including single-cell omics, spatial transcriptomics, and artificial intelligence (AI)-driven integration of multimodal data-offer new opportunities to align biomarker profiles with evolving disease states and improve patient stratification. Building on the model of companion diagnostics (CDx) in oncology, integrating multimodal biomarker strategies holds promise for guiding personalized interventions, improving clinical outcomes, and deepening our mechanistic understanding of microglial contributions across the neurodegenerative spectrum.}, }
@article {pmid40640528, year = {2025}, author = {McGuigan, A and Blair, HA}, title = {Tofersen: A Review in Amyotrophic Lateral Sclerosis Associated with SOD1 Mutations.}, journal = {CNS drugs}, volume = {39}, number = {9}, pages = {903-912}, pmid = {40640528}, issn = {1179-1934}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics ; *Superoxide Dismutase-1/genetics ; Mutation ; *Oligonucleotides/therapeutic use/adverse effects/pharmacology ; *Oligonucleotides, Antisense/therapeutic use/adverse effects ; }, abstract = {Tofersen (QALSODY[®]) is the first drug approved for the treatment of amyotrophic lateral sclerosis (ALS) associated with superoxide dismutase 1 (SOD1) mutations. Tofersen is an antisense oligonucleotide that induces SOD1 mRNA degradation. In the 28-week, placebo-controlled, multinational, phase III VALOR trial, intrathecally administered tofersen reduced plasma concentrations of neurofilament proteins (biomarker for neuro-axonal injury) and total SOD1 protein in cerebrospinal fluid in patients with SOD1 mutation-associated ALS. These reductions were sustained in a long-term, open-label extension study. The decline in functional outcomes was not significantly reduced with tofersen treatment compared with placebo in the 28-week phase III trial, although in the longer-term open-label study, early tofersen initiation was associated with slowed functional decline versus delayed tofersen initiation. Tofersen had an acceptable tolerability profile in clinical trials with a favourable benefit-to-risk balance. In summary, tofersen is a new disease-modifying therapy for patients with ALS attributed to an SOD1 mutation, offering reductions in levels of a biomarker associated with neurodegeneration and disease progression, with an acceptable tolerability profile.}, }
@article {pmid40639550, year = {2025}, author = {Mondal, M and Chouksey, A and Gurjar, V and Tiwari, R and Srivasatava, RK and Mishra, PK}, title = {Micro(nano)plastics in the brain: Epigenetic perturbations in progression to neurodegenerative diseases.}, journal = {Neurotoxicology and teratology}, volume = {110}, number = {}, pages = {107521}, doi = {10.1016/j.ntt.2025.107521}, pmid = {40639550}, issn = {1872-9738}, mesh = {Humans ; *Neurodegenerative Diseases/chemically induced/genetics ; *Epigenesis, Genetic/drug effects ; Animals ; *Brain/drug effects/metabolism ; Mitochondria/drug effects ; DNA Methylation/drug effects ; Disease Progression ; }, abstract = {As global plastic production escalates, micro(nano)plastics (MNPs) have become pressing ecological and biomedical concerns. These pollutants are increasingly implicated in the pathogenesis of neurodegenerative diseases. Due to their nanoscale size and surface reactivity, MNPs can cross the blood-brain barrier, accumulating in neural tissues. Once internalized, they disrupt neuronal homeostasis by inducing oxidative stress, mitochondrial dysfunction, and chronic neuroinflammation, key processes in neurodegenerative progression. Mitochondria, central to neuronal energy and redox regulation, are particularly vulnerable, leading to impaired ATP production, elevated ROS, and pro-apoptotic signaling. Recent studies reveal that MNPs also induce epigenetic changes, including aberrant DNA methylation, histone modifications, and dysregulation of non-coding RNAs. These alterations can result in synaptic instability, persistent transcriptional reprogramming, and heightened susceptibility to diseases like Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis. The mitochondrial epigenome is a vital target of MNP-induced disruption, offering potential biomarkers like methylated mtDNA and microRNAs for early diagnosis and prognosis. Understanding the molecular mechanisms behind these epigenetic alterations is essential for developing practical diagnostic tools and therapies. This review provides a comprehensive overview of MNP-induced neurodegeneration, focusing on mitochondrial and epigenetic disruptions. Moreover, it explores emerging biosensing technologies for detecting MNP-induced epigenetic alterations, highlighting the urgent need for further investigation to fully understand the neurotoxic potential of MNPs and develop preventive and therapeutic strategies for mitigating their effects on brain health.}, }
@article {pmid40629407, year = {2025}, author = {Choi, Y and Chung, WS}, title = {Glial phagocytosis for synapse and toxic proteins in neurodegenerative diseases.}, journal = {Molecular neurodegeneration}, volume = {20}, number = {1}, pages = {81}, pmid = {40629407}, issn = {1750-1326}, support = {2020M3E5D9079912//Ministry of Science and ICT, South Korea/ ; 2021R1A2C3005704//Ministry of Science and ICT, South Korea/ ; 2022M3E5E8081188//Ministry of Science and ICT, South Korea/ ; IBS-R025-A1//Institute for Basic Science/ ; }, mesh = {Humans ; *Neuroglia/metabolism/pathology ; *Neurodegenerative Diseases/metabolism/pathology ; *Phagocytosis/physiology ; *Synapses/metabolism/pathology ; Animals ; }, abstract = {Glia, as resident immune and supportive cells of the central nervous system, play a critical role in maintaining brain homeostasis. One of their key homeostatic functions is phagocytic capacity in pruning synapses and removing cellular debris/protein aggregates, a process vital for synaptic plasticity and brain maintenance. However, these phagocytic functions are often dysregulated with aging and in neurodegenerative diseases (NDs), such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and frontotemporal dementia. This review aims to examine the phagocytic roles of glia under both physiological and pathological conditions, with a special focus on their interactions with misfolded protein aggregates, including amyloid beta, tau, alpha synuclein, prion, huntingtin, and TAR DNA-binding protein 43. We also explore the fate of ingested molecules after being phagocytosed by glia-whether they are degraded, accumulate intracellularly, or are transferred between cells-and their implications for disease progression. Finally, we review current therapeutic strategies and the potential approaches for modulating glial phagocytosis to mitigate several NDs. We believe that understanding the exact mechanisms of glial phagocytosis and clearance will serve as key elements in developing future treatments for NDs.}, }
@article {pmid40626296, year = {2025}, author = {Li, D and Wang, P and Zhang, M and Zhang, X and Yao, H and Liu, X}, title = {Advances in examination methods for adolescent idiopathic scoliosis.}, journal = {Pediatric discovery}, volume = {3}, number = {1}, pages = {e2518}, pmid = {40626296}, issn = {2835-5598}, abstract = {The purpose of this article is to provide an overview of techniques for evaluating patients with adolescent idiopathic scoliosis (AIS). It encompasses the history, clinical examinations, and diagnostic imaging methods for AIS. These methods include digital radiological examination, EOS® imaging, nuclear medicine, ultrasound, body surface topography techniques such as the Moiré pattern technique, raster stereophotography, and DIERS formetric 4D as well as computed tomography and magnetic resonance imaging (MRI). Traditionally, full-spine standing X-rays have been the standard for diagnosing AIS. High-quality clinical assessments may continue as a reference for assessing other spinal deformities. However, the new diagnostic imaging methods aim to reduce radiation exposure while maintaining image quality and practicality. Emerging technologies demonstrate strong reliability and effectiveness in diagnostic imaging of AlS. These techniques may be beneficial for diagnosing and monitoring AIS and its progression without requiring high levels of radiation exposure. The article is a search and summary of the PubMed electronic database to understand the current and future status of AIS imaging technology, which can not only help to introduce other researchers to the field but also serve as a valuable source for healthcare professionals to study existing methods, develop new ones, or select evaluation strategies.}, }
@article {pmid40625110, year = {2025}, author = {Luo, Y and Xiong, S and Ehdaie, A and Sun, H and Yang, G and Luo, D and Li, J and Wang, X and Zhang, Z and Cai, L and Liu, H and Shehata, M}, title = {Predictive Parameters for Impending Steam Pops During High-Power Short-Duration Ablation for Atrial Fibrillation.}, journal = {Pacing and clinical electrophysiology : PACE}, volume = {48}, number = {8}, pages = {836-842}, doi = {10.1111/pace.70003}, pmid = {40625110}, issn = {1540-8159}, support = {20240216//Liu Hanxiong Famous Doctor Studio of Chengdu/ ; 2024NSFSC1709//the Natural Science Foundation of Sichuan Province/ ; CSY-YN-01-2023-041//Scientific Research Project of The Third People's Hospital of Chengdu/ ; }, mesh = {Humans ; *Atrial Fibrillation/surgery ; Male ; Female ; Retrospective Studies ; *Catheter Ablation/adverse effects/methods ; Middle Aged ; *Steam ; Aged ; }, abstract = {BACKGROUND: High-power short-duration (HPSD) radiofrequency ablation (RFA) for atrial fibrillation (AF) treatment carries the risk of steam pops (SPs) due to rapid tissue heating. However, methods to predict impending SP during HPSD-RFA remain undefined.<br><br>OBJECTIVE: This study aims to establish a quantitative criterion for predicting SPs during HPSD-RFA.<br><br>METHODS: Retrospective analysis was performed on 489 patients undergoing HPSD-RFA for AF, focusing on corresponding RFA parameters in those who experienced SPs.<br><br>RESULTS: Among 1943 ablation lesions (ALs) delivered in 18 patients with SPs, 24 ALs had SP occurrence. Tip temperature, RFA duration, and ablation index were not significantly different between SP ALs and non-SP ALs. The mean contact force was significantly higher in SP ALs (12&#xa0;g vs. 9, p < 0.001). All SPs adhered to the following criteria: impedance drop &#x2265;8&#x3a9; during the first 4&#xa0;s of RFA, impedance variability <5&#x3a9; within the first 4&#xa0;s of RFA (24/24&#xa0;vs. 79/247, p < 0.001), no events in the posterior wall of the left atrium, impedance drop &#x2265;12&#x3a9; within 4-12&#xa0;s. By halting delivery of RFA early with this finding in approximately five ALs per patient, the risk of SP complications could be significantly mitigated.<br><br>CONCLUSION: Monitoring impedance trends in the initial 4&#xa0;s of HPSD-RFA can effectively predict impending SP occurrences. Automated algorithms should be developed to halt RFA delivery in this setting.}, }
@article {pmid40621104, year = {2025}, author = {Rosene, MJ and Benitez, BA}, title = {Cysteine string protein α and a link between rare and common neurodegenerative dementias.}, journal = {NPJ dementia}, volume = {1}, number = {1}, pages = {15}, pmid = {40621104}, issn = {3005-1940}, abstract = {The maintenance of protein homeostasis and overall protein quality control dysfunction are associated with dementia. Cysteine string protein α (CSPα) is an endolysosomal cochaperone that facilitates the fusion of secretory and synaptic vesicles to the cell membrane. CSPα interacts with multiple proteins related to the proteostasis network and exocytic pathways and is often dysfunctional in synaptopathies. Since the initial discovery of CSPα 30 years ago, subsequent research has demonstrated a protective role of CSPα, especially in synaptic maintenance. However, the discovery of heterozygous CSPα mutations in 2011 causing adult-onset neuronal ceroid lipofuscinosis (ANCL) shifted the back-then prevalent dogma of unique synaptic function to include an endolysosomal role for CSPα. Recently, CSPα has been involved in the exocytosis of aggregate-prone proteins through either the misfolding-associated protein secretion (MAPS) or unconventional secretory pathways linking the molecular mechanism of rare and common neurodegenerative diseases. Here, we propose a novel molecular and pathophysiological model of CSPα-associated dementia, outline the increasing evidence of a broader role of CSPα in neurodegeneration, propose the role of CSPα in the synaptic secretion of neurodegenerative-associated proteins, and discuss the modulation of CSPα as a molecular target for common dementias.}, }
@article {pmid40620684, year = {2025}, author = {Chen, P and Wang, F and Ling, B and Zhu, Y and Lin, H and Huang, J and Wang, X}, title = {Mesenchymal Stem Cell-Derived Extracellular Vesicles: Emerging Therapies for Neurodegenerative Diseases.}, journal = {International journal of nanomedicine}, volume = {20}, number = {}, pages = {8547-8565}, pmid = {40620684}, issn = {1178-2013}, mesh = {Humans ; *Neurodegenerative Diseases/therapy ; *Mesenchymal Stem Cells/cytology ; *Extracellular Vesicles/metabolism/transplantation ; Biomarkers/metabolism ; *Mesenchymal Stem Cell Transplantation/methods ; }, abstract = {Neurodegenerative diseases are a group of chronic diseases characterized by a gradual loss of neurons that worsens over time and dysfunction. These diseases are extremely harmful, not only affecting the physical health of the patients, but also having a serious impact on their quality of life. They mainly include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Amyotrophic lateral sclerosis (ALS), etc. Their pathogenesis is complex, and it is difficult for the existing treatments to effectively slow down the progression of the disease. In recent years, Mesenchymal Stem Cells (MSCs) have received widespread attention for their anti-inflammatory, immunomodulatory and neuroprotective properties. In this context, MSC-derived Extracellular Vesicles (MSC-EVs) have demonstrated unique therapeutic potential as a cell-free therapeutic strategy. MSC-EVs are rich in bioactive substances such as proteins, lipids, mRNAs and miRNAs, which can pass through the blood-brain barrier and be targeted to the diseased area to regulate neuronal survival, synaptic plasticity and neuroinflammatory responses. In addition, compared with stem cell therapy, MSC-EVs have the advantages of low immunogenicity, easy storage and transportation, and avoiding ethical controversies. However, their clinical application still faces challenges: standardized isolation and purification techniques have not been unified, vesicle loading efficiency and targeting need to be further optimized, and long-term safety needs to be systematically evaluated. This review focuses on the role of MSC-EVs in the development of neurological diseases and explores their possible dual roles, both favorable and unfavorable, in the context of neurological diseases. In addition, this review provides a review of current studies on EVs as potential biomarkers for the diagnosis and treatment of neurodegenerative diseases and provides a comprehensive review of the prospects and challenges of MSC-EVs in clinical applications.}, }
@article {pmid40618376, year = {2025}, author = {Scirocco, E and Allen, MD and Giacomelli, E and Ajroud-Driss, S and Andrews, J and Banack, S and Bede, P and Benatar, M and Cheung, K and Corcia, P and de Carvalho, M and Elman, L and Fink, JK and Genge, A and Hardiman, O and Harms, M and Heitzman, D and Jang, G and Kano, O and Kiernan, MC and Lee, I and Ludolph, A and Mehta, P and Ozdinler, H and Rezania, K and Schito, P and Sherman, AV and Silani, V and Sorenson, E and Turner, MR and Van Den Berg, L and Mitsumoto, H and Paganoni, S}, title = {Toward therapeutic trials in primary lateral sclerosis.}, journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration}, volume = {}, number = {}, pages = {1-8}, doi = {10.1080/21678421.2025.2527123}, pmid = {40618376}, issn = {2167-9223}, abstract = {Primary lateral sclerosis (PLS) is a rare neurodegenerative disorder primarily affecting the upper motor neurons. People living with PLS experience progressive physical and communication disability, which typically evolves slowly over several years. In contrast to amyotrophic lateral sclerosis (ALS), life expectancy is anticipated to be normal. Disease-modifying medications are not available and PLS drug development has been challenging. This review considers recent advances and ongoing initiatives aimed at promoting clinical trial readiness for PLS. Ongoing clinical research efforts include patient registries and biorepositories, natural history studies, outcome measure validation, and biomarker development. These international collaborative efforts are essential for developing the first therapeutic trials for people living with PLS.}, }
@article {pmid40614949, year = {2025}, author = {Sarkar, SK and Gubert, C and Hannan, AJ}, title = {The microbiota-inflammasome-brain axis as a pathogenic mediator of neurodegenerative disorders.}, journal = {Neuroscience and biobehavioral reviews}, volume = {176}, number = {}, pages = {106276}, doi = {10.1016/j.neubiorev.2025.106276}, pmid = {40614949}, issn = {1873-7528}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/immunology/microbiology ; *Inflammasomes/metabolism/immunology ; *Gastrointestinal Microbiome/physiology ; Animals ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; *Brain/metabolism/immunology ; *Receptors, Purinergic P2X7/metabolism ; }, abstract = {In various neurodegenerative disorders, inflammation and associated inflammasome activation play an important role. The most prevalent and extensively researched inflammasomes are NLRP3 inflammasomes, which are triggered by pathogens or danger signals mediating inflammatory reaction. Extracellular ATP also activates NLRP3 by stimulating the purinergic receptor P2X7 (P2X7R). Central and peripheral cells, including those in the gut, have been shown to have activated inflammasomes during pathological changes co-occurring with inflammation in various neurodegenerative disorders. Gut injury or dysfunction is increasingly recognised as one of the peripheral pathogenic characteristics of many neurodegenerative disorders, and has been found to associate with changes in gut microbes. In this article, we review data from preclinical and clinical studies regarding the involvement of the NLRP3 inflammasome and the purinergic receptor P2X7R in the pathophysiology of major CNS disorders involving neurodegeneration, including Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), Huntington's disease (HD), and the most common form of motor neuron disease, amyotrophic lateral sclerosis (ALS). We also scrutinise the relationship of the NLRP3 inflammasome to intestinal microbiota alterations in these diseases. Both the NLRP3 inflammasome and P2X7R have been shown to play important roles in the pathogenesis and progression of these neurodegenerative diseases. However, most studies have focused on central nervous system (CNS) pathology, particularly within the brain, with comparatively less attention given to their contribution to gut pathology. Additionally, changes in the microbial ecosystems of the intestine have also been implicated in these disorders. However, the association between gut microbiota alterations and inflammasome activity in the pathology of these neurodegenerative disorders remains poorly understood. Therefore, further investigation is urgently needed to explore the microbiota-inflammasome-brain axis in these neurodegenerative conditions, in order to better understand their contribution to disease pathogenesis and progression, and identify novel therapeutic targets and new approaches to prevention and treatment.}, }
@article {pmid40612293, year = {2025}, author = {Bayleyegn Derso, T and Mengistu, BA and Demessie, Y and Fenta, MD and Getnet, K}, title = {Neural stem cells in adult neurogenesis and their therapeutic applications in neurodegenerative disorders: a concise review.}, journal = {Frontiers in molecular medicine}, volume = {5}, number = {}, pages = {1569717}, pmid = {40612293}, issn = {2674-0095}, abstract = {The idea of using stem cell therapy to treat neurodegenerative diseases has undergone significant change over the years and has made significant progress recently. Neurotrophins, growth factors, and transcription factors regulate neural stem cell proliferation and differentiation. Disruption of these regulatory mechanisms, including negative feedback, can contribute to neurodegenerative diseases. Contemporary research highlights a growing global concern regarding diverse neurodegenerative disorders affecting both humans and animals. These conditions arise from neuronal cell death, axonal regeneration failure, and impairment of neuronal structure. Current pharmacological treatments primarily offer symptomatic relief without altering disease progression. Consequently, researchers are investigating innovative therapeutic strategies, with neural stem cell therapy emerging as a promising avenue. Adult neural stem cells, embryonic neural stem cells, and induced pluripotent stem cells represent potential cell sources, although challenges such as ethical considerations and technical limitations remain. The therapeutic application of neural stem cells holds significant promise for addressing neurodegenerative diseases, including Alzheimer's disease, stroke, amyotrophic lateral sclerosis, spinal cord injury, and multiple sclerosis. Neural stem cell therapy aims to replenish lost neurons and promote neural regeneration in these conditions. While clinical trials have demonstrated some success in improving cognitive and motor functions in individuals with neurodegenerative impairments, challenges such as immunological rejection, the identification of compatible cell sources, ethical concerns, treatment efficacy, and potential side effects necessitate thorough investigation before widespread clinical implementation. Despite these challenges, neural stem cell-based therapy offers substantial potential for revolutionizing the treatment of neurodegenerative diseases and central nervous system injuries. This paper, therefore, explores adult neurogenesis and the therapeutic potential of neural stem cells within the dynamic field of neurodegenerative disorders.}, }
@article {pmid40610071, year = {2025}, author = {Selvaraj, C and Vijayalakshmi, P and Desai, D and Manoharan, J}, title = {Proteostasis imbalance: Unraveling protein aggregation in neurodegenerative diseases and emerging therapeutic strategies.}, journal = {Advances in protein chemistry and structural biology}, volume = {146}, number = {}, pages = {1-34}, doi = {10.1016/bs.apcsb.2024.11.008}, pmid = {40610071}, issn = {1876-1631}, mesh = {Humans ; *Proteostasis ; *Neurodegenerative Diseases/metabolism/therapy/pathology ; Animals ; Autophagy ; *Protein Aggregation, Pathological/metabolism/therapy/pathology ; *Protein Aggregates ; }, abstract = {Neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, and ALS are defined by the accumulation of misfolded and aggregated proteins, which impair cellular function and result in progressive neuronal death. This chapter examines the critical function of proteostasis-cellular protein homeostasis-in sustaining neuronal health and its disruption as a key factor in disease progression. Proteostasis is upheld by a complex array of mechanisms, which encompass molecular chaperones, the ubiquitin-proteasome system, autophagy-lysosomal pathways, and mitochondrial quality control. Impairment of these systems leads to protein misfolding and aggregation, resulting in toxic cellular environments that promote neurodegeneration. Novel therapeutic approaches focus on restoring proteostasis through the enhancement of cellular protein folding, degradation, and clearance mechanisms. This encompasses small molecule chaperones, gene therapy, RNA-based treatments, immunotherapy, autophagy inducers, and stem cell-based approaches, each addressing distinct components of the proteostasis network to mitigate or prevent disease progression. While these therapies show potential, challenges persist, such as possible side effects, selective targeting, and the efficacy of blood-brain barrier penetration. Personalized medicine and combination therapies customized to specific disease profiles are increasingly recognized for their potential to improve efficacy and safety. This chapter consolidates recent developments in therapies aimed at proteostasis, addresses the challenges encountered in clinical applications, and outlines potential future directions for transformative treatments. Ongoing research indicates that proteostasis modulation may significantly alter the course of neurodegenerative disease treatment, potentially enhancing patient outcomes and quality of life.}, }
@article {pmid40609398, year = {2025}, author = {Yazdanian, T and Azimi, P and Babu, S}, title = {Cervical spinal cord MRI in ALS individuals: a systematic review and meta-analysis.}, journal = {NeuroImage. Clinical}, volume = {47}, number = {}, pages = {103832}, pmid = {40609398}, issn = {2213-1582}, abstract = {BACKGROUND: Disease tracking and prognostication of amyotrophic lateral sclerosis (ALS) can be quite challenging in people living with ALS, due to the complexity of central nervous system disease biology. This systematic review and meta-analysis aim to summarize cervical spinal cord quantitative MRI (qMRI) biomarker changes in individuals with ALS.<br><br>METHODS: PubMed, Scopus, Cochrane Library, and Web of Science databases were searched up to August 2023. The terms used were "ALS", "cervical spinal cord", "MRI"," diffusion tensor imaging (DTI)", " fractional anisotropy (FA)", " mean diffusivity (MD) "," magnetization transfer ratio (MTR)", " cross-sectional area (CSA)", " radial diffusivity (RD) ", and " atrophy ". The Newcastle-Ottawa scale (NOS) was used to assess study quality. We calculated the pooled: 1) Standardized mean difference (SMD) and 95% CIs for comparative assessment of qMRI parameters in ALS individuals and the healthy population. 2) Estimate the mean of qMRI parameters for normative values in two groups by CMA software. Heterogeneity and publication bias were determined by the I-squared statistic and funnel plots.<br><br>RESULTS: Thirty studies, with 1817 participants (35.9&#xa0;% female) were included in this review, and 29 had a NOS &#x2265; 5 which indicates high-quality of data overall. The SMD analysis showed (a) significant decrease in CSA along the whole length of cervical cord (C1-C7) (p value&#xa0;<&#xa0;0.0001), with a preferential thinning of the cervical enlargement region (C4-C6 region) (p value&#xa0;<&#xa0;0.0001) (b) significant decrease in FA (p value&#xa0;<&#xa0;0.0001), particularly FA left lateral corticospinal tract (p value&#xa0;<&#xa0;0.0001) and (c) a significant increase in MD (p value&#xa0;<&#xa0;0.0001) in ALS individuals compared to controls. The pooled analysis reveals that the mean (SD) values for ALS individuals versus controls for (a) CSA (in mm[2]) were C1 [73.4 (0.75), 78.5 (0.67), 6.9&#xa0;% difference]; C2 [70.6 (3.1), 71.5 (3.5), 1.2&#xa0;% difference]; C3 [69.8(1.5), 74.9 (1.9), 7.3&#xa0;% difference]; C4 [71.9 (1.8), 77.6 (2.8), 7.9&#xa0;% difference]; C5 [71.8 (2.5), 79.5 (3.3), 10.7&#xa0;% difference]; C6 [66.8 (2.7), 73.7 (3.7), 10.3&#xa0;% difference]; C7 [56.7 (F2.2), 62.1 (2.5), 9.5&#xa0;% difference]; (b) FA [0.54 (0.03), 0.56 (0.03)]; (c) MD[1.11 (0.18), 0.88(0)]; and (d) FA LLCST [ 0.65 (0.04), 0.77 (0.04)], respectively. The mean (SD) value of the MTR and RD for ALS individuals was 40.3 (2.3), and 0.70 (0.0).<br><br>CONCLUSIONS: qMRI metrics of spinal cord show discriminatory potential between ALS and healthy controls. The selective atrophy of the cervical enlargement (C4-C6) is replicable across multiple studies as seen in this metanalysis and hence is a potential imaging marker for quantifying and tracking lower motor neuron degeneration in ALS.}, }
@article {pmid40608189, year = {2025}, author = {Sharma, VK}, title = {Dysbiosis and Neurodegeneration in ALS: Unraveling the Gut-Brain Axis.}, journal = {Neuromolecular medicine}, volume = {27}, number = {1}, pages = {50}, pmid = {40608189}, issn = {1559-1174}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/physiopathology/microbiology/therapy ; *Dysbiosis/complications/physiopathology/therapy ; *Gastrointestinal Microbiome/physiology ; Animals ; *Brain-Gut Axis/physiology ; *Brain/physiopathology ; }, abstract = {Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a neurodegenerative disorder marked by the progressive degeneration of motor neurons in the brain and spinal cord. Despite decades of research, ALS remains incurable, diagnostically elusive, and is accompanied by rapid clinical decline, morbidity, and mortality. Its pathophysiology involves a complex interplay of genetic mutations (SOD1, C9/f72), environmental triggers, oxidative stress, neuroinflammation, and the accumulation of misfolded proteins, such as TDP-43 and SOD1. These factors disrupt cellular homeostasis aggravates excitotoxicity and neuronal death. Existing treatments, such as riluzole (a glutamate release modulator) and edaravone (a free radical scavenger), offer limited benefits, modestly prolonging survival or slowing functional decline without halting progression. Investigational approaches include antisense oligonucleotides targeting mutant SOD1 or C9orf72 genes, stem cell-based motor neuron replacement, and biomarker discovery to enable earlier diagnosis and progression monitoring. ALS patients frequently exhibit gastrointestinal (GI) symptoms, including dysphagia, sialorrhea, constipation, delayed gastric emptying, and pancreatic/parotid deficiencies. These observations underscore a close association between GI dysfunction and ALS pathogenesis. Also, recent studies implicate the gut-brain-microbiota axis in disease evolution, with microbial metabolites influencing neuroimmune interactions, synaptic plasticity, myelination, and skeletal muscle function. These studies indicate that dysbiosis-an imbalance in gut microbiota-may have a crucial role in ALS progression by impairing intestinal barrier integrity, promoting endotoxemia, and driving systemic inflammation. Conversely, ALS progression itself worsens dysbiosis, creating a vicious cycle of neuroinflammation and neurodegeneration. Preclinical and clinical evidence suggests that interventions targeting gut microbiota-such as prebiotics, probiotics, antibiotics, or phage therapy-could alleviate symptoms and slow disease progression and specific probiotic strains have also shown promise in reducing oxidative stress and inflammation in animal models. These findings highlight the urgent need to elucidate the functional role of gut microbiota in ALS to unlock novel diagnostic and therapeutic avenues. This review synthesizes current knowledge on the pathophysiology of ALS, with a focus on the emerging role of the gut-brain-microbiota axis. It highlights how dysbiosis influences diverse disease markers and neurodegenerative mechanisms, offering insights into potential therapeutic strategies and identifying key research gaps and future directions.}, }
@article {pmid40608121, year = {2025}, author = {Ruzi, Z and Zha, W and Yuan, HY and Liu, J}, title = {RNA G-quadruplexes: emerging regulators of gene expression and therapeutic targets.}, journal = {Functional &amp; integrative genomics}, volume = {25}, number = {1}, pages = {143}, pmid = {40608121}, issn = {1438-7948}, support = {22262002//National Natural Science Foundation of China/ ; }, mesh = {*G-Quadruplexes ; Humans ; *Gene Expression Regulation ; *RNA/chemistry/genetics/metabolism ; Animals ; Neoplasms/genetics ; SARS-CoV-2 ; Neurodegenerative Diseases/genetics ; Alternative Splicing ; }, abstract = {RNA G-quadruplexes (rG4s) are non-canonical, four-stranded secondary structures formed by guanine-rich RNA sequences. These dynamic elements have garnered significant attention for their critical roles in regulating gene expression, including translation, alternative splicing, mRNA localization, and stability. This review synthesizes recent progress in understanding the structural determinants and formation dynamics of rG4s, highlighting the contributions of sequence motifs, ionic conditions, and RNA-binding proteins to their stability and function. Functional studies reveal that rG4s modulate key oncogenic transcripts (e.g., MYC, BCL2), contribute to splicing regulation, and influence intracellular RNA trafficking. In pathological contexts, rG4s have been implicated in the molecular etiology of cancers, neurodegenerative diseases such as amyotrophic lateral sclerosis and Fragile X syndrome, and viral replication mechanisms in pathogens including HIV and SARS-CoV-2. Advances in high-throughput techniques, such as G4-seq, rG4-seq, and live-cell imaging, have facilitated the global identification and characterization of rG4s in physiological and disease settings. Moreover, the therapeutic targeting of rG4s using small molecules holds promise for selective gene regulation and biomarker development. Comparative analyses across in vitro, in vivo, and clinical studies underscore the cell-type-specific and context-dependent roles of rG4s, especially in mediating stress responses and apoptosis. Despite methodological limitations and challenges in achieving targeted delivery, rG4s represent a compelling frontier for precision medicine. This review outlines current insights and future directions toward harnessing rG4 biology for therapeutic innovation.}, }
@article {pmid40604407, year = {2025}, author = {Goff, M and Hindi, A and Hammond, J and Jacobs, S}, title = {Access or continuity: a zero sum game? A systematic review of the literature examining the relationship between access and continuity in primary healthcare.}, journal = {BMC primary care}, volume = {26}, number = {1}, pages = {202}, pmid = {40604407}, issn = {2731-4553}, support = {Do the organisational and workforce developments associated with the introduction of primary care networks (PCNs) affect patients' experience of continuity of care?//Health Foundation/ ; Do the organisational and workforce developments associated with the introduction of primary care networks (PCNs) affect patients' experience of continuity of care?//Health Foundation/ ; Do the organisational and workforce developments associated with the introduction of primary care networks (PCNs) affect patients' experience of continuity of care?//Health Foundation/ ; Policy Research Unit in Health and Social Care Systems and Commissioning//National Institute for Health and Care Research/ ; }, mesh = {Humans ; *Continuity of Patient Care/organization &amp; administration ; *Primary Health Care/organization &amp; administration ; *Health Services Accessibility ; United Kingdom ; }, abstract = {BACKGROUND: In recent years there has been a policy drive in the UK to improve patients' access to appointments in primary care. However, the focus on timely access could undermine continuity of care. This paper aims to investigate how continuity of care and access to care are interrelated and their relative importance for patients and healthcare professionals.<br><br>METHODS: A systematic review was conducted using six academic databases (EMBASE, PubMed, Scopus, Web of Science, CINAHL and PsycINFO). Reference lists of included studies and Google Scholar were searched for additional papers. Included were peer-reviewed journal articles in English based on studies in primary care settings from any country, publication date and study design, based on data from any stakeholders. Conference abstracts, opinion papers, reports and literature reviews, studies in secondary or tertiary care or continuity between healthcare settings and studies about development of instruments to measure continuity of care or examining outcomes only were excluded. Fifty-six papers were identified for inclusion in the review. Studies presented differing perspectives on continuity and access, conceptualisations of access and continuity, and, measures used. We conducted thematic analysis of the literature and used Haggerty et al.'s (2003) conceptualization of continuity and Boyle et al.'s (2020) conceptualization of access to synthesise the data.<br><br>FINDINGS: Themes arising were: system-level, practice-level and patient-level factors that influence access and continuity of care, what is important to patients, and how providers can support access and continuity of care. We found that 'choice of access' has the strongest relationship with relational continuity, however, 'physical access', or the ability to get and 'attend' an appointment, supersedes other dimensions of access as necessary but not sufficient for continuity of care.<br><br>CONCLUSIONS: Our synthesis provides evidence that experiencing continuity depend on the combination of patients' demographic characteristics and health conditions, with situational circumstances, including characteristics of the health system and provider, which are more or less changeable. We propose a theoretical framing of the relationships between the dimensions of access and continuity. It can support policymakers and providers in understanding how to balance providing both access and continuity for patients.}, }
@article {pmid40603051, year = {2025}, author = {Ito, L and Galipon, J}, title = {[Development of RNA Hydrogels as a Potential System for Intracellular Biomimicry: A Method for the In Vitro Synthesis of ALS/FTD-related (G4C2)n RNA with over 100 Repeats].}, journal = {Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan}, volume = {145}, number = {7}, pages = {601-607}, doi = {10.1248/yakushi.24-00209-3}, pmid = {40603051}, issn = {1347-5231}, mesh = {*Amyotrophic Lateral Sclerosis/genetics ; *RNA/chemical synthesis/genetics/chemistry ; Humans ; *Hydrogels ; G-Quadruplexes ; C9orf72 Protein/genetics ; DNA-Directed RNA Polymerases ; *Repetitive Sequences, Nucleic Acid/genetics ; Viral Proteins ; *Biomimetics/methods ; RNA-Binding Proteins/metabolism ; *Frontotemporal Dementia/genetics ; }, abstract = {In the motor neurons of amyotrophic lateral sclerosis (ALS) patients, excessive (G4C2)n repeats in the intronic region of the C9orf72 gene are transcribed to RNA, forming G-quadruplexes that sequester RNA-binding proteins, leading to gelation within the cytoplasm as one of the many mechanisms leading to pathogenesis. While ALS patients frequently harbor over 700 repeats, this kind of 100% GC-rich region is very difficult to clone, and past studies report the necessity to add additional sequences in the middle to clone more than a few dozen repeats. The goal of this study was the in vitro production of the longest repetitive RNA to date consisting solely of (G4C2)n repeats. T4 DNA ligase was used to connect (G4C2)10 stretches of DNA with 3nt overhangs. Then, using a heat-resistant T7 RNA polymerase, the RNA obtained contained transcripts over 100 repeats. Artificial biomimetic RNA gels generated by scaling up this synthesis method are expected to contribute to elucidating the molecular mechanisms of repetitive sequence-related pathogenesis, as well as screening for drugs that can disrupt the gel structure.}, }
@article {pmid40603049, year = {2025}, author = {Tsuiji, H}, title = {[Elucidation of the Molecular Mechanism Underlying Aberrant Formation of RNA Granules in Neurons of ALS Patients and Its Regulation].}, journal = {Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan}, volume = {145}, number = {7}, pages = {583-588}, doi = {10.1248/yakushi.24-00209-1}, pmid = {40603049}, issn = {1347-5231}, mesh = {*Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism/therapy/etiology ; Humans ; RNA-Binding Protein FUS/metabolism ; *DNA-Binding Proteins/metabolism/genetics ; C9orf72 Protein/genetics ; *RNA/metabolism/genetics ; *Motor Neurons/metabolism ; Animals ; RNA Splicing/genetics ; RNA-Binding Proteins/metabolism ; *Cytoplasmic Granules/metabolism ; Dipeptides/metabolism ; Protein Biosynthesis/genetics ; Spliceosomes/metabolism ; DNA Repeat Expansion/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease characterized by progressive muscle atrophy throughout the body. In nearly all ALS patients, abnormal accumulation of the RNA-binding protein TDP-43 is observed in degenerating motor neurons. We have found that RNA-binding proteins such as TDP-43 and FUS are concentrated in GEM bodies, where they contribute to the integrity of the spliceosome machinery involved in pre-RNA splicing. Additionally, the most common cause of ALS, repeat expansion in the C9orf72 gene, triggers abnormal repeat-associated non-AUG (RAN) translation, leading to the accumulation of neurotoxic dipeptide repeat (DPR) proteins. We have identified that these DPR proteins may inhibit GEM body formation and contribute to ALS pathology. Furthermore, therapeutic approaches to suppress RAN translation using dCas13 technology are under development, offering promising new strategies to address abnormalities in RNA metabolism in ALS.}, }
@article {pmid40589786, year = {2025}, author = {Arreola-Aldape, CA and Moran-Guerrero, JA and Pons-Monnier, GK and Flores-Salcido, RE and Martinez-Ledesma, E and Ruiz-Manriquez, LM and Razo-Alvarez, KR and Mares-Custodio, D and Avalos-Montes, PJ and Figueroa-Sanchez, JA and Ortiz-Lopez, R and Martínez, HR and Cuevas-Diaz Duran, R}, title = {A systematic review and functional in-silico analysis of genes and variants associated with amyotrophic lateral sclerosis.}, journal = {Frontiers in neuroscience}, volume = {19}, number = {}, pages = {1598336}, pmid = {40589786}, issn = {1662-4548}, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disease characterized by the deterioration of upper and lower motor neurons. Affected patients experience progressive muscle weakness, including difficulty in swallowing and breathing; being respiratory failure the main cause of death. However, there is considerable phenotypic heterogeneity, and its diagnosis is based on clinical criteria. Moreover, most ALS cases remain unexplained, suggesting a complex genetic background.<br><br>METHODS: To better understand the molecular mechanisms underlying ALS, we comprehensively analyzed, filtered and classified genes from 4,293 abstracts retrieved from PubMed, 7,343 variants from ClinVar, and 33 study accessions from GWAS catalog. To address the importance of ALS-associated genes and variants, we performed diverse bioinformatic analyses, including gene set enrichment, drug-gene interactions, and differential gene expression analysis using public databases.<br><br>RESULTS: Our analysis yielded a catalog of 300 genes with 479 ALS-associated variants. Most of these genes and variants are found in coding regions and their proteins are allocated to the cytoplasm and the nucleus, underscoring the relevance of toxic protein aggregates. Moreover, protein-coding genes enriched ALS-specific pathways, for example spasticity, dysarthria and dyspnea. ALS-associated genes are targeted by commonly used drugs, including Riluzole and Edaravone, and by the recently approved antisense oligonucleotide therapy (Tofersen). Moreover, we observed transcriptional dysregulation of ALS-associated genes in peripheral blood mononuclear cell and postmortem cortex samples.<br><br>CONCLUSION: Overall, this ALS catalog can serve as a foundational tool for advancing early diagnosis, identifying biomarkers, and developing personalized therapeutic strategies.}, }
@article {pmid40589142, year = {2025}, author = {Tiwari, R and Paswan, A and Tiwari, G and Reddy, VJS and Posa, MK}, title = {Perspectives on Fecal Microbiota Transplantation: Uses and Modes of Administration.}, journal = {Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology}, volume = {41}, number = {}, pages = {e20250014}, doi = {10.62958/j.cjap.2025.014}, pmid = {40589142}, issn = {1000-6834}, mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; *Gastrointestinal Microbiome ; Feces/microbiology ; *Nervous System Diseases/therapy ; }, abstract = {Fecal microbiota Transplantation (FMT), often referred to as stool transplantation, fecal transfusion, and fecal bacteria therapy, is considered one of the most medical innovations of the 20th century. Fecal microbiota Transplantation entails filtering and dilution of a healthy donor's feces before injecting it into the recipient's digestive system. In China, it was first administered orally in the fourth century for diarrhea and food poisoning under the name "Yellow Soup." It has recently been widely employed in a variety of clinical settings, including cases of Clostridium difficile infection that are recurring and resistant. By replacing the unhealthy intestinal microbiota with a healthy bacterial community, the FMT treatment aims to enhance the intestinal flora. It also looks at neurological conditions where alterations in gut microbiota are prevalent. We have discussed FMT in the context of its use in conditions affecting the nerve system, such as neurological and other conditions (multiple sclerosis, Parkinson's disease, Alzheimer's disease, stroke, epilepsy, Amyotrophic lateral sclerosis, Tourette syndrome, neuropathic pain, Huntington's diseases, etc.), as well as the role of gut microbiota in many neurological disorders.}, }
@article {pmid40587877, year = {2025}, author = {Moalefshahri, R and Hashemy, SI and Hosseini, H and Sahebkar, A}, title = {Neuroprotective effect of Kaempferol through modulation of autophagy.}, journal = {Nutritional neuroscience}, volume = {}, number = {}, pages = {1-17}, doi = {10.1080/1028415X.2025.2524702}, pmid = {40587877}, issn = {1476-8305}, abstract = {Objective: Autophagy is a critical cellular mechanism that ensures the breakdown of damaged or unnecessary components. This process helps ensure cellular health by maintaining cellular balance, protecting cells from stress, and providing an alternative energy source during metabolic stress. Disruptions in autophagy have been linked to neurological disorders.Method: In this review, the neuroprotective effects of Kaempferol through autophagy modulation are elaborated. Methods: An electronic search in scientific databases was performed to find relevant studies exploring the neuroprotective effects of kaempferol mediated via modulation of autophagy.Results: Kaempferol, a natural flavonoid found in fruits, vegetables, and plant-based products like tea, has been shown to demonstrate a variety of health-promoting properties, including antimicrobial, antioxidant, and antiinflammatory effects. This review summarizes the current understanding of how Kaempferol modulates autophagy and discusses its potential impact on various neurological disorders, including Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, ischemic stroke, and depression. Studies increasingly indicate that Kaempferol could be a vital factor in maintaining neural health by influencing autophagy mechanisms.Conclusion: Numerous studies have established Kaempferol's neuroprotective potential through autophagy regulation, which suggests opprotunities for potential therapeutic applications.}, }
@article {pmid40585388, year = {2025}, author = {Wang, X and Sun, Y and Han, C and Meng, X and Wen, K and Wu, J and Min, P and Li, K and Zhang, Y}, title = {Research trends of piezoelectric materials in neurodegenerative disease applications.}, journal = {Bioactive materials}, volume = {52}, number = {}, pages = {366-392}, pmid = {40585388}, issn = {2452-199X}, abstract = {Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and huntington's disease, pose significant threats to human health, with current treatment options remaining limited. Piezoelectric materials, known for their ability to convert mechanical energy into electrical signals at the nanoscale, hold great promise in the diagnosis and treatment of neurodegenerative diseases due to their excellent electromechanical properties, environmental stability, and sensitivity. This review systematically outlines the working principles and classifications of piezoelectric materials. Subsequently, the recent advances in piezoelectric materials and their applications in the diagnosis and treatment of neurodegenerative diseases are highlighted. Finally, the challenges and perspectives regarding the development of future piezoelectric materials are discussed. This review aims to provide a comprehensive reference for the further application of piezoelectric materials in neurodegenerative diseases.}, }
@article {pmid40584177, year = {2025}, author = {Wu, Q and Yang, J and Duan, Y and Ma, Y and Zhang, Y and Tan, S and Wang, J and Wang, Y and Liu, B and Zhang, J and Liu, X}, title = {Environmental risk factors, protective factors, and biomarkers for amyotrophic lateral sclerosis: an umbrella review.}, journal = {Frontiers in aging neuroscience}, volume = {17}, number = {}, pages = {1541779}, pmid = {40584177}, issn = {1663-4365}, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the rapid loss of motor neurons. Given the significant global economic impact of ALS, effective preventive measures are urgently needed to reduce the incidence of this devastating disease. Recent meta-analyses have explored potential links between environmental factors, biomarkers, and ALS occurrence. However, the findings of these studies have been inconsistent and controversial. Therefore, we present a comprehensive umbrella review of recent meta-analyses to systematically summarize the available epidemiological evidence and evaluate its credibility.<br><br>METHODS: A systematic search was conducted in PubMed and Embase from inception until 01 October 2024, to identify meta-analyses of observational studies examining associations between environmental risk factors, protective factors, biomarkers, and ALS susceptibility. For each meta-analysis, summary effect estimates, 95% confidence intervals (CIs), 95% prediction intervals, study heterogeneity, small study effects, and excess significance biases were calculated independently by two investigators. The methodological quality was evaluated using the AMSTAR 2 criteria. The strength of the epidemiological evidence was categorized into five levels based on predefined criteria.<br><br>RESULTS: Out of 1,902 articles identified, 43 met the inclusion criteria, resulting in 103 included meta-analyses. These analyses covered 46 environmental risk and protective factors (344,597 cases, 71,415,574 population) and 57 cerebrospinal fluid (CSF) and serum biomarkers (30,941 cases, 2,180,797 population). The evidence was classified as convincing (Class I) for the regular use of antihypertensive drugs (OR: 0.85, 95% CI: 0.81-0.88) and highly suggestive (Class II) for premorbid body mass index (OR: 0.97, 95% CI: 0.95 to 0.98), trauma (OR: 1.51, 95% CI: 1.32 to 1.73), CSF NFL levels (SMD: 2.06, 95% CI: 1.61 to 2.51), serum NFL levels (SMD: 1.57, 95% CI: 1.29 to 1.85), ferritin levels (SMD: 0.66, 95% CI: 0.50 to 0.83), and uric acid levels (SMD: -0.72; 95% CI: -0.98 to -0.46).<br><br>DISCUSSION: This umbrella review offers new insights into the epidemiological evidence regarding the associations between environmental factors, biomarkers, and ALS susceptibility. We aim for our study to enhance the understanding of the roles of environmental factors and biomarkers in ALS occurrence and assist clinicians in developing evidence-based prevention and control strategies.}, }
@article {pmid40583472, year = {2025}, author = {Salehirozveh, M and Dehghani, P and Mijakovic, I}, title = {Nanopore-Based Neurotransmitter Detection: Advances, Challenges, and Future Perspectives.}, journal = {ACS nano}, volume = {19}, number = {27}, pages = {24404-24424}, pmid = {40583472}, issn = {1936-086X}, mesh = {*Nanopores ; *Neurotransmitter Agents/analysis ; Humans ; *Nanotechnology/methods ; *Biosensing Techniques/methods ; Animals ; }, abstract = {Neurotransmitters play a pivotal role in neural communication, synaptic plasticity, and overall brain function. Disruptions in neurotransmitter homeostasis are closely linked to various neurological and neuropsychiatric disorders, including Alzheimer's disease, Parkinson's disease, epilepsy, schizophrenia, depression, and amyotrophic lateral sclerosis. This review explores the critical role of neurotransmitters in neurological disorders and highlights recent advances in nanopore-based neurotransmitter detection. Solid-state nanopores (SSNs), with their superior mechanical and chemical durability, have emerged as highly sensitive molecular sensors capable of real-time monitoring of neurotransmitter dynamics. We discuss the integration of SSNs into diagnostic frameworks, emphasizing their potential for early disease detection and personalized therapeutic interventions. Additionally, we examine the complementary role of nanopipettes in neurotransmitter detection, focusing on their high spatial resolution and real-time monitoring capabilities. The review also addresses the challenges and future perspectives of nanopore-based sensing technology, including the need for improved sensitivity, stability, and reproducibility. By integrating insights from neuroscience, bioengineering, and nanotechnology, this review aims to provide a comprehensive overview of how nanopore sensing can revolutionize neurotransmitter analysis and contribute to the development of next-generation diagnostic and therapeutic approaches for neurological diseases.}, }
@article {pmid40580685, year = {2025}, author = {Deng, Z and Chen, H and Chen, J and Du, Z and Zhou, W and Yuan, Z}, title = {Multifaceted roles of extracellular vesicles in the interplay of neuroinflammation and neurodegenerative diseases.}, journal = {Biochimica et biophysica acta. Molecular basis of disease}, volume = {1871}, number = {7}, pages = {167960}, doi = {10.1016/j.bbadis.2025.167960}, pmid = {40580685}, issn = {1879-260X}, mesh = {Humans ; *Extracellular Vesicles/metabolism/pathology ; *Neurodegenerative Diseases/pathology/metabolism ; Animals ; *Neuroinflammatory Diseases/pathology/metabolism ; Blood-Brain Barrier/metabolism/pathology ; Biomarkers/metabolism ; Cell Communication ; }, abstract = {Despite advances in understanding neurodegenerative disease mechanisms, effective treatments remain elusive. Extracellular vesicles (EVs), key mediators of intercellular communication within the central nervous system (CNS), are increasingly recognized for their involvement in the pathogenesis of neurodegenerative disorders like Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS) and Huntington's disease (HD). In vivo studies demonstrate EVs' crucial role in maintaining CNS homeostasis, modulating neuroinflammatory responses, and influencing tissue repair and regeneration following injury, thereby impacting disease progression and recovery. Their unique properties, including small size and ability to cross the blood-brain barrier (BBB), position them as promising candidates for both biomarkers and therapeutics in CNS diseases. This review delves into the significant impact of neuroinflammation on neurodegenerative conditions, specifically focusing on the multifaceted contributions of EVs and their intricate interplay with the inflammatory landscape. We explore EV biogenesis, cargo composition, diverse roles in neuroinflammation (including intercellular communication and neuroprotection), their potential as biomarkers and drug delivery vehicles across the BBB for diagnosis or treatment of neuroinflammation implemented neurodegenerative diseases.}, }
@article {pmid40580315, year = {2025}, author = {Jellinger, KA}, title = {Co-occurrence of amyotrophic lateral sclerosis and multiple sclerosis: a rare but interesting association.}, journal = {Journal of neural transmission (Vienna, Austria : 1996)}, volume = {}, number = {}, pages = {}, pmid = {40580315}, issn = {1435-1463}, support = {Society for the Promotion of Research in Experimental Neurology, Vienna, Austria//Society for the Promotion of Research in Experimental Neurology, Vienna, Austria/ ; }, abstract = {Multiple sclerosis (MS) is an inflammatory demyelinating disease with highly variable clinical course and usual onset in younger age, caused by genetic and environmental factors. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that affects motor neurons in the brain and spinal cord, resulting in gradual loss of voluntary muscle and respiratory control. Both ALS and MS exhibit distinct underlying causes and disease mechanisms, despite some shared clinical effects. About 10% of ALS are linked to genetic factors, such as C9orf72, the remaining sporadic ones being potentially influenced by environmental, toxic and oxidative stress, while MS is an autoimmune disorder where the immune system leads to inflammation and attacks the myelin sheath, genetic predisposition and viral infections playing a role in its susceptibility. The co-occurrence of ALS and MS is extremely rare, with 46 cases being reported in the available literature from 1986 to 2024, while in the earlier literature, cases with coincidental muscular atrophy simulating ALS were described. In the overwhelming majority, ALS manifested between one and 41 years after the onset of MS; only in four cases was ALS present before detection of MS. The concurrence of MS and ALS can be explained by similarities in their pathogenesis related to neurodegeneration, inflammation, and/or genetic susceptibility. The role of rare genetic ALS forms in this comorbidity deserves further studies. The shared inflammatory component with a cascade of oxidative stress and other noxious mechanisms leads to progressive motor and bulbar or other symptoms that underscore the potential for cross-disease research to yield insights applicable to both conditions and their relations to immune-mediated disorders.}, }
@article {pmid40580199, year = {2025}, author = {Allen, MD and Van Eijk, RPA and Knox, L and Carlton, J and Hobson, E and Mcdermott, CJ and Murray, D and Berry, J and Meyer, T and Genge, A}, title = {Variability across versions of the self-administered ALSFRS-R: a review and call for harmonization.}, journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration}, volume = {}, number = {}, pages = {1-6}, doi = {10.1080/21678421.2025.2522400}, pmid = {40580199}, issn = {2167-9223}, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease predominantly affecting motor neurons resulting in substantial, progressive disability. The amyotrophic lateral sclerosis functional rating scale - revised (ALSFRS-R) is commonly used to assess and monitor functional status in patients with ALS. Additionally, it is the current regulatory accepted primary outcome measure documenting functional status in ALS clinical trials. The ALSFRS-R was originally designed to be administered to a patient by a trained professional. But over time it has been adapted to be performed independently by patients or their caregivers without assistance. Several different versions of the self-administered ALSFRS-R have been created over the past two decades, each with subtle but important differences. Some of these differences are related to language used in item wording or the platform for which the scale was intended to be administered (e.g. digitally). These differences across versions of the self-administered scale may be problematic as they could increase the heterogeneity of data collected across clinical trials or complicate interpretation of results across trials. Therefore, we highlight the need for a harmonized version of the self-administered ALSFRS-R to be used across all clinics and clinical trial sites internationally.}, }
@article {pmid40578028, year = {2025}, author = {Yang, JL and Qian, SY and Chen, ML and Wang, LX and Wang, Y and Liu, JJ and Xi, CS and Yang, YX and Li, Y and Gao, C and Zheng, GQ}, title = {Skeletal muscle, neuromuscular organoids and assembloids: a scoping review.}, journal = {EBioMedicine}, volume = {118}, number = {}, pages = {105825}, pmid = {40578028}, issn = {2352-3964}, mesh = {*Organoids/cytology/metabolism ; Humans ; *Neuromuscular Junction/metabolism ; *Muscle, Skeletal/metabolism/cytology ; Cell Differentiation ; Animals ; Motor Neurons/metabolism/cytology ; Induced Pluripotent Stem Cells/cytology/metabolism ; }, abstract = {Skeletal muscle organoids (SKMOs), neuromuscular organoids (NMOs), and assembloids have emerged as powerful in vitro models that simulate the intricate cellular interactions between muscle and nerve, offering a promising approach to study function, development, and disease at the neuromuscular junction (NMJ). Given the relevance of NMJ dysfunction in diseases such as amyotrophic lateral sclerosis (ALS), these models provide insights into disease modelling. Scoping reviews are particularly valuable when exploring broad or emerging areas, as they help identify key concepts and evolving methodologies. Here, we conducted a scoping review by searching five databases, ultimately including 17 studies focussing on the development and application of SKMOs, NMOs, and assembloids in muscle function modelling. We highlight recent advancements and summarise various differentiation protocols, primarily utilising the Wnt signalling pathway agonist CHIR99021 and basic fibroblast growth factor (bFGF) to induce pluripotent stem cells into 2D neuromesodermal progenitors, further differentiated into SKMOs, NMOs, and assembloids. We also reviewed their cellular compositions, including motor neurons, neural stem cells, terminal Schwann cells, and astrocytes, alongside related research outcomes. Additionally, we discuss key challenges such as iPSC donor selection, standardisation, vascularisation, and 3D organoid imaging. This scoping review provides a foundation for future research on muscle function modelling.}, }
@article {pmid40576748, year = {2025}, author = {Gupta, MK and Chauhan, K and Bhardwaj, S and Srivastava, R}, title = {Innovative Interventions: Postbiotics and Psychobiotics in Neurodegenerative Disease Treatment.}, journal = {Probiotics and antimicrobial proteins}, volume = {}, number = {}, pages = {}, pmid = {40576748}, issn = {1867-1314}, abstract = {Neurodegenerative disorders, including Huntington's disease, Amyotrophic lateral sclerosis, Alzheimer's disease, and Parkinson's disease, create more challenges as the population gets older and there are no curative therapies available. Recent advances in gut microbiome research have spotlighted postbiotics and psychobiotics as innovative therapeutic strategies targeting the gut-brain axis to alleviate neurodegenerative symptoms and slow disease progression. Postbiotics, which are metabolites and cellular components released by probiotic bacteria, and psychobiotics, a class of probiotics with potential mental health benefits, offer novel approaches to neuroprotection. This chapter examines the ways in which postbiotics and psychobiotics modulate inflammation, oxidative stress, neurotrophic factors, and gut barrier integrity to provide neuroprotective effects. We review scientific research that highlights the efficacy of specific microbial strains and their metabolites in enhancing cognitive function and reducing neurodegeneration. In addition, we explore the consequences of diet and specific nutrition on strengthening the therapeutic results of these medications. The purpose of this chapter is to provide a detailed analysis of the existing data supporting the use of postbiotics and psychobiotics in both the prevention and management of neurological diseases. By integrating perspectives from microbiology, neurology, and clinical nutrition, we highlight the potential of these interventions to enhance patient outcomes and quality of life. In addition, we discuss the translational limitations and future research approaches required to successfully transition these microbiome-based treatments from the laboratory to clinical practice, emphasizing the importance of a holistic and personalized approach in combating neurodegenerative diseases.}, }
@article {pmid40572054, year = {2025}, author = {Arnahoutova, K and De Geest, S and Mielke, J and Boaz, A and Schoemans, H and Valenta, S}, title = {Exploring Stakeholder Involvement in Intervention Implementation Studies: Systematic Evidence Synthesis With an Evidence Gap Map Approach.}, journal = {Evaluation &amp; the health professions}, volume = {}, number = {}, pages = {1632787251352837}, doi = {10.1177/01632787251352837}, pmid = {40572054}, issn = {1552-3918}, abstract = {Stakeholder involvement (SI) is essential for effective and sustainable intervention implementation, yet practical guidance is lacking. This study mapped SI use in implementation science studies, identified gaps, and proposed a practical framework for improved SI planning. Using an evidence gap map approach, this study built on Mielke et al.'s (2022) methodology, which identified implementation studies from 2015-2020. The search was updated to include studies from 2021-2023 from PubMed, using the same search strategy and inclusion criteria. Data extraction followed the Guidance for Reporting on Involvement of Patients and the Public reporting checklist. From 10,184 studies, a random sample of 2,005 was screened, adding 162 implementation science studies to Mielke et al.'s 110, totaling 272 studies for SI analysis. SI was reported in 89% of studies, but often lacked depth and strategic planning. Stakeholders were mainly engaged during the preparatory phase. Most studies involved micro- and meso-level stakeholders, rarely including macro-level stakeholders. Few described stakeholder selection or preparation. SI was mostly consultative, via interviews, surveys, and focus groups, with limited active collaboration. SI processes and costs were rarely evaluated. Our findings underscore the need for structured, comprehensive SI planning and offer practical recommendations to strengthen SI efforts in implementation research.}, }
@article {pmid40566997, year = {2025}, author = {Wu, J and Yan, S and Bian, Y and Liu, R and Lyu, X and Zhang, Z and Huang, S and Chen, T and Cheng, L}, title = {The Impact of Splicing Dysregulation on Neuromuscular Disorders and Current Neuromuscular Genetic Therapies.}, journal = {Journal of neurochemistry}, volume = {169}, number = {6}, pages = {e70133}, doi = {10.1111/jnc.70133}, pmid = {40566997}, issn = {1471-4159}, support = {ZR2022QC052//Natural Science Foundation of Shandong Province/ ; 32200464//National Natural Science Foundation of China/ ; ZD2021036//Science and Technology Project of Hebei Education Department/ ; }, mesh = {Humans ; *Genetic Therapy/methods/trends ; *Neuromuscular Diseases/genetics/therapy ; Animals ; *RNA Splicing/genetics ; Alternative Splicing ; }, abstract = {Eukaryotic genes contain non-coding segments known as introns, which interrupt coding sequences. Consequently, eukaryotic transcription produces precursor messenger RNA (pre-mRNA) that relies on precise splicing to remove highly diverse introns from the genome and to generate the mature mRNA essential for maintaining normal cellular activities. The extensive heterogeneity of neurons necessitates complex splicing regulation, particularly alternative splicing, to ensure the accuracy of gene expression in neurogenesis, signal transduction, and synaptic function and to maintain stability and adaptability in the nervous system. With the improvement of genetic testing technology, aberrant splicing has been identified as a contributing factor to the pathogenesis of neuromuscular disorders (NMDs) such as spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS), Duchenne muscular dystrophy (DMD), myotonic dystrophy (DM), Charcot-Marie-Tooth disease (CMT), myasthenia gravis (MG), and multiple sclerosis (MS). Studying the correlation between splicing defects and neuromuscular disorders is crucial for gaining a more comprehensive understanding of the pathogenesis of these diseases and for developing effective therapies. In this review, we introduce the intricate process and key factors of pre-mRNA splicing, with a focus on aberrant splicing and pathogenesis in several major neuromuscular disorders, providing an overview of the latest therapeutic strategies.}, }
@article {pmid40566744, year = {2025}, author = {Bai, J and Cheng, K and Zhang, N and Chen, Y and Ni, J and Wang, Z}, title = {Research advances in dysphagia animal models.}, journal = {Animal models and experimental medicine}, volume = {}, number = {}, pages = {}, doi = {10.1002/ame2.70054}, pmid = {40566744}, issn = {2576-2095}, support = {82172531//National Natural Science Foundation of China/ ; 2021Y9105//Joint Funds for the Innovation of Science and Technology, Fujian Province/ ; }, abstract = {Dysphagia is a common complication of stroke, Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). The construction of animal models of dysphagia is an important way to explore its pathogenesis and treatment. At present, the animal models of dysphagia mainly include rodents, nonhuman primates, and other mammals, such as pigs and dogs. This review systematically summarizes the establishment and evaluation of dysphagia animal models in stroke, PD, and ALS in three kinds of experimental animals, providing a basis for the selection of appropriate animal models of dysphagia.}, }
@article {pmid40565515, year = {2025}, author = {Falduti, A and Giovinazzo, A and Lo Feudo, E and Rocca, V and Brighina, F and Messina, A and Conforti, FL and Iuliano, R}, title = {The Role of Non-Coding RNAs in ALS.}, journal = {Genes}, volume = {16}, number = {6}, pages = {}, pmid = {40565515}, issn = {2073-4425}, support = {Project P20225J5NB//Project P20225J5NB "Identifying pathogenic pathways in sporadic Amyotrophic Lateral Sclerosis: a genetic, omics and functional study" PRIN PNRR/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics/pathology ; Humans ; *RNA, Long Noncoding/genetics ; *MicroRNAs/genetics ; *RNA, Circular/genetics ; Motor Neurons/metabolism/pathology ; Animals ; *RNA, Untranslated/genetics ; Biomarkers/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects motor neurons, leading to muscle weakness, paralysis, and eventually death. The pathogenesis of ALS is influenced by genetic factors, environmental factors, and age-related dysfunctions. These factors, taken together, are responsible for sporadic cases of ALS, which account for approximately 85-90% of ALS cases, while familial ALS accounts for the remaining 10-15% of cases, usually with dominant traits. Despite advances in understanding and studying the disease, the cause of the onset of ALS remains unknown. Emerging evidence suggests that non-coding RNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), play crucial roles in the pathogenesis of the disease. An abnormal expression of these molecules is implicated in various ALS-related processes, including motor neuron survival, protein aggregation, and inflammation. Here, we describe the dysregulation of non-coding RNAs in the pathogenic mechanism of ALS, highlighting the potential roles of miRNAs, lncRNAs, and circRNAs as biomarkers or therapeutic targets to examine the progression of the disease.}, }
@article {pmid40565514, year = {2025}, author = {Roque-Ramírez, B and Ríos-López, KE and López-Hernández, LB}, title = {Decoding Neuromuscular Disorders: The Complex Role of Genetic and Epigenetic Regulators.}, journal = {Genes}, volume = {16}, number = {6}, pages = {}, pmid = {40565514}, issn = {2073-4425}, mesh = {Humans ; *Epigenesis, Genetic ; *Neuromuscular Diseases/genetics ; DNA Methylation/genetics ; Amyotrophic Lateral Sclerosis/genetics ; Animals ; }, abstract = {Neuromuscular disorders (NMDs), such as amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), and muscular dystrophies (e.g., Duchenne muscular dystrophy, DMD), are primarily driven by genetic mutations but are critically modulated by epigenetic mechanisms such as DNA methylation, histone modifications, and noncoding RNA activity. These epigenetic processes contribute to phenotypic variability and disease progression, and emerging evidence suggests that environmental factors, particularly nutrition and exercise, may further influence the molecular pathways that modulate these diseases. Dietary bioactive compounds (e.g., polyphenols and omega-3 fatty acids) exhibit epigenetic modulatory properties, which could mitigate oxidative stress, inflammation, and muscle degeneration in NMDs. For example, the inhibition of DNMTs and HDACs by curcumin in ALS models and the promyogenic effects of green tea catechins in DMD suggest plausible, though still requiring investigation, therapeutic avenues. However, the clinical application of nutriepigenetic interventions is preliminary and requires further validation. This review examines the interaction of genetic and epigenetic factors in ALS, SMA, and muscular dystrophies, highlighting their combined role in the heterogeneity of these diseases. Integrative therapeutic strategies combining gene therapies, epigenetic modulators, and lifestyle interventions may offer a multidimensional approach to the management of NMD. A deeper understanding of these interactions will be essential for advancing precision medicine and improving patient outcomes.}, }
@article {pmid40565135, year = {2025}, author = {Bono, N and Fruzzetti, F and Farinazzo, G and Candiani, G and Marcuzzo, S}, title = {Perspectives in Amyotrophic Lateral Sclerosis: Biomarkers, Omics, and Gene Therapy Informing Disease and Treatment.}, journal = {International journal of molecular sciences}, volume = {26}, number = {12}, pages = {}, pmid = {40565135}, issn = {1422-0067}, support = {//Italian Ministry of Health (RRC)/ ; T4-AN-09 prog. ZRPOS2//CALabria HUB per Ricerca Innovativa ed Avanzata- CALHUB.RIA "Creazione di Hub delle Sci-enze della Vita"/ ; ZRA124//AriSLA foundation, "Bulb-Omics"/ ; PNRR-MCNT2-2023-12377336//the European Union - Next Generation EU - NRRP M6C2 - Investment 2.1 Enhancement and strengthening of biomedical research in the NHS/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/therapy/genetics/diagnosis/metabolism ; Humans ; *Genetic Therapy/methods ; *Biomarkers/metabolism ; C9orf72 Protein/genetics ; Animals ; Gene Editing ; Superoxide Dismutase-1/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of upper and lower motor neurons, leading to muscle weakness, paralysis, and ultimately respiratory failure. Despite advances in understanding its genetic basis, particularly mutations in Chromosome 9 Open Reading Frame 72 (C9orf72), superoxide dismutase 1 (SOD1), TAR DNA-binding protein (TARDBP), and Fused in Sarcoma (FUS) gene, current diagnostic methods result in delayed intervention, and available treatments offer only modest benefits. This review examines innovative approaches transforming ALS research and clinical management. We explore emerging biomarkers, including the fluid-based markers such as neurofilament light chain, exosomes, and microRNAs in biological fluids, alongside the non-fluid-based biomarkers, including neuroimaging and electrophysiological markers, for early diagnosis and patient stratification. The integration of multi-omics data reveals complex molecular mechanisms underlying ALS heterogeneity, potentially identifying novel therapeutic targets. We highlight current gene therapy strategies, including antisense oligonucleotides (ASOs), RNA interference (RNAi), and CRISPR/Cas9 gene editing systems, alongside advanced delivery methods for crossing the blood-brain barrier. By bridging molecular neuroscience with bioengineering, these technologies promise to revolutionize ALS diagnosis and treatment, advancing toward truly disease-modifying interventions for this previously intractable condition.}, }
@article {pmid40564128, year = {2025}, author = {Drewes, N and Fang, X and Gupta, N and Nie, D}, title = {Pharmacological and Pathological Implications of Sigma-1 Receptor in Neurodegenerative Diseases.}, journal = {Biomedicines}, volume = {13}, number = {6}, pages = {}, pmid = {40564128}, issn = {2227-9059}, abstract = {Originally identified as a potential receptor for opioids, the sigma-1 receptor is now recognized as an intracellular chaperone protein associated with mitochondria-associated membranes at the endoplasmic reticulum (ER). Over the past two decades, extensive research has revealed that the sigma-1 receptor regulates many cellular processes, such as calcium homeostasis, oxidative stress responses, protein folding, and mitochondrial function. The various functions of the sigma-1 receptor highlight its role as a central modulator of neuronal health and may be a promising pharmacological target across multiple neurodegenerative conditions. Herein, we provide an overview of the current pharmacological understanding of the sigma-1 receptor with an emphasis on the signaling mechanisms involved. We examine its pathological implications in common neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and multiple sclerosis. We then highlight how sigma-1 receptor modulation may influence disease progression as well as potential pharmacological mechanisms to alter disease outcomes. The translational potential of sigma-1 receptor therapies is discussed, as well as the most up-to-date results of ongoing clinical trials. This review aims to clarify the therapeutic potential of the sigma-1 receptor in neurodegeneration and guide future research in these diseases.}, }
@article {pmid40563824, year = {2025}, author = {Hasan, A and Scuderi, SA and Capra, AP and Giosa, D and Bonomo, A and Ardizzone, A and Esposito, E}, title = {An Updated and Comprehensive Review Exploring the Gut-Brain Axis in Neurodegenerative Disorders and Neurotraumas: Implications for Therapeutic Strategies.}, journal = {Brain sciences}, volume = {15}, number = {6}, pages = {}, pmid = {40563824}, issn = {2076-3425}, abstract = {The gut-brain axis (GBA) refers to the biochemical bidirectional communication between the central nervous system (CNS) and the gastrointestinal tract, linking brain and gut functions. It comprises a complex network of interactions involving the endocrine, immune, autonomic, and enteric nervous systems. The balance of this bidirectional pathway depends on the composition of the gut microbiome and its metabolites. While the causes of neurodegenerative diseases (NDDs) vary, the gut microbiome plays a crucial role in their development and prognosis. NDDs are often associated with an inflammation-related gut microbiome. However, restoring balance to the gut microbiome and reducing inflammation may have therapeutic benefits. In particular, introducing short-chain fatty acid-producing bacteria, key metabolites that support gut homeostasis, can help counteract the inflammatory microbiome. This strong pathological link between the gut and NDDs underscores the gut-brain axis (GBA) as a promising target for therapeutic intervention. This review, by scrutinizing the more recent original research articles published in PubMed (MEDLINE) database, emphasizes the emerging notion that GBA is an equally important pathological marker for neurological movement disorders, particularly in Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, Huntington's disease and neurotraumatic disorders such as traumatic brain injury and spinal cord injury. Additionally, the GBA presents a promising therapeutic target for managing these diseases.}, }
@article {pmid40563773, year = {2025}, author = {Swash, M and de Carvalho, M}, title = {Dynamics of Onset and Progression in Amyotrophic Lateral Sclerosis.}, journal = {Brain sciences}, volume = {15}, number = {6}, pages = {}, pmid = {40563773}, issn = {2076-3425}, abstract = {This review focuses on the complexities of amyotrophic lateral sclerosis (ALS) onset, highlighting the insidious nature of the disease and the challenges in defining its precise origin and early pathogenic mechanisms. The clinical presentation of ALS is characterised by progressive muscle weakness and wasting, often with widespread fasciculations, reflecting lower motor neuron hyperexcitability. The disease's pathogenesis involves a prolonged preclinical phase of neuronal proteinopathy, particularly TDP-43 accumulation, which eventually leads to motor neuron death and overt ALS. This review discusses the difficulties in detecting this transition and the implications for early therapeutic intervention. It also addresses the involvement of both the upper and lower motor neuron systems, as well as the importance of following presymptomatic patients with genetic mutations. The significance of understanding the distinct processes of TDP-43 deposition and subsequent neuronal degeneration in developing effective treatments is emphasised.}, }
@article {pmid40563772, year = {2025}, author = {Artioli, G and Guardamagna, L and Succi, N and Guasconi, M and Diamanti, O and Dellafiore, F}, title = {Relational, Ethical, and Care Challenges in ALS: A Systematic Review and Qualitative Metasynthesis of Nurses' Perspectives.}, journal = {Brain sciences}, volume = {15}, number = {6}, pages = {}, pmid = {40563772}, issn = {2076-3425}, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that leads to severe functional decline and death, imposing significant physical, emotional, and ethical burdens on patients and healthcare providers. With no curative treatment, ALS care depends on the early and sustained integration of palliative care to address complex and evolving needs. Nurses play a pivotal role in this process, yet their lived experiences remain underexplored. This study aimed to synthesize qualitative evidence on nurses' experiences in ALS care, with a focus on emotional, ethical, and palliative dimensions.<br><br>METHODS: A meta-synthesis of qualitative studies was conducted using Sandelowski and Barroso's four-step method. A systematic search across five databases identified eight studies exploring nurses' experiences with ALS care. Thematic synthesis was applied to extract overarching patterns.<br><br>RESULTS: Three core themes emerged: (1) Relational Dimension: From challenges to empathy and Trust and mistrust-emphasizing communication barriers and the value of relational trust; (2) Care Dimension: Competence, Palliative care needs, and Rewarding complexity-highlighting the emotional demands of care, the need for timely palliative integration, and the professional meaning derived from ALS care; (3) Ethical Dimension: Medical interventionism and Patient-centered values-exploring dilemmas around life-sustaining treatments, patient autonomy, and end-of-life decisions.<br><br>CONCLUSION: Nurses in ALS care face complex emotional and ethical challenges that call for strong institutional support and palliative training. Enhancing palliative care integration from diagnosis, alongside targeted education and psychological support, is crucial to improving care quality and sustaining the well-being of both patients and nurses.}, }
@article {pmid40563328, year = {2025}, author = {Chong, ZZ and Souayah, N}, title = {Oxidative Stress: Pathological Driver in Chronic Neurodegenerative Diseases.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {14}, number = {6}, pages = {}, pmid = {40563328}, issn = {2076-3921}, abstract = {Oxidative stress has become a common impetus of various diseases, including neurodegenerative diseases. This review introduces the generation of reactive oxygen species (ROSs) in the nervous system, the cellular oxidative damage, and the high sensitivity of the brain to ROSs. The literature review focuses on the roles of oxidative stress in neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). Oxidative stress occurs when excessively produced free radicals are beyond the capability of endogenous antioxidants to scavenge, leading to the oxidation of proteins, lipids, and nucleic acids, stimulating neuroinflammatory responses, causing neuronal dysfunction, senescence, and death. The dysfunctional mitochondria and aberrant activities of metabolic enzymes are the major source of ROSs. The high vulnerability of the nervous system to ROSs underlies the critical roles of oxidative stress in neurodegenerative diseases. Gene mutations and other risk factors promote the generation of ROSs, which have been considered a crucial force causing the main pathological features of AD, PD, HD, and ALS. As a result, antioxidants hold therapeutic potential in these neurodegenerative diseases. The elucidation of the pathogenic mechanisms of oxidative stress will facilitate the development of antioxidants for the treatment of these diseases.}, }
@article {pmid40562281, year = {2025}, author = {Sharma, J and Thakur, A and Rain, M and Khosla, R and Maity, K and Mathur, GR and Anand, A}, title = {Interplay between exercise and neuregulin in providing neuroprotection.}, journal = {Behavioural brain research}, volume = {493}, number = {}, pages = {115710}, doi = {10.1016/j.bbr.2025.115710}, pmid = {40562281}, issn = {1872-7549}, mesh = {Humans ; Animals ; *Neuroprotection/physiology ; *Neurodegenerative Diseases/metabolism/prevention &amp; control ; *Neuregulins/metabolism/therapeutic use ; *Exercise/physiology ; *Neuroprotective Agents ; }, abstract = {Exercise has been shown to have a positive impact on brain health including neuroprotective function. It has been demonstrated to increase the synthesis of neurotrophic factors, support neuronal survival, and improve neuroplasticity. Concurrently, neuregulin plays a vital role in the development, maintenance, and repair of both the central and peripheral nervous system. The link between exercise and neuregulin in mediating neuroprotection has been the subject of increased research to better understand the possible applications for the deterrence of neurodegenerative disorders. Understanding this link is of great interest because it has the potential to lead to new strategies for preventing or slowing the progression of neurodegenerative diseases. With an emphasis on exercise-induced neuregulin-mediated neuroprotection, this article reviews the literature on the neuroprotective effects of exercise and neuregulin. The synergistic effects of exercise and neuregulin on neuroprotection will be clarified and valuable insights will be gained from this review, with potential implications for the development of novel therapeutic strategies for neurodegenerative diseases such as Amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), Alzheimer's disease (AD) and Huntington's disease (HD).}, }
@article {pmid40560475, year = {2025}, author = {Bamber, R and Stavroulakis, T and McDermott, C and Carlton, J}, title = {Health-related quality of life of informal carers in ALS: a systematic review of person reported outcome measures.}, journal = {Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation}, volume = {}, number = {}, pages = {}, pmid = {40560475}, issn = {1573-2649}, support = {NIHR301648//National Institute for Health and Care Research/ ; }, abstract = {PURPOSE: Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative condition with swift progression. The devastating impact of ALS affects the health-related quality of life (HRQoL) of informal carers. Various person reported outcome measures (PROMs) have been used to assess HRQoL in informal carers in ALS, yet their validity remains unclear. This review aimed to identify and evaluate the content validity of HRQoL PROMs for informal carers in ALS.<br><br>METHODS: This review was conducted according to best practice COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) methodology. Two literature searches were conducted in November 2023 and April 2024 across MEDLINE, PsycINFO, Embase, CINAHL, the Cochrane Database of Systematic Reviews, CENTRAL and Google Scholar, to identify HRQoL PROMs used with informal carers in ALS, PROM development articles, and psychometric literature. Evidence synthesis followed COSMIN guidance.<br><br>RESULTS: 12,276 articles were screened, and 109 PROMs were identified, with 43 undergoing full COSMIN assessment. Content validity ratings were 'Inconsistent' or 'Insufficient' for all PROMs. All PROMs, except the CarerQoL, were rated 'Insufficient' for comprehensiveness. Only 18.6% of PROMs included informal carers in development. Quality of evidence supporting content validity ratings was 'Very Low' for 93% of PROMs.<br><br>CONCLUSION: HRQoL PROMs used with informal carers in ALS lack evidence to support their content validity, restricting their utility for this purpose. Existing literature on the impact of caring in ALS on informal carers' HRQoL should be interpreted cautiously. Further research is required to establish the content validity of HRQoL PROMs used for this cohort.}, }
@article {pmid40559965, year = {2025}, author = {Kim, WW and Zarus, G and Alman, B and Ruiz, P and Han, M and Mehta, P and Ji, C and Qureshi, H and Antonini, J and Shoeb, M}, title = {Metal-Induced Genotoxic Events: Possible Distinction Between Sporadic and Familial ALS.}, journal = {Toxics}, volume = {13}, number = {6}, pages = {}, pmid = {40559965}, issn = {2305-6304}, abstract = {Metal exposure is a potential risk factor for amyotrophic lateral sclerosis (ALS). Increasing evidence suggests that elevated levels of DNA damage are present in both familial (fALS) and sporadic (sALS) forms of ALS, characterized by the selective loss of motor neurons in the brain, brainstem, and spinal cord. However, identifying and differentiating initial biomarkers of DNA damage response (DDR) in both forms of ALS remains unclear. The toxicological profiles from the Agency for Toxic Substances and Disease Registry (ATSDR) and our previous studies have demonstrated the influence of metal exposure-induced genotoxicity and neurodegeneration. A comprehensive overview of the ATSDR's toxicological profiles and the available literature identified 15 metals (aluminum (Al), arsenic (As), cadmium (Cd), chromium (Cr), cobalt (Co), copper (Cu), iron (Fe), lead (Pb), manganese (Mn), mercury (Hg), nickel (Ni), selenium (Se), uranium (U), vanadium (V), and zinc (Zn)) showing exposure-induced genotoxicity indicators associated with ALS pathogenesis. Genetic factors including mutations seen in ALS types and with concomitant metal exposure were distinguished, showing that heavy metal exposure can exacerbate the downstream effect of existing genetic mutations in fALS and may contribute to motor neuron degeneration in sALS. Substantial evidence associates heavy metal exposure to genotoxic endpoints in both forms of ALS; however, a data gap has been observed for several of these endpoints. This review aims to (1) provide a comprehensive overview of metal exposure-induced genotoxicity in ALS patients and experimental models, and its potential role in disease risk, (2) summarize the evidence for DNA damage and associated biomarkers in ALS pathogenesis, (3) discuss possible mechanisms for metal exposure-induced genotoxic contributions to ALS pathogenesis, and (4) explore the potential distinction of genotoxic biomarkers in both forms of ALS. Our findings support the association between metal exposure and ALS, highlighting under or unexplored genotoxic endpoints, signaling key data gaps. Given the high prevalence of sALS and studies showing associations with environmental exposures, understanding the mechanisms and identifying early biomarkers is vital for developing preventative therapies and early interventions. Limitations include variability in exposure assessment and the complexity of gene-environment interactions. Studies focusing on longitudinal exposure assessments, mechanistic studies, and biomarker identification to inform preventative and therapeutic strategies for ALS is warranted.}, }
@article {pmid40559225, year = {2025}, author = {Elgenidy, A and Hassan, IA and Hamed, Y and Hashem, HA and Abuel-Naga, O and Abdel-Rahman, HI and Mohamed, KR and Hamed, BM and Shehab, MA and Zeyada, M and Kassab, S and Abdelgawad, SSA and Ibrahim, AI and Hasanin, EH and Elhoufey, AA and Mahmoud, KH and Saad, K}, title = {Sonographic Evaluation of Peripheral Nerves and Cervical Nerve Roots in Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis.}, journal = {Medical sciences (Basel, Switzerland)}, volume = {13}, number = {2}, pages = {}, pmid = {40559225}, issn = {2076-3271}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/pathology ; Ultrasonography/methods ; *Peripheral Nerves/diagnostic imaging/pathology ; *Spinal Nerve Roots/diagnostic imaging/pathology ; Middle Aged ; }, abstract = {BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease that leads to nerve atrophy. Ultrasonography has a significant role in the diagnosis of ALS.<br><br>AIM: We aimed to sonographically assess the size of all peripheral nerves and cervical nerve roots in ALS compared to controls.<br><br>METHODS: We searched MEDLINE (PubMed), Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, and Scopus using comprehensive MeSH terms for the keywords nerve, ultrasound, and ALS. We extracted data regarding cross-sectional area (CSA) or diameter for the following nerves: vagus, phrenic, tibial, fibular, sural, radial, ulnar, and median nerves, and the roots of C5, C6, C7, and C8 in both ALS patients and controls.<br><br>RESULTS: Our study included 2683 participants, of which 1631 were ALS patients (mean age = 60.36), 792 were healthy controls (mean age = 57.79), and 260 were patients with other neurological disorders. ALS patients had significantly smaller nerve size compared to controls. Nerve size differences were observed in the vagus nerve [MD = -0.23], phrenic nerve [MD = -0.25], C5 nerve root [SMD = -0.94], C6 nerve root [SMD = -1.56], C7 nerve root [SMD = -1.18], C8 nerve root [MD = -1.9], accessory nerve [MD = -0.32], sciatic nerve [MD = -11], tibial nerve [MD = -0.68], sural nerve [MD = -0.32,], ulnar nerve [MD = -0.80], and median nerve [MD = -1.21].<br><br>CONCLUSIONS: Our findings showed that ALS patients have a sonographically smaller nerve size than healthy controls. Therefore, this is a potential marker for neuronal diseases.}, }
@article {pmid40558500, year = {2025}, author = {Mai, HA and Thomas, CM and Nge, GG and Elefant, F}, title = {Modulating Cognition-Linked Histone Acetyltransferases (HATs) as a Therapeutic Strategy for Neurodegenerative Diseases: Recent Advances and Future Trends.}, journal = {Cells}, volume = {14}, number = {12}, pages = {}, pmid = {40558500}, issn = {2073-4409}, support = {RF1 NS095799/NS/NINDS NIH HHS/United States ; 2RF1NS095799//National Institutes of Health NINDS/ ; 2RF1NS095799/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Neurodegenerative Diseases/therapy/enzymology/drug therapy ; *Histone Acetyltransferases/metabolism ; *Cognition/physiology ; Animals ; Protein Processing, Post-Translational ; Histones/metabolism ; Epigenesis, Genetic ; Acetylation ; Aging ; }, abstract = {Recent investigations into the neuroepigenome of the brain are providing unparalleled understanding into the impact of post-translational modifications (PTMs) of histones in regulating dynamic gene expression patterns required for adult brain cognitive function and plasticity. Histone acetylation is one of the most well-characterized PTMs shown to be required for neuronal function and cognition. Histone acetylation initiates neural circuitry plasticity via chromatin control, enabling neurons to respond to external environmental stimuli and adapt their transcriptional responses accordingly. While interplay between histone acetylation and deacetylation is critical for these functions, dysregulation during the aging process can lead to significant alterations in the neuroepigenetic landscape. These alterations contribute to impaired cognitive functions, neuronal cell death, and brain atrophy, all hallmarks of age-related neurodegenerative disease. Significantly, while age-related generation of DNA mutations remains irreversible, most neuroepigenetic PTMs are reversible. Thus, manipulation of the neural epigenome is proving to be an effective therapeutic strategy for neuroprotection in multiple types of age-related neurodegenerative disorders (NDs) that include Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD). Here, we highlight recent progress in research focusing on specific HAT-based neuroepigenetic mechanisms that underlie cognition and pathogenesis that is hallmarked in age-related NDs. We further discuss how these findings have potential to be translated into HAT-mediated cognitive-enhancing therapeutics to treat these debilitating disorders.}, }
@article {pmid40555284, year = {2025}, author = {Park, KH and Kim, KW}, title = {Optogenetics to biomolecular phase separation in neurodegenerative diseases.}, journal = {Molecules and cells}, volume = {48}, number = {8}, pages = {100247}, pmid = {40555284}, issn = {0219-1032}, mesh = {*Optogenetics/methods ; Humans ; *Neurodegenerative Diseases/metabolism/genetics ; Animals ; Phase Separation ; }, abstract = {Neurodegenerative diseases involve toxic protein aggregation. Recent evidence suggests that biomolecular phase separation, a process in which proteins and nucleic acids form dynamic, liquid-like condensates, plays a key role in this aggregation. Optogenetics, originally developed to control neuronal activity with light, has emerged as a powerful tool to investigate phase separation in living systems. This is achieved by fusing disease-associated proteins to light-sensitive oligomerization domains, enabling researchers to induce or reverse condensate formation with precise spatial and temporal control. This review highlights how optogenetic systems such as OptoDroplet are being used to dissect the mechanisms of neurodegenerative disease. We examine how these tools have been applied in models of neurodegenerative diseases, such as amyotrophic lateral sclerosis, Alzheimer's, Parkinson's, and Huntington's disease. These studies implicate small oligomeric aggregates as key drivers of toxicity and highlight new opportunities for therapeutic screening. Finally, we discuss advances in light-controlled dissolution of condensates and future directions for applying optogenetics to combat neurodegeneration. By enabling precise, dynamic control of protein phase behavior in living systems, optogenetic approaches provide a powerful framework for elucidating disease mechanisms and informing the development of targeted therapies.}, }
@article {pmid40551453, year = {2025}, author = {Ahmad, AAK and Tehan, PE and Hopson, AM and Roberts, EG and Rose, AJ}, title = {Evaluation of eHealth Interventions to Prevent Pressure Injuries: A Scoping Review.}, journal = {International wound journal}, volume = {22}, number = {7}, pages = {e70680}, pmid = {40551453}, issn = {1742-481X}, support = {G2300448//University of Newcastle, College of Health, Medicine and Well-being: CWMWB Industry Pilot/ ; }, mesh = {Humans ; *Pressure Ulcer/prevention &amp; control ; *Telemedicine ; Male ; Female ; }, abstract = {The aim of this scoping review was to map the literature pertaining to the use of eHealth interventions to prevent pressure injuries in populations at risk of the complication, and describe the interventions encountered with the help of Greenhalgh et al.'s Nonadoption, Abandonment, Scale-up, Spread and Sustainability framework. Articles were retrieved using database queries to CINAHL, Medline, ScienceDirect and the Cochrane library with a search string strategy that considered articles from the inception of each database until the 29th of January 2024. The interventions from the 27 included studies were then evaluated using the Nonadoption, Abandonment, Scale-up, Spread and Sustainability framework. The included studies had a publication date range from 1997 to 2023 and included diverse study designs encompassing experimental trials, qualitative designs, mixed-methods, cohort studies and randomised control trials (including secondary analyses). There was a preference for app-based interventions (15/27) that are installed on smartphones, while other interventions encompassed a bed with sensors that automatically adjusted air cell pressure, clinical support algorithms and continuous sensing devices. In conclusion, this scoping review provides an overview of the various technological solutions currently available for pressure injury prevention as well as recommendations for improving the long-term adoption of future eHealth interventions.}, }
@article {pmid40550228, year = {2025}, author = {Tiwari, A and Singh, B and Singh, GK and Meena, J and Agrawal, AK and Kumar, S and Modi, G}, title = {Unveiling Exosome Potential: Transforming Treatments for Neurodegeneration.}, journal = {ACS applied bio materials}, volume = {8}, number = {7}, pages = {5406-5423}, doi = {10.1021/acsabm.5c00096}, pmid = {40550228}, issn = {2576-6422}, mesh = {*Exosomes/chemistry/metabolism ; Humans ; *Neurodegenerative Diseases/drug therapy/metabolism ; Animals ; *Biocompatible Materials/chemistry ; Drug Delivery Systems ; }, abstract = {Exosomes, tiny extracellular vesicles, hold significant potential as biological nanocarriers for diverse therapeutic agents due to their exceptional ability to navigate through the barriers of biological systems. This comprehensive review delves into the capability of exosomes in the therapy of neurodegenerative disorders, concentrating on their potential for targeted drug delivery. It examines the complex processes involved in exosome-mediated drug delivery, including targeting, cellular uptake, intracellular trafficking, and therapeutic release. Insights from preclinical studies and clinical trials are exploited, highlighting the impactful applications of exosomes, particularly in the treatment of Parkinson's, Alzheimer's, ALS, and Huntington's diseases. The review also addresses challenges such as immunogenicity, scalability, and regulatory obstacles while exploring emerging technologies like advanced exosome engineering, personalized medicine, and the integration of nanotechnology. Overall, this review accentuates the potential impact of exosome-based treatments in biomedicine alongside the critical need to overcome existing barriers.}, }
@article {pmid40544973, year = {2025}, author = {Thakur, N and Kumar, T and Singh, C and Kumar, R and Kumar, A}, title = {Cell membrane-coated nanoparticles for neurodegenerative disorders management.}, journal = {International journal of pharmaceutics}, volume = {681}, number = {}, pages = {125875}, doi = {10.1016/j.ijpharm.2025.125875}, pmid = {40544973}, issn = {1873-3476}, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy ; Animals ; *Cell Membrane/metabolism/chemistry ; *Nanoparticles/chemistry/administration &amp; dosage ; Drug Delivery Systems/methods ; Blood-Brain Barrier/metabolism ; Drug Carriers/chemistry ; *Nanoparticle Drug Delivery System/chemistry ; }, abstract = {Neurodegenerative disorders (ND) are accompanied by neuronal death because of progressive destruction in neuronal structure and function. Due to various neurological conditions, there is a significant number of deaths every year around the world. The healthcare burden is also increasing each year. Development and progress in nanotechnology enable the creation of nanocarriers that transport drugs to the site of disease, thereby enhancing the therapeutic performance of the drug. However, the transport of nanocarrier-based therapeutics to the brain is restricted by barriers such as the Blood-Brain Barrier (BBB) and Blood-Cerebrospinal Fluid Barrier (BCFB), which are further impeded by P-glycoproteins. Hence, current research and development focus on overcoming these obstacles. A biomimetic drug delivery system is one of the best ways to overcome these challenges. One of the promising biomimetic drug delivery systems is cell membrane-coated nanoparticles. In this review, we have comprehensively reviewed the recent progress and development in various cell membrane coated nanoparticle-based drug delivery systems for the effective management of a range of neurodegenerative diseases such as Alzheimer's Disease, Parkinson's Disease, Glioblastoma, Ischemic Stroke, Huntington's Disease, Amyotrophic Lateral Sclerosis, Glioma, Peripheral Nerve Injury, and Motor Neuron Disorder. We also reviewed the challenges associated with cell membrane-coated nanoparticles, such as biosafety hurdles, toxicity, regulatory requirements, and clinical translation. Ultimately, we provided the conclusions and future research directions that must be investigated to overcome the current limitations.}, }
@article {pmid40544661, year = {2025}, author = {Zelek, WM and Tenner, AJ}, title = {Complement therapeutics in neurodegenerative diseases.}, journal = {Immunobiology}, volume = {230}, number = {4}, pages = {153089}, doi = {10.1016/j.imbio.2025.153089}, pmid = {40544661}, issn = {1878-3279}, mesh = {Humans ; *Neurodegenerative Diseases/immunology/therapy/drug therapy/metabolism/etiology ; *Complement System Proteins/metabolism/immunology ; Animals ; Brain/immunology ; Complement Activation/drug effects ; }, abstract = {Neurodegenerative diseases (NDDs) such as Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis pose considerable therapeutic challenges, not only due to their complex pathophysiology, but also because any effective drug must be capable of penetrating the brain. Inflammation is a key feature of NDDs. Increasingly, the complement system, long studied in the context of host defence, has emerged as a central player in the brain, with roles extending far beyond its classical immune functions. Complement contributes to synaptic pruning and immune surveillance, but when dysregulated, it can drive chronic inflammation, synapse loss, and neurodegeneration. Complement is also implicated in neurodevelopmental and neuropsychiatric diseases, including schizophrenia and mood disorders, where overactivation of the cascade impacts brain maturation and circuit stability. In this review, we take a broad view of roles of the complement system in both health and disease in the central nervous system (CNS). We summarise key mechanisms through which complement contributes to pathology, discuss emerging therapeutic strategies, and consider major hurdles in CNS drug development, including brain delivery and the need for patient stratification. As our understanding of the pathological roles of the complement system in the brain advances, it is becoming clear that complement therapeutics may offer a novel approach in slowing neurodegeneration, and in addressing a broader spectrum of disorders affecting the brain.}, }
@article {pmid40543562, year = {2025}, author = {Pope, E and Ameral, V and Falcón, A and Smith, J and Shoemaker-Hunt, SJ and Bounthavong, M and McCullough, M and Kim, B}, title = {Knowledge and attitudes regarding substance use disorder treatment and harm reduction practices among US pharmacists: a scoping review.}, journal = {Journal of the American Pharmacists Association : JAPhA}, volume = {}, number = {}, pages = {102462}, doi = {10.1016/j.japh.2025.102462}, pmid = {40543562}, issn = {1544-3450}, abstract = {BACKGROUND: Pharmacists are uniquely positioned to address substance use disorders (SUDs) and expand harm reduction services due to their accessibility and expertise in medication management. However, attitudinal and structural barriers may limit their full potential in this role.<br><br>OBJECTIVE: This scoping review examines pharmacists' knowledge, attitudes, and engagement in SUD treatment and harm reduction.<br><br>METHODS: A scoping review was conducted using Levac et al.'s enhancement of Arksey and O'Malley's framework. A systematic search of MEDLINE (PubMed), PsycInfo, Embase, ProQuest Health &amp; Medical, and ProQuest Psychology was performed on August 3, 2024, yielding 87 articles addressing pharmacists' knowledge, attitudes, and practices related to SUD and harm reduction.<br><br>RESULTS: Pharmacists generally acknowledge the efficacy of medications for opioid use disorder (MOUDs) in reducing opioid-related mortality but often hold stigmatizing beliefs about individuals with SUDs. While supportive of harm reduction strategies, such as naloxone distribution and needle and syringe programs, engagement varies widely. Significant gaps in education and training persist, leaving pharmacists with limited confidence and practical experience in SUD care, despite their reported familiarity with MOUDs and naloxone pharmacology.<br><br>CONCLUSION: This review highlights a complex interplay of support, barriers, and knowledge gaps shaping pharmacists' roles in SUD treatment and harm reduction. Targeted education, supportive policies, and interprofessional collaboration are crucial to enabling pharmacists to provide stigma-free, comprehensive care for individuals with SUDs.}, }
@article {pmid40541317, year = {2025}, author = {Frecska, E and Kovács, A and Szabo, A}, title = {The protective effect of DMT against neurodegeneration.}, journal = {International review of neurobiology}, volume = {181}, number = {}, pages = {395-420}, doi = {10.1016/bs.irn.2025.04.010}, pmid = {40541317}, issn = {2162-5514}, mesh = {Humans ; Animals ; *Neurodegenerative Diseases/metabolism/drug therapy/prevention &amp; control ; *Neuroprotective Agents/therapeutic use/pharmacology ; *Receptors, sigma/agonists/metabolism ; *Reperfusion Injury/metabolism/drug therapy ; Sigma-1 Receptor ; }, abstract = {This paper explores the therapeutic potential of DMT in neuroprotective strategies, particularly concerning ischemia-reperfusion injury (IRI) and neurodegenerative disorders. Besides its potent serotonin receptor actions, DMT is also an endogenous agonist of the sigma-1 receptor (Sig-1R). Sigma receptors are a unique family of proteins with high expression in the brain and spinal cord and have been involved in the etiology, symptom course and treatment of several central nervous system disorders. Our previous theoretical and experimental work strongly suggest that targeting sigma (and serotonin) receptors via DMT may be particularly useful for treatment in a number of neurological conditions like stroke, global brain ischemia, Alzheimer's disease, and amyotrophic lateral sclerosis. In this article, we briefly overview the function of Sig1-R in cellular bioenergetics with a focus on the processes involved in IRI and summarize the results of our previous preclinical (in vitro and in vivo) DMT studies aiming at mitigating IRI and related cellular neuropathologies. We conclude that the effect of DMT may involve a universal role in cellular protective mechanisms suggesting therapeutic potentials against different components and types of IRIs emerging in local and generalized brain ischemia after stroke or cardiac arrest. The multiple neuroprotective mechanisms facilitated by DMT may position it as a model molecule for developing pharmacological treatments for neurodegenerative disorders.}, }
@article {pmid40540128, year = {2025}, author = {Bonan, L and Bombardi, M and Di Lionardo, A and Vitiello, M and Morresi, S and Longoni, M}, title = {Co-occurence of amyotrophic lateral sclerosis and sarcoidosis: a case report and systematic review of the literature.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {46}, number = {9}, pages = {4209-4217}, pmid = {40540128}, issn = {1590-3478}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/diagnosis ; Male ; Middle Aged ; *Sarcoidosis/complications/diagnosis/drug therapy ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting motor neurons, with 90% of cases being sporadic. Sarcoidosis is an inflammatory disease affecting multiple organs, with neurological complications occurring in 5-10% of patients. Only isolated cases of this extremely rare combination of the two diseases have been reported.<br><br>METHODS: We present the case of a 45-year-old man diagnosed with ALS after a 2-year history of progressive upper limb weakness who was incidentally found to be affected by thoraco-abdominal lymphadenopathy. The biopsy confirmed the co-presence of sarcoidosis. We also make a systematic review of the literature of this rare combination.<br><br>RESULTS: The patient showed stabilization of the neurological condition and the pneumological disease after administration of immunosuppressive treatment.<br><br>CONCLUSION: Our case report and literature review highlight peculiar clinical characteristics of this extremely rare combination of diseases, deepening the understanding of this peculiar phenotype.}, }
@article {pmid40540117, year = {2025}, author = {Blanchet Garneau, A and Lavoie, P and Bélisle, M and Cassivi, C and Chamoun, L and Bytyqi, T}, title = {Outcomes of antiracist pedagogy in health professions education: a scoping review.}, journal = {Advances in health sciences education : theory and practice}, volume = {}, number = {}, pages = {}, pmid = {40540117}, issn = {1573-1677}, abstract = {In health professions education, there is a call to rethink pedagogical practices and institutions that often perpetuate racism, colonialism, and other systems of oppression. Researchers have stressed the importance of integrating critical pedagogies, such as antiracist pedagogy, to help learners understand societal and structural factors behind health inequities and recognize power dynamics in health science and healthcare. Various antiracist pedagogical interventions have been designed, but their outcomes remain unclear. Based on Levac et al.'s framework, a scoping review was conducted to map the literature evaluating the outcomes of antiracist pedagogy in health professions education. A systematic database search was conducted between April and June 2022 for articles describing evaluation methods and outcomes of antiracist pedagogical interventions in health professions education. We included 41 articles in the final selection. The data was organized within the following themes: aim of intervention, type of intervention, evaluation tools, outcomes and indicators for each of Kirkpatrick's levels of training evaluation, theoretical frameworks, and authors' positionalities. The thematic analysis revealed that, in most cases, evaluations targeted participants' attitudes on systemic racism, their racial identity and critical awareness, as well as their satisfaction with the activities. The antiracist pedagogical interventions were rarely evaluated beyond learners' perceptions. Discrepancies were also raised between the principles of antiracist education and the use of antiracist pedagogy to design, implement and evaluate the outcomes of antiracist pedagogical interventions in health professions education. Although only a few interventions had transformative outcomes beyond individuals, we identified promising pedagogical strategies to foster engagement and motivation to transform professional practices.}, }
@article {pmid40538061, year = {2025}, author = {Guo, Z and Zhang, X and Li, Y and Chen, Y and Xu, Y}, title = {Splicing to keep splicing: A feedback system for cellular homeostasis and state transition.}, journal = {Clinical and translational medicine}, volume = {15}, number = {6}, pages = {e70369}, pmid = {40538061}, issn = {2001-1326}, support = {82173292//National Natural Science Foundation of China/ ; 62171365//National Natural Science Foundation of China/ ; 62471378//National Natural Science Foundation of China/ ; 2024SF-GJHX-40//the Key Research and Development Projects of Shaanxi Province/ ; QCYRCXM-2022-209//the Key Research and Development Projects of Shaanxi Province/ ; YX6J021//Young Talent Support Plan of Xi'an Jiaotong University/ ; 2022-11//Basic-Clinical Medical Integration &amp; Innovation Project of Xi'an Jiaotong University/ ; }, mesh = {Humans ; *Homeostasis/genetics ; *Alternative Splicing/genetics ; Feedback, Physiological ; Nonsense Mediated mRNA Decay ; }, abstract = {BACKGROUND: Alternative splicing (AS) plays a crucial role in regulating gene expression and governing proteomic diversity by generating multiple protein isoforms from a single gene. Increasing evidence has highlighted the regulation for pre-mRNA splicing of the splicing factors (SFs). This review aims to examine featured mechanisms and examples of SF regulation by AS, focusing on paradigmatic feedback loops and their biological implications.<br><br>MAIN BODY OF THE ABSTRACT: We specifically focus on the autoregulation and inter-regulation of SFs through AS machinery. These interactions give rise to a feedback system, where the negative feedback loops aid in maintaining cellular homeostasis, and the positive feedback loops play roles in triggering cellular state transitions. We examine the growing evidence highlighting the specific mechanisms employed by SFs to autoregulate their own splicing, including AS-coupled nonsense-mediated mRNA decay (AS-NMD), nuclear retention, and alternative 3'UTR regulation. We showcase the influence of AS feedback in amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and cancer. Furthermore, we discuss how master splicing factors can dominantly orchestrate splicing cascades, leading to widespread impacts in cellular processes. We also discuss how non-coding RNAs, particularly circular RNAs and microRNAs, engage in the splicing regulatory networks. Lastly, we showcase how negative and positive feedback loops can collaboratively achieve remarkable biological functions during the cell fate decision.<br><br>SHORT CONCLUSION: This review highlights the regulation of SFs by AS, providing enriched information for future investigations that aim at deciphering the intricate interplay within splicing regulatory networks.<br><br>KEY POINTS: Negative feedback of alternative splicing maintains cellular homeostasis. Positive feedback of alternative splicing triggers cellular state transitions. Alternative splicing forms integrated feedback networks with circRNAs and microRNAs to reciprocally regulate their expression and function. The coordinated interplay of distinct splicing feedback mechanisms orchestrates precise cell fate transitions. Future directions and therapeutic possibilities that could transform alternative splicing research into treatments.}, }
@article {pmid40535632, year = {2025}, author = {Tang, X and Wang, C and Tian, S and Wen, H and Zhang, H}, title = {Acupuncture for neurodegenerative diseases: mechanisms, efficacy, and future research directions.}, journal = {American journal of translational research}, volume = {17}, number = {5}, pages = {3703-3717}, pmid = {40535632}, issn = {1943-8141}, abstract = {In recent years, acupuncture has shown good therapeutic efficacy in treating neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. Studies have demonstrated that acupuncture alleviates symptoms primarily by suppressing neuroinflammation, enhancing autophagy, improving synaptic plasticity, and optimizing mitochondrial function. As molecular research advances, the underlying mechanisms of acupuncture in these conditions have become increasingly clear. This review summarizes recent progress in understanding the efficacy and molecular mechanisms of acupuncture in neurodegenerative diseases, providing a theoretical support for its clinical application.}, }
@article {pmid40534528, year = {2025}, author = {Ertural, B and Çiçek, BN and Kurnaz, IA}, title = {RNA Therapeutics: Focus on Antisense Oligonucleotides in the Nervous System.}, journal = {Biomolecules &amp; therapeutics}, volume = {33}, number = {4}, pages = {572-581}, pmid = {40534528}, issn = {1976-9148}, abstract = {RNA therapeutics represent a disruptive technology that has transformed drug discovery and manufacturing, gaining significant prominence during the COVID-19 pandemic. RNA therapeutics encompass diverse molecules like antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), microRNAs (miRNAs), RNA aptamers, and messenger RNAs (mRNAs), which can function through different mechanisms. RNA therapeutics are increasingly used to treat various diseases, including neurological disorders. For example, ASO therapies such as nusinersen for spinal muscular atrophy and eteplirsen for Duchenne muscular dystrophy are successful applications of RNA-based treatment. Emerging ASO treatments for Huntington's disease and amyotrophic lateral sclerosis are also promising, with ongoing clinical trials demonstrating significant reductions in disease-associated proteins. Still, delivery of these molecules remains a pivotal challenge in RNA therapeutics, especially for ASOs in penetrating the blood-brain barrier to target neurological disorders effectively. Nanoparticle-based formulations have emerged as leading strategies to enhance RNA stability, reduce immunogenicity, and improve cellular uptake. Despite these advances, significant hurdles remain, including optimizing pharmacokinetics, minimizing off-target effects, and ensuring sustained therapeutic efficacy. Regulatory frameworks are evolving to accommodate the unique challenges of RNA-based therapies, including ASOs with efforts underway to establish comprehensive guidelines for RNA therapeutics, yet there are also sustainable manufacturing issues that need to be considered for long-term feasibility. By addressing these challenges, RNA therapeutics hold immense potential to revolutionize treatment paradigms for neurological disorders. Looking forward, the future of RNA therapeutics in neurology appears promising but requires continued interdisciplinary collaboration and technological innovation.}, }
@article {pmid40533880, year = {2025}, author = {Liu, W and Wang, S and Zhang, T and Zhu, H and Chang, N and Zhang, L and Hu, Z}, title = {A Review of Preparation of Low-Carbon Cementitious Materials from Chemically Activated Red Mud: Synergy, Hydration Mechanism, Rheological Properties and Applications.}, journal = {Langmuir : the ACS journal of surfaces and colloids}, volume = {41}, number = {25}, pages = {15735-15751}, doi = {10.1021/acs.langmuir.5c01088}, pmid = {40533880}, issn = {1520-5827}, abstract = {Red mud, a byproduct of the alumina refining process, is generated at a rate of 1-2.5 tonnes per tonne of alumina produced. In 2022, China's alumina production totaled 77.475 million tonnes, contributing over 4 billion tonnes of accumulated red mud, which is the third-largest industrial solid waste in the country. Red mud's high alkalinity and presence of toxic elements pose environmental challenges, particularly in terms of disposal. This review provides a comprehensive examination of red mud-based cementitious materials, focusing on their preparation, properties, and environmental impact. By combining red mud with high-calcium and silica-aluminum solid wastes and enhancing its reactivity through mechanical grinding or thermal activation, red mud's cementitious activity can be significantly improved. Optimized compositions, with a Ca/Si ratio of 2.05 and Al/S ratio of 0.70, have achieved compressive strengths of up to 63.9 MPa at 28 day. Durability studies highlight the material's resistance to chloride ion penetration and sulfate attack, with reduced permeability enhancing long-term performance. Additionally, environmental assessments confirm that stabilization and solidification techniques effectively mitigate heavy metal leaching, ensuring compliance with EPA standards. Despite these advancements, challenges remain in optimizing red mud activation processes, improving rheological properties, and reducing production costs. Future research should focus on refining activation methods, enhancing hydration mechanisms, and developing scalable industrial applications. By addressing these gaps, red mud-based cementitious materials can become a sustainable solution for eco-friendly construction, supporting global efforts to repurpose industrial byproducts into low-carbon, durable building materials.}, }
@article {pmid40528459, year = {2025}, author = {Yang, M and Zhang, A and Chen, M and Cao, J}, title = {Advances in Circulating Biomarkers for Neurodegenerative Diseases, Traumatic Brain Injuries, and Central Nervous System Tumors.}, journal = {Annals of laboratory medicine}, volume = {45}, number = {4}, pages = {381-390}, pmid = {40528459}, issn = {2234-3814}, mesh = {Humans ; *Brain Injuries, Traumatic/diagnosis/blood ; *Neurodegenerative Diseases/diagnosis/blood ; *Biomarkers/blood/cerebrospinal fluid ; *Central Nervous System Neoplasms/diagnosis/blood ; Enzyme-Linked Immunosorbent Assay ; tau Proteins/blood/cerebrospinal fluid ; }, abstract = {Neurological disorders, including neurodegenerative diseases, traumatic brain injuries (TBI), and central nervous system (CNS) tumors, are complex conditions that significantly impact patients globally. Timely diagnosis and monitoring are critical for improving outcomes, driving the need for reliable biomarkers. Specifically, biomarkers detectable in cerebrospinal fluid (CSF) and blood offer important insights into disease presence and progression. This review explores the evolution of circulating blood biomarkers for neurodegenerative diseases, TBI, and CNS tumors, highlighting advanced detection technologies from enzyme-linked immunosorbent assays (ELISAs) to electrochemiluminescence (ECL) assays, single-molecule arrays (Simoa), and mass spectrometry. Advanced technologies with enhanced sensitivity and specificity, particularly in detecting low-abundance analytes, facilitate the investigation of CSF biomarkers for various neurological disorders. We also describe the progress in blood-based biomarkers for , emerging as less invasive alternatives to CSF sampling. Clinically, the implementation of Alzheimer's disease (AD) blood biomarkers Aβ42/Aβ40 ratio and Apolipoprotein E isoform-specific peptide can aid the diagnosis, while p-tau181 and p-tau217 differentiates AD dementia from non-AD neurodegenerative diseases. Blood glial fibrillary acidic protein and ubiquitin C-terminal hydrolase-L1 are used in ruling out mild TBI. Despite these innovations, challenges remain, including assay standardization, sensitivity/specificity trade-offs, and the requirement for longitudinal studies to understand biomarker utility over time. Future research should focus on addressing these challenges to fully realize the potential of blood-based biomarkers in neurological disorder diagnostics and patient care.}, }
@article {pmid40527647, year = {2025}, author = {Thijs, Z and Calzada, A and Sosa, M and Dumican, M}, title = {The Association Between Bilingualism and Voice Quality in Spanish-English Bilingual Speakers: A Systematic Review.}, journal = {Journal of voice : official journal of the Voice Foundation}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jvoice.2025.05.027}, pmid = {40527647}, issn = {1873-4588}, abstract = {OBJECTIVE/HYPOTHESIS: The vast majority of the global population speaks more than one language. In the United States, Spanish-English bilingual speakers are the largest bilingual group. Yet, the potential effect of being bilingual, specifically a Spanish-English speaker, on voice quality is poorly understood. The current study consequently set out to systematically review the literature on the association between being a Spanish-English bilingual speaker and voice quality.<br><br>STUDY DESIGN: Systematic review.<br><br>METHODS: A systematic review of association was conducted using Moola et al's guidelines. A search string was developed and run in May 2024 across three databases: MEDLINE (via PubMed), CINAHL via EBSCOhost, and Scopus. After duplicate removal, title, and abstract screening, full-text screening was performed, and peer-reviewed articles considering voice quality measures in Spanish-English bilingual speakers were included. Data were extracted and presented in table format, and the quality of the articles was assessed using the Checklist for Analytical Cross-Sectional Studies.<br><br>RESULTS: In total, 685 records were retrieved, with 485 remaining after duplicate removal. After title and abstract screening, 25 full texts were screened, including 8 articles in the review. Five studies included acoustic measures describing voice quality, with only three including auditory-perceptual analysis. The most commonly considered vocal trait in Spanish-English bilinguals was vocal fry, with the included studies pointing to increased vocal fry use when speaking English.<br><br>CONCLUSIONS: Only a few articles discuss potential vocal changes in Spanish-English bilinguals. Further research is needed to elucidate any potential vocal changes related to being a bilingual speaker, as the current small number of studies and mixed findings make drawing conclusions difficult. More standardization across voice and language assessment could be beneficial.}, }
@article {pmid40525139, year = {2025}, author = {Abou Izzeddine, N and Ahmad, K and Bacha, C and Jabbour, M and Najjar, M and Salhab, S and Ghadieh, HE and Kanaan, A and Azar, S and Khattar, ZA and Harb, F}, title = {The microbial guardians: Unveiling the role of gut microbiota in shaping neurodegenerative disease.}, journal = {IBRO neuroscience reports}, volume = {19}, number = {}, pages = {17-37}, pmid = {40525139}, issn = {2667-2421}, abstract = {The gut microbiota, a complex community of microorganisms residing in the digestive tract, plays a pivotal role in human health. Recent studies have highlighted its significant impact on neurodegenerative diseases, conditions that pose profound challenges to affected individuals and society at large. This review explores the intricate relationship between gut microbiota and the progression of neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and Amyotrophic Lateral Sclerosis. We delve into the dynamic ecosystem of gut microbiota, examining factors influencing its composition and the bidirectional communication established via the gut-brain axis. Emerging evidence suggests that gut microbiota can modulate neurodegenerative disease progression through mechanisms including inflammatory responses, production of neuroactive substances, and regulation of neurotransmitters. Furthermore, we discuss the potential therapeutic implications of targeting gut microbiota with probiotics, prebiotics, and postbiotics. While promising, these interventions face challenges and limitations that must be addressed through ongoing research. Understanding the role of gut microbiota in neurodegenerative diseases is crucial for developing innovative therapeutic strategies and improving patient outcomes.}, }
@article {pmid40524150, year = {2025}, author = {Cozzi, M and Tedesco, B and Ferrari, V and Chierichetti, M and Pramaggiore, P and Cornaggia, L and Magdalena, R and Brodnanova, M and Mohamed, A and Milioto, C and Piccolella, M and Galbiati, M and Rusmini, P and Crippa, V and Gellera, C and Magri, S and Taroni, F and Cristofani, R and Poletti, A}, title = {One gene, many phenotypes: the role of KIF5A in neurodegenerative and neurodevelopmental diseases.}, journal = {Cell communication and signaling : CCS}, volume = {23}, number = {1}, pages = {287}, pmid = {40524150}, issn = {1478-811X}, support = {PRIN- Progetti di ricerca di interesse nazionale - bando 2022, PNRR finanziato dall'Unione europea- Next Generation EU, componente M4C2, investimento 1.1 n. P20225R4Y5//Ministero dell'Universit&#xe0; e della Ricerca/ ; PRIN-Progetti di ricerca di interesse nazionale n. 2022EFLFL8//Ministero dell'Universit&#xe0; e della Ricerca/ ; 23236//AFM-T&#xe9;l&#xe9;thon/ ; 739510//European Network for Rare Neurological Disorders/ ; piano di sviluppo della ricerca (PSR) UNIMI//Universit&#xe0; degli Studi di Milano/ ; R21 AR080407/AR/NIAMS NIH HHS/United States ; Travelling Fellowship n. JCSTF2205742//Company of Biologists/ ; R21AR080407/AR/NIAMS NIH HHS/United States ; RF-2018-12367768//Ministero della Salute/ ; . 2021-1544//Fondazione Cariplo/ ; Scientific Exchange Grant n. 9643//European Molecular Biology Organization/ ; 2025 grant//CureHSPB8,USA/ ; PRIN-Progetti di ricerca di interesse nazionale n. 2020PBS5MJ//Ministero dell'Universit&#xe0; e della Ricerca/ ; CP 20/2018 (Care4NeuroRare)//Fondazione Regionale per la Ricerca Biomedica/ ; 2020 grant//Kennedy's Disease Association/ ; 2018 grant//Kennedy's Disease Association/ ; }, abstract = {UNLABELLED: Kinesin family member 5 A (KIF5A) is a neuron-specific molecular motor involved in anterograde transport. KIF5A mediates a wide range of trafficking processes that are only partially shared with the other members of the KIF5 family. Since 2002, several disease-causing mutations have been found in the KIF5A gene and a link between the specific domain in the encoded protein affected by mutations and the associated phenotype has become evident. Point mutations targeting KIF5A motor and stalk domains, that are expected to impair KIF5A motility, mainly associate with spastic paraplegia type 10 (SPG10) and axonal Charcot-Marie-Tooth (CMT) disease. Oppositely, translational frameshifts causing the elongation of KIF5A tail enhance KIF5A migration towards cell periphery, induce kinesin aggregation, and are linked to amyotrophic lateral sclerosis (ALS) or neonatal intractable myoclonus (NEIMY). This review correlates KIF5A structure and roles in neuronal trafficking with its involvement in the above-mentioned neurodegenerative and neurodevelopmental conditions.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12964-025-02277-x.}, }
@article {pmid40523602, year = {2025}, author = {Horikawa, I and Yamada, L and Harris, BT and Harris, CC}, title = {Δ133p53α-mediated inhibition of astrocyte senescence and neurotoxicity as a possible therapeutic approach for neurodegenerative diseases.}, journal = {Neuroscience}, volume = {580}, number = {}, pages = {54-61}, pmid = {40523602}, issn = {1873-7544}, support = {ZIA BC011496/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Humans ; *Astrocytes/metabolism/drug effects/pathology ; *Cellular Senescence/physiology ; *Tumor Suppressor Protein p53/metabolism ; *Neurodegenerative Diseases/metabolism/therapy ; Animals ; Protein Isoforms/metabolism ; }, abstract = {Non-neuronal glial cells in the brain, such as astrocytes, play essential roles in maintaining the functional integrity of neuronal cells. A growing body of evidence suggests that cellular senescence of astrocytes, characterized by loss of proliferative potential and secretion of neurotoxic cytokines, makes significant contribution to neurotoxicity in Alzheimer's disease and a wide range of other neurodegenerative diseases. This review discusses the beneficial effects of Δ133p53α, a natural p53 protein isoform that inhibits p53-mediated cellular senescence, thereby protecting astrocytes from senescence, highlights its potential as a therapeutic target, and underscores the need for continued research in this area. Both in senescent human astrocytes in culture, whether induced by replicative exhaustion, irradiation or exposure to amyloid-β, and in brain tissues with increased senescent astrocytes from patients with Alzheimer's disease, the expression levels of endogenous Δ133p53α protein were consistently and significantly reduced. The lentiviral vector-driven expression of Δ133p53α protected cultured human astrocytes from cellular senescence and neurotoxic secretory phenotype, leading to their cellular reprogramming to a neuroprotective state associated with neurotrophic growth factors. We thus propose that Δ133p53α is worth testing as a therapeutic target that can be enhanced in a wide range of neurodegenerative diseases with accumulated senescent astrocytes, including Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, and chronic traumatic encephalopathy due to traumatic brain injury. We hypothesize that a Δ133p53α-mediated cellular reprogramming approach and a senolytic or senomorphic approach, both targeting non-neuronal cells, may be complementary with each other, and may cooperate with neuron-protecting or amyloid-β-targeting therapies currently in use.}, }
@article {pmid40519824, year = {2025}, author = {Michalec, B and Forbes, CE and Pardon, K and Ayala, B and Beltran, DG and Douille, C and Felix, K and Gnall, S and Hoenack, M and McKeever, B and Nguyen, D and Piemonte, N and Portle, S}, title = {A scoping review of emotional contagion research with human subjects: identifying common trends of previous research and potential areas for future research.}, journal = {Frontiers in psychology}, volume = {16}, number = {}, pages = {1573375}, pmid = {40519824}, issn = {1664-1078}, abstract = {INTRODUCTION: Emotional contagion (EC) involves the automatic mimicry and synchronization of expressions, vocalizations, and movements, resulting in emotional alignment between individuals. Despite consistent scholastic explorations of the various nuances and tenets associated with emotional contagion processes and outcomes, there has yet to be a thorough review of human subjects-based emotional contagion research.<br><br>METHODS: This review examines human subjects EC research trends, analyzing 277 articles (published from 1992 to 2022) to identify common conceptualizations, triggers, and measurement methods.<br><br>RESULTS: Analyses indicated that Hatfield et al.'s classic conceptualization is the most cited, and common triggers include facial expressions in images and videos, and real-time interactions - though many studies did not stimulate EC. While many studies did utilize validated EC scales, about 28% of the studies reviewed used non-validated questions to measure EC. Moreover, the EC research reviewed heavily relies on college-aged, predominantly white participants, indicating a need for more diverse samples.<br><br>DISCUSSION: Future EC research should explore processes and nuances associated with EC among older adults, minoritized groups, and diverse contexts (e.g., healthcare, schools), using novel triggers and multiple measurement methods.}, }
@article {pmid40516772, year = {2025}, author = {Rawat, E and Sharma, S and Vyas, S and Alsaidan, OA and Kapoor, DU and Prajapati, BG}, title = {Advances in alginate-based nanoformulations: Innovative and effective strategies for targeting and treating brain disorders.}, journal = {International journal of pharmaceutics}, volume = {681}, number = {}, pages = {125851}, doi = {10.1016/j.ijpharm.2025.125851}, pmid = {40516772}, issn = {1873-3476}, mesh = {*Alginates/chemistry/administration &amp; dosage ; Humans ; *Brain Diseases/drug therapy ; Animals ; *Drug Delivery Systems/methods ; *Nanoparticles/chemistry/administration &amp; dosage ; Blood-Brain Barrier/metabolism ; Drug Carriers/chemistry ; }, abstract = {Brain disorders, encompassing neurodegenerative conditions and intracranial neoplasms, present formidable obstacles in the realm of pharmacological delivery due to the existence of athe blood-brain barrier (BBB) and the restricted bioavailability of therapeutic agents. Alginate-derived nanoformulations have emerged as highly promising systems for drug delivery, offering attributes such as biocompatibility, regulated release, and improved targeting efficacies. This review investigates contemporary advancements in alginate-based nanoformulations, with a particular emphasis on their efficacy in surmounting obstacles to successful pharmacological delivery to the brain. Initially, we furnish a comprehensive overview of alginate, underscoring its pertinent properties, biomedical applications, and inherent limitations. Subsequently, the discourse progresses to strategies for nanoformulation, which encompass lipid-based, polymeric, and inorganic methodologies, with a focus on their benefits in relation to cerebral targeting. Moreover, this review entails the therapeutic potential of alginate-based nanoformulations in addressing significant neurological disorders, including Alzheimer's disease, Parkinson's disease, brain tumours, traumatic brain injury, epilepsy, and amyotrophic lateral sclerosis. By amalgamating cutting-edge nanotechnology with the distinctive properties of alginate, these formulations signify a promising pathway for the advancement of efficacious therapies aimed at brain targeting. Additionally, prospective research trajectories and challenges associated with the optimization of alginate-based nanocarriers for clinical applications are also elucidated.}, }
@article {pmid40515812, year = {2025}, author = {Jellinger, KA}, title = {Prevalence and impact of comorbidities in amyotrophic lateral sclerosis.}, journal = {Journal of neural transmission (Vienna, Austria : 1996)}, volume = {}, number = {}, pages = {}, pmid = {40515812}, issn = {1435-1463}, support = {Society for the Promotion of Research in Experimental Neurology, Vienna, Austria//Society for the Promotion of Research in Experimental Neurology, Vienna, Austria/ ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of multifaceted nature and variable progression that poses considerable challenges to our understanding of its evolution and interplay with different comorbid conditions. The etiopathogenesis of ALS is still unexplained and multimorbidity is common, but its influence on the ALS susceptibility and disease course is a matter of discussion. This study using medical databases tries to find diseases associated with ALS and their impact on disease onset and progression. Diseases associated with the risk of ALS include diabetes mellitus, dyslipidemias and cardiovascular comorbidities that may play an important role in the prognosis of ALS. Hypometabolic disorders and cardiovascular diseases may have a protective effect on ALS incidence, while coronary heart disease and hypertension have a negative effect on disease progression. Other comorbidities include Parkinson disease, TDP-43 pathology, progressive supranuclear palsy, progressive aphasia, myasthenia gravis, cancer and autoimmune disorders, while there is no evidence for a shared genetic background of common risk variants in ALS and multiple sclerosis. Among non-motor manifestations of ALS, cognitive and behavioral impairments are important. Other comorbidities include sleep disorders, traumatic encephalopathy, sarcoidosis, prionopathies, schizophrenia, cervical spondylotic myelopathy, psoriasis and others. The tremendous heterogeneity of concomitant pathologies and comorbidities observed across the ALS spectrum may be caused by a complex interplay between genetic, pathogenetic, inflammatory and other risk factors that are still poorly understood. Further research should provide increasing insight into their relationship with motor system disorders in order to find better diagnostic tools and probable effective therapies for these disease-modifying comorbidities.}, }
@article {pmid40513028, year = {2025}, author = {Bromberg, MB}, title = {What Is in the Literature.}, journal = {Journal of clinical neuromuscular disease}, volume = {26}, number = {4}, pages = {176-183}, doi = {10.1097/CND.0000000000000526}, pmid = {40513028}, issn = {1537-1611}, mesh = {Humans ; *Motor Neuron Disease/therapy/diagnosis ; *Amyotrophic Lateral Sclerosis/therapy/diagnosis ; }, abstract = {This issue of What Is in the Literature focuses on articles over the past year on clinical aspects of motor neuron disease, including amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS). Disease-modifying treatment for ALS remains a challenge as 2 formal drug trials did not hold up to retesting. There are new thoughts based on a multistep model to partially explain why ALS develops relatively late in life. New information on fluid biomarkers, sex differences, efficacy of medical marijuana for common symptoms, and cognitive dysfunction are discussed. For the clinic, there are updated guidelines for multidisciplinary management. Other articles address how frequently the topic of sexual health is brought up in the clinic, and insights into how patients view end-of-life issues and quality of life when using tracheal ventilation. PLS has diagnostic challenges and practical aspects, which are reviewed.}, }
@article {pmid40511793, year = {2025}, author = {Parks, ASE and Gotlib Conn, L and Amog, K and Bodmer, NS and King, JW and McLaren, AMR and Reid, M and Kishibe, T and Abrahao, A and Zinman, L and Sale, JEM}, title = {Age and life stage in the experience of amyotrophic lateral sclerosis: a scoping review.}, journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration}, volume = {}, number = {}, pages = {1-27}, doi = {10.1080/21678421.2025.2515914}, pmid = {40511793}, issn = {2167-9223}, abstract = {Objective: Understanding the experiences of people living with amyotrophic lateral sclerosis (plwALS) is necessary to appreciate their unique needs. Age and stage in the life course influence how illness is experienced; however, the extent to which age-specific complexities of living with ALS have been examined remains unexplored. This review aims to map the available evidence exploring age, age-graded role, or life-course transition with regards to the experience of ALS and to identify age-specific gaps in the literature. Methods: A scoping review guided by Joanna Briggs Institute methodology was undertaken. Eligible articles included peer-reviewed primary research studies, published in English from 2010 onward, investigating illness experience of adults with ALS with consideration for how age, age-graded roles, or life-course transitions influenced experience. Database sources included: Ovid's Medline, Embase, and PsycINFO; EBSCO CINAHL; and ProQuest Sociological Abstracts. Findings related to ALS experience and dimensions of age were summarized descriptively and categorized using qualitative content analysis. Results: Six thousand one hundred and eighty individual records were identified and screened. Forty-five articles, reporting 42 studies, were included. Findings regarding thoughts, feelings, or emotions of plwALS were most common and varied depending on whether they were in reference to chronological age or age-graded role. Despite the importance of life-course transitions for illness experience, they were not routinely considered. Conclusion: Numerous aspects of the experience of plwALS have been reported in reference to age; however, the significance of age-graded roles and life-course transitions warrants further examination. Recognition of age-related complexities of living with ALS will facilitate more personalized ALS care.}, }
@article {pmid40510202, year = {2025}, author = {Li, L and Lv, L and Wang, Z and Liu, X and Wang, Q and Zhu, H and Jiang, B and Han, Y and Pan, X and Zhou, X and Ren, L and Chang, Z}, title = {From copper homeostasis to cuproptosis: a new perspective on CNS immune regulation and neurodegenerative diseases.}, journal = {Frontiers in neurology}, volume = {16}, number = {}, pages = {1581045}, pmid = {40510202}, issn = {1664-2295}, abstract = {Copper, an essential trace element for the human body, plays a key role in energy metabolism, mitochondrial respiration, redox reactions, and neural signal transmission. The recently proposed concept of "cuproptosis" has further revealed the unique status of copper in cellular regulation: when copper abnormally accumulates within cells, it can directly bind to the lipoylated proteins of the mitochondrial TCA cycle, triggering protein aggregation and metabolic disorders, ultimately leading to cell death. This form of cell death plays an important role in various neurodegenerative diseases of the central nervous system, such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and stroke. This review summarizes recent research on the mechanisms of cuproptosis, providing new perspectives and a theoretical basis for understanding the pathogenesis of these neurodegenerative diseases.}, }
@article {pmid40508048, year = {2025}, author = {Tolochko, C and Shiryaeva, O and Alekseeva, T and Dyachuk, V}, title = {Amyotrophic Lateral Sclerosis: Pathophysiological Mechanisms and Treatment Strategies (Part 2).}, journal = {International journal of molecular sciences}, volume = {26}, number = {11}, pages = {}, pmid = {40508048}, issn = {1422-0067}, mesh = {*Amyotrophic Lateral Sclerosis/physiopathology/drug therapy/metabolism/therapy/etiology/pathology ; Humans ; Oxidative Stress/drug effects ; Animals ; Antioxidants/therapeutic use/pharmacology ; Motor Neurons/metabolism/pathology/drug effects ; Glutamic Acid/metabolism ; Neuroprotective Agents/therapeutic use ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease associated with damage to motor neurons and leading to severe muscle weakness and, eventually, death. Over the past decade, understanding of the key pathogenetic links of ALS, including glutamate-mediated excitotoxicity and oxidative stress, has significantly advanced. This review considers the recent evidence on molecular mechanisms of these processes, as well as the therapeutic strategies aimed at their modulation. Special attention is paid to antiglutamatergic and antioxidant drugs as approaches to the ALS pathogenetic therapy.}, }
@article {pmid40506782, year = {2025}, author = {Briscoe, S and Martin Pintado, C and Sutcliffe, K and Melendez-Torres, GJ and Garside, R and Lawal, HM and Orr, N and Shaw, L and Thompson Coon, J}, title = {Evidence of inequities experienced by the rare disease community with respect to receipt of a diagnosis and access to services: a scoping review of UK and international evidence.}, journal = {Orphanet journal of rare diseases}, volume = {20}, number = {1}, pages = {303}, pmid = {40506782}, issn = {1750-1172}, support = {NIHR200695//National Institute for Health and Care Research/ ; }, mesh = {Humans ; *Health Services Accessibility ; *Healthcare Disparities ; *Rare Diseases/diagnosis ; United Kingdom ; }, abstract = {BACKGROUND: People with a rare disease find it difficult to obtain a diagnosis and access appropriate services. Evidence suggests that this can lead to health inequity amongst the rare disease community, i.e. systemic, unfair and avoidable differences in health opportunities and outcomes. This scoping review aims to identify and describe evidence on health inequities experienced by the rare disease community with regards to receipt of a diagnosis and access to health and social care services.<br><br>METHODS: We searched ASSIA, CINAHL, Embase, HMIC, MEDLINE and Social Policy and Practice for relevant studies. Studies were double screened at title and abstract and full-text using pre-specified inclusion criteria. As this research was commissioned by the UK National Institute for Health and Care Research Policy Research Programme, primary studies were limited to UK settings. These were supplemented with international systematic reviews. We also applied a 2010 date limit. Relevant data were extracted and presented narratively and tabulated.<br><br>RESULTS: One hundred thirty-six studies met the inclusion criteria, including 96 primary studies and 40 systematic reviews. The most frequently occurring rare diseases were motor neurone disease, cystic fibrosis and sickle cell disease. Seventeen types of inequity were identified: delayed diagnosis, lack of knowledge amongst clinicians, lack of information provision, limited services provision (across six different services), limited services for undiagnosed conditions, lack of care co-ordination; in addition, inequity was identified relating to place of residence, race/ethnicity, gender, socioeconomic status, age and disability.<br><br>CONCLUSION: This review has drawn attention to experiences of the rare disease community with respect to receipt of a diagnosis and access to services which are different to experiences in the general population, and within the rare disease community itself. Some of these experiences are clearly attributable to factors which are unfair, avoidable and systemic, particularly those which relate to specific groups in the rare disease community. Experiences relating to delayed diagnosis, lack of knowledge, information, care co-ordination and access to various services, also appeared to indicate inequity. These issues are less likely to be encountered with respect to more common diseases experienced in the general population.}, }
@article {pmid40500504, year = {2025}, author = {Niu, J and Verkhratsky, A and Butt, A and Yi, C}, title = {Oligodendroglia in Ageing and Age-Dependent Neurodegenerative Diseases.}, journal = {Advances in neurobiology}, volume = {43}, number = {}, pages = {363-405}, pmid = {40500504}, issn = {2190-5215}, mesh = {Humans ; *Oligodendroglia/pathology/physiology/metabolism ; *Neurodegenerative Diseases/pathology/physiopathology/metabolism ; *Aging/pathology/physiology ; Animals ; }, abstract = {The central nervous system is susceptible to gradual decline with age, affecting all types of glial cells in the process. Compared to other glial cells, the oligodendroglial lineage is highly vulnerable to ageing and undergoes significant characteristic changes that impact upon its structure and impair its physiological functions. Therefore, the ageing and degeneration of oligodendroglia become major risk factors for neurodegenerative diseases. During the age-related disease process, changes in oligodendroglia lead to a decline in their ability to regenerate myelin and respond to the aged microenvironment, which are closely linked to the pathogenesis of neurodegenerative diseases, facilitating the emergence of these diseases in older populations. In this chapter, we introduce the physiological changes of oligodendroglia during ageing and the related mechanisms and then summarise their pathophysiological contributions to age-related cognitive disorders. Finally, we discuss potential therapeutic strategies that target oligodendroglia for future research on neurodegenerative diseases.}, }
@article {pmid40498024, year = {2025}, author = {Pisoni, L and Donini, L and Gagni, P and Pennuto, M and Ratti, A and Verde, F and Ticozzi, N and Mandrioli, J and Calvo, A and Basso, M}, title = {Barriers in the Nervous System: Challenges and Opportunities for Novel Biomarkers in Amyotrophic Lateral Sclerosis.}, journal = {Cells}, volume = {14}, number = {11}, pages = {}, pmid = {40498024}, issn = {2073-4409}, support = {MUR PNRR project iNEST - Interconnected Nord-Est Innovation Ecosystem (ECS00000043)//NextGenerationEU/ ; PERMEALS - PNRR-MAD-2022-12375731//Ministero della Salute/ ; CUP E53D23019700001, project "MYSTICALS"//European Union - Next Generation EU, Mission 4, Component 1/ ; RF-2016-02361616//Ministero della Salute/ ; EVTestInALS//AriSLA/ ; Aldo Ravelli Center for Neurotechnology and Experimental Brain Therapeutics//Universit&#xe0; degli Studi di Milano/ ; MUR-PRIN 2022 project EV-PRINT 2022CS9H53//Next Generation EU/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/pathology/diagnosis ; *Biomarkers/metabolism ; Extracellular Vesicles/metabolism ; Animals ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a complex neurodegenerative disorder characterized by wide phenotypic heterogeneity. Despite efforts to carefully define and stratify ALS patients according to their clinical and genetic features, prognosis prediction still remains unreliable. Biomarkers that reflect changes in the central nervous system would be useful, but the physical impossibility of direct sampling and analysis of the nervous system makes them challenging to validate. A highly explored option is the identification of neuronal-specific markers that could be analyzed in peripheral biofluids. This review focuses on the description of the physical and biological barriers to the central nervous system and of the composition of biofluids in which ALS disease biomarkers are actively searched. Finally, we comment on already validated biomarkers, such as the neurofilament light chain, and show the potential of extracellular vesicles (EVs) and cell-free DNA as additional biomarkers for disease prediction.}, }
@article {pmid40495464, year = {2025}, author = {Majtan, T and Mijatovic, E and Petrosino, M}, title = {Understanding the Impact of Mutations in the Cystathionine Beta-Synthase Gene: Towards Novel Therapeutics for Homocystinuria.}, journal = {Molecular and cellular biology}, volume = {45}, number = {8}, pages = {327-342}, doi = {10.1080/10985549.2025.2511338}, pmid = {40495464}, issn = {1098-5549}, mesh = {Humans ; *Homocystinuria/genetics/drug therapy/enzymology ; *Cystathionine beta-Synthase/genetics/metabolism/chemistry ; Animals ; *Mutation ; Protein Folding ; Molecular Chaperones/therapeutic use ; }, abstract = {Protein misfolding and conformational instability drive protein conformational disorders, causing either accelerated degradation and loss-of-function, as in inherited metabolic disorders like lysosomal storage disorders, or toxic aggregation and gain-of-function, as in neurodegenerative diseases like Alzheimer's disease or amyotrophic lateral sclerosis. Classical homocystinuria (HCU), an inborn error of sulfur amino acid metabolism, results from cystathionine beta-synthase (CBS) deficiency. CBS regulates methionine conversion into metabolites critical for redox balance (cysteine, glutathione) and signaling (H2S). Pathogenic missense mutations in the CBS gene often impair folding, cofactor binding, stability or oligomerization rather than targeting the key catalytic residues of the CBS enzyme. Advances in understanding of CBS folding and assembly as well as CBS interactions with cellular proteostasis network offer potential for therapies using pharmacological chaperones (PCs), i.e., compounds facilitating proper folding, assembly or cellular trafficking. This review discusses progress in identifying PCs for HCU, including chemical chaperones, cofactors, and proteasome inhibitors. We outline future directions, focusing on high-throughput screening and structure-based drug design to develop CBS-specific PCs. These could stabilize mutant CBS, enhance its stability and restore activity, providing new treatments for HCU and possibly other conditions related to dysregulated CBS, such as cancer or Down's syndrome.}, }
@article {pmid40495142, year = {2025}, author = {Matting, L and Pfeifer, K and Sudeck, G and Jung, A and Langhirt, F and Geidl, W}, title = {Physical activity promotion in physical therapy, exercise therapy and other movement-based therapies: a scoping review and content analysis of intervention studies and theoretical works.}, journal = {The international journal of behavioral nutrition and physical activity}, volume = {22}, number = {1}, pages = {72}, pmid = {40495142}, issn = {1479-5868}, mesh = {Humans ; *Exercise ; *Exercise Therapy/methods ; *Health Promotion/methods ; *Physical Therapy Modalities ; Noncommunicable Diseases/therapy ; }, abstract = {BACKGROUND: Movement-based therapists, including physical, exercise, and sport therapists, play a key role in promoting physical activity in individuals with non-communicable diseases. However, no clear consensus exists on effective intervention approaches. This scoping review examines available intervention studies and theoretical works for physical activity promotion in movement-based therapy.<br><br>METHODS: In accordance with Colquhoun et al.'s framework and PRISMA-ScR guidelines, we systematically searched PubMed, Scopus, Web of Science, and PsycINFO until March 31, 2024. Eligible records described physical activity-promoting concepts including interventional studies and theoretical works applicable in movement-based therapies for individuals with non-communicable diseases. Data extraction covered assessment, therapeutic content, didactic-methodological principles, and theoretical underpinnings. Interventions were categorized based on behavior change techniques (BCTs), the behavior change wheel, and a clinical reasoning model for clients behavior change. Network analysis explored relationships between therapeutic content and didactic-methodological principles.<br><br>RESULTS: Fifty-seven records met inclusion criteria; 77% were intervention studies, and 23% were theoretical works. Most concepts originated from orthopedics/rheumatology (23%), neurology (21%), and oncology (9%), while 12% were generic concepts. Across concepts, 66 biopsychosocial assessment instruments and 60 BCTs were applied (Median BCTs per concept: 11.5, range: 4-37). Key didactic-methodological principles included tailoring/individualization (n&#x2009;=&#x2009;47), active participation (n&#x2009;=&#x2009;39), collaborative communication (n&#x2009;=&#x2009;21), and patient self-responsibility and independence (n&#x2009;=&#x2009;14). Least mentioned was facilitating positive movement experiences and enjoyment of physical activity (n&#x2009;=&#x2009;3). Network analysis identified action planning, goal setting, and feedback as central BCTs.<br><br>CONCLUSION: This review provides an overview of 57 physical activity promotion concepts used in movement-based therapies for individuals with non-communicable diseases. Findings reveal considerable heterogeneity, highlighting diverse strategies used by movement-based therapists to influence physical activity behavior.<br><br>TRIAL REGISTRATION: Open Science Framework (OSF), December 23, 2022 (DOI: https://doi.org/10.17605/OSF.IO/AXZSJ).}, }
@article {pmid40493155, year = {2025}, author = {Kang, A and Qiao, Y and Pan, S and Yan, F and Chen, H and Bai, Y}, title = {From RIPK1 to Necroptosis: Pathogenic Mechanisms in Neurodegenerative Diseases.}, journal = {Neurochemical research}, volume = {50}, number = {3}, pages = {194}, pmid = {40493155}, issn = {1573-6903}, support = {24JRRA346//Natural Science Foundation of Gansu Province/ ; CY2023-QN-B03//"Cuiying Science and Technology Program" of the Second Hospital of Lanzhou University/ ; (23)0207//Foundation for International Medical Exchanges/ ; (23)1263//China Health Promotion Foundation/ ; }, mesh = {Humans ; *Necroptosis/physiology/drug effects ; *Receptor-Interacting Protein Serine-Threonine Kinases/metabolism ; *Neurodegenerative Diseases/metabolism/pathology/drug therapy ; Animals ; Signal Transduction/physiology ; }, abstract = {Receptor-interacting protein kinase 1 (RIPK1)-mediated necroptosis, a newly identified mode of regulated cell death, represents a significant pathogenic mechanism in multiple neurodegenerative disorders. Substantial experimental evidence indicates that RIPK1 regulates necroptotic cell death pathways in both neuronal and glial cell populations through activation of the canonical RIPK3-MLKL signaling cascade, thereby exacerbating neuroinflammatory responses and accelerating neurodegenerative progression. The pathological relevance of this molecular pathway has been extensively validated across multiple major neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). Pharmacological interventions targeting RIPK1 or its downstream effectors-particularly RIPK3 and MLKL-have demonstrated significant efficacy in mitigating disease-associated pathological manifestations. This highlights the RIPK1 signaling axis as a promising therapeutic target for neuroprotective strategies. Consequently, thorough investigation of RIPK1-mediated necroptosis in neurodegenerative settings holds considerable translational potential. Such inquiry deepens mechanistic understanding of disease pathogenesis while accelerating the advancement of innovative therapeutic approaches with direct clinical relevance.}, }
@article {pmid40488810, year = {2025}, author = {Kulkarni, SR and Thokchom, B and Abbigeri, MB and Bhavi, SM and Singh, SR and Metri, N and Yarajarla, RB}, title = {The role of L-DOPA in neurological and neurodegenerative complications: a review.}, journal = {Molecular and cellular biochemistry}, volume = {}, number = {}, pages = {}, pmid = {40488810}, issn = {1573-4919}, abstract = {L-DOPA remains a cornerstone treatment for Parkinson's disease and is increasingly recognized for its role in various neurological and neurodegenerative disorders. As a direct precursor to dopamine, L-DOPA is synthesized from L-tyrosine through the action of tyrosine hydroxylase and is subsequently converted into dopamine via aromatic L-amino acid decarboxylase. Its ability to cross the blood-brain barrier (BBB) makes it a crucial therapeutic agent for restoring dopaminergic neurotransmission, thereby influencing motor function, cognition, and neuroprotection. Beyond Parkinson's, L-DOPA's therapeutic potential extends to neurodegenerative conditions such as Alzheimer's disease, Huntington's disease, multiple sclerosis, Lewy body dementia, and amyotrophic lateral sclerosis, where dopamine modulation plays a critical role. Furthermore, L-DOPA has demonstrated efficacy in neurological disorders including epilepsy, peripheral neuropathy, cerebrovascular diseases, and traumatic brain injury, suggesting broader neurobiological applications. However, long-term use is associated with challenges such as motor fluctuations, dyskinesias, and loss of therapeutic efficacy due to progressive neurodegeneration and alterations in dopaminergic pathways. Recent advancements in drug delivery systems, combination therapies, and nanotechnology, including plant-derived carbon dots, offer promising strategies to enhance L-DOPA's effectiveness while mitigating its limitations. This comprehensive review explores L-DOPA's synthesis, pharmacokinetics, mechanism of action, and its evolving role in neurological diseases, while highlighting ongoing challenges and future directions for optimizing its clinical application.}, }
@article {pmid40488544, year = {2025}, author = {Benzo-Iglesias, MJ and Rocamora-Pérez, P and Valverde-Martínez, ML&#xc1; and García-Luengo, AV and Benzo-Iglesias, PM and López-Liria, R}, title = {Efficacy of respiratory muscle training in improving pulmonary function and survival in patients with amyotrophic lateral sclerosis: a systematic review and meta-analysis.}, journal = {Therapeutic advances in respiratory disease}, volume = {19}, number = {}, pages = {17534666251346095}, pmid = {40488544}, issn = {1753-4666}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/mortality/therapy/diagnosis ; *Respiratory Muscles/physiopathology ; *Breathing Exercises/adverse effects/methods ; Randomized Controlled Trials as Topic ; Quality of Life ; Muscle Strength ; *Lung/physiopathology ; Treatment Outcome ; Recovery of Function ; Male ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects motor neurons, resulting in muscle weakness, loss of function, and ultimately death due to respiratory failure. Due to the lethal prognosis of ALS, respiratory muscle training has been proposed as a potentially beneficial intervention.<br><br>OBJECTIVES: To systematically review the efficacy of respiratory muscle training on lung function and respiratory muscle strength in ALS patients.<br><br>DESIGN: A systematic review and meta-analysis of randomized controlled trials.<br><br>DATA SOURCES AND METHODS: Articles published in PubMed, PEDro, Scopus, and Web of Science databases up to July 2024. The Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 statement guideline was followed. Included studies had (1) ALS patients, (2) respiratory muscle training, (3) physical exercise, usual care or no intervention were provided as a comparison group, (4) assessments of lung function, respiratory muscle strength, quality of life, survival, fatigue, and functional capacity outcome measures, and (5) a randomized controlled trial design. Methodological quality was analyzed using the PEDro scale, and risk of bias with the Cochrane Collaboration Risk of Bias Tool. Meta-analyses were performed with Review Manager software.<br><br>RESULTS: Five randomized controlled trials with 170 participants were included. The results showed that respiratory muscle training improved muscle strength, particularly maximum expiratory and inspiratory pressures. One study suggested inspiratory muscle training as a survival predictor in ALS patients. No significant effects were observed in forced vital capacity or quality of life. No adverse effects were reported.<br><br>CONCLUSION: Respiratory muscle training improves ventilatory function, particularly respiratory muscle strength, in people with ALS. While evidence is limited, it shows promise as an adjuvant therapy to enhance quality of life and survival. It has been registered in the PROSPERO (CRD42024568235).}, }
@article {pmid40485888, year = {2025}, author = {Liu, Y and Ren, Y and Song, P}, title = {Traditional Chinese medicine for intractable and rare diseases: Research progress and future strategies.}, journal = {Intractable &amp; rare diseases research}, volume = {14}, number = {2}, pages = {109-121}, pmid = {40485888}, issn = {2186-3644}, abstract = {Rare diseases have become a global public health challenge due to their low prevalence, difficult diagnosis, and limited treatment options. Intractable diseases are more common but often involve complex mechanisms, treatment with limited efficacy, and high medical costs, placing a heavy burden on patients and healthcare systems. In recent years, traditional Chinese medicine (TCM) has demonstrated unique advantages in the treatment of intractable and rare diseases and has gradually become an important complementary treatment. The current work is a systematic review of the progress of clinical and experimental research on TCM in typical rare diseases such as amyotrophic lateral sclerosis (ALS), systemic lupus erythematosus (SLE), mitochondrial encephalomyopathy, aplastic anemia (AA), and Wilson's disease (WD). It focuses on the multi-target therapeutic mechanisms of key Chinese herbal compound formulas, including immune regulation, antioxidative stress, and neuroprotection. The core TCM theories of "syndrome differentiation", "different treatments for the same disease" and the "same treatment for different diseases" are also discussed in the context of personalized medicine. In recent years, China has continuously promoted the development of TCM through a series of national plans and supportive policies, such as the 14th Five-Year Plan for TCM development, funding for key special projects, expedited approval pathways, and expanded coverage by medical insurance. These efforts have provided strong support for the clinical translation of TCM and technological innovation in the field of intractable and rare diseases. Notwithstanding the encouraging advances, the field of Chinese medicine continues to grapple with numerous challenges. In the future, the enhancement of mechanistic studies and quality multicenter clinical trials needs to be promoted while further enhancing policy support and international collaboration to substantiate the scientific basis and clinical value of TCM in the prevention and treatment of intractable and rare diseases.}, }
@article {pmid40482451, year = {2025}, author = {Attiq, A and Afzal, S and Raman, H and Ahmad, W}, title = {Neuroinflammation to neurodegeneration: Boulevard of broken nerves.}, journal = {International immunopharmacology}, volume = {161}, number = {}, pages = {115015}, doi = {10.1016/j.intimp.2025.115015}, pmid = {40482451}, issn = {1878-1705}, mesh = {Humans ; Animals ; *Neuroinflammatory Diseases/immunology/drug therapy/therapy ; *Neurodegenerative Diseases/immunology/drug therapy/therapy ; *Anti-Inflammatory Agents/therapeutic use ; Cytokines/metabolism ; }, abstract = {Neuroinflammation is caused by various factors, such as the activation of glial cells, the excessive release of chemokines and cytokines, and the accumulation of blood cells in the brain parenchyma. The inflammatory processes occur in acute and chronic phases, with traumatic brain injuries triggering the release of neurotoxins from CNS-specific glial cells. Furthermore, activation of microglia, astrocytes, and mast cells worsens the situation by producing pro-inflammatory cytokines, chemokines and glia maturation factors. Chronic activation of astroglia and microglial cells promotes loss of neurons, memory, and impaired learning capacity, leading to neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis. These implications have led to a rational search for inflammatory druggable targets. Based on various preclinical and clinical studies, NSAIDs (aspirin, ibuprofen, diclofenac, and mefenamic acid), SSRIs (fluoxetine and sertraline), antipsychotics (risperidone), corticosteroids (dexamethasone), antidiabetics (metformin and rosiglitazone), and statins (simvastatin and atorvastatin) have exhibited promising results. These drugs have anti-inflammatory and neuromodulation activities that enhance neuroplasticity and effectively manage neurodegenerative symptoms. In addition, non-pharmacological interventions such as art creation and physical exercise have been linked with improving neural development and stimulating the production of anti-inflammatory cytokines, which can attenuate disease progression and promote synaptic plasticity. Hence, it is imperative to understand the complex interplay between glial cells, inflammatory signalling and neural pathways. We reviewed the interconnected pathways between neuroinflammation and neurodegeneration. Moreover, recommendations for pharmacological and non-pharmacological interventions to address these issues are discussed herein.}, }
@article {pmid40479789, year = {2025}, author = {Hosseini, MM and Masoumian Hosseini, ST and Haghighi, E and Qayumi, K and Ebrahimipour, H and Pourabbasi, A and Koohpaei, A and Alizadeh, M and Shafiei, Z}, title = {The revolutionary impact of 6G technology on empowering health and building a smart society: A scoping review.}, journal = {Computers in biology and medicine}, volume = {194}, number = {}, pages = {110496}, doi = {10.1016/j.compbiomed.2025.110496}, pmid = {40479789}, issn = {1879-0534}, mesh = {Humans ; *Wireless Technology ; Telemedicine ; Delivery of Health Care ; Artificial Intelligence ; Computer Security ; }, abstract = {OBJECTIVE: This scoping review investigates the potential of 6G technology in healthcare, particularly in smart city settings, focusing on its enhanced data capabilities, AI's role in healthcare optimization, infrastructure support, interoperability, quality standards, and privacy and security concerns.<br><br>PATIENTS AND METHODS: The scoping review followed the Arksey and O'Malley framework, with Levac et al.'s methodological advancements. The review team searched academic databases like PubMed/Medline, SCOPUS, Embase, Web of Sciences, and IEEE Xplore. They also explored grey literature sources like Google Scholar, OpenGrey, and Web of Science Conference Proceedings. A search strategy was developed, and 145 studies were selected from an initial pool of 9835 records from 2010 to 2025. The review categorized 145 studies into three phases, focusing on deploying 6G technology in healthcare, the infrastructure required, and ethical considerations related to the technology's ethical implications.<br><br>RESULT: Phase one focused on advancements like real-time imaging, performing medical procedures remotely, using predictive tools to analyze data, and providing care tailored to individual patients. Phase two examined how the next generation of wireless technology (6G) could interact with communication systems, including techniques to handle large amounts of data (massive MIMO) and using extremely high-frequency signals (terahertz communications) to transfer information faster. Phase three explored ethical concerns about applying 6G technology, such as systems that make decisions based on user intentions (intent-driven management) and organizing information around data-based designs (data-driven architecture). The review highlights how 6G technology could revolutionize patient care and medical services by enabling faster data transfers, reducing delays, increasing system capacity, and incorporating artificial intelligence.<br><br>CONCLUSION: The scoping review shows the capability of the transformative potential of 6G technology, particularly in healthcare and urban development, emphasizing its enhanced data transfer speeds, reduced latency, and increased capacity that can significantly improve patient care through better remote monitoring, security, and telemedicine services. It stresses the vital role of policymakers in guiding the development of 6G infrastructure, ensuring effective spectrum allocation, and implementing robust security measures while addressing health and electromagnetic exposure concerns. Policymakers are urged to adopt security-by-design principles, adhere to international standards, and foster collaboration among academia, industry, and government to drive innovation and ensure the responsible deployment of 6G technology. By stimulating research and establishing clear performance metrics, they can facilitate continuous improvement and adaptation, ultimately benefiting society as a whole. The review concludes that strategic policy formulation is essential for maximizing the advantages of 6G technology, leading to more intelligent, productive, and sustainable societal frameworks.}, }
@article {pmid40476303, year = {2025}, author = {Mustafa, MA and Bansal, P and Pallavi, MS and Panigrahi, R and Nathiya, D and Kumar, S and Al-Hasnaawei, S and Chauhan, AS and Singla, S}, title = {Exploring the Role of NLRP3 in Neurodegeneration: Cutting-Edge Therapeutic Strategies and Inhibitors.}, journal = {Developmental neurobiology}, volume = {85}, number = {3}, pages = {e22982}, doi = {10.1002/dneu.22982}, pmid = {40476303}, issn = {1932-846X}, mesh = {*NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/antagonists &amp; inhibitors ; Humans ; Animals ; *Neurodegenerative Diseases/metabolism/drug therapy ; *Inflammasomes/metabolism ; *Neuroprotective Agents/pharmacology ; }, abstract = {Inflammasomes, particularly the NLRP3 inflammasome, play a pivotal role in mediating neuroinflammation in neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and Huntington's disease (HD). Recent findings indicate that the activation of the NLRP3 inflammasome in microglia and astrocytes triggers the release of pro-inflammatory cytokines, including IL-1β and IL-18, which contribute to chronic inflammation and neuronal damage. This process accelerates neurodegeneration and exacerbates disease progression. Misfolded protein aggregates, mitochondrial dysfunction, and oxidative stress are key factors in the pathological activation of the NLRP3 inflammasome in these diseases. Recent studies have highlighted that targeting the NLRP3 inflammasome, either through direct inhibitors like MCC950 or natural compounds such as oridonin and β-hydroxybutyrate, shows promise in mitigating neuroinflammation and protecting neuronal integrity. These inhibitors have demonstrated neuroprotective effects in animal models of AD, PD, and MS, presenting a new therapeutic approach for halting disease progression. However, the complexity of NLRP3 regulation requires further investigation to balance its inflammatory and protective roles. This review examines the recent advancements in NLRP3 inflammasome research and discusses potential strategies for modulating inflammasome activity to slow or prevent the progression of neurodegenerative diseases.}, }
@article {pmid40470490, year = {2025}, author = {Ren, S and Che, X and Hu, S and Feng, X and Zhang, J and Shi, P}, title = {The effect of exercise intervention on amyotrophic lateral sclerosis: a systematic review and meta-analysis.}, journal = {Frontiers in neurology}, volume = {16}, number = {}, pages = {1499407}, pmid = {40470490}, issn = {1664-2295}, abstract = {OBJECTIVE: Quantitative evaluation of the effect of exercise intervention in amyotrophic lateral sclerosis (ALS).<br><br>METHODS: The CNKI, WOS, PubMed, and Scopus databases were searched by computer, and randomized controlled trials (RCTs) of exercise intervention in ALS were screened out according to the inclusion and exclusion criteria of the PICOS principle. Stata 12.0 software was used for statistical analysis.<br><br>RESULTS: A total of 12 RCTs including 430 participants were included. Meta-analysis results show that exercise intervention can significantly improve the overall function, walking test (WT) distance and maximum expiratory pressure (MEP) of ALS patients (p <&#x202f;0.05). However, exercise interventions did not show significant effects on fatigue, maximum inspiratory pressure (MIP), forced vital capacity (FVC), and peak expiratory flow (PEF) in ALS patients (p >&#x202f;0.05). Subgroup analysis showed that resistance exercise is the most effective intervention for improving the function of ALS patients, while aerobic exercise is the most effective intervention for improving FVC in ALS patients.<br><br>CONCLUSION: Exercise intervention in ALS has a positive effect, but due to the small number of included studies and possible heterogeneity, risk of bias and sensitivity issues, further research is needed.}, }
@article {pmid40468389, year = {2025}, author = {Rummens, J and Da Cruz, S}, title = {RNA-binding proteins in ALS and FTD: from pathogenic mechanisms to therapeutic insights.}, journal = {Molecular neurodegeneration}, volume = {20}, number = {1}, pages = {64}, pmid = {40468389}, issn = {1750-1326}, support = {G064721N//Fonds Wetenschappelijk Onderzoek/ ; 1S15218N//Fonds Wetenschappelijk Onderzoek/ ; 962700//Muscular Dystrophy Association/ ; SAO-FRA 20230035//Alzheimer's Research Foundation/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; *Frontotemporal Dementia/metabolism/pathology/genetics ; *RNA-Binding Proteins/metabolism/genetics ; Animals ; DNA-Binding Proteins/metabolism ; RNA-Binding Protein FUS/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are devastating neurodegenerative disorders with overlapping clinical, genetic and pathological features. A large body of evidence highlights the critical role of RNA-binding proteins (RBPs) - in particular TAR DNA-binding protein 43 (TDP-43) and Fused in sarcoma (FUS) - in the pathogenesis of these diseases. These RBPs normally regulate various key aspects of RNA metabolism in the nervous system (by assembling into transient biomolecular condensates), but undergo cytoplasmic mislocalization and pathological aggregation in ALS and FTD. Furthermore, emerging evidence suggests that RBP-containing aggregates may propagate through the nervous system in a prion-like manner, driving the progression of these neurodegenerative diseases. In this review, we summarize the genetic and neuropathological findings that establish RBP dysfunction as a central theme in ALS and FTD, and discuss the role of disease-associated RBPs in health and disease. Furthermore, we review emerging evidence regarding the prion-like properties of RBP pathology, and explore the downstream mechanisms that drive neurodegeneration. By unraveling the complex role of RBPs in ALS and FTD, we ultimately aim to provide insights into potential avenues for therapeutic intervention in these incurable disorders.}, }
@article {pmid40464816, year = {2025}, author = {Savran, Z and Baltaci, SB and Aladag, T and Mogulkoc, R and Baltaci, AK}, title = {Vitamin D and Neurodegenerative Diseases Such as Multiple Sclerosis (MS), Parkinson's Disease (PD), Alzheimer's Disease (AD), and Amyotrophic Lateral Sclerosis (ALS): A Review of Current Literature.}, journal = {Current nutrition reports}, volume = {14}, number = {1}, pages = {77}, pmid = {40464816}, issn = {2161-3311}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/drug therapy ; *Vitamin D/metabolism ; Multiple Sclerosis ; Alzheimer Disease ; Parkinson Disease ; Receptors, Calcitriol/metabolism ; Amyotrophic Lateral Sclerosis ; Oxidative Stress/drug effects ; Animals ; Cholecalciferol ; }, abstract = {PURPOSE OF REVIEW: This review explores the role of Vitamin D3 and its derivatives as inhibitors of pathological metabolic modifications in neurodegenerative diseases. The manuscript investigates how Vitamin D3 impacts neuronal calcium regulation, antioxidative pathways, immunomodulation, and neuroprotection during detoxification, beyond its known functions in intestinal, bone, and kidney calcium and phosphorus absorption, as well as bone mineralization.<br><br>RECENT FINDINGS: Recent studies have highlighted the synthesis of the active metabolite 1,25(OH)2D3 (vitamin D) in glial cells via the hydroxylation process of CY-P24A1, an enzyme in the cytochrome P450 system in the brain. The effects of vitamin D occur through the vitamin D receptor (VDR), a nuclear steroid receptor, which has been identified in various brain regions, including the cerebellum, thalamus, hypothalamus, basal ganglia, hippocampus, olfactory system, temporal, and orbital regions. Neurodegeneration is primarily associated with oxidative stress, protein aggregation, neuroinflammation, mitochondrial dysfunction, apoptosis, and autophagy changes, all of which Vitamin D and VDR are believed to influence. Vitamin D and VDR are recognized as both environmental and genetic factors in the etiopathogenesis of neurodegenerative diseases such as Multiple Sclerosis (MS), Parkinson's Disease (PD), Alzheimer's Disease (AD), and Amyotrophic Lateral Sclerosis (ALS). A deficiency in Vitamin D is postulated to have detrimental effects on the brain and other diseases throughout various stages of life. This review consolidates findings from clinical and experimental studies, as well as past publications, focusing on the implications of Vitamin D deficiency in these neurodegenerative conditions. Current articles published in PubMed were extensively considered for this review.}, }
@article {pmid40464500, year = {2025}, author = {Dedoni, S and Avdoshina, V and Olianas, MC and Onali, P}, title = {Role of Lysophosphatidic Acid in Neurological Diseases: From Pathophysiology to Therapeutic Implications.}, journal = {Frontiers in bioscience (Landmark edition)}, volume = {30}, number = {5}, pages = {28245}, doi = {10.31083/FBL28245}, pmid = {40464500}, issn = {2768-6698}, mesh = {Humans ; *Lysophospholipids/metabolism ; *Nervous System Diseases/physiopathology/metabolism/drug therapy ; Animals ; Receptors, Lysophosphatidic Acid/metabolism ; Signal Transduction ; }, abstract = {Lysophosphatidic acid (LPA), a bioactive lipid molecule, has been identified as a critical regulator of several cellular processes in the central nervous system, with significant impacts on neuronal function, synaptic plasticity, and neuroinflammatory responses. While Alzheimer's disease, Multiple Sclerosis, and Parkinson's disease have garnered considerable attention due to their incidence and socioeconomic significance, many additional neurological illnesses remain unclear in terms of underlying pathophysiology and prospective treatment targets. This review synthesizes evidence linking LPA's function in neurological diseases such as traumatic brain injury, spinal cord injury, cerebellar ataxia, cerebral ischemia, seizures, Huntington's disease, amyotrophic lateral sclerosis, Hutchinson-Gilford progeria syndrome, autism, migraine, and human immunodeficiency virus (HIV)-associated complications Despite recent advances, the specific mechanisms underlying LPA's actions in various neurological disorders remain unknown, and further research is needed to understand the distinct roles of LPA across multiple disease conditions, as well as to investigate the therapeutic potential of targeting LPA receptors in these pathologies. The purpose of this review is to highlight the multiple functions of LPA in the aforementioned neurological diseases, which frequently share the same poor prognosis due to a scarcity of truly effective therapies, while also evaluating the role of LPA, its receptors, and signaling as promising actors for the development of alternative therapeutic strategies to those proposed today.}, }
@article {pmid40464332, year = {2025}, author = {Naim, A and Farooqui, AM and Badruddeen,  and Khan, MI and Akhtar, J and Ahmad, A and Islam, A}, title = {The Role of Kinases in Neurodegenerative Diseases: From Pathogenesis to Treatment.}, journal = {The European journal of neuroscience}, volume = {61}, number = {11}, pages = {e70156}, doi = {10.1111/ejn.70156}, pmid = {40464332}, issn = {1460-9568}, mesh = {Humans ; *Neurodegenerative Diseases/enzymology/drug therapy/metabolism ; Animals ; *Protein Kinases/metabolism ; Protein Kinase Inhibitors/therapeutic use ; }, abstract = {Neurodegenerative diseases are characterized by progressive neuronal loss and dysfunction, with protein kinases playing crucial roles in their pathogenesis. This article explores the involvement of protein kinases in these disorders, focusing on their contributions to disease mechanisms, potential as therapeutic targets and challenges in developing effective treatments. In Alzheimer's disease, kinases such as CDK5, GSK3β and MARK4 are implicated in tau hyperphosphorylation and the formation of neurofibrillary tangles. Kinases also regulate amyloid-β processing and plaque formation. In Parkinson's disease, LRRK2, PINK1 and other kinases contribute to α-synuclein pathology, mitochondrial dysfunction and neuroinflammation. LRRK2 inhibitors and PROTACs have shown promise in preclinical models. Huntington's disease involves altered kinase activity, with CK2, GSK3 and MAPK pathways influencing mutant huntingtin toxicity and aggregation. Kinases are also implicated in less common neurodegenerative diseases, such as ALS and spinocerebellar ataxias. Despite the therapeutic potential of targeting kinases, challenges remain, including the complexity of kinase networks, blood-brain barrier permeability and the lack of robust biomarkers. Emerging technologies, such as covalent inhibitors, targeted protein degradation and combination therapies, offer new avenues for addressing these challenges and developing more effective treatments for neurodegenerative diseases.}, }
@article {pmid40463912, year = {2025}, author = {Liu, T and Sun, W and Guo, S and Yuan, Z and Zhu, M and Lu, J and Chen, T and Qu, Y and Feng, C and Yang, T}, title = {Role of mitochondrial quality control in neurodegenerative disease progression.}, journal = {Frontiers in cellular neuroscience}, volume = {19}, number = {}, pages = {1588645}, pmid = {40463912}, issn = {1662-5102}, abstract = {Neurodegenerative diseases are a diverse group of neurological disorders, in which abnormal mitochondrial function is closely associated with their development and progression. This has generated significant research interest in the field. The proper functioning of mitochondria relies on the dynamic regulation of the mitochondrial quality control system. Key processes such as mitochondrial biogenesis, mitophagy, and mitochondrial dynamics (division/fusion) are essential for maintaining this balance. These processes collectively govern mitochondrial function and homeostasis. Therefore, the mitochondrial quality control system plays a critical role in the onset and progression of neurodegenerative diseases. This article provides a concise overview of the molecular mechanisms involved in mitochondrial biogenesis, mitophagy, and mitochondrial dynamics, explores their interactions, and summarizes current research progress in understanding the mitochondrial quality control system in the context of neurodegenerative diseases.}, }
@article {pmid40460337, year = {2025}, author = {van Unnik, JWJ and Ing, L and Oliveira Santos, M and McDermott, CJ and de Carvalho, M and van Eijk, RPA}, title = {Remote Monitoring of Amyotrophic Lateral Sclerosis Using Digital Health Technologies: Shifting Toward Digitalized Care and Research?.}, journal = {Neurology}, volume = {105}, number = {1}, pages = {e213738}, pmid = {40460337}, issn = {1526-632X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/diagnosis ; *Telemedicine ; Wearable Electronic Devices ; Videoconferencing ; Digital Technology ; *Biomedical Technology ; Monitoring, Physiologic/methods ; Digital Health ; }, abstract = {Current care and research pathways for amyotrophic lateral sclerosis (ALS) primarily rely on regularly scheduled visits to specialized centers. These visits provide intermittent clinical information to health care professionals and require patients to travel to the clinic. Digital health technologies enable continuous data collection directly from the patient's home, bringing new opportunities for personalized, timely care and a refined assessment of disease severity in clinical trials. In this review, we summarize the state of the art in digital health technologies for remote monitoring of patients with ALS, ranging from televisits through videoconferencing to sensor-based wearable devices. We explore how these technologies can benefit clinical care and advance treatment development. Despite significant progress, real-world adoption of these technologies remains limited. An overview is provided of the key barriers hindering their widespread implementation and the opportunities to advance the field. Significantly, there is an urgent need for harmonization across stakeholders through consensus guidelines and consortia. These efforts are essential to accelerate progress and harness the full potential of digital health technologies to better meet the needs of patients.}, }
@article {pmid40459673, year = {2025}, author = {Dengri, C and Mayberry, W and Koriesh, A and Nouh, A}, title = {Neurology of Androgens and Androgenic Supplements.}, journal = {Current neurology and neuroscience reports}, volume = {25}, number = {1}, pages = {39}, pmid = {40459673}, issn = {1534-6293}, mesh = {Humans ; *Androgens/metabolism/therapeutic use ; *Nervous System Diseases/drug therapy/metabolism ; *Dietary Supplements ; Receptors, Androgen/metabolism ; Animals ; Testosterone/therapeutic use ; }, abstract = {PURPOSE OF REVIEW: This article explores the intricate relationship between androgens, androgen receptors, and the central nervous system. We examine the role of physiologically derived androgens and androgenic supplements in neurodevelopment and neuroplasticity and delve into the involvement of androgen pathways in the pathogenesis of various neurological disorders.<br><br>RECENT FINDINGS: This review highlights the increasing recognition of testosterone and androgen signaling in various neurological conditions, with evidence of both protective and harmful effects depending on dosage and context. Although limited to experimental use, testosterone replacement therapy (TRT) may serve potential benefits in the management of multiple sclerosis, epilepsy, headache, Duchenne muscular dystrophy, amyotrophic lateral sclerosis, and Parkinson disease. On the other hand, androgen-blocking treatments may help alter disease progression in spinal and bulbar muscular atrophy. Testosterone supplementation can have potential adverse events when used at a supratherapeutic level, and prenatal testosterone exposure is believed to contribute to the pathogenesis of neurodevelopmental disease. Additionally, androgen-blocking agents could increase the risk of neurodegenerative conditions, such as Parkinson disease and Alzheimer disease. Despite the above findings, there is no established indication of TRT or androgen-blocking medication in neurological disorders. The body of evidence highlighting the involvement of androgens and androgen receptors (ARs) in pathogenesis of neurological diseases is growing. This includes ongoing research exploring the potential therapeutic targets involving the androgen signaling pathway for management of neurological disorders. Future placebo-controlled clinical trials are essential to determine the efficacy and safety of TRT or androgen-blocking therapies in managing neurological disease.}, }
@article {pmid40454774, year = {2025}, author = {Madrer, N and Perera, ND and Uccelli, NA and Abbondanza, A and Andersen, JV and Carsana, EV and Demmings, MD and Fernandez, RF and de Fragas, MG and Gbadamosi, I and Kulshrestha, D and Lima-Filho, RAS and Marian, OC and Markussen, KH and McGovern, AJ and Neal, ES and Sarkar, S and Šimončičová, E and Soto-Verdugo, J and Yandiev, S and Fernández-Moncada, I}, title = {Neural Metabolic Networks: Key Elements of Healthy Brain Function.}, journal = {Journal of neurochemistry}, volume = {169}, number = {6}, pages = {e70084}, pmid = {40454774}, issn = {1471-4159}, mesh = {Humans ; *Brain/metabolism ; Animals ; *Nerve Net/metabolism ; *Energy Metabolism/physiology ; *Metabolic Networks and Pathways/physiology ; *Neurons/metabolism ; }, abstract = {Neural networks are responsible for processing sensory stimuli and driving the synaptic activity required for brain function and behavior. This computational capacity is expensive and requires a steady supply of energy and building blocks to operate. Importantly, the neural networks are composed of different cell populations, whose metabolic profiles differ between each other, thus endowing them with different metabolic capacities, such as, for example, the ability to synthesize specific metabolic precursors or variable proficiency to manage their metabolic waste. These marked differences likely prompted the emergence of diverse intercellular metabolic interactions, in which the shuttling and cycling of specific metabolites between brain cells allows the separation of workload and efficient control of energy demand and supply within the central nervous system. Nevertheless, our knowledge about brain bioenergetics and the specific metabolic adaptations of neural cells still warrants further studies. In this review, originated from the Fourth International Society for Neurochemistry (ISN) and Journal of Neurochemistry (JNC) Flagship School held in Schmerlenbach, Germany (2022), we describe and discuss the specific metabolic profiles of brain cells, the intercellular metabolic exchanges between these cells, and how these bioenergetic activities shape synaptic function and behavior. Furthermore, we discuss the potential role of faulty brain metabolic activity in the etiology and progression of Alzheimer's disease, Parkinson disease, and Amyotrophic lateral sclerosis. We foresee that a deeper understanding of neural networks metabolism will provide crucial insights into how higher-order brain functions emerge and reveal the roots of neuropathological conditions whose hallmarks include impaired brain metabolic function.}, }
@article {pmid40446958, year = {2025}, author = {Yuan, L and Yang, Y and Guo, Y and Deng, H}, title = {Genetic architecture of amyotrophic lateral sclerosis: a comprehensive review.}, journal = {Journal of genetics and genomics = Yi chuan xue bao}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jgg.2025.05.008}, pmid = {40446958}, issn = {1673-8527}, abstract = {Amyotrophic lateral sclerosis (ALS), one of the most prevalent neurodegenerative disorders, is pathologically characterized by the progressive degeneration of both upper and lower motor neurons, leading to muscle weakness, paralysis, and death within 2-4 years post-diagnosis. ALS is categorized into familial ALS (FALS) and sporadic ALS, with FALS accounting for approximately 10% of ALS cases. As a genetically heterogeneous disease, ALS exhibits diverse inheritance patterns, including autosomal dominant, autosomal recessive, and X-linked transmission, and genetic factors play pivotal roles in disease pathogenesis. To date, at least 34 disease-causing loci and 32 genes for ALS have been identified. The investigations of mutant protein products and the establishment of animal models have unraveled potential pathogenic pathways, offering insights into the mechanisms of neurodegeneration in ALS. This review focuses on ALS clinical characteristics, neuropathological features, causative loci/genes, genetic susceptibility factors, animal models, and pathogenic mechanisms, with particular attention to recent advances in genetic findings and pathogenic pathways of ALS. Elucidation of the genetic basis of ALS could provide the scientific foundation for personalized treatments to address this recalcitrant disease.}, }
@article {pmid40439916, year = {2025}, author = {Porel, P and Hunjan, G and Kaur, N and Sharma, V and Kaur, M and Mittal, Y and Kaur, R and Aran, KR}, title = {Unlocking the neuroprotective potential of peptide nucleic acids 5 (PNA5) in neurological diseases: molecular mechanisms to therapeutic approaches.}, journal = {Metabolic brain disease}, volume = {40}, number = {5}, pages = {213}, pmid = {40439916}, issn = {1573-7365}, mesh = {Humans ; *Peptide Nucleic Acids/therapeutic use/pharmacology ; Animals ; *Nervous System Diseases/drug therapy/metabolism ; *Neuroprotective Agents/therapeutic use/pharmacology ; Blood-Brain Barrier/drug effects/metabolism ; }, abstract = {Peptide nucleic acids (PNAs) are synthetic nucleic acid analogues offering distinct structural and functional advantages over conventional RNA and DNA, positioning them as powerful molecules in molecular biology. Recently, PNAs have gained significant attention for their potential in the prevention and management of neurological diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), stroke, traumatic brain injury (TBI), spinal cord injury (SCI), depression, and anxiety. PNA5, a specific PNA variant, is highly expressed in neocortical association regions, particularly in primates, and plays a critical role in high-level cognitive functions such as reasoning, decision-making, and problem-solving. It can form stable, sequence-specific hybridizations with nucleic acids, resist nuclease degradation, and efficiently cross cellular membranes, making them ideal candidates for targeting disease-related genes in the brain. PNA5 has shown neuroprotective properties by improving cognitive function, reducing neuroinflammation, and preserving the integrity of the blood-brain barrier (BBB). Additionally, it supports critical processes such as neural migration, axon guidance, and synaptogenesis, which are vital for maintaining proper brain function. This review explores the mechanisms by which PNAs, particularly PNA5, exert therapeutic effects in neurological disorders. It highlights their role in gene modulation, protein regulation, and potential strategies for enhancing PNA delivery to the central nervous system (CNS) and its related disorders.}, }
@article {pmid40439808, year = {2025}, author = {Singh, H and Gupta, R and Gupta, M and Ahmad, A}, title = {Aging-induced alterations in microglial cells and their impact on neurodegenerative disorders.}, journal = {Molecular biology reports}, volume = {52}, number = {1}, pages = {515}, pmid = {40439808}, issn = {1573-4978}, mesh = {Humans ; *Microglia/metabolism/pathology ; *Neurodegenerative Diseases/metabolism/pathology ; *Aging/pathology/metabolism ; Animals ; Brain/metabolism/pathology ; Cellular Senescence ; }, abstract = {Senescence causes deterioration in the functioning and physiology of an organism. Microglia, the standing resident immune brain cells transform from neuroprotective to neurotoxic with age. Rapid process motility and cellular migration of microglia in the developing brain, and other characteristics are regarded to be crucial for immunological defense and tissue repair. As they mature, microglia not only differ in their morphology but also in their functioning. However, the exact mechanism related to the atrophies caused by aged microglia or their role in neurodegenerative diseases is still uncertain. The aim of this updated review is to provide insights of how aging microglial cells change and how this influences the development of neurodegenerative diseases. As life expectancy rises, there is an increase in the accumulation of iron, ROS/NOS, protein misfolding and insufficient clearing of debris. This is attributed to the age-dependent alterations in the genes linked to energy metabolism, mitochondrial and lysosome function, and neuroinflammation. Aging microglia often shifts towards a pro-inflammatory state with a reduction of anti-inflammatory cytokines. Aging microglia fail to clear amyloid-beta plaques, accelerates tau-pathology and enhances the chronic neuroinflammation, exacerbating the α-synuclein aggregation. These changes significantly impacted the onset of various neurogenerative disorders such as amyotrophic lateral sclerosis, Parkinson's disease, and Alzheimer's disease etc. However, it is important to note that these microglial aging effects might not be perceived as absolute, due to various limitations such as microglial heterogeneity, intercellular complexity across brain regions and variability in human aging owing to genetic and epigenetic variations. Regardless of this the future perspective of such insights are of immense relevance as novel therapeutic approaches can be formulated if the molecular and cellular mechanisms of aging microglial perturbations are understood. Future research should focus on restoring microglial homeostasis to mitigate the effects of aging on the brain and slowing the progression of neurodegenerative diseases.}, }
@article {pmid40431734, year = {2025}, author = {Kim, DH and Kim, JH and Jeon, MT and Kim, KS and Kim, DG and Choi, IS}, title = {The Role of TDP-43 in SARS-CoV-2-Related Neurodegenerative Changes.}, journal = {Viruses}, volume = {17}, number = {5}, pages = {}, pmid = {40431734}, issn = {1999-4915}, support = {25-BR-02-03//Korea Brain Research Institute/ ; }, mesh = {Humans ; *DNA-Binding Proteins/metabolism/genetics ; *COVID-19/complications/metabolism/virology/pathology ; *SARS-CoV-2/physiology ; *Neurodegenerative Diseases/metabolism/virology/pathology/etiology ; Virus Replication ; Animals ; }, abstract = {The coronavirus disease 2019 (COVID-19) pandemic has been linked to long-term neurological effects with multifaceted complications of neurodegenerative diseases. Several studies have found that pathological changes in transactive response DNA-binding protein of 43 kDa (TDP-43) are involved in these cases. This review explores the causal interactions between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and TDP-43 from multiple perspectives. Some viral proteins of SARS-CoV-2 have been shown to induce pathological changes in TDP-43 through its cleavage, aggregation, and mislocalization. SARS-CoV-2 infection can cause liquid-liquid phase separation and stress granule formation, which accelerate the condensation of TDP-43, resulting in host RNA metabolism disruption. TDP-43 has been proposed to interact with SARS-CoV-2 RNA, though its role in viral replication remains to be fully elucidated. This interaction potentially facilitates viral replication, while viral-induced oxidative stress and protease activity accelerate TDP-43 pathology. Evidence from both clinical and experimental studies indicates that SARS-CoV-2 infection may contribute to long-term neurological sequelae, including amyotrophic lateral sclerosis-like and frontotemporal dementia-like features, as well as increased phosphorylated TDP-43 deposition in the central nervous system. Biomarker studies further support the link between TDP-43 dysregulation and neurological complications of long-term effects of COVID-19 (long COVID). In this review, we presented a novel integrative framework of TDP-43 pathology, bridging a gap between SARS-CoV-2 infection and mechanisms of neurodegeneration. These findings underscore the need for further research to clarify the TDP-43-related neurodegeneration underlying SARS-CoV-2 infection and to develop therapeutic strategies aimed at mitigating long-term neurological effects in patients with long COVID.}, }
@article {pmid40429767, year = {2025}, author = {Bokulic Panichi, L and Stanca, S and Dolciotti, C and Bongioanni, P}, title = {The Role of Oligodendrocytes in Neurodegenerative Diseases: Unwrapping the Layers.}, journal = {International journal of molecular sciences}, volume = {26}, number = {10}, pages = {}, pmid = {40429767}, issn = {1422-0067}, mesh = {Humans ; *Oligodendroglia/metabolism/pathology ; *Neurodegenerative Diseases/pathology/metabolism/etiology ; Animals ; Myelin Sheath/metabolism/pathology ; }, abstract = {Neurodegenerative diseases (NDs), including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis/motor neuron disease, and multiple sclerosis, are characterized by progressive loss of neuronal structure and function, leading to severe cognitive, motor, and behavioral impairments. They pose a significant and growing challenge due to their rising prevalence and impact on global health systems. The societal and emotional toll on patients, caregivers, and healthcare infrastructures is considerable. While significant progress has been made in elucidating the pathological hallmarks of these disorders, the underlying cellular and molecular mechanisms remain incompletely understood. Increasing evidence implicates oligodendrocytes and their progenitors-oligodendrocyte progenitor cells (OPCs)-in the pathogenesis of several NDs, beyond their traditionally recognized role in demyelinating conditions such as MS. Oligodendrocytes are essential for axonal myelination, metabolic support, and neural circuit modulation in the central nervous system. Disruptions in oligodendrocyte function and myelin integrity-manifesting as demyelination, hypomyelination, or dysmyelination-have been associated with disease progression in various neurodegenerative contexts. This review consolidates recent findings on the role of OPCs in NDs, explores the concept of myelin plasticity, and discusses therapeutic strategies targeting oligodendrocyte dysfunction. By highlighting emerging research in oligodendrocyte biology, this review aims to provide a short overview of its relevance to neurodegenerative disease progression and potential therapeutic advances.}, }
@article {pmid40428407, year = {2025}, author = {Škarica, M and Acsadi, G and Živković, SA}, title = {Pontocerebellar Hypoplasia Type 1 and Associated Neuronopathies.}, journal = {Genes}, volume = {16}, number = {5}, pages = {}, pmid = {40428407}, issn = {2073-4425}, mesh = {Humans ; *Olivopontocerebellar Atrophies/genetics/pathology ; *Cerebellar Diseases/genetics/pathology ; }, abstract = {Pontocerebellar hypoplasia is a rare neurodegenerative syndrome characterized by severe hypoplasia or atrophy of pons and cerebellum that may be associated with other brain malformations, microcephaly, optic nerve atrophy, dystonia, ataxia and neuromuscular disorders. At this time, there are 17 variants of PCH distinguished by clinical presentation and distinctive radiological and biochemical features in addition to pontine and cerebellar hypoplasia. PCH1 is defined as PCH variant associated with anterior horn degeneration in the spinal cord with muscle weakness and hypotonia, and is associated with recessive variants in genes VRK1, EXOSC3, EXOSC8, EXOSC9 and SLC25A46. Neuromuscular manifestations may clinically present as amyotrophic lateral sclerosis (ALS), motor neuropathy (HMN) or neuronopathy (non-5q spinal muscular atrophy; SMA) or sensorimotor polyneuropathy (HMSN). Physiologic functions of PCH1-associated genes include regulation of RNA metabolism, mitochondrial fission and neuronal migration. Overall, complex phenotypes associated with PCH1 gene variants ranging from PCH and related neurodevelopmental disorders combined with neuromuscular disorders to isolated neuromuscular disorders have variable outcomes with isolated neuromuscular disorders typically having later onset with better outcomes. Improved understanding of pathogenesis of pontocerebellar hypoplasia and its association with motor neuronopathies and peripheral neuropathies may provide us with valuable insights and lead to potential new therapeutic targets for neurodegenerative disorders.}, }
@article {pmid40428092, year = {2025}, author = {Vaccarino, F and Quattrocchi, CC and Parillo, M}, title = {Susceptibility-Weighted Imaging (SWI): Technical Aspects and Applications in Brain MRI for Neurodegenerative Disorders.}, journal = {Bioengineering (Basel, Switzerland)}, volume = {12}, number = {5}, pages = {}, pmid = {40428092}, issn = {2306-5354}, abstract = {Susceptibility-weighted imaging (SWI) is a magnetic resonance imaging (MRI) sequence sensitive to substances that alter the local magnetic field, such as calcium and iron, allowing phase information to distinguish between them. SWI is a 3D gradient-echo sequence with high spatial resolution that leverages both phase and magnitude effects. The interaction of paramagnetic (such as hemosiderin and deoxyhemoglobin), diamagnetic (including calcifications and minerals), and ferromagnetic substances with the local magnetic field distorts it, leading to signal changes. Neurodegenerative diseases are typically characterized by the progressive loss of neurons and their supporting cells within the neurovascular unit. This cellular decline is associated with a corresponding deterioration of both cognitive and motor abilities. Many neurodegenerative disorders are associated with increased iron accumulation or microhemorrhages in various brain regions, making SWI a valuable diagnostic tool in clinical practice. Suggestive SWI findings are known in Parkinson's disease, Lewy body dementia, atypical parkinsonian syndromes, multiple sclerosis, cerebral amyloid angiopathy, amyotrophic lateral sclerosis, hereditary ataxias, Huntington's disease, neurodegeneration with brain iron accumulation, and chronic traumatic encephalopathy. This review will assist radiologists in understanding the technical framework of SWI sequences for a correct interpretation of currently established MRI findings and for its potential future clinical applications.}, }
@article {pmid40427919, year = {2025}, author = {Howarth, NE and Ji, C and Batten, J and Pearce, AJ and Dawes, H and White, AJ and DeLuca, G and Bureau, S and Nowinski, CJ and Miller, MA}, title = {Neurodegenerative Disease and Association Football (NDAF): Systematic Review and Meta-Analysis.}, journal = {International journal of environmental research and public health}, volume = {22}, number = {5}, pages = {}, pmid = {40427919}, issn = {1660-4601}, mesh = {Humans ; *Neurodegenerative Diseases/epidemiology/etiology ; *Soccer/injuries ; *Football/injuries ; Risk Factors ; }, abstract = {There is increasing concern that head injuries in Association Football (or soccer) may lead to adverse health outcomes. The aim of this study was to determine whether head impacts or injuries are associated with an increased risk of neurodegenerative disease. We performed a systematic search using PubMed, Embase, and Ovid (up to April 2025). Studies included investigated neurodegenerative diseases in football in comparison to control athletic and general populations. Data were extracted according to PRISMA guidelines. Studies with an odds ratio (OR) were included in the meta-analysis. A total of ten studies were included in this review, of which nine were suitable for meta-analysis from eight cohorts. The risk for developing any neurodegeneration was 1.69 OR (95%CI 1.11 to 2.59; p = 0.01); for Dementia, it was 2.16 OR (95%CI 1.60 to 2.93; p < 0.01; for Motor Neurone Disease (MND), it was 1.39 OR (95%CI 0.67 to 2.53; p = 0.21); for Parkinson's Disease (PD), it was 1.14 OR (95%CI 0.55 to 2.89; p = 0.79). Heterogeneity was reduced following the removal of two studies and the revised risk scores for any neurodegenerative disease; Dementia increased, with that for MND reaching significance, 1.81 OR (95%CI 1.22 to 2.30; p = 0.01), but there remained no association with PD. Evidence suggests that professional football significantly increases the odds of neurodegenerative disease.}, }
@article {pmid40427436, year = {2025}, author = {Minuti, A and Raffaele, I and Scuruchi, M and Lui, M and Muscarà, C and Calabrò, M}, title = {Role and Functions of Irisin: A Perspective on Recent Developments and Neurodegenerative Diseases.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {14}, number = {5}, pages = {}, pmid = {40427436}, issn = {2076-3921}, support = {Current Research Funds 2025 (RRC-2025-23686388)//Ministero della Salute/ ; }, abstract = {Irisin is a peptide derived from fibronectin type III domain-containing protein 5 (FNDC5) and is primarily produced by muscle fibers under the regulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) during exercise. Irisin has been the subject of extensive research due to its potential as a metabolic regulator and its antioxidant properties. Notably, it has been associated with protective actions within the brain. Despite growing interest, many questions remain regarding the molecular mechanisms underlying its effects. This review summarizes recent findings on irisin, highlighting its pleiotropic functions and the biological processes and molecular cascades involved in its action, with a particular focus on the central nervous system. Irisin plays a crucial role in neuron survival, differentiation, growth, and development, while also promoting mitochondrial homeostasis, regulating apoptosis, and facilitating autophagy-processes essential for normal neuronal function. Emerging evidence suggests that irisin may improve conditions associated with non-communicable neurological diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, frontotemporal dementia, and multiple sclerosis. Given its diverse benefits, irisin holds promise as a novel therapeutic agent for preventing and treating neurological diseases.}, }
@article {pmid40426973, year = {2025}, author = {Ivantsik, O and Exarchos, TP and Vrahatis, AG and Vlamos, P and Krokidis, MG}, title = {Exploring Protein Misfolding in Amyotrophic Lateral Sclerosis: Structural and Functional Insights.}, journal = {Biomedicines}, volume = {13}, number = {5}, pages = {}, pmid = {40426973}, issn = {2227-9059}, support = {TAEDR-0535850.//This work was partially supported by the European Union-Next Generation EU, Greece 2.0 Na-tional Recovery and Resilience Plan Flagship program TAEDR-0535850./ ; }, abstract = {Protein functionality depends on its proper folding, making protein misfolding crucial for the function of proteins and, by extension, cells and the whole organism. Increasing evidence supports the role of protein misfolding in the pathogenesis of neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS). ALS is a rapidly progressive disease diagnosed at a prevalence of 5 cases per 100,000, with approximately 2-3 patients per 100,000 diagnosed each year. To date, there is no cure, and the disease usually leads to death within 2 to 5 years from diagnosis. There are two types of the disorder: familial ALS (fALS), accounting for approximately 10% of cases, and sporadic (sALS), accounting for the remaining 90%. The hallmark of ALS, regardless of type, is the protein aggregates found in patients' tissues. This suggests that the disruption of proteostasis plays a critical role in the development of the disease. Herein, we stress the distinct factors that lead to protein misfolding and aggregate formation in ALS. Specifically, we highlight several triggering factors affecting protein misfolding, namely mutations, errors in the processes of protein production and trafficking, and failures of folding and chaperone machinery. Gaining a deeper understanding of protein aggregation will improve our comprehension of disease pathogenesis and potentially uncover new therapeutic approaches.}, }
@article {pmid40422183, year = {2025}, author = {Verde, EM and Secco, V and Ghezzi, A and Mandrioli, J and Carra, S}, title = {Molecular Mechanisms of Protein Aggregation in ALS-FTD: Focus on TDP-43 and Cellular Protective Responses.}, journal = {Cells}, volume = {14}, number = {10}, pages = {}, pmid = {40422183}, issn = {2073-4409}, support = {SUMOsolvable//AriSLA/ ; AHA MCA 2022//Giovanni Armenise-Harvard Foundation and AirAlzh/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; *DNA-Binding Proteins/metabolism/genetics ; *Frontotemporal Dementia/metabolism/pathology/genetics ; *Protein Aggregates ; *Protein Aggregation, Pathological/metabolism ; Animals ; Protein Processing, Post-Translational ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) are two neurodegenerative disorders that share common genes and pathomechanisms and are referred to as the ALS-FTD spectrum. A hallmark of ALS-FTD pathology is the abnormal aggregation of proteins, including Cu/Zn superoxide dismutase (SOD1), transactive response DNA-binding protein 43 (TDP-43), fused in sarcoma/translocated in liposarcoma (FUS/TLS), and dipeptide repeat proteins resulting from C9orf72 hexanucleotide expansions. Genetic mutations linked to ALS-FTD disrupt protein stability, phase separation, and interaction networks, promoting misfolding and insolubility. This review explores the molecular mechanisms underlying protein aggregation in ALS-FTD, with a particular focus on TDP-43, as it represents the main aggregated species inside pathological inclusions and can also aggregate in its wild-type form. Moreover, this review describes the protective mechanisms activated by the cells to prevent protein aggregation, including molecular chaperones and post-translational modifications (PTMs). Understanding these regulatory pathways could offer new insights into targeted interventions aimed at mitigating cell toxicity and restoring cellular function.}, }
@article {pmid40419749, year = {2025}, author = {Monteiro Neto, JR and de Souza, GF and Dos Santos, VM and de Holanda Paranhos, L and Ribeiro, GD and Magalhães, RSS and Queiroz, DD and Eleutherio, ECA}, title = {SOD1, A Crucial Protein for Neural Biochemistry: Dysfunction and Risk of Amyotrophic Lateral Sclerosis.}, journal = {Molecular neurobiology}, volume = {}, number = {}, pages = {}, pmid = {40419749}, issn = {1559-1182}, support = {201.174/2022//Funda&#xe7;&#xe3;o Carlos Chagas Filho de Amparo &#xe0; Pesquisa do Estado do Rio de Janeiro/ ; 201.174/2022//Funda&#xe7;&#xe3;o Carlos Chagas Filho de Amparo &#xe0; Pesquisa do Estado do Rio de Janeiro/ ; 201.174/2022//Funda&#xe7;&#xe3;o Carlos Chagas Filho de Amparo &#xe0; Pesquisa do Estado do Rio de Janeiro/ ; 201.174/2022//Funda&#xe7;&#xe3;o Carlos Chagas Filho de Amparo &#xe0; Pesquisa do Estado do Rio de Janeiro/ ; 201.174/2022//Funda&#xe7;&#xe3;o Carlos Chagas Filho de Amparo &#xe0; Pesquisa do Estado do Rio de Janeiro/ ; 201.174/2022//Funda&#xe7;&#xe3;o Carlos Chagas Filho de Amparo &#xe0; Pesquisa do Estado do Rio de Janeiro/ ; 201.174/2022//Funda&#xe7;&#xe3;o Carlos Chagas Filho de Amparo &#xe0; Pesquisa do Estado do Rio de Janeiro/ ; 201.174/2022//Funda&#xe7;&#xe3;o Carlos Chagas Filho de Amparo &#xe0; Pesquisa do Estado do Rio de Janeiro/ ; PROBRAL 88881.986154/2024-01//CAPES-DAAD/ ; PROBRAL 88881.986154/2024-01//CAPES-DAAD/ ; PROBRAL 88881.986154/2024-01//CAPES-DAAD/ ; PROBRAL 88881.986154/2024-01//CAPES-DAAD/ ; PROBRAL 88881.986154/2024-01//CAPES-DAAD/ ; PROBRAL 88881.986154/2024-01//CAPES-DAAD/ ; PROBRAL 88881.986154/2024-01//CAPES-DAAD/ ; PROBRAL 88881.986154/2024-01//CAPES-DAAD/ ; 309635/2023-3//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; 309635/2023-3//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; 309635/2023-3//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; 309635/2023-3//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; 309635/2023-3//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; 309635/2023-3//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; 309635/2023-3//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; 309635/2023-3//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; }, abstract = {Neurons are very susceptible to oxidative stress. They are the major consumers of oxygen in the brain, which is used to provide energy through oxidative phosphorylation, the major source of reactive oxygen species (ROS). In addition, compared to other tissues, neurons have lower levels of catalase and glutathione and increased susceptibility to lipid peroxidation due to the elevated levels of unsaturated fatty acids. These characteristics increasingly emphasize the antioxidant enzyme Cu/Zn superoxide dismutase 1 (SOD1) to maintain neuronal redox homeostasis. In the last decade, SOD1 gained additional roles which are also important to the metabolism of neurons. SOD1 controls the production of ROS by the electron transport chain, activates the expression of genes involved in the protection against oxidative stress, and regulates the shift from oxidative to fermentative metabolism involved in astrocyte-neuron metabolic cooperation. Furthermore, impaired interaction between the phosphatase calcineurin and SOD1 seems to result in TDP-43 hyperphosphorylation, the main proteinopathy found in amyotrophic lateral sclerosis (ALS) patients. However, this enzyme is ubiquitously expressed, mutated, and damaged forms of SOD1 cause disease in motor neurons. In this review, we discuss the pivotal functions of SOD1 in neuronal biochemistry and their implications for ALS.}, }
@article {pmid40414644, year = {2025}, author = {Manusha, S and Varsha, N and Varshini, R and Sivamani, Y and Pokkuluri, KS and Elayaperumal, S}, title = {Altered microbiome influence on the enteric neuromuscular system in amyotrophic lateral sclerosis (ALS).}, journal = {International review of neurobiology}, volume = {180}, number = {}, pages = {95-123}, doi = {10.1016/bs.irn.2025.04.006}, pmid = {40414644}, issn = {2162-5514}, mesh = {*Amyotrophic Lateral Sclerosis/microbiology/physiopathology ; Humans ; *Gastrointestinal Microbiome/physiology ; *Enteric Nervous System/physiopathology/microbiology ; *Dysbiosis/physiopathology ; Animals ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurological disease marked by the degeneration of motor neurons, leading to muscle weakness and paralysis. While the cause of ALS is uncertain, research indicates that changes in the gut microbiome may influence the disease's progression. This chapter explores how alterations in gut microbiota affect the enteric neuromuscular system (ENS) in ALS. In ALS patients, disrupted gut microbiota are linked to the brain-gut axis, impacting both gastrointestinal function and neuronal health. Studies show that microbial changes are associated with inflammation, immune instability, and neurodegeneration, which exacerbate the disease. Gastrointestinal issues like constipation and dysphagia in ALS are tied to ENS dysregulation. Understanding the connections between the gut microbiome, ENS, and central nervous system (CNS) may lead to novel therapies targeting neurodegeneration and microbial dysbiosis in ALS.}, }
@article {pmid40411245, year = {2025}, author = {Giacobbe, A and Hiana, J and Wang, O and Benatar, M and Wicks, P and Mascias Cadavid, J and Jhooty, S and McDermott, C and Pattee, G and Bertorini, T and Heiman-Patterson, T and Ratner, D and Barkhaus, P and Carter, G and Jackson, C and Denson, K and Brown, A and Armon, C and Sun, Y and Nguyen, A and Bedlack, R and Li, X}, title = {ALSUntangled #79: alpha-lipoic acid.}, journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration}, volume = {}, number = {}, pages = {1-5}, doi = {10.1080/21678421.2025.2507166}, pmid = {40411245}, issn = {2167-9223}, abstract = {Alpha-lipoic acid (ALA) is a naturally occurring fatty acid. It serves as an essential cofactor for enzymatic reactions in mitochondrial energy production, is a potent antioxidant and has anti-inflammatory effects, which are plausible mechanisms in slowing ALS progression. In ALS preclinical studies, ALA slowed motor function decline and improved survival. There were self-reported cases of improved muscle strength in ALS patients when ALA was taken with numerous additional supplements, making it difficult to discern its efficacy. One small, 6-month open-label study showed improved quality of life, fatigue, and mood after participants took it with B vitamins and amino acids for the first 3 months. So far, no clinical trials have been published in people living with amyotrophic lateral sclerosis (PALS). Given the insufficient clinical data, we cannot endorse ALA and will support more research on its efficacy in slowing ALS progression.}, }
@article {pmid40406043, year = {2025}, author = {Wang, L and Ma, L and Gao, Z and Wang, Y and Qiu, J}, title = {Significance of gene therapy in neurodegenerative diseases.}, journal = {Frontiers in neuroscience}, volume = {19}, number = {}, pages = {1515255}, pmid = {40406043}, issn = {1662-4548}, abstract = {Gene therapy is an approach that employs vectors to deliver genetic material to target cells, aiming to correct genes with pathogenic mutations and modulate one or more genes responsible for disease progression. It holds significant value for clinical applications and offers broad market potential due to the large patient population affected by various conditions. For instance, in 2023, the Food and Drug Administration (FDA) approved 55 new drugs, including five specifically for gene therapy targeting hematologic and rare diseases. Recently, with advancements in understanding the pathogenesis and development of neurodegenerative diseases (NDDs), gene therapy has emerged as a promising avenue for treating Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and spinal muscular atrophy (SMA), particularly in personalized medicine. Notably, the FDA has approved three clinical applications for combating SMA, utilizing viral vectors delivered via intravenous and intrathecal injections. However, gene therapy for other NDDs remains in clinical trials, necessitating improvements in viral vectors, exploration of new vectors, optimization of delivery routes, and further investigation into pathogenesis to identify novel targets. This review discusses recent advancements in gene therapy for NDDs, offering insights into developing new therapeutic strategies.}, }
@article {pmid40405710, year = {2025}, author = {Clift, A and Rowen, D and Knox, L and Griffiths, AW and McDermott, CJ}, title = {A Systematic Review of Attributes Influencing Preferences for Treatments and Interventions in People With Amyotrophic Lateral Sclerosis (ALS).}, journal = {Muscle &amp; nerve}, volume = {72}, number = {3}, pages = {359-382}, pmid = {40405710}, issn = {1097-4598}, support = {//National Institute for Health and Care Research/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/psychology ; *Patient Preference/psychology ; Quality of Life/psychology ; Patient-Centered Care ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that has no cure, and treatments predominantly focus on improving quality of life. Patient-centred care is central to bringing about meaningful improvements to quality of life. This review addresses the lack of consolidated evidence on what matters most to people with ALS (pwALS) by synthesizing 44 preference-based studies covering six different treatment and intervention categories. Data-based convergent synthesis identified five overarching factors influencing preferences: ease of use, accessibility, making life easier, autonomy, and safety/reliability. Simplifying and enhancing accessibility of treatment delivery across disease stages aligns with the nature of neurodegenerative disorders such as ALS, where function declines as the disease progresses. The value in perceived and real control reflects the profound impact ALS has on an individual's independence. Safety and reliability are crucial for people with ALS and are recognized as fundamental requirements for quality healthcare. The themes identified in this review can inform the attributes of preference elicitation methods. Systematically varying the levels of these attributes elicits quantitative measures of preferences. These findings can be used to inform and develop healthcare policy and clinical practice in ALS care. Specifically, preferences related to drug treatments can then be integrated into target product profiles (TPPs) to align drug development with the needs and values of pwALS. Integrating patient preferences into clinical practice promotes patient-centred care, increasing both patient satisfaction and treatment effectiveness.}, }
@article {pmid40405223, year = {2025}, author = {Yoonesi, S and Abedi Azar, R and Arab Bafrani, M and Yaghmayee, S and Shahavand, H and Mirmazloumi, M and Moazeni Limoudehi, N and Rahmani, M and Hasany, S and Idjadi, FZ and Aalipour, MA and Gharedaghi, H and Salehi, S and Asadi Anar, M and Soleimani, MS}, title = {Facial expression deep learning algorithms in the detection of neurological disorders: a systematic review and meta-analysis.}, journal = {Biomedical engineering online}, volume = {24}, number = {1}, pages = {64}, pmid = {40405223}, issn = {1475-925X}, mesh = {Humans ; *Deep Learning ; *Facial Expression ; *Nervous System Diseases/diagnosis ; }, abstract = {BACKGROUND: Neurological disorders, ranging from common conditions like Alzheimer's disease that is a progressive neurodegenerative disorder and remains the most common cause of dementia worldwide to rare disorders such as Angelman syndrome, impose a significant global health burden. Altered facial expressions are a common symptom across these disorders, potentially serving as a diagnostic indicator. Deep learning algorithms, especially convolutional neural networks (CNNs), have shown promise in detecting these facial expression changes, aiding in diagnosing and monitoring neurological conditions.<br><br>OBJECTIVES: This systematic review and meta-analysis aimed to evaluate the performance of deep learning algorithms in detecting facial expression changes for diagnosing neurological disorders.<br><br>METHODS: Following PRISMA2020 guidelines, we systematically searched PubMed, Scopus, and Web of Science for studies published up to August 2024. Data from 28 studies were extracted, and the quality was assessed using the JBI checklist. A meta-analysis was performed to calculate pooled accuracy estimates. Subgroup analyses were conducted based on neurological disorders, and heterogeneity was evaluated using the I[2] statistic.<br><br>RESULTS: The meta-analysis included 24 studies from 2019 to 2024, with neurological conditions such as dementia, Bell's palsy, ALS, and Parkinson's disease assessed. The overall pooled accuracy was 89.25% (95% CI 88.75-89.73%). High accuracy was found for dementia (99%) and Bell's palsy (93.7%), while conditions such as ALS and stroke had lower accuracy (73.2%).<br><br>CONCLUSIONS: Deep learning models, particularly CNNs, show strong potential in detecting facial expression changes for neurological disorders. However, further work is needed to standardize data sets and improve model robustness for motor-related conditions.}, }
@article {pmid40403957, year = {2025}, author = {Zeng, L and Yang, J and Zhang, C and Zhu, J and Zhong, S and Liu, X and Xie, H and Wang, L and Chen, L and Zhong, M and Hua, F and Liang, W}, title = {Miro1: A potential target for treating neurological disorders.}, journal = {Neuroscience}, volume = {577}, number = {}, pages = {228-239}, doi = {10.1016/j.neuroscience.2025.05.019}, pmid = {40403957}, issn = {1873-7544}, mesh = {Humans ; Animals ; *rho GTP-Binding Proteins/metabolism ; *Nervous System Diseases/metabolism/drug therapy ; *Mitochondria/metabolism ; *Mitochondrial Proteins/metabolism ; Neurons/metabolism ; }, abstract = {The Miro1 protein is a member of the mitochondrial Rho GTPase (Miro) protein family and plays a crucial role in regulating the dynamic processes of mitochondria and participating in cellular movement and mitochondrial transport. In the nervous system, it ensures adequate energy supply for normal neuronal function and synaptic transmission. Additionally, Miro1 actively participates in the regulation of mitochondrial quality control and stress responses within neurons. Its primary function is to sense intracellular stress signals to regulate mitochondrial movement and metabolism, thereby adapting to environmental changes. Multiple studies have indicated that the Miro1 protein is associated with the pathogenesis of various neurological disorders, such as Alzheimer's Disease(AD), Parkinson's Disease(PD), and Amyotrophic Lateral Sclerosis(ALS). This article reviews the mechanistic role of Miro1 in these diseases and summarizes the latest research on its involvement in neurological disorders. These efforts aim to provide unified treatment strategies for certain neurological disorders and explore the potential for treating complex neurological diseases.}, }
@article {pmid40403503, year = {2025}, author = {Dhapola, R and Paidlewar, M and Kumari, S and Sharma, P and Vellingiri, B and Medhi, B and HariKrishnaReddy, D}, title = {cGAS-STING and neurodegenerative diseases: A molecular crosstalk and therapeutic perspective.}, journal = {International immunopharmacology}, volume = {159}, number = {}, pages = {114902}, doi = {10.1016/j.intimp.2025.114902}, pmid = {40403503}, issn = {1878-1705}, mesh = {Humans ; *Nucleotidyltransferases/metabolism ; *Neurodegenerative Diseases/drug therapy/metabolism/immunology ; *Membrane Proteins/metabolism ; Animals ; Signal Transduction ; }, abstract = {Neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (MS) and Frontotemporal Dementia (FTD) share key pathological features, including neuroinflammation, oxidative stress, mitochondrial dysfunction, autophagic dysfunction, and DNA damage. By identifying cytosolic DNA and triggering the type I interferon response, the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway regulates neuroinflammation. Dysregulated cGAS-STING signaling has been linked to neuroinflammation and neuronal degeneration across multiple neurodegenerative conditions. In many neurodegenerative disorders, neuroinflammation is mediated by the cGAS-STING pathway. Mitochondrial malfunction and impaired autophagy cause cytosolic DNA buildup in Huntington's, Parkinson's, and Alzheimer's diseases, which activates cGAS-STING and drives chronic inflammation. This pathway is triggered by TDP-43 pathology and nucleic acid dysregulation in ALS and FTD, which leads to neuronal destruction. Both central demyelination and peripheral immunological responses are linked to cGAS-STING activation in multiple sclerosis. Various inhibitors, such as RU.521, H-151, and naturally occurring compounds like metformin, potentially attenuate cGAS-STING-mediated neuroinflammation and associated pathologies. H-151 significantly decreased the expression of pro-inflammatory markers in murine macrophage J774 cells activated with cGAMP: TNF-α by 68 %, IFN-β by 84 %, and CXCL10 by 96 %. cGAS-STING inhibitors target neuroinflammation, offering a disease-modifying approach unlike current symptomatic treatments. However, challenges like blood-brain barrier penetration, off-target effects, and immune suppression hinder clinical translation, necessitating optimized drug delivery and immune modulation. With a focus on its potential for future clinical applications, this review explores the role of the cGAS-STING pathway in neurodegeneration and new treatment approaches.}, }
@article {pmid40400898, year = {2025}, author = {Aziz, S and Anbreen, S and Shahzad, S and Ahmed, MS and Sharma, V and Yang, J and Ali, L}, title = {Investigating nanoparticle's utilization in stem cell therapy for neurological disorders.}, journal = {American journal of stem cells}, volume = {14}, number = {1}, pages = {1-13}, pmid = {40400898}, issn = {2160-4150}, abstract = {Stem cell therapy is a promising area of regenerative medicine, offering potential treatments for various life-threatening disorders. Stem cells are classified based on their differentiation potential into totipotent, pluripotent, and multipotent stem cells. Among them, mesenchymal stem cells (MSCs) are widely used in regenerative medicine due to their tissue regeneration capabilities and ability to differentiate into multiple cell types. Stem cells are being explored for treating neurodegenerative disorders like Parkinson's, Alzheimer's, Huntington's, and amyotrophic lateral sclerosis (ALS). These conditions result from progressive neuronal degeneration, leading to irreversible damage. Challenges such as cell survival, immune rejection, tumor formation, and ethical concerns related to embryonic stem cells need to be addressed. Nanotechnology is emerging as a tool for enhancing stem cell therapy, improving targeted delivery and effectiveness. Nanoparticles possess the ability to create microenvironments as substrates, facilitate targeted administration, and enable real-time, precise imaging of stem cells. This review explores the integration of stem cells and nanotechnology as regenerative medicine tool for neurodegenerative disease treatment, analyzing current strategies and therapeutic approaches. Integrating nanotechnology with stem cell therapy may significantly improve targeted delivery and enhance regenerative outcomes for neurodegenerative disorders.}, }
@article {pmid40398684, year = {2025}, author = {Naufal, E and Shadbolt, C and Wouthuyzen-Bakker, M and Rele, S and Sahebjada, S and Thuraisingam, S and Babazadeh, S and Choong, PF and Dowsey, MM}, title = {Clinical prediction models to guide treatment of periprosthetic joint infections: a systematic review and meta-analysis.}, journal = {The Journal of hospital infection}, volume = {162}, number = {}, pages = {53-61}, doi = {10.1016/j.jhin.2025.04.035}, pmid = {40398684}, issn = {1532-2939}, mesh = {Humans ; *Prosthesis-Related Infections/therapy ; }, abstract = {BACKGROUND: Several clinical prediction models that aim to guide decisions about the management of periprosthetic joint infections (PJIs) have been developed. While some models have been recommended for use in clinical settings, their suitability remains uncertain.<br><br>METHODS: We systematically reviewed and critically appraised all multi-variable prediction models for the treatment of PJI. We searched MEDLINE, EMBASE, Web of Science, and Google Scholar from inception until 1[st] March 2024 and included studies that developed or validated models that predict the outcome of PJI. We used PROBAST (Prediction model Risk Of Bias ASsessment Tool) to assess the risk of bias and applicability. Model performance estimates were pooled via random effect meta-analysis.<br><br>RESULTS: Thirteen predictive models and seven external validations were identified. Methodological issues were identified in all studies. Pooled estimates indicated that the KLIC (Kidney, Liver, Index surgery, Cemented prosthesis, C-reactive protein) score had fair discriminative performance (pooled c-statistic 0.62, 95% CI 0.55-0.69). Both the &#x3c4;[2] (0.02) and I[2] (33.4) estimates indicated that between-study heterogeneity was minimal. Meta-analysis indicated Shohat et al.'s model had good discriminative performance (pooled c-statistic 0.74, 95% CI 0.57-0.85). Both the &#x3c4;[2] (0.0) and I[2] (0.0) indicated that between study heterogeneity was minimal.<br><br>CONCLUSIONS: Clinicians should be aware of limitations in the methods used to develop available models to predict outcomes of PJI. As no models have consistently demonstrated adequate performance across external validation studies, it remains unclear whether any available models would provide reliable information if used to guide clinical decision making.}, }
@article {pmid40398193, year = {2025}, author = {Carra, S and Fabian, B and Taghavi, H and Milanetti, E and Giliberti, V and Ruocco, G and Shepherd, J and Vendruscolo, M and Fuxreiter, M}, title = {Virus-like particles of retroviral origin in protein aggregation and neurodegenerative diseases.}, journal = {Molecular aspects of medicine}, volume = {103}, number = {}, pages = {101369}, doi = {10.1016/j.mam.2025.101369}, pmid = {40398193}, issn = {1872-9452}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/virology/pathology ; *Protein Aggregates ; *Endogenous Retroviruses/metabolism/genetics ; *Protein Aggregation, Pathological/metabolism/virology ; Animals ; *Virion/metabolism ; Protein Folding ; }, abstract = {A wide range of human diseases are associated with protein misfolding and amyloid aggregates. Recent studies suggest that in certain neurological disorders, including Amyotrophic Lateral Sclerosis (ALS), Frontotemporal Dementia (FTD) and various tauopathies, protein aggregation may be promoted by virus-like particles (VLPs) formed by endogenous retroviruses (ERVs). The molecular mechanisms by which these VLPs contribute to protein aggregation, however, remain enigmatic. Here, we discuss possible molecular mechanisms of ERV-derived VLPs in the formation and spread of protein aggregates. An intriguing possibility is that liquid-like condensates may facilitate the formation of both protein aggregates and ERV-derived VLPs. We also describe how RNA chaperoning, and the encapsulation and trafficking of misfolded proteins, may contribute to protein homeostasis through the elimination of protein aggregates from cells. Based on these insights, we discuss future potential therapeutic opportunities.}, }
@article {pmid40396445, year = {2025}, author = {Hu, X and Cheng, J and Yuan, R and Zhou, Y and Rao, J and Wan, Y and Li, Y and Zhang, X and Li, R}, title = {Gold nanoparticles: diagnostic and therapeutic applications in neurodegenerative disorders.}, journal = {Journal of drug targeting}, volume = {}, number = {}, pages = {1-18}, doi = {10.1080/1061186X.2025.2509287}, pmid = {40396445}, issn = {1029-2330}, abstract = {Neurodegenerative disorders (NDDs), including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and prion diseases, pose a significant and escalating health challenge in the context of an ageing population. Gold nanoparticles (GNPs) have emerged as promising agents in the diagnostic and therapeutic realms of NDDs, due to their unique ability to enhance drug delivery across the blood-brain barrier (BBB). This paper presents a comprehensive review of the application of GNPs in the context of NDDs diagnosis and therapy, highlighting their potential to transform patient management. Additionally, we systematically address the critical challenges associated with the use of GNPs in the treatment and diagnosis of NDDs, focusing on pharmacokinetics and metabolism, toxicity, long-term biocompatibility, regulatory challenges and cost-effectiveness. Furthermore, we synthesise ongoing clinical studies to provide a holistic perspective on the current state of research in this field. We also explore the prospective trajectories and clinical translational potential of GNPs, which may usher in a new era in the treatment of NDDs.}, }
@article {pmid40395983, year = {2025}, author = {Beckers, J and Van Damme, P}, title = {The role of autophagy in the pathogenesis and treatment of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).}, journal = {Autophagy reports}, volume = {4}, number = {1}, pages = {2474796}, pmid = {40395983}, issn = {2769-4127}, abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) represent two extremes of a neurodegenerative disease spectrum characterised by overlapping genetic, clinical, and neuropathological features. This review covers the intricate relationship between both ALS and FTD and defects in the autophagy and endolysosomal pathway as recent evidence has pointed towards alterations in these pathways as being a root cause of disease pathogenesis. Here, we review the current knowledge on the interplay between ALS/FTD and lysosomebased proteostasis pathways and carefully asses the steps of the autophagy and endolysosomal pathways that are impaired by ALS or FTDcausing variants. Finally, we present a comprehensive overview of therapeutic strategies aimed at restoring autophagic and lysosomal function as potential avenues for mitigating the impact of these devastating diseases. Through this review, we aim to enhance the understanding of the pathophysiological mechanisms involving autophagy and/or the endolysosomal system that underlie the ALS-FTD spectrum and underscore the necessity for specific therapeutic approaches that target these shared vulnerabilities.}, }
@article {pmid40395088, year = {2025}, author = {Zhang, S and Gu, J and Yang, Y and Li, J and Ni, L}, title = {Evolution Trend of Brain Science Research: An Integrated Bibliometric and Mapping Approach.}, journal = {Brain and behavior}, volume = {15}, number = {5}, pages = {e70451}, pmid = {40395088}, issn = {2162-3279}, support = {2020Z388//Jiangsu Postdoctoral Research Foundation/ ; //Top Talent Support Program for young and middle-aged people of the Wuxi Health Committee/ ; M202033//Wuxi Health Commission Scientific Research Project/ ; 24CC00903//Beijing Academy of Science and Technology Think Tank Research Project/ ; ZYYB05//Wuxi Administration of Traditional Chinese Medicine/ ; }, mesh = {*Bibliometrics ; Humans ; *Biomedical Research/trends ; *Neurosciences/trends ; *Brain/physiology ; United States ; China ; }, abstract = {BACKGROUND: Brain science research is considered the crown jewel of 21st-century scientific research; the United States, the United Kingdom, and Japan have elevated brain science research to a national strategic level. This study employs bibliometric analysis and knowledge graph visualization to map global trends, research hotspots, and collaborative networks in brain science, providing insights into the field's evolving landscape and future directions.<br><br>METHODS: We analyzed 13,590 articles (1990-2023) from the Web of Science Core Collection using CiteSpace and VOSviewer. Metrics included publication volume, co-authorship networks, citation patterns, keyword co-occurrence, and burst detection. Analytical tools such as VOSviewer, CiteSpace, and online bibliometric platforms were employed to facilitate this investigation.<br><br>RESULTS: The United States, China, and Germany dominated research output, with China's publications rising from sixth to second globally post-2016, driven by national initiatives like the China Brain Project. However, China exhibited limited international collaboration compared to the United States and European Union. Key journals included Human Brain Mapping and Journal of Neural Engineering, while emergent themes centered on "task analysis," "deep learning," and "brain-computer interfaces" (BCIs). Research clusters revealed three focal areas: (1) Brain Exploration (e.g., fMRI, diffusion tensor imaging), (2) Brain Protection (e.g., stroke rehabilitation, amyotrophic lateral sclerosis therapies), and (3) Brain Creation (e.g., neuromorphic computing, BCIs integrated with AR/VR). Despite China's high output, its influence lagged in highly cited scholars, reflecting a "quantity-over-quality" challenge.<br><br>CONCLUSION: Brain science research is in a golden period of development. This bibliometric analysis offers the first comprehensive review, encapsulating research trends and progress in brain science. It reveals current research frontiers and crucial directions, offering a strategic roadmap for researchers and policymakers to navigate countries when planning research layouts.}, }
@article {pmid40389567, year = {2025}, author = {Wu, WL and Gong, XX and Qin, ZH and Wang, Y}, title = {Molecular mechanisms of excitotoxicity and their relevance to the pathogenesis of neurodegenerative diseases-an update.}, journal = {Acta pharmacologica Sinica}, volume = {}, number = {}, pages = {}, pmid = {40389567}, issn = {1745-7254}, abstract = {Glutamate excitotoxicity is intricately linked to the pathogenesis of neurodegenerative diseases, exerting a profound influence on cognitive functions such as learning and memory in mammals. Glutamate, while crucial for these processes, can lead to neuronal damage and death when present in excessive amounts. Our previous review delved into the cascade of excitotoxic injury events and the underlying mechanisms of excitotoxicity. Building on that foundation, this update summarizes the latest research on the role of excitotoxicity in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, as well as new cutting-edge techniques applied in the study of excitotoxicity. We also explore the mechanisms of action of various excitotoxicity inhibitors and their clinical development status. This comprehensive analysis aims to enhance our understanding of the nexus between excitotoxicity and neurodegenerative diseases, offering valuable insights for therapeutic strategies in these conditions.}, }
@article {pmid40389171, year = {2025}, author = {Das, D and Das, A and Bhattacharya, K and Koch, KP and Deuri, DJ and Saikia, D and Chanu, NR and Deka, S}, title = {Xanthones as neuroprotective agents: A comprehensive review of their role in the prevention and treatment of neurodegenerative diseases.}, journal = {Ageing research reviews}, volume = {109}, number = {}, pages = {102772}, doi = {10.1016/j.arr.2025.102772}, pmid = {40389171}, issn = {1872-9649}, mesh = {*Xanthones/therapeutic use/pharmacology/chemistry ; Humans ; *Neuroprotective Agents/therapeutic use/pharmacology ; *Neurodegenerative Diseases/drug therapy/prevention &amp; control ; Animals ; }, abstract = {Over the recent years, numerous research efforts have been focused toward xanthones, a class of heterocyclic compounds characterized by a three-ring core structure and a diverse range of biological activities. Despite extensive studies, no xanthone-based molecule has successfully progressed through clinical trials to reach pharmaceutical applications. Xanthones belong to the class of secondary metabolites that exist naturally, found in various plant species, and their structural diversity has been further expanded through synthetic modifications to enhance their pharmacological efficacy. This review provides a comprehensive description of the therapeutic potential of xanthone derivatives within the scope of neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, and neuroinflammation. Existing literature has been rigorously examined to highlight the pharmacological relevance of xanthones in these disorders. Additionally, the pathophysiological aspects of each disease are discussed in detail to establish a mechanistic understanding of how xanthone derivatives may exert neuroprotective effects. Furthermore, the SAR of xanthones is explored to elucidate key molecular features responsible for their bioactivity, providing insights into rational drug design. By synthesizing and critically analyzing the existing research, this review is focused in highlighting the therapeutic relevance of xanthones in neurodegenerative diseases and their potential as lead candidates for further drug development.}, }
@article {pmid40388191, year = {2025}, author = {De Marchi, F and Lombardi, I and Bombaci, A and Diamanti, L and Olivero, M and Perciballi, E and Tornabene, D and Vulcano, E and Ferrari, D and Mazzini, L}, title = {Recent therapeutic advances in the treatment and management of amyotrophic lateral sclerosis: the era of regenerative medicine.}, journal = {Expert review of neurotherapeutics}, volume = {25}, number = {7}, pages = {773-789}, doi = {10.1080/14737175.2025.2508781}, pmid = {40388191}, issn = {1744-8360}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy ; *Regenerative Medicine/methods ; Genetic Therapy/methods ; Stem Cell Transplantation/methods ; Animals ; }, abstract = {INTRODUCTION: Despite decades of research, effective disease-modifying treatments for Amyotrophic Lateral Sclerosis (ALS) remain scarce. The emergence of regenerative medicine presents a new frontier for ALS treatment.<br><br>AREAS COVERED: This review is based on a comprehensive literature search using PubMed, Scopus and clinical trials databases on the recent therapeutic advancements in ALS, giving focus to regenerative medicine. The article includes coverage of stem cell-based therapies, including mesenchymal, neural and induced pluripotent stem cells; all of which may offer potential neuroprotective and immunomodulatory effects. Gene therapy, particularly antisense oligonucleotides targeting ALS-related mutations, has gained traction, with tofersen becoming the first FDA-approved genetic therapy for ALS. The article also covers emerging approaches such as extracellular vesicles, immune-modulating therapies, and bioengineering techniques, including CRISPR-based gene editing and cellular reprogramming, that hold promise for altering disease progression.<br><br>EXPERT OPINION: While regenerative medicine provides hope for ALS patients, significant challenges remain. Biomarkers will play a crucial role in guiding personalized treatment strategies, ensuring targeted interventions. Future research should prioritize optimizing combinatory approaches, integrating different therapy strategies to maximize patient outcomes. Although regenerative medicine is still in its early clinical stages, its integration into ALS treatment paradigms could redefine disease management and alter its natural course.}, }
@article {pmid40383754, year = {2025}, author = {Heidari, N and Ghannadzadeh Kermani Pour, R and Farshbafnadi, M and Heidari, A and Ghane, Y}, title = {A systematic review of tumor necrosis factor-α blockers, anti-interleukins, and small molecule inhibitors for dissecting cellulitis of the scalp treatment.}, journal = {Orphanet journal of rare diseases}, volume = {20}, number = {1}, pages = {236}, pmid = {40383754}, issn = {1750-1172}, mesh = {Humans ; *Cellulitis/drug therapy ; *Scalp/pathology/drug effects ; *Scalp Dermatoses/drug therapy ; *Skin Diseases, Genetic/drug therapy ; *Tumor Necrosis Factor-alpha/antagonists &amp; inhibitors ; }, abstract = {BACKGROUND: Dissecting cellulitis of the scalp (DCS) is a type of neutrophilic scarring alopecia identified by the development of folliculitis with clusters of perifollicular pustules and then progresses to abscesses and intercommunicating sinus formation. In the absence of evidence-based guidelines, the treatment of DCS remains a therapeutic challenge. Our study aimed to assess the safety and efficacy of biologics, including tumor necrosis factor-α (TNF-α) blockers, anti-interleukins (ILs), and small molecule inhibitors, including Janus kinase (JAK) inhibitors and phosphodiesterase inhibitors in treating DCS.<br><br>METHODS: PubMed/Medline, Scopus, and Ovid Embase databases were systematically searched until February 4th, 2024. Study selection was restricted to case reports, case series, cohort studies, and clinical trials published in English-language. NIH and Murad et al.'s quality assessment tools were utilized for critical appraisal.<br><br>RESULTS: A total of 34 articles involving 81 patients met the inclusion criteria. The immunomodulators studied for the treatment of DCS include adalimumab, infliximab, certolizumab pegol, ustekinumab, secukinumab, guselkumab, risankizumab, tildrakizumab, apremilast, upadacitinib, and baricitinib. Our findings implied that TNF-&#x3b1; blockers and IL inhibitors were associated with clinical improvement in most individuals with moderate-to-severe DCS, especially in those who had failed earlier treatments. Moreover, certolizumab pegol could be a safe option for DCS in pregnancy. In addition, the prescription of small molecule inhibitors, including JAK inhibitors and apremilast in DCS patients, demonstrated a significant amelioration in DCS symptoms with a desirable safety profile. Nevertheless, the available data was limited, warranting further investigation. Besides, all aforementioned immunomodulators are still debated for their effectiveness on hair regrowth and reversing the scarring process.<br><br>CONCLUSIONS: The application of immunomodulators in treating DCS was associated with satisfactory outcomes, although there is still a need to assess the long-term safety and effectiveness of these therapeutic agents in preventing disease progression and new flare-ups.}, }
@article {pmid40381433, year = {2025}, author = {Begh, MZA and Zehravi, M and Bhuiyan, MAK and Molla, MR and Raman, K and Emran, TB and Ullah, MH and Ahmad, I and Osman, H and Khandaker, MU}, title = {Recent advances in stem cell approaches to neurodegeneration: A comprehensive review with mechanistic insight.}, journal = {Pathology, research and practice}, volume = {271}, number = {}, pages = {156013}, doi = {10.1016/j.prp.2025.156013}, pmid = {40381433}, issn = {1618-0631}, mesh = {Humans ; *Neurodegenerative Diseases/therapy ; *Stem Cell Transplantation/methods ; Animals ; }, abstract = {The progressive nature of neurodegenerative diseases (NDs), such as Parkinson's disease, Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis, presents substantial problems because current treatments are still obscure. Stem cell-based treatments are emerging as a viable solution to address the significant gaps in treating these severe diseases. This study provides a comprehensive analysis of the latest advancements in stem cell research, focusing on the treatment of NDs. Various types of stem cells, such as adult, induced pluripotent, and embryonic stem cells, and their potential applications in immunomodulation, neurotrophic factor release, and neuronal development are also discussed. Recent clinical studies reveal outcomes, challenges, and solutions, with advancements in disease-specific neural cell production, gene editing, and improved stem cell transplantation transport strategies. The review discussed future perspectives on developing more effective stem cell-based interventions. Biomaterials are being used for cell distribution and personalized medicine techniques to improve treatment outcomes, while exploring stem cell treatments for NDs and identifying areas for further research.}, }
@article {pmid40378897, year = {2025}, author = {Fontanelli, L and Nisini, N and Pirola, S and Recchia, FA}, title = {Neuromuscular and cardiac organoids and assembloids: Advanced platforms for drug testing.}, journal = {Pharmacology &amp; therapeutics}, volume = {272}, number = {}, pages = {108876}, doi = {10.1016/j.pharmthera.2025.108876}, pmid = {40378897}, issn = {1879-016X}, mesh = {*Organoids/drug effects ; Humans ; Animals ; Induced Pluripotent Stem Cells/cytology ; Drug Evaluation, Preclinical/methods ; *Neuromuscular Junction/drug effects ; }, abstract = {The inherent technical difficulties, ethical/regulatory issues and costs of experimental studies in animal models is prompting investigators to replace as much as possible living organisms with in vitro physiological models named organoids and assembloids. Generated from induced pluripotent stem cells, these three-dimensional structures approximate the complexity of tissues and their interactions, enabling personalized disease modelling and drug testing. The integration of multiple components in assembloids further enhances their predictive value for multi-system interactions and toxicities. This review describes how neuromuscular organoids, incorporating functional neuromuscular junctions and contractile muscle tissue, have been used to replicate, in vitro, complex neuromuscular morpho-functional structures, offering very valuable platforms to study molecular mechanisms and drug effects in models of incurable diseases such as spinal muscular atrophy and amyotrophic lateral sclerosis. In the cardiological field, cardiac organoids and assembloids are proving reliable models for testing drug effects at molecular, morphological, electrophysiological and mechanical level. Recently, the integration of neuronal components into cardiac organoids has provided a potential approach to investigate autonomic function, a fundamental aspect of many neurological, neuromuscular and cardiac diseases. Challenges and limitations still remain, including the non-uniform differentiation protocols across studies, the incomplete maturation of cell phenotypes, and the lack of integrated pharmacokinetic modelling. We discussed some future developments aimed at overcoming such hurdles. Despite their current limitations, organoids and assembloids clearly hold great promises and will help advancing many fields of biomedicine.}, }
@article {pmid40374790, year = {2025}, author = {Verma, KK and Gaur, PK and Gupta, SL and Lata, K and Kaushik, R and Sharma, V}, title = {Metabolomics: a new frontier in neurodegenerative disease biomarker discovery.}, journal = {Metabolomics : Official journal of the Metabolomic Society}, volume = {21}, number = {3}, pages = {67}, pmid = {40374790}, issn = {1573-3890}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/diagnosis ; *Biomarkers/metabolism/analysis ; *Metabolomics/methods ; Animals ; }, abstract = {BACKGROUND: Neurodegenerative disorders are a group of debilitating diseases affecting the central nervous system, and are characterized by the progressive loss of neurons, leading to declines in cognitive function, movement, and overall quality of life. While the exact causes remain elusive, it's believed that a combination of genetic, environmental, and lifestyle factors contribute to their development. Metabolites, the end products of cellular processes, reflect the physiological state of an organism. By analysing these molecules, researchers can gain a deeper understanding of the underlying metabolic changes associated with neurodegenerative disorders.<br><br>AIM OF REVIEW: This review aims to explore the possibilities between metabolites and their association with neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), Multiple sclerosis (MS) and Huntington's disease (HD).<br><br>Metabolomic studies could potentially illuminate altered biochemical pathways, facilitating earlier detection and treatment of these conditions. Metabolomic investigations have revealed the role of oxidative stress, alterations in glucose and fat metabolism, mitochondrial dysfunction, apoptosis, glutamate excitotoxicity and alterations in myelin composition in neurodegenerative disorders. The common metabolic biomarkers identified includes glutamate, taurine, uric acid, branched chain amino acids, acylcarnitine, creatinine, choline, with some more amino acids and lipids. Metabolomics offers valuable insights into disease mechanisms and potential therapeutic targets by identifying biochemical and metabolic alterations, but still there are several aspects to be explored for accurate mapping of metabolites with specific pathway involved in the disease.}, }
@article {pmid40371978, year = {2025}, author = {Shafran, R and Egan, SJ}, title = {Widening the Reach: The Broad Impact of Unguided Self-Help for Eating Disorders.}, journal = {The International journal of eating disorders}, volume = {58}, number = {8}, pages = {1432-1435}, pmid = {40371978}, issn = {1098-108X}, mesh = {Humans ; *Feeding and Eating Disorders/therapy/psychology/prevention &amp; control ; *Cognitive Behavioral Therapy/methods ; *Self Care ; Self Concept ; }, abstract = {A systematic review and meta-analysis conducted by Linardon and colleagues on 27 controlled trials using pure self-help for the prevention and treatment of eating disorders, reported small benefits for co-occurring difficulties such as anxiety, depression, distress and self-esteem. The findings were strongest for pre-selected samples considered at risk or who were symptomatic, and are consistent with literature from other areas indicating that focused interventions have a positive impact on comorbid difficulties. The meta-analysis raises questions about the optimal approach to address comorbidity both within and beyond pure self-help. Understanding the wider impact of disorder-specific approaches compared to transdiagnostic approaches is critical to helping clinicians determine what interventions to use and when. It is notable that CBT interventions across disorders often share treatment techniques and methods to optimize the generalization of learning across difficulties, but such common elements are rarely made explicit. The value of session-by-session measurement as an essential tool to guide clinical decision-making in the context of comorbid difficulties is emphasized. Whilst further work is needed, particularly in clinical samples, the message from Linardon et al.'s meta-analysis is straightforward-pure self-help for the prevention and treatment of eating disorders can have a broad impact in improving mental health.}, }
@article {pmid40364088, year = {2025}, author = {Plotti, F and Martinelli, A and Terranova, C and De Cicco Nardone, C and Montera, R and Luvero, D and Guzzo, F and Di Donato, V and Cundari, GB and Manco, S and Angioli, R}, title = {Laparoscopic Lateral Suspension (LLS) for Pelvic Organ Prolapse (POP): Update and Systematic Review of Prospective and Randomised Trials.}, journal = {Journal of clinical medicine}, volume = {14}, number = {9}, pages = {}, pmid = {40364088}, issn = {2077-0383}, abstract = {Background: Pelvic organ prolapse (POP) significantly impacts women's quality of life, especially in postmenopausal patients. Although laparoscopic sacrocolpopexy (LSC) is the gold standard for advanced apical prolapse, its complexity and risk of complications have led to alternative approaches like laparoscopic lateral suspension (LLS), a minimally invasive technique with promising results. Methods: A comprehensive search using PubMed databases was performed. The search was conducted from June 2024 to September 2024. The search string used was as follows: (pelvic organ prolapse) AND (lateral suspension) OR (laparoscopic lateral suspension). We included randomized controlled trials, prospective cohort studies, prospective observational studies, and case studies. We excluded retrospective studies, small case series, case reports, and articles not published in English. All selected articles were screened based on the titles and abstracts. Relevant data were extracted and tabulated. Results: An overall number of 12 studies were included in our analysis. LLS demonstrated high anatomical success rates: 91.15% for the anterior, 94.95% for the central, and 86.55% for the posterior compartments. The randomized controlled studies exhibit comparable effectiveness between both methods (LLS vs. LSC) and LLS appears to be the best option for anterior repair or anterior-apical repair. Patient satisfaction rates exceeded 90%, with reduced operative times (123 ± 33 min and 193 ± 55.6 min for ALS and ASC, respectively). According to the Claiven-Dindo scale, 0.17% of postoperative complications were graded more than III. The rate of mesh erosion was 0% to 10%. The technique showed particular benefit for uterine preservation and in obese patients but was less effective for severe posterior prolapse. Conclusions: Laparoscopic lateral suspension offers a safe, effective alternative for POP management, with significant anatomical and functional benefits. Its minimally invasive nature, shorter surgery time, and high satisfaction rates make it suitable for tailored patient care. Further studies should standardize evaluation metrics and assess long-term outcomes. The review was not registered. No funding was received. The authors declare no competing interests.}, }
@article {pmid40362582, year = {2025}, author = {Kitaoka, Y and Uchihashi, T and Kawata, S and Nishiura, A and Yamamoto, T and Hiraoka, SI and Yokota, Y and Isomura, ET and Kogo, M and Tanaka, S and Spigelman, I and Seki, S}, title = {Role and Potential of Artificial Intelligence in Biomarker Discovery and Development of Treatment Strategies for Amyotrophic Lateral Sclerosis.}, journal = {International journal of molecular sciences}, volume = {26}, number = {9}, pages = {}, pmid = {40362582}, issn = {1422-0067}, support = {24K13154//Japan Society for the Promotion of Science/ ; 21K10091//Japan Society for the Promotion of Science/ ; 24K13113//Japan Society for the Promotion of Science/ ; 23K09351//Japan Society for the Promotion of Science/ ; 24K13112//Japan Society for the Promotion of Science/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/therapy/diagnosis/metabolism ; Humans ; *Biomarkers/metabolism ; *Artificial Intelligence ; Proteomics/methods ; Neuroimaging/methods ; Deep Learning ; }, abstract = {Neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), present significant challenges owing to their complex pathologies and a lack of curative treatments. Early detection and reliable biomarkers are critical but remain elusive. Artificial intelligence (AI) has emerged as a transformative tool, enabling advancements in biomarker discovery, diagnostic accuracy, and therapeutic development. From optimizing clinical-trial designs to leveraging omics and neuroimaging data, AI facilitates understanding of disease and treatment innovation. Notably, technologies such as AlphaFold and deep learning models have revolutionized proteomics and neuroimaging, offering unprecedented insights into ALS pathophysiology. This review highlights the intersection of AI and ALS, exploring the current state of progress and future therapeutic prospects.}, }
@article {pmid40362512, year = {2025}, author = {Chong, ZZ and Souayah, N}, title = {Targeting Gene C9orf72 Pathogenesis for Amyotrophic Lateral Sclerosis.}, journal = {International journal of molecular sciences}, volume = {26}, number = {9}, pages = {}, pmid = {40362512}, issn = {1422-0067}, mesh = {*C9orf72 Protein/genetics/metabolism ; *Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism/therapy ; Humans ; DNA Repeat Expansion ; Animals ; Mutation ; Autophagy ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal adult neurodegenerative disorder. Since no cure has been found, finding effective therapeutic targets for ALS remains a major challenge. Gene C9orf72 mutations with the formation of hexanucleotide repeat (GGGGCC) expansion (HRE) have been considered the most common genetic pathogenesis of ALS. The literature review indicates that the C9orf72 HRE causes both the gain-of-function toxicity and loss of function of C9ORF72. The formation of RNA foci and dipeptide repeats (DPRs) resulting from HRE is responsible for toxic function gain. The RNA foci can interfere with RNA processing, while DPRs directly bind to and sequester associated proteins to disrupt processes of rRNA synthesis, mRNA translation, autophagy, and nucleocytoplasmic transport. The mutations of C9orf72 and HRE result in the loss of functional C9ORF72. Under physiological conditions, C9ORF72 binds to Smith-Magenis chromosome region 8 and WD repeat-containing protein and forms a protein complex. Loss of C9ORF72 leads to autophagic impairment, increased oxidative stress, nucleocytoplasmic transport impairment, and inflammatory response. The attempted treatments for ALS have been tried by targeting C9orf72 HRE; however, the outcomes are far from satisfactory yet. More studies should be performed on pharmacological and molecular modulators against C9orf72 HRE to evaluate their efficacy by targeting HRE.}, }
@article {pmid40362304, year = {2025}, author = {Shiryaeva, O and Tolochko, C and Alekseeva, T and Dyachuk, V}, title = {Targets and Gene Therapy of ALS (Part 1).}, journal = {International journal of molecular sciences}, volume = {26}, number = {9}, pages = {}, pmid = {40362304}, issn = {1422-0067}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/genetics/pathology ; *Genetic Therapy/methods ; Animals ; Superoxide Dismutase-1/genetics ; C9orf72 Protein/genetics ; Mutation ; Gene Editing ; RNA-Binding Protein FUS/genetics ; Oligonucleotides, Antisense/therapeutic use ; CRISPR-Cas Systems ; DNA-Binding Proteins/genetics ; RNA Interference ; MicroRNAs/genetics ; Disease Models, Animal ; RNA, Small Interfering/genetics ; Motor Neurons/metabolism/pathology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the selective death of motor neurons, which causes muscle atrophy. Genetic forms of ALS are recorded only in 10% of cases. However, over the past decade, studies in genetics have substantially contributed to our understanding of the molecular mechanisms underlying ALS. The identification of key mutations such as SOD1, C9orf72, FUS, and TARDBP has led to the development of targeted therapy that is gradually being introduced into clinical trials, opening up a broad range of opportunities for correcting these mutations. In this review, we aimed to present an extensive overview of the currently known mechanisms of motor neuron degeneration associated with mutations in these genes and also the gene therapy methods for inhibiting the expression of their mutant proteins. Among these, antisense oligonucleotides, RNA interference (siRNA and miRNA), and gene-editing (CRISPR/Cas9) methods are of particular interest. Each has shown its efficacy in animal models when targeting mutant genes, whereas some of them have proven to be efficient in human clinical trials.}, }
@article {pmid40360341, year = {2025}, author = {Lin, W and Huang, C and Tan, Z and Xu, H and Wei, W and Wang, L}, title = {Cu[II]-bis(thioureido) Complex: A Potential Radiotracer for Detecting Oxidative Stress and Neuroinflammation in Neurodegenerative Diseases.}, journal = {Seminars in nuclear medicine}, volume = {55}, number = {4}, pages = {577-586}, doi = {10.1053/j.semnuclmed.2025.03.008}, pmid = {40360341}, issn = {1558-4623}, mesh = {Humans ; *Oxidative Stress ; *Neurodegenerative Diseases/diagnostic imaging/metabolism/complications ; Animals ; *Copper/chemistry ; *Neuroinflammatory Diseases/diagnostic imaging/metabolism/complications ; Positron-Emission Tomography ; Radioactive Tracers ; *Thiosemicarbazones/chemistry ; }, abstract = {Neurodegenerative diseases, characterized by progressive neuronal degeneration and associated with neuroinflammation and oxidative stress, present significant challenges in diagnosis and treatment. This review explores the potential of copper(II)-bis(thiosemicarbazone) complexes, particularly Cu-ATSM, as a dual-purpose radiopharmaceutical for imaging and therapeutic interventions. Cu-ATSM exhibits unique redox-dependent retention in pathological microenvironments, driven by mitochondrial dysfunction and hyper-reductive states, which enables the noninvasive detection of oxidative stress via positron emission tomography (PET). Preclinical studies demonstrate its efficacy in mitigating neuroinflammation by suppressing glial activation, reducing the secretion of pro-inflammatory cytokines (e.g., TNF-α, MCP-1), and increasing the expression of neuroprotective metallothionein-1 (MT1). Some Clinical research reveals elevated [64]Cu-ATSM uptake in Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS) patients, correlating with disease severity and regional oxidative stress markers. Furthermore, Cu-ATSM derivatives show promise in modulating blood-brain barrier (BBB) permeability, enhancing amyloid-β clearance, and restoring copper homeostasis in ALS models. Despite these advances, limitations such as small cohort sizes and heterogeneity in clinical studies underscore the need for larger-scale validation. Multimodal imaging integrating PET and MRI, alongside novel structural analogs targeting Aβ plaques and redox imbalances, emerges as a strategic direction for future research. Collectively, Cu-ATSM represents a transformative tool for elucidating neuropathological mechanisms and advancing therapeutic strategies in neurodegenerative disorders.}, }
@article {pmid40355001, year = {2025}, author = {Ognard, J and El Hajj, G and Verma, O and Ghozy, S and Kadirvel, R and Kallmes, DF and Brinjikji, W}, title = {Advances in endovascular brain computer interface: Systematic review and future implications.}, journal = {Journal of neuroscience methods}, volume = {420}, number = {}, pages = {110471}, doi = {10.1016/j.jneumeth.2025.110471}, pmid = {40355001}, issn = {1872-678X}, mesh = {*Brain-Computer Interfaces/trends ; Animals ; Humans ; *Endovascular Procedures/methods/trends ; *Brain/physiology ; Electrodes, Implanted ; }, abstract = {BACKGROUND: Brain-computer interfaces (BCIs) translate neural activity into real-world commands. While traditional invasive BCIs necessitate craniotomy, endovascular BCIs offer a minimally invasive alternative using the venous system for electrode placement.<br><br>NEW METHOD: This systematic review evaluates the technical feasibility, safety, and clinical outcomes of endovascular BCIs, discussing their future implications. A systematic review was conducted per PRISMA guidelines. The search spanned PubMed, Web of Science, and Scopus databases using keywords related to neural interfaces and endovascular approaches. Studies were included if they reported on endovascular BCIs in preclinical or clinical settings. Dual independent screening and extraction focused on electrode material, recording capabilities, safety parameters, and clinical efficacy.<br><br>RESULTS: From 1385 initial publications, 26 met the inclusion criteria. Seventeen studies investigated the Stentrode device. Among the 24 preclinical studies, 16 used ovine or rodent models, and 9 addressed engineering or simulation aspects. Two clinical studies reported six ALS patients successfully using an endovascular BCI for digital communication. Preclinical data established the endovascular ovine model, demonstrating stable neural recordings and vascular changes with long-term implantation. Key challenges include thrombosis risk, long-term electrode stability, and anatomical variability.<br><br>Endovascular BCI reduced invasiveness, improved safety profiles, with comparable neural recording fidelity to invasive methods, and promising preliminary clinical outcomes in severely paralyzed patients.<br><br>CONCLUSIONS: Early results are promising, but clinical data remain scarce. Further research is needed to optimize signal processing, enhance electrode biocompatibility, and refine endovascular procedures for broader clinical applications.}, }
@article {pmid40353906, year = {2025}, author = {Kleinerova, J and Querin, G and Pradat, PF and Siah, WF and Bede, P}, title = {New developments in imaging in ALS.}, journal = {Journal of neurology}, volume = {272}, number = {6}, pages = {392}, pmid = {40353906}, issn = {1432-1459}, support = {JPND-Cofund-2-2019-1/HRBI_/Health Research Board/Ireland ; HRB EIA-2017-019/HRBI_/Health Research Board/Ireland ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/physiopathology/pathology ; *Neuroimaging/methods/trends ; *Brain/diagnostic imaging ; Magnetic Resonance Imaging ; }, abstract = {Neuroimaging in ALS has contributed considerable academic insights in recent years demonstrating genotype-specific topological changes decades before phenoconversion and characterising longitudinal propagation patterns in specific phenotypes. It has elucidated the radiological underpinnings of specific clinical phenomena such as pseudobulbar affect, apathy, behavioural change, spasticity, and language deficits. Academic concepts such as sexual dimorphism, motor reserve, cognitive reserve, adaptive changes, connectivity-based propagation, pathological stages, and compensatory mechanisms have also been evaluated by imaging. The underpinnings of extra-motor manifestations such as cerebellar, sensory, extrapyramidal and cognitive symptoms have been studied by purpose-designed imaging protocols. Clustering approaches have been implemented to uncover radiologically distinct disease subtypes and machine-learning models have been piloted to accurately classify individual patients into relevant diagnostic, phenotypic, and prognostic categories. Prediction models have been developed for survival in symptomatic patients and phenoconversion in asymptomatic mutation carriers. A range of novel imaging modalities have been implemented and 7 Tesla MRI platforms are increasingly being used in ALS studies. Non-ALS MND conditions, such as PLS, SBMA, and SMA, are now also being increasingly studied by quantitative neuroimaging approaches. A unifying theme of recent imaging papers is the departure from describing focal brain changes to focusing on dynamic structural and functional connectivity alterations. Progressive cortico-cortical, cortico-basal, cortico-cerebellar, cortico-bulbar, and cortico-spinal disconnection has been consistently demonstrated by recent studies and recognised as the primary driver of clinical decline. These studies have led the reconceptualisation of ALS as a "network" or "circuitry disease".}, }
@article {pmid40350993, year = {2025}, author = {Vedeler, A and Tartaglia, GG and Pastore, A}, title = {Annexin, a Protein for All Seasons: From Calcium Dependent Membrane Metabolism to RNA Recognition.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {47}, number = {7}, pages = {e70019}, pmid = {40350993}, issn = {1521-1878}, support = {ASTRA_855923//ERC&#xa0;/ ; PNRRCN00000041andEPNRRCN3//Piano Nazionale di Ripresa e Resilienza of Italian MUR/ ; IVBM4PAP_101098989//EIC Pathfinder/ ; ARUK_PG2019B-020//ARUK&#xa0;/ ; }, mesh = {*Annexins/metabolism/chemistry ; Humans ; *Calcium/metabolism ; Animals ; *Cell Membrane/metabolism ; *RNA/metabolism ; *RNA-Binding Proteins/metabolism ; Protein Binding ; }, abstract = {Annexins are a protein family well known to bind to phospholipids in a calcium-dependent way. They are involved in several different crucial cellular processes such as cell division, calcium signaling, membrane repair, vesicle trafficking, and apoptosis. Although RNA binding for some members of the family was reported long ago, it was only recently that it was shown that a common feature of the family is also the ability to bind RNA, a discovery that has added significantly to our perception of the cellular role of these proteins. In the present review, we discuss the properties of annexins under an updated light and the current knowledge on the RNA binding properties of annexins. We then focus specifically on annexin A11, because this is a less characterized member of the family but, at the same time, a potentially important component of the mRNA transport machinery in neurons. We hope to offer to the reader a more complete picture of the annexins' binding properties and new tools to evaluate the multifaceted functions of this important protein family.}, }
@article {pmid40350723, year = {2025}, author = {Kuznetsova, DR and Kutlubaev, MA and Pervushina, EV}, title = {[Oculomotor disorders in patients with amyotrophic lateral sclerosis].}, journal = {Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova}, volume = {125}, number = {4}, pages = {7-12}, doi = {10.17116/jnevro20251250417}, pmid = {40350723}, issn = {1997-7298}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/physiopathology ; *Ocular Motility Disorders/etiology/physiopathology/diagnosis ; Saccades ; Eye Movements ; }, abstract = {Oculomotor disorders are not typical manifestations of amyotrophic lateral sclerosis (ALS). Occasionally, this disease is associated with vertical gaze paresis, presenting a distinct type as «ALS+progressive supranuclear palsy». Studies using eye-tracking methods have revealed a variety of subclinical oculomotor disorders in this disease. These disorders can manifest as changes in reflex and voluntary saccades, antisaccades, smooth tracking eye movements, and fixations. A significant association between oculomotor disorders and clinical manifestations of ALS was reported. The occurrence of oculomotor disorders indicates the involvement of broader neuroanatomical structures, including the prefrontal cortex and basal ganglia. The lack of consistency in the data from different studies and their limited number emphasize the need for further research in this area.}, }
@article {pmid40350633, year = {2025}, author = {Ishiura, H}, title = {[Genetics of Motor Neuron Diseases and Hereditary Spastic Paraplegia].}, journal = {Brain and nerve = Shinkei kenkyu no shinpo}, volume = {77}, number = {5}, pages = {481-491}, doi = {10.11477/mf.188160960770050481}, pmid = {40350633}, issn = {1881-6096}, mesh = {Humans ; *Spastic Paraplegia, Hereditary/genetics/diagnosis/therapy ; *Motor Neuron Disease/genetics/diagnosis ; }, abstract = {Motor neuron diseases encompass a range of phenotypes, including amyotrophic lateral sclerosis (ALS), primary lateral sclerosis (PLS), progressive muscular atrophy (PMA), and spinal muscular atrophy (SMA). Related conditions include spinal and bulbar muscular atrophy (SBMA) and hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P). Hereditary spastic paraplegia (HSP)-a group of disorders primarily affecting the corticospinal tract-also exhibits diverse clinical manifestations. This review summarizes the genetic basis of these diseases, along with their clinical characteristics, diagnostic approaches, and disease-specific therapies.}, }
@article {pmid40350140, year = {2025}, author = {Amin, MA and Zehravi, M and Sweilam, SH and Shatu, MM and Durgawale, TP and Qureshi, MS and Durgapal, S and Haque, MA and Vodeti, R and Panigrahy, UP and Ahmad, I and Khan, SL and Emran, TB}, title = {Neuroprotective potential of epigallocatechin gallate in Neurodegenerative Diseases: Insights into molecular mechanisms and clinical Relevance.}, journal = {Brain research}, volume = {1860}, number = {}, pages = {149693}, doi = {10.1016/j.brainres.2025.149693}, pmid = {40350140}, issn = {1872-6240}, mesh = {Humans ; *Catechin/analogs &amp; derivatives/pharmacology/therapeutic use ; *Neuroprotective Agents/pharmacology/therapeutic use ; *Neurodegenerative Diseases/drug therapy/metabolism ; Animals ; Oxidative Stress/drug effects ; Clinical Relevance ; }, abstract = {Neurodegenerative diseases (NDs) such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis pose significant challenges due to their complex pathophysiology and lack of effective treatments. Green tea, rich in the epigallocatechin gallate (EGCG) polyphenolic component, has demonstrated potential as a neuroprotective agent with numerous medicinal applications. EGCG effectively reduces tau and Aβ aggregation in ND models, promotes autophagy, and targets key signaling pathways like Nrf2-ARE, NF-κB, and MAPK. This review explores the molecular processes that underlie EGCG's neuroprotective properties, including its ability to regulate mitochondrial dysfunction, oxidative stress, neuroinflammation, and protein misfolding. Clinical research indicates that EGCG may enhance cognitive and motor abilities, potentially inhibiting disease progression despite absorption and dose optimization limitations. The substance has been proven to slow the amyloidogenic process, prevent protein aggregation, decrease amyloid cytotoxicity, inhibit fibrillogenesis, and restructure fibrils for synergistic therapeutic effects. The review highlights the potential of EGCG as a natural, multi-targeted strategy for NDs but emphasizes the need for further clinical trials to enhance its therapeutic efficacy.}, }
@article {pmid40347374, year = {2025}, author = {Varshney, V and Gabble, BC and Bishoyi, AK and Varma, P and Qahtan, SA and Kashyap, A and Panigrahi, R and Nathiya, D and Chauhan, AS}, title = {Exploring Exosome-Based Approaches for Early Diagnosis and Treatment of Neurodegenerative Diseases.}, journal = {Molecular neurobiology}, volume = {}, number = {}, pages = {}, pmid = {40347374}, issn = {1559-1182}, abstract = {Neurodegenerative diseases (NDs), like Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic Lateral Sclerosis (ALS), present an increasingly significant global health burden, primarily due to the lack of effective early diagnostic tools and treatments. Exosomes-nano-sized extracellular vesicles secreted by nearly all cell types-have emerged as promising candidates for both biomarkers and therapeutic agents in NDs. This review examines the biogenesis, molecular composition, and diverse functions of exosomes in NDs. Exosomes play a crucial role in mediating intercellular communication. They are capable of reflecting the biochemical state of their parent cells and have the ability to cross the blood-brain barrier (BBB). In doing so, they facilitate the propagation of pathological proteins, such as amyloid-beta (Aβ), tau, and alpha-synuclein (α-syn), while also enabling the targeted delivery of neuroprotective compounds. Recent advancements in exosome isolation and engineering have opened up new possibilities for diagnostic and therapeutic strategies. These range from the discovery of non-invasive biomarkers to innovative approaches in gene therapy and drug delivery systems. However, challenges related to standardization, safety, and long-term effects must be addressed before exosomes can be translated into clinical applications. This review highlights both the promising potential and the obstacles that must be overcome to leverage exosomes in the treatment of NDs and the transformation of personalized medicine.}, }
@article {pmid40344943, year = {2025}, author = {Zhou, ZD and Yi, L and Popławska-Domaszewicz, K and Chaudhuri, KR and Jankovic, J and Tan, EK}, title = {Glucagon-like peptide-1 receptor agonists in neurodegenerative diseases: Promises and challenges.}, journal = {Pharmacological research}, volume = {216}, number = {}, pages = {107770}, doi = {10.1016/j.phrs.2025.107770}, pmid = {40344943}, issn = {1096-1186}, mesh = {Humans ; *Glucagon-Like Peptide-1 Receptor Agonists ; Animals ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Neuroprotective Agents/therapeutic use ; *Hypoglycemic Agents/therapeutic use ; Glucagon-Like Peptide-1 Receptor/metabolism ; }, abstract = {Glucagon-like peptide-1 (GLP-1) receptor agonists (GRA) belong to a class of compounds that reduce blood glucose and energy intake by simulating actions of endogenous incretin hormone GLP-1 after it is released by the gut following food consumption. They are used to treat type 2 diabetes mellitus (T2DM) and obesity and have systemic effects on various organs, including the brain, liver, pancreas, heart, and the gut. Patients with T2DM have a higher risk of developing neurodegenerative diseases (NDs), including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD), accompanied by more severe motor deficits and faster disease progression, suggesting dysregulation of insulin signaling in these diseases. Experimental studies have shown that GRA have protective effects to modulate neuroinflammation, oxidative stress, mitochondrial and autophagic functions, and protein misfolding. Hence the compounds have generated enormous interest as novel therapeutic agents against NDs. To date, clinical trials have shown that three GRA, exenatide, liraglutide and lixisenatide can improve motor deficits as an add-on therapy in PD patients and liraglutide can improve cognitive function in AD patients. The neuroprotective effects of these and other GRA, such as PT320 (a sustained-released exenatide) and semaglutide, are still under investigation. The dual GLP-1/gastric inhibitory polypeptide (GIP) receptor agonists have been demonstrated to have beneficial effects in AD and PD mice models. Overall, GRA are highly promising novel drugs, but future clinical studies should identify which subsets of patients should be targeted as potential candidates for their symptomatic and/or neuroprotective benefits, investigate whether combinations with other classes of drugs can further augment their efficacy, and evaluate their long-term disease-modifying and adverse effects.}, }
@article {pmid40340943, year = {2025}, author = {Kellett, EA and Bademosi, AT and Walker, AK}, title = {Molecular mechanisms and consequences of TDP-43 phosphorylation in neurodegeneration.}, journal = {Molecular neurodegeneration}, volume = {20}, number = {1}, pages = {53}, pmid = {40340943}, issn = {1750-1326}, mesh = {Humans ; *DNA-Binding Proteins/metabolism ; Phosphorylation/physiology ; Animals ; *Neurodegenerative Diseases/metabolism ; Amyotrophic Lateral Sclerosis/metabolism ; }, abstract = {Increased phosphorylation of TDP-43 is a pathological hallmark of several neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, the regulation and roles of TDP-43 phosphorylation remain incompletely understood. A variety of techniques have been utilized to understand TDP-43 phosphorylation, including kinase/phosphatase manipulation, phosphomimic variants, and genetic, physical, or chemical inducement in a variety of cell cultures and animal models, and via analyses of post-mortem human tissues. These studies have produced conflicting results: suggesting incongruously that TDP-43 phosphorylation may either drive disease progression or serve a neuroprotective role. In this review, we explore the roles of regulators of TDP-43 phosphorylation including the putative TDP-43 kinases c-Abl, CDC7, CK1, CK2, IKKβ, p38α/MAPK14, MEK1, TTBK1, and TTBK2, and TDP-43 phosphatases PP1, PP2A, and PP2B, in disease. Building on recent studies, we also examine the consequences of TDP-43 phosphorylation on TDP-43 pathology, especially related to TDP-43 mislocalisation, liquid-liquid phase separation, aggregation, and neurotoxicity. By comparing conflicting findings from various techniques and models, this review highlights both the discrepancies and unresolved aspects in the understanding of TDP-43 phosphorylation. We propose that the role of TDP-43 phosphorylation is site and context dependent, and includes regulation of liquid-liquid phase separation, subcellular mislocalisation, and degradation. We further suggest that greater consideration of the normal functions of the regulators of TDP-43 phosphorylation that may be perturbed in disease is warranted. This synthesis aims to build towards a comprehensive understanding of the complex role of TDP-43 phosphorylation in the pathogenesis of neurodegeneration.}, }
@article {pmid40340620, year = {2025}, author = {Shen, D and Liu, A and Yang, X and Liu, Q and Liu, M and Cui, L}, title = {Exploring oculomotor challenges in amyotrophic lateral sclerosis: a comprehensive review.}, journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration}, volume = {26}, number = {5-6}, pages = {478-484}, doi = {10.1080/21678421.2025.2501690}, pmid = {40340620}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/complications/diagnosis ; *Ocular Motility Disorders/etiology/physiopathology/diagnosis ; *Eye Movements/physiology ; Disease Progression ; *Cognitive Dysfunction/physiopathology/etiology ; }, abstract = {Traditionally understood as a motor neuron disease, amyotrophic lateral sclerosis (ALS) is now recognized to involve broader neurodegenerative processes, including the oculomotor system. This narrative review summarizes current evidence on oculomotor dysfunction in ALS, with a focus on its relationship to disease-related motor and cognitive impairments. Specifically, the review examines key eye-tracking (ET) metrics, including saccades, smooth pursuit, and fixation, highlighting their potential to reflect both motor and extramotor degeneration. Notably, patients with bulbar-onset ALS exhibit more pronounced oculomotor impairments. By synthesizing findings on the connection between oculomotor dysfunction and cognitive decline, this review underscores the potential of ET as a noninvasive tool for assessing ALS progression. Oculomotor metrics, as part of a broader understanding of ALS's impact on multiple neural networks, may offer valuable insights to refine patient assessment and care strategies, particularly in advanced disease stages.}, }
@article {pmid40338639, year = {2025}, author = {Barchiesi, MA and Calabrese, A and Costa, R and Di Pillo, F and D'Uffizi, A and Tiburzi, L and Zahid, E}, title = {Continuous glucose monitoring in type 2 diabetes: a systematic review of barriers and opportunities for care improvement.}, journal = {International journal for quality in health care : journal of the International Society for Quality in Health Care}, volume = {37}, number = {3}, pages = {}, pmid = {40338639}, issn = {1464-3677}, mesh = {Humans ; *Diabetes Mellitus, Type 2/blood ; *Blood Glucose Self-Monitoring/methods/instrumentation ; Blood Glucose/analysis ; Quality Improvement ; Telemedicine ; Continuous Glucose Monitoring ; }, abstract = {BACKGROUND: Diabetes mellitus, particularly type 2 diabetes (T2DM), is a chronic disease associated with serious complications, such as heart disease, kidney failure, and blindness. Continuous glucose monitoring (CGM) systems have emerged as a more effective alternative to traditional fingerstick testing, offering patients greater control over their condition. Despite their potential benefits, several barriers to CGM sensor use persist, limiting their widespread adoption among patients with T2DM. This review explores the barriers to CGM sensor use, particularly from the patient's perspective.<br><br>METHODS: A systematic literature review is conducted following PRISMA guidelines. The search focuses on studies published between January 2018 and June 2024 and is performed in two primary databases, PubMed and Scopus, selected for their relevance to T2DM research. Studies are included if they explore challenges and barriers to CGM adoption, report patient perspectives, or provide insights into the usability and accessibility of technology. The data are analyzed using deductive content analysis, applying Wilson et al.'s thematic categories as a predefined framework to systematically classify and interpret barriers to CGM adoption. This approach ensures methodological consistency and alignment with existing research on eHealth adoption challenges.<br><br>RESULTS: The review identifies several key barriers to CGM sensor use despite the benefits, such as improved glucose control and reduced hypoglycemic events. Major challenges include the high cost of sensors, wearability issues, discomfort from adhesive materials, and concerns about the visibility of the sensors. Additionally, patients report difficulties in interpreting the large volumes of data generated by CGM systems, as well as discomfort or fear related to sensor insertion. Lack of technological support, low health literacy, and insufficient social support are also identified as factors contributing to non-adoption.<br><br>CONCLUSIONS: Policymakers and healthcare providers are encouraged to address these barriers by developing patient-centered strategies that support the adoption of CGM sensors. Successfully overcoming these challenges can further support integrating CGM sensors with the Chronic Care Model and Automated Insulin Delivery systems. As an implication, this integration has the potential to enhance glycemic control and improve patient quality of life in the management of T2DM. Furthermore, addressing these barriers may drive advancements in sensor design, improve accessibility, and minimize the environmental impact of CGM sensor use.}, }
@article {pmid40333317, year = {2025}, author = {Simula, ER and Jasemi, S and Cossu, D and Fais, M and Cossu, I and Chessa, V and Canu, M and Sechi, LA}, title = {Human Endogenous Retroviruses as Novel Therapeutic Targets in Neurodegenerative Disorders.}, journal = {Vaccines}, volume = {13}, number = {4}, pages = {}, pmid = {40333317}, issn = {2076-393X}, support = {PNRR-MCNT1-2023-12376993//Ministero della Salute/ ; 2022BP837R//MUR, PRIN 2022/ ; 22//Regione Autonoma Sardegna grant: legge regionale 12 22 December 2022/ ; e.INS Ecosystem of Innovation for Next Generation Sardinia spoke n 5//European Union/ ; }, abstract = {Human Endogenous Retroviruses comprise approximately 8% of the human genome, serving as fragments of ancient retroviral infections. Although they are generally maintained in a silenced state by robust epigenetic mechanisms, specific HERV groups, particularly HERV-W and HERV-K, can become derepressed under specific pathological conditions, thereby contributing to the initiation and progression of neuroinflammatory and neurodegenerative processes. Preclinical studies and clinical trials, such as those investigating monoclonal antibodies, indicate that directly targeting these elements may offer a novel therapeutic strategy. In this review, we provide an overview of HERVs' biology, examine their role in neurodegenerative diseases such as amyotrophic lateral sclerosis, multiple sclerosis, Alzheimer's disease, and Parkinson's disease, and explore their therapeutic prospects, highlighting both the challenges and the potential future research directions needed to translate these approaches into clinical interventions.}, }
@article {pmid40332510, year = {2025}, author = {Stacchiotti, C and Mazzella di Regnella, S and Cinotti, M and Spalloni, A and Volpe, E}, title = {Neuroinflammation and Amyotrophic Lateral Sclerosis: Recent Advances in Anti-Inflammatory Cytokines as Therapeutic Strategies.}, journal = {International journal of molecular sciences}, volume = {26}, number = {8}, pages = {}, pmid = {40332510}, issn = {1422-0067}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/metabolism/pathology/immunology ; *Cytokines/therapeutic use/metabolism ; Animals ; *Neuroinflammatory Diseases/drug therapy/metabolism/pathology ; *Anti-Inflammatory Agents/therapeutic use/pharmacology ; Blood-Brain Barrier/metabolism ; Inflammation ; }, abstract = {Neuroinflammation is an inflammatory response occurring within the central nervous system (CNS). The process is marked by the production of pro-inflammatory cytokines, chemokines, small-molecule messengers, and reactive oxygen species. Microglia and astrocytes are primarily involved in this process, while endothelial cells and infiltrating blood cells contribute to neuroinflammation when the blood-brain barrier (BBB) is damaged. Neuroinflammation is increasingly recognized as a pathological hallmark of several neurological diseases, including amyotrophic lateral sclerosis (ALS), and is closely linked to neurodegeneration, another key feature of ALS. In fact, neurodegeneration is a pathological trigger for inflammation, and neuroinflammation, in turn, contributes to motor neuron (MN) degeneration through the induction of synaptic dysfunction, neuronal death, and inhibition of neurogenesis. Importantly, resolution of acute inflammation is crucial for avoiding chronic inflammation and tissue destruction. Inflammatory processes are mediated by soluble factors known as cytokines, which are involved in both promoting and inhibiting inflammation. Cytokines with anti-inflammatory properties may exert protective roles in neuroinflammatory diseases, including ALS. In particular, interleukin (IL)-10, transforming growth factor (TGF)-β, IL-4, IL-13, and IL-9 have been shown to exert an anti-inflammatory role in the CNS. Other recently emerging immune regulatory cytokines in the CNS include IL-35, IL-25, IL-37, and IL-27. This review describes the current understanding of neuroinflammation in ALS and highlights recent advances in the role of anti-inflammatory cytokines within CNS with a particular focus on their potential therapeutic applications in ALS. Furthermore, we discuss current therapeutic strategies aimed at enhancing the anti-inflammatory response to modulate neuroinflammation in this disease.}, }
@article {pmid40332015, year = {2025}, author = {Duță, C and Dogaru, CB and Muscurel, C and Stoian, I}, title = {Nanozymes: Innovative Therapeutics in the Battle Against Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {26}, number = {8}, pages = {}, pmid = {40332015}, issn = {1422-0067}, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/metabolism ; Oxidative Stress/drug effects ; Animals ; Antioxidants/therapeutic use/chemistry/pharmacology ; *Nanostructures/chemistry/therapeutic use ; Reactive Oxygen Species/metabolism ; }, abstract = {Neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD), represent a significant challenge to global health due to their progressive nature and the absence of curative treatments. These disorders are characterized by oxidative stress, protein misfolding, and neuroinflammation, which collectively contribute to neuronal damage and death. Recent advancements in nanotechnology have introduced nanozymes-engineered nanomaterials that mimic enzyme-like activities-as promising therapeutic agents. This review explores the multifaceted roles of nanozymes in combating oxidative stress and inflammation in neurodegenerative conditions. By harnessing their potent antioxidant properties, nanozymes can effectively scavenge reactive oxygen species (ROS) and restore redox balance, thereby protecting neuronal function. Their ability to modify surface properties enhances targeted delivery and biocompatibility, making them suitable for various biomedical applications. In this review, we highlight recent findings on the design, functionality, and therapeutic potential of nanozymes, emphasizing their dual role in addressing oxidative stress and pathological features such as protein aggregation. This synthesis of current research underscores the innovative potential of nanozymes as a proactive therapeutic strategy to halt disease progression and improve patient outcomes in neurodegenerative disorders.}, }
@article {pmid40328798, year = {2025}, author = {Wu, X and Yang, Z and Zou, J and Gao, H and Shao, Z and Li, C and Lei, P}, title = {Protein kinases in neurodegenerative diseases: current understandings and implications for drug discovery.}, journal = {Signal transduction and targeted therapy}, volume = {10}, number = {1}, pages = {146}, pmid = {40328798}, issn = {2059-3635}, support = {32070961//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/enzymology/genetics/pathology ; *Drug Discovery ; *Protein Kinases/genetics/metabolism ; *Protein Kinase Inhibitors/therapeutic use ; Signal Transduction/drug effects/genetics ; Phosphorylation ; Animals ; }, abstract = {Neurodegenerative diseases (e.g., Alzheimer's, Parkinson's, Huntington's disease, and Amyotrophic Lateral Sclerosis) are major health threats for the aging population and their prevalences continue to rise with the increasing of life expectancy. Although progress has been made, there is still a lack of effective cures to date, and an in-depth understanding of the molecular and cellular mechanisms of these neurodegenerative diseases is imperative for drug development. Protein phosphorylation, regulated by protein kinases and protein phosphatases, participates in most cellular events, whereas aberrant phosphorylation manifests as a main cause of diseases. As evidenced by pharmacological and pathological studies, protein kinases are proven to be promising therapeutic targets for various diseases, such as cancers, central nervous system disorders, and cardiovascular diseases. The mechanisms of protein phosphatases in pathophysiology have been extensively reviewed, but a systematic summary of the role of protein kinases in the nervous system is lacking. Here, we focus on the involvement of protein kinases in neurodegenerative diseases, by summarizing the current knowledge on the major kinases and related regulatory signal transduction pathways implicated in diseases. We further discuss the role and complexity of kinase-kinase networks in the pathogenesis of neurodegenerative diseases, illustrate the advances of clinical applications of protein kinase inhibitors or novel kinase-targeted therapeutic strategies (such as antisense oligonucleotides and gene therapy) for effective prevention and early intervention.}, }
@article {pmid40328546, year = {2025}, author = {Kleinerova, J and Tan, EL and Delaney, S and Smyth, M and Bede, P}, title = {Advances and research priorities in the respiratory management of ALS: Historical perspectives and new technologies.}, journal = {Revue neurologique}, volume = {181}, number = {6}, pages = {525-534}, doi = {10.1016/j.neurol.2025.04.008}, pmid = {40328546}, issn = {0035-3787}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/complications/history ; *Biomedical Research/trends ; History, 19th Century ; History, 20th Century ; History, 21st Century ; Noninvasive Ventilation/methods ; Respiratory Insufficiency/therapy/etiology ; }, abstract = {Respiratory involvement has been identified as a cardinal feature of amyotrophic lateral sclerosis (ALS) since its earliest descriptions in the 19th century. Since these initial reports, considerable research has been undertaken to clarify the pathophysiology and progression rates associated with respiratory compromise and effective management strategies have been developed. Clinical trials routinely incorporate respiratory measures as study end points, non-invasive ventilation is now widely used in the home setting, cough-assist techniques are commonly used, advanced neurophysiology techniques and wearable technologies have been integrated into respiratory monitoring protocols, and palliative guidelines have been developed to effectively manage respiratory distress. Despite the widespread implementation of these interventions, epidemiology studies are inconsistent and some studies suggest that survival in ALS has not improved significantly with the introduction of these measures. The outcomes of diaphragmatic pacing trials have been disappointing, advanced neurophysiology techniques are not routinely utilised, spinal and brainstem imaging are not commonly undertaken and significant geographical differences exist in proceeding to tracheostomy. The worldwide COVID pandemic has given impetus for remote monitoring, connected devices, video-consultations, and timely vaccinations in ALS; lessons that are invaluable long after the pandemic. Respiratory monitoring and management in ALS is a swiftly evolving facet of ALS care with considerable quality of life benefits.}, }
@article {pmid40325332, year = {2025}, author = {Liu, S and Feng, A and Li, Z}, title = {Neuron-Derived Extracellular Vesicles: Emerging Regulators in Central Nervous System Disease Progression.}, journal = {Molecular neurobiology}, volume = {}, number = {}, pages = {}, pmid = {40325332}, issn = {1559-1182}, abstract = {The diagnosis and exploration of central nervous system (CNS) diseases remain challenging due to the blood-brain barrier (BBB), complex signaling pathways, and heterogeneous clinical manifestations. Neurons, as the core functional units of the CNS, play a pivotal role in CNS disease progression. Extracellular vesicles (EVs), capable of crossing the BBB, facilitate intercellular and cell-extracellular matrix (ECM) communication, making neuron-derived extracellular vesicles (NDEVs) a focal point of research. Recent studies reveal that NDEVs, carrying various bioactive substances, can exert either pathogenic or protective effects in numerous CNS diseases. Additionally, NDEVs show significant potential as biomarkers for CNS diseases. This review summarizes the emerging roles of NDEVs in CNS diseases, including Alzheimer's disease, depression, traumatic brain injury, schizophrenia, ischemic stroke, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. It aims to provide a novel perspective on developing therapeutic and diagnostic strategies for CNS diseases through the study of NDEVs.}, }
@article {pmid40320859, year = {2025}, author = {Watanabe, S and Yamanaka, K}, title = {Mitochondria and Endoplasmic Reticulum Contact Site as a Regulator of Proteostatic Stress Responses in Neurodegenerative Diseases.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {47}, number = {7}, pages = {e70016}, pmid = {40320859}, issn = {1521-1878}, support = {23K06826//Ministry of Education, Culture, Sports, Science and Technology, Japan/Japan Society for the Promotion of Science/ ; 19KK0214//Ministry of Education, Culture, Sports, Science and Technology, Japan/Japan Society for the Promotion of Science/ ; 22H00467//Ministry of Education, Culture, Sports, Science and Technology, Japan/Japan Society for the Promotion of Science/ ; JP22ek0109426//Japan Agency for Medical Research and Development/ ; JP24wm0425014//Japan Agency for Medical Research and Development/ ; JP24wm0625301//Japan Agency for Medical Research and Development/ ; //Takeda Science Foundation/ ; //Mochida Memorial Foundation for Medical and Pharmaceutical Research/ ; //Kowa Life Science Foundation/ ; //Novartis Foundation/ ; }, mesh = {Humans ; *Mitochondria/metabolism ; *Endoplasmic Reticulum/metabolism ; *Neurodegenerative Diseases/metabolism/pathology ; Animals ; *Proteostasis ; Calcium/metabolism ; Autophagy ; Amyotrophic Lateral Sclerosis/metabolism ; Mitochondrial Membranes/metabolism ; Alzheimer Disease/metabolism ; }, abstract = {Recent evidence indicates that the mitochondria-endoplasmic reticulum (ER) contact site is a novel microdomain essential for cellular homeostasis. Various proteins are accumulated at the mitochondria-associated membrane (MAM), an ER subcomponent closely associated with the mitochondria, contributing to Ca[2+] transfer to the mitochondria, lipid synthesis, mitochondrial fission/fusion, and autophagy. These functions are disrupted in the diseases, particularly in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Alzheimer's disease. In this review, we summarize the disruption of protein homeostasis in various neurodegenerative diseases, present recent works on the mechanisms of MAM aberration, including ours mainly focused on ALS, and then discuss challenges and prospects for future MAM-targeted therapies in neurodegenerative diseases.}, }
@article {pmid40320052, year = {2025}, author = {Nadeem, A and Sharma, P and Gupta, P and Sandeep, P and Sharma, B and Sharma, N and Yadav, M and Dhiman, N}, title = {Exploring Neuregulin3: From physiology to pathology, a novel target for rational drug design.}, journal = {Biochemical pharmacology}, volume = {238}, number = {}, pages = {116964}, doi = {10.1016/j.bcp.2025.116964}, pmid = {40320052}, issn = {1873-2968}, mesh = {Humans ; Animals ; *Drug Design ; *Neuregulins/metabolism/genetics ; Neoplasms/drug therapy/metabolism/pathology ; *Drug Delivery Systems/methods/trends ; }, abstract = {Neuregulin 3 (NRG3) is an epidermal growth factor related protein that binds to and stimulates the Erb-B2 receptor tyrosine kinase 4 (ErbB4). NRG3 is a multifunctional protein with fifteen alternative splicing isoforms categorized into four classes. Numerous physiological processes, such as the formation of cortical plate, cortical patterning, synaptic development, neuronal proliferation, regulation of neurotransmission, control of impulsive behavior, mammary gland morphogenesis, spermatogonial proliferation and cardiac homeostasis are influenced by NRG3. Besides its physiological roles, NRG3 also modulates anxiogenic phenotypes. It is a susceptibility gene for schizophrenia, autism spectrum disorder and Hirschsprung's Disease. Furthermore, anxiety during nicotine withdrawal is dependent on NRG3-ErbB4 signaling. Research on a range of solid carcinomas, such as brain tumors, ovarian cancer, gastrointestinal cancer and breast cancer, has demonstrated NRG3 gene as a therapeutic target. NRG3 also has potential involvement in epilepsy, angular limb malformation in Rambouillet rams, amyotrophic lateral sclerosis and polythelia. Nevertheless, little is known about the molecular characteristics, activities specific to isoforms, and molecular mechanisms of NRG3. Examining its potential involvement in a range of physiological processes and pathological states is a unique area that needs in-depth study and may offer new mechanistic insights and comprehension of these elements. Thus, the purpose of this review is to shed light on the utility of NRG3 as a potential target in various health and disease conditions.}, }
@article {pmid40319325, year = {2025}, author = {Mehdizadeh, S and Mamaghani, M and Hassanikia, S and Pilehvar, Y and Ertas, YN}, title = {Exosome-powered neuropharmaceutics: unlocking the blood-brain barrier for next-gen therapies.}, journal = {Journal of nanobiotechnology}, volume = {23}, number = {1}, pages = {329}, pmid = {40319325}, issn = {1477-3155}, mesh = {*Exosomes/metabolism/chemistry ; *Blood-Brain Barrier/metabolism/drug effects ; Humans ; Animals ; *Drug Delivery Systems/methods ; *Neuropharmacology/methods ; Drug Carriers/chemistry ; }, abstract = {BACKGROUND: The blood-brain barrier (BBB) presents a formidable challenge in neuropharmacology, limiting the delivery of therapeutic agents to the brain. Exosomes, nature's nanocarriers, have emerged as a promising solution due to their biocompatibility, low immunogenicity, and innate ability to traverse the BBB. A thorough examination of BBB anatomy and physiology reveals the complexities of neurological drug delivery and underscores the limitations of conventional methods.<br><br>MAIN BODY: This review explores the potential of exosome-powered neuropharmaceutics, highlighting their structural and functional properties, biogenesis, and mechanisms of release. Their intrinsic advantages in drug delivery, including enhanced stability and efficient cellular uptake, are discussed in detail. Exosomes naturally overcome BBB barriers through specific translocation mechanisms, making them a compelling vehicle for targeted brain therapies. Advances in engineering strategies, such as genetic and biochemical modifications, drug loading techniques, and specificity enhancement, further bolster their therapeutic potential. Exosome-based approaches hold immense promise for treating a spectrum of neurological disorders, including Alzheimer's, Parkinson's, amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), brain tumors, stroke, and psychiatric conditions.<br><br>CONCLUSION: By leveraging their innate properties and engineering innovations, exosomes offer a versatile platform for precision neurotherapeutics. Despite their promise, challenges remain in clinical translation, including large-scale production, standardization, and regulatory considerations. Future research directions in exosome nanobiotechnology aim to refine these therapeutic strategies, unlocking new avenues for treating neurological diseases. This review underscores the transformative impact of exosome-based drug delivery, paving the way for next-generation therapies that can effectively penetrate the BBB and revolutionize neuropharmacology.}, }
@article {pmid40316871, year = {2025}, author = {Veit, W and Browning, H and Garcia-Pelegrin, E and Davies, JR and DuBois, JG and Clayton, NS}, title = {Dimensions of corvid consciousness.}, journal = {Animal cognition}, volume = {28}, number = {1}, pages = {35}, pmid = {40316871}, issn = {1435-9456}, mesh = {*Consciousness ; Animals ; Animal Welfare ; *Crows ; }, abstract = {Corvids have long been a target of public fascination and of scientific attention, particularly in the study of animal minds. Using Birch et al.'s (2020) 5-dimensional framework for animal consciousness we ask what it is like to be a corvid and propose a speculative but empirically informed answer. We go on to suggest future directions for research on corvid consciousness and how it can inform ethical treatment and animal welfare legislation.}, }
@article {pmid40314791, year = {2025}, author = {Iuzzolino, VV and Scaravilli, A and Carignani, G and Senerchia, G and Pontillo, G and Dubbioso, R and Cocozza, S}, title = {Mapping motor and extra-motor gray and white matter changes in ALS: a comprehensive review of MRI insights.}, journal = {Neuroradiology}, volume = {67}, number = {7}, pages = {1683-1696}, pmid = {40314791}, issn = {1432-1920}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/pathology ; *White Matter/diagnostic imaging/pathology ; *Magnetic Resonance Imaging/methods ; *Gray Matter/diagnostic imaging/pathology ; Disease Progression ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease primarily affecting motor neurons, yet with substantial clinical variability. Furthermore, beyond motor symptoms, ALS patients also show non-motor features, reflecting its classification as a multi-system disorder. The identification of reliable biomarkers is a critical challenge for improving diagnosis, tracking disease progression, and predicting patient outcomes. This review explores macro- and microstructural alterations in ALS, focusing on gray matter (GM) and white matter (WM) as observed through Magnetic Resonance Imaging (MRI). This approach synthesizes not only the expected involvement of motor areas but also highlights emerging evidence that these changes extend to extra-motor areas, such as the frontal and temporal lobes, underscoring the complex pathophysiology of ALS. The review emphasizes the potential of MRI as a non-invasive tool to provide new biomarkers by assessing both GM and WM integrity, a key advancement in ALS research. Additionally, it addresses existing discrepancies in findings and stresses the need for standardized imaging protocols. It also highlights the role of multi-modal MRI approaches in deepening our understanding of ALS pathology, emphasizing the importance of combining structural and diffusion MRI techniques to offer more comprehensive insights into ALS progression, ultimately advancing the potential for personalized treatment strategies and improving patient outcomes.}, }
@article {pmid40309800, year = {2025}, author = {Manai, AL and Caria, P and Noli, B and Contini, C and Manconi, B and Etzi, F and Cocco, C}, title = {VGF and Its Derived Peptides in Amyotrophic Lateral Sclerosis.}, journal = {Brain sciences}, volume = {15}, number = {4}, pages = {}, pmid = {40309800}, issn = {2076-3425}, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by a progressive degeneration in the neurons of the frontal cortex, spinal cord, and brainstem, altering the correct release of neurotransmitters. The disease affects every muscle in the body and could cause death three to five years after symptoms first occur. There is currently no efficient treatment to stop the disease's progression. The lack of identification of potential therapeutic strategies is a consequence of the delayed diagnosis due to the absence of accurate ALS early biomarkers. Indeed, neurotransmitters altered in ALS are not measurable in body fluids at quantities that allow for testing, making their use as diagnostic tools a challenge. Contrarily, neuroproteins and neuropeptides are chemical messengers produced and released by neurons, and most of them have the potential to enter bodily fluids. To find out new possible ALS biomarkers, the research of neuropeptides and proteins is intensified using mass spectrometry and biochemical-based assays. Neuropeptides derived from the proVGF precursor protein act as signaling molecules within neurons. ProVGF and its derived peptides are expressed in the nervous and endocrine systems but are also widely distributed in body fluids such as blood, urine, and cerebrospinal fluid, making them viable options as disease biomarkers. To highlight the proVGF and its derived peptides' major roles as ALS diagnostic biomarkers, this review provides an overview of the VGF peptide alterations in spinal cord and body fluids and outlines the limitations of the reported investigations.}, }
@article {pmid40309789, year = {2025}, author = {Khan, S and Kallis, L and Mee, H and El Hadwe, S and Barone, D and Hutchinson, P and Kolias, A}, title = {Invasive Brain-Computer Interface for Communication: A Scoping Review.}, journal = {Brain sciences}, volume = {15}, number = {4}, pages = {}, pmid = {40309789}, issn = {2076-3425}, abstract = {BACKGROUND: The rapid expansion of the brain-computer interface for patients with neurological deficits has garnered significant interest, and for patients, it provides an additional route where conventional rehabilitation has its limits. This has particularly been the case for patients who lose the ability to communicate. Circumventing neural injuries by recording from the intact cortex and subcortex has the potential to allow patients to communicate and restore self-expression. Discoveries over the last 10-15 years have been possible through advancements in technology, neuroscience, and computing. By examining studies involving intracranial brain-computer interfaces that aim to restore communication, we aimed to explore the advances made and explore where the technology is heading.<br><br>METHODS: For this scoping review, we systematically searched PubMed and OVID Embase. After processing the articles, the search yielded 41 articles that we included in this review.<br><br>RESULTS: The articles predominantly assessed patients who had either suffered from amyotrophic lateral sclerosis, cervical cord injury, or brainstem stroke, resulting in tetraplegia and, in some cases, difficulty speaking. Of the intracranial implants, ten had ALS, six had brainstem stroke, and thirteen had a spinal cord injury. Stereoelectroencephalography was also used, but the results, whilst promising, are still in their infancy. Studies involving patients who were moving cursors on a screen could improve the speed of movement by optimising the interface and utilising better decoding methods. In recent years, intracortical devices have been successfully used for accurate speech-to-text and speech-to-audio decoding in patients who are unable to speak.<br><br>CONCLUSIONS: Here, we summarise the progress made by BCIs used for communication. Speech decoding directly from the cortex can provide a novel therapeutic method to restore full, embodied communication to patients suffering from tetraplegia who otherwise cannot communicate.}, }
@article {pmid40309514, year = {2025}, author = {Li, V and Huang, Y}, title = {Oligonucleotide therapeutics for neurodegenerative diseases.}, journal = {NeuroImmune pharmacology and therapeutics}, volume = {4}, number = {1}, pages = {1-11}, pmid = {40309514}, issn = {2750-6665}, support = {R44 DC018463/DC/NIDCD NIH HHS/United States ; R44 DC018762/DC/NIDCD NIH HHS/United States ; }, abstract = {Recently there has been a surge in interest involving the application of oligonucleotides, including small interfering RNA (siRNA) and antisense oligonucleotides (ASOs), for the treatment of chronic diseases that have few available therapeutic options. This emerging class of drugs primarily operates by selectively suppressing target genes through antisense and/or RNA interference mechanisms. While various commercial medications exist for delivering oligonucleotides to the hepatic tissue, achieving effective delivery to extra hepatic tissues remains a formidable challenge. Here, we review recent advances in oligonucleotide technologies, including nanoparticle delivery, local administration, and 2'-O-hexadecyl (C16)-conjugation that work to extend the applicability of siRNAs and ASOs to nerve tissues. We discuss critical factors pivotal for the successful clinical translations of these modified or engineered oligonucleotides in the context of treating neurodegenerative diseases such as Alzheimer's disease and amyotrophic lateral sclerosis.}, }
@article {pmid40305176, year = {2025}, author = {Erichsen, PA and Henriksen, EE and Nielsen, JE and Ejlerskov, P and Simonsen, AH and Toft, A}, title = {Immunological Fluid Biomarkers in Frontotemporal Dementia: A Systematic Review.}, journal = {Biomolecules}, volume = {15}, number = {4}, pages = {}, pmid = {40305176}, issn = {2218-273X}, support = {0084960//Novo Nordisk Foundation/ ; R450-2023-989//Lundbeck Foundation/ ; }, mesh = {Humans ; *Frontotemporal Dementia/immunology/blood/cerebrospinal fluid ; *Biomarkers/cerebrospinal fluid/blood ; Alzheimer Disease/immunology/blood/cerebrospinal fluid ; Amyotrophic Lateral Sclerosis/blood/immunology/cerebrospinal fluid ; Chitinase-3-Like Protein 1/cerebrospinal fluid/blood ; Glial Fibrillary Acidic Protein/cerebrospinal fluid/blood ; Chemokine CCL2/cerebrospinal fluid/blood ; }, abstract = {Dysregulated immune activation plays a key role in the pathogenesis of neurodegenerative diseases, including frontotemporal dementia (FTD). This study reviews immunological biomarkers associated with FTD and its subtypes. A systematic search of PubMed and Web of Science was conducted for studies published before 1 January 2025, focusing on immunological biomarkers in CSF or blood from FTD patients with comparisons to healthy or neurological controls. A total of 124 studies were included, involving 6686 FTD patients and 202 immune biomarkers. Key findings include elevated levels of GFAP and MCP1/CCL2 in both CSF and blood and consistently increased CHIT1 and YKL-40 in CSF. Complement proteins from the classical activation pathway emerged as promising targets. Distinct immune markers were found to differentiate FTD from Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS), with GFAP, SPARC, and SPP1 varying between FTD and AD and IL-15, HERV-K, NOD2, and CHIT1 differing between FTD and ALS. A few markers, such as Galectin-3 and PGRN, distinguished FTD subtypes. Enrichment analysis highlighted IL-10 signaling and immune cell chemotaxis as potential pathways for further exploration. This study provides an overview of immunological biomarkers in FTD, emphasizing those most relevant for future research on immune dysregulation in FTD pathogenesis.}, }
@article {pmid40302786, year = {2025}, author = {Vijayaraghavan, M and Murali, SP and Thakur, G and Li, XJ}, title = {Role of glial cells in motor neuron degeneration in hereditary spastic paraplegias.}, journal = {Frontiers in cellular neuroscience}, volume = {19}, number = {}, pages = {1553658}, pmid = {40302786}, issn = {1662-5102}, support = {R01 NS118066/NS/NINDS NIH HHS/United States ; }, abstract = {This review provides a comprehensive overview of hereditary spastic paraplegias (HSPs) and summarizes the recent progress on the role of glial cells in the pathogenesis of HSPs. HSPs are a heterogeneous group of neurogenetic diseases characterized by axonal degeneration of cortical motor neurons, leading to muscle weakness and atrophy. Though the contribution of glial cells, especially astrocytes, to the progression of other motor neuron diseases like amyotrophic lateral sclerosis (ALS) is well documented, the role of glial cells and the interaction between neurons and astrocytes in HSP remained unknown until recently. Using human pluripotent stem cell-based models of HSPs, a study reported impaired lipid metabolisms and reduced size of lipid droplets in HSP astrocytes. Moreover, targeting lipid dysfunction in astrocytes rescues axonal degeneration of HSP cortical neurons, demonstrating a non-cell-autonomous mechanism in axonal deficits of HSP neurons. In addition to astrocytes, recent studies revealed dysfunctions in HSP patient pluripotent stem cell-derived microglial cells. Increased microgliosis and pro-inflammation factors were also observed in HSP patients' samples, pointing to an exciting role of innate immunity and microglia in HSP. Building upon these recent studies, further investigation of the detailed molecular mechanism and the interplay between glial cell dysfunction and neuronal degeneration in HSP by combining human stem cell models, animal models, and patient samples will open avenues for identifying new therapeutic targets and strategies for HSP.}, }
@article {pmid40301152, year = {2025}, author = {Armas, JMB and Taoro-González, L and Fisher, EMC and Acevedo-Arozena, A}, title = {Challenges of modelling TDP-43 pathology in mice.}, journal = {Mammalian genome : official journal of the International Mammalian Genome Society}, volume = {36}, number = {2}, pages = {465-481}, pmid = {40301152}, issn = {1432-1777}, mesh = {Animals ; *DNA-Binding Proteins/genetics/metabolism ; Mice ; *Disease Models, Animal ; *TDP-43 Proteinopathies/genetics/pathology/metabolism ; Humans ; Mutation ; Amyotrophic Lateral Sclerosis/genetics/pathology ; Cell Nucleus/genetics/metabolism ; Cytoplasm/metabolism/genetics ; }, abstract = {TDP-43 is a normally nuclear RNA binding protein that under pathological conditions may be excluded from the nucleus and deposited in the cytoplasm in the form of insoluble polyubiquitinated and polyphosphorylated inclusions. This nuclear exclusion coupled with cytoplasmic accumulation is called TDP-43 pathology and contributes to a range of disorders collectively known as TDP-43 proteinopathies. These include the great majority of amyotrophic lateral sclerosis (ALS) cases, all limbic-predominant age-related TDP-43 encephalopathy (LATE), as well as up to 50% of frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD) cases. Thus, TDP-43 pathology is a common feature underlying a wide range of neurodegenerative conditions. However, modelling it has proven to be challenging, particularly generating models with concomitant TDP-43 loss of nuclear function and cytoplasmic inclusions. Here, focussing exclusively on mice, we discuss TDP-43 genetic models in terms of the presence of TDP-43 pathology, and we consider other models with TDP-43 pathology due to mutations in disparate genes. We also consider manipulations aimed at producing TDP-43 pathology, and we look at potential strategies to develop new, much needed models to address the many outstanding questions regarding how and why TDP-43 protein leaves the nucleus and accumulates in the cytoplasm, causing downstream dysfunction and devastating disease.}, }
@article {pmid40300682, year = {2025}, author = {Li, Z and Xing, J}, title = {Role of sirtuins in cerebral ischemia-reperfusion injury: Mechanisms and therapeutic potential.}, journal = {International journal of biological macromolecules}, volume = {310}, number = {Pt 4}, pages = {143591}, doi = {10.1016/j.ijbiomac.2025.143591}, pmid = {40300682}, issn = {1879-0003}, mesh = {Humans ; *Sirtuins/metabolism/genetics ; *Reperfusion Injury/metabolism/drug therapy/pathology ; Animals ; *Brain Ischemia/metabolism/drug therapy/pathology ; }, abstract = {The high incidence and mortality rate of cardiac arrest (CA) establishes it as a critical clinical challenge in emergency medicine globally. Despite continuous advances in advanced life support (ALS) technology, the prognosis for patients experiencing cardiac arrest remains poor, with cerebral ischemia and reperfusion injury (CIRI) being a significant determinant of adverse neurological outcomes and increased mortality. Sirtuins (SIRTs) are a class of highly evolutionarily conserved NAD[+]-dependent histone deacylenzymes capable of regulating the expression of various cytoprotective genes to play a neuroprotective role in CIRI. SIRTs mainly regulate the levels of downstream proteins such as PGC 1-α, Nrf 2, NLRP 3, FoxOs, and PINK 1 to inhibit inflammatory response, attenuate oxidative stress, improve mitochondrial dysfunction, promote angiogenesis, and inhibit apoptosis while reducing CIRI. Natural active ingredients are widely used in regulating the protein level of SIRTs in the body because of their multi-components, multi-pathway, multi-target, and minimal toxic side effects. However, these naturally active ingredients still face many challenges related to drug targeting, pharmacokinetic properties, and drug delivery. The emergence and vigorous development of new drug delivery systems, such as nanoparticles, micromilk, and exosomes, provide strong support for solving the above problems. In the context of the rapid development of molecular biology technology, non-coding RNA (NcRNA), represented by miRNA and LncRNA, offers great potential for achieving gene-level precision medicine. In the context of multidisciplinary integration, combining SIRTs proteins with biotechnology, omics technologies, artificial intelligence, and material science will strongly promote the deepening of their basic research and expand their clinical application. This review describes the major signaling pathways of targeting SIRTs to mitigate CIRI, as well as the current research status of Chinese and Western medicine and medical means for the intervention level of SIRTs. Meanwhile, the challenges and possible solutions in the clinical application of targeted drugs are summarized. In the context of medical and industrial crossover, the development direction of SIRTs in the future is discussed to provide valuable reference for basic medical researchers and clinicians to improve the clinical diagnosis and treatment effects of CIRI.}, }
@article {pmid40300213, year = {2025}, author = {Sun, Y and Vermulst, M}, title = {The hidden costs of imperfection: transcription errors in protein aggregation diseases.}, journal = {Current opinion in genetics &amp; development}, volume = {93}, number = {}, pages = {102350}, pmid = {40300213}, issn = {1879-0380}, support = {R01 AG054641/AG/NIA NIH HHS/United States ; R01 AG075130/AG/NIA NIH HHS/United States ; R01 AG083065/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Transcription, Genetic/genetics ; *Protein Aggregation, Pathological/genetics/pathology ; Protein Folding ; *Alzheimer Disease/genetics/pathology ; *Neurodegenerative Diseases/genetics/pathology ; *Protein Aggregates/genetics ; Amyloid/genetics ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; Aging/genetics/pathology ; Prions/genetics ; Mutation ; }, abstract = {At first glance, biological systems appear to operate with remarkable precision and order. Yet, closer examination reveals that this perfection is an illusion, biological processes are inherently prone to errors. Here, we describe recent evidence that indicates that errors that occur during transcription play an important role in neurological diseases. These errors, though transient, can have lasting consequences when they generate mutant proteins with amyloid or prion-like properties. Such proteins can seed aggregation cascades, converting wild-type counterparts into misfolded conformations, ultimately leading to toxic deposits seen in diseases like Alzheimer's and amyotrophic lateral sclerosis. These observations help to paint a fuller picture of the origins of neurodegenerative diseases in aging humans and suggest a unified mechanism by which they may arise.}, }
@article {pmid40299664, year = {2025}, author = {Nogueira-Machado, JA and Rocha-Silva, F and Gomes, NA}, title = {The Role of mTOR in Amyotrophic Lateral Sclerosis.}, journal = {Biomedicines}, volume = {13}, number = {4}, pages = {}, pmid = {40299664}, issn = {2227-9059}, abstract = {Background: Amyotrophic lateral sclerosis (ALS) is a rare, progressive, and incurable disease characterized by muscle weakness and paralysis. Recent studies have explored a possible link between ALS pathophysiology and mTOR signaling. Recent reports have linked the accumulation of protein aggregates, dysfunctional mitochondria, and homeostasis to the development of ALS. mTOR plays a pivotal role in controlling autophagy and affecting energy metabolism, in addition to supporting neuronal growth, plasticity, and the balance between apoptosis and autophagy, all of which are important for homeostasis. Aim: This mini-review approaches the regulatory roles of mTOR signaling pathways, their interaction with other metabolic pathways, and their potential to modulate ALS progression. Significance: It discusses how these metabolic signaling pathways affect the neuromuscular junction, producing symptoms of muscle weakness and atrophy similar to those seen in patients with ALS. The discussion includes the concepts of neurocentric and peripheral and the possible connection between mTOR and neuromuscular dysfunction in ALS. Conclusions: It highlights the therapeutic potential of mTOR signaling and interconnections with other metabolic routes, making it a promising biomarker and therapeutic target for ALS.}, }
@article {pmid40299512, year = {2025}, author = {Eslami, M and Adampour, Z and Fadaee Dowlat, B and Yaghmayee, S and Motallebi Tabaei, F and Oksenych, V and Naderian, R}, title = {A Novel Frontier in Gut-Brain Axis Research: The Transplantation of Fecal Microbiota in Neurodegenerative Disorders.}, journal = {Biomedicines}, volume = {13}, number = {4}, pages = {}, pmid = {40299512}, issn = {2227-9059}, abstract = {The gut-brain axis (GBA) represents a sophisticated bidirectional communication system connecting the central nervous system (CNS) and the gastrointestinal (GI) tract. This interplay occurs primarily through neuronal, immune, and metabolic pathways. Dysbiosis in gut microbiota has been associated with multiple neurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS). In recent years, fecal microbiota transplantation (FMT) has gained attention as an innovative therapeutic approach, aiming to restore microbial balance in the gut while influencing neuroinflammatory and neurodegenerative pathways. This review explores the mechanisms by which FMT impacts the gut-brain axis. Key areas of focus include its ability to reduce neuroinflammation, strengthen gut barrier integrity, regulate neurotransmitter production, and reinstate microbial diversity. Both preclinical and clinical studies indicate that FMT can alleviate motor and cognitive deficits in PD and AD, lower neuroinflammatory markers in MS, and enhance respiratory and neuromuscular functions in ALS. Despite these findings, several challenges remain, including donor selection complexities, uncertainties about long-term safety, and inconsistencies in clinical outcomes. Innovations such as synthetic microbial communities, engineered probiotics, and AI-driven analysis of the microbiome hold the potential to improve the precision and effectiveness of FMT in managing neurodegenerative conditions. Although FMT presents considerable promise as a therapeutic development, its widespread application for neurodegenerative diseases requires thorough validation through well-designed, large-scale clinical trials. It is essential to establish standardized protocols, refine donor selection processes, and deepen our understanding of the molecular mechanisms behind its efficacy.}, }
@article {pmid40299102, year = {2025}, author = {Zhang, G and Huang, S and Wei, M and Wu, Y and Wang, J}, title = {Excitatory Amino Acid Transporters as Therapeutic Targets in the Treatment of Neurological Disorders: Their Roles and Therapeutic Prospects.}, journal = {Neurochemical research}, volume = {50}, number = {3}, pages = {155}, pmid = {40299102}, issn = {1573-6903}, support = {2023JJB140089//Guangxi Youth Science Foundation Project/ ; 82201694//the National Natural Scientific Foundation of China/ ; 2022AC21033//Guangxi Science and technology base and talent project/ ; 2022KY0349//Guangxi university young and middle-aged teachers' basic ability improvement project/ ; }, mesh = {Humans ; Animals ; *Nervous System Diseases/metabolism/drug therapy ; *Glutamate Plasma Membrane Transport Proteins/metabolism ; Glutamic Acid/metabolism ; }, abstract = {Excitatory amino acid transporters (EAATs) are pivotal regulators of glutamate homeostasis in the central nervous system and orchestrate synaptic glutamate clearance through transmembrane transport and the glutamine‒glutamate cycle. The five EAAT subtypes (GLAST/EAAT1, GLT-1/EAAT2, EAAC1/EAAT3, EAAT4, and EAAT5) exhibit spatiotemporal-specific expression patterns in neurons and glial cells, and their dysfunction is implicated in diverse neurological pathologies, including epilepsy, amyotrophic lateral sclerosis (ALS), schizophrenia, depression, and retinal degeneration. Mechanistic studies revealed that astrocytic GLT-1 deficiency disrupts glutamate clearance in ALS motor neurons, whereas GLAST genetic variants are linked to both epilepsy susceptibility and glaucomatous retinal ganglion cell degeneration. Three major challenges persist in ongoing research: ① subtype-specific regulatory mechanisms remain unclear; ② compensatory functions of transporters vary significantly across disease models; and ③ clinical translation lacks standardized evaluation criteria. The interaction mechanisms and dynamic roles of EAATs in neurological disorders were systematically investigated in this study, and an integrated approach combining single-cell profiling, stem cell-based disease modeling, and drug screening platforms was proposed. These findings lay the groundwork for novel therapeutic strategies targeting glutamate homeostasis.}, }
@article {pmid40299101, year = {2025}, author = {Sarkar, S and Porel, P and Kosey, S and Aran, KR}, title = {Unraveling the role of CGRP in neurological diseases: a comprehensive exploration to pathological mechanisms and therapeutic implications.}, journal = {Molecular biology reports}, volume = {52}, number = {1}, pages = {436}, pmid = {40299101}, issn = {1573-4978}, mesh = {Humans ; *Calcitonin Gene-Related Peptide/metabolism/genetics ; Animals ; Neuroprotective Agents/pharmacology/therapeutic use/metabolism ; *Neurodegenerative Diseases/metabolism/drug therapy/pathology ; *Nervous System Diseases/metabolism ; Signal Transduction ; Receptors, Calcitonin Gene-Related Peptide/metabolism ; Oxidative Stress ; }, abstract = {Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Multiple sclerosis (MS), Amyotrophic lateral sclerosis (ALS), and Spinal muscular atrophy (SMA) are neurodegenerative diseases (NDDs) characterized by progressive neuronal degeneration. Recent studies provide compelling information regarding the contribution of Calcitonin Gene-Related Peptide (CGRP), a potent neuropeptide, in regulating neuroinflammation, vasodilation, and neuronal survival in these disorders. This review systematically delves into the multidimensional aspects of CGRP as both a neuroprotective agent and a neurotoxic factor in NDDs. The neuroprotective effects of CGRP include suppression of inflammation, regulation of intracellular signaling pathways, and promotion of neuronal growth and survival. However, under pathological conditions, its overexpression or dysregulation is associated with oxidative stress, excitotoxicity, and neuronal death. The therapeutic use of CGRP and its receptor antagonists in migraine provides substantial evidence for CGRP's therapeutic potential, which can be further explored for the management of NDDs. However, since the bidirectional nature of CGRP effects is evident, it is crucial to gain an accurate insight into its mechanisms to target only the neuropeptide's beneficial effects while completely avoiding the undesired consequences. Further studies should focus on understanding the context-dependent activity of CGRP in the hope of designing targeted therapy for NDDs, which could gradually transform the current pharmacological management of NDDs.}, }
@article {pmid40298821, year = {2025}, author = {Bortolotti, M and Polito, L and Battelli, MG and Bolognesi, A}, title = {Xanthine Oxidoreductase: A Double-Edged Sword in Neurological Diseases.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {14}, number = {4}, pages = {}, pmid = {40298821}, issn = {2076-3921}, abstract = {Non-communicable neurological disorders are the second leading cause of death, and their burden continues to increase as the world population grows and ages. Oxidative stress and inflammation are crucially implicated in the triggering and progression of multiple sclerosis, Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease, and even stroke. In this narrative review, we examine the role of xanthine oxidoreductase (XOR) activities and products in all the above-cited neurological diseases. The redox imbalance responsible for oxidative stress could arise from excess reactive oxygen and nitrogen species resulting from the activities of XOR, as well as from the deficiency of its main product, uric acid (UA), which is the pivotal antioxidant system in the blood. In fact, with the exception of stroke, serum UA levels are inversely related to the onset and progression of these neurological disorders. The inverse correlation observed between the level of uricemia and the presence of neurological diseases suggests a neuroprotective role for UA. Oxidative stress and inflammation are also caused by ischemia and reperfusion, a condition in which XOR action has been recognized as a contributing factor to tissue damage. The findings reported in this review could be useful for addressing clinical decision-making and treatment optimization.}, }
@article {pmid40294208, year = {2025}, author = {Winek, K and Soreq, H}, title = {Emerging roles of transfer RNA fragments in the CNS.}, journal = {Brain : a journal of neurology}, volume = {148}, number = {8}, pages = {2631-2645}, pmid = {40294208}, issn = {1460-2156}, support = {5P01AG014449-21/GF/NIH HHS/United States ; 11183//Israel Science Foundation/ ; 835/23//Israel Science Foundation/ ; P01 AG014449/AG/NIA NIH HHS/United States ; 3213/19//Israel Science Foundation/ ; 1770/20//Israel Science Foundation/ ; }, mesh = {Humans ; *RNA, Transfer/metabolism/genetics ; Animals ; *Central Nervous System/metabolism ; *Central Nervous System Diseases/genetics/metabolism ; *RNA, Small Untranslated/metabolism/genetics ; }, abstract = {Transfer RNA-derived small RNAs (tsRNAs), previously considered inactive tRNA degradation products, have now been shown to be functional small non-coding RNAs. They may play important roles within the CNS and in brain-body interactions, both during normal developmental stages as well as in diverse brain pathologies. Among the cell types found in the CNS, tsRNAs are particularly abundant in neurons. Correspondingly, neurons show cell type specific tRNA expression profiles when compared to other cells of the CNS under homeostatic conditions and defects in tRNA processing may lead to neurological disorders. Disease-specific tsRNA profiles have been identified in a number of CNS disorders, including amyotrophic lateral sclerosis and epilepsy. Elevated levels of specific tsRNAs have been found in the blood before the onset of epileptic seizures; and age-related, sex-specific loss of mitochondrial genome-originated tsRNAs in the nucleus accumbens of female patients is correlated with accelerated cognitive deterioration in Alzheimer's disease. Disease-related tsRNA signatures have also been identified in the CSF of patients with Parkinson's disease, and nucleated blood cells from ischaemic stroke patients show specific elevation of cholinergic-targeted tsRNAs. The mechanisms of action of tsRNAs are still being elucidated but include targeting complementary mRNA to impact RNA levels and translation in a miRNA-like manner, direct interaction with RNA binding proteins, or interference with translation machinery. The function of tsRNAs may be affected by the chemical modifications they inherit from the originating tRNA molecules, which impact tsRNAs production and may modulate their interactions with proteins. Research on the genetics, biochemical properties and regulatory roles of tsRNAs has expanded rapidly in recent years, facilitated by novel sequencing strategies, which include the removal of tRNA modifications and chemically blocked ends that hinder amplification and adapter ligation. Future in-depth profiling of tsRNAs levels, mode(s) of function, and identification of interacting proteins and RNAs may together shed light on the impact of tsRNAs on neuronal function, and enable novel diagnostics/therapeutics avenues for brain diseases in age, sex and disease-specific manner.}, }
@article {pmid40290120, year = {2025}, author = {Hong, Y and Song, Y and Wang, W and Shi, J and Chen, X}, title = {Mitochondrial DNA editing: Key to the treatment of neurodegenerative diseases.}, journal = {Genes &amp; diseases}, volume = {12}, number = {4}, pages = {101437}, pmid = {40290120}, issn = {2352-3042}, abstract = {Neuronal death is associated with mitochondrial dysfunction caused by mutations in mitochondrial DNA. Mitochondrial DNA becomes damaged when processes such as replication, repair, and nucleotide synthesis are compromised. This extensive accumulation of damaged mitochondrial DNA subsequently disrupts the normal function of mitochondria, leading to aging, degeneration, or even death of neurons. Mitochondrial dysfunction stands as a pivotal factor in the development of neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis. Recognizing the intricate nature of their pathogenesis, there is an urgent need for more effective therapeutic interventions. In recent years, mitochondrial DNA editing tools such as zinc finger nucleases, double-stranded DNA deaminase toxin A-derived cytosine base editors, and transcription activator-like effector ligand deaminases have emerged. Their emergence will revolutionize the research and treatment of mitochondrial diseases. In this review, we summarize the advancements in mitochondrial base editing technology and anticipate its utilization in neurodegenerative diseases, offering insights that may inform preventive strategies and therapeutic interventions for disease phenotypes.}, }
@article {pmid40288591, year = {2025}, author = {Servi, R and Akkoç, RF and Aksu, F and Servi, S}, title = {Therapeutic potential of enzymes, neurosteroids, and synthetic steroids in neurodegenerative disorders: A critical review.}, journal = {The Journal of steroid biochemistry and molecular biology}, volume = {251}, number = {}, pages = {106766}, doi = {10.1016/j.jsbmb.2025.106766}, pmid = {40288591}, issn = {1879-1220}, mesh = {Humans ; *Neurosteroids/therapeutic use/pharmacology ; *Neurodegenerative Diseases/drug therapy/metabolism ; Animals ; *Steroids/therapeutic use ; *Neuroprotective Agents/therapeutic use/pharmacology ; Alzheimer Disease/drug therapy/metabolism ; }, abstract = {Neurodegenerative disorders present a significant challenge to healthcare systems, mainly due to the limited availability of effective treatment options to halt or reverse disease progression. Endogenous steroids synthesized in the central nervous system, such as pregnenolone (PREG), dehydroepiandrosterone (DHEA), progesterone (PROG), and allopregnanolone (ALLO), have been identified as potential therapeutic agents for neurodegenerative diseases. Neurosteroids such as ALLO, DHEA, and PROG, as well as their synthetic analogs like Ganaxolene, Fluasterone, and Olexoxime, offer promising effects for conditions such as Alzheimer's disease (AD) and depression. Moreover, Brexanolone and Ganaxolone are synthetic steroids approved for the treatment of postpartum depression and epilepsy, respectively. Neurosteroids such as ALLO are crucial in modulating GABAergic neurotransmission and reducing neuroinflammation. These compounds enhance the activity of GABA-A receptors, leading to increased inhibitory signaling in the brain, which can help regulate mood, cognition, and neuroprotection. Small clinical trials and observational studies indicate that ALLO may have cognitive benefits, but no large-scale, definitive meta-analysis confirms a 20 % improvement in AD patients. Mitochondrial dysfunction plays a vital role in the pathogenesis of numerous neurological diseases due to the high-energy demand and sensitivity of neurons to oxidative stress. Reduced mitochondrial function leads to amyloid-beta plaques and tau tangles accumulation in AD. In Parkinson's disease (PD), mitochondrial dysfunction resulting from the PINK1 or Parkin genes leads to energy deficiencies and the accumulation of toxic byproducts. Mutations in genes such as SOD1, C9orf72, and TDP-43 have been associated with mitochondrial dysfunction in amyotrophic lateral sclerosis (ALS). Moreover, studies on these neurodegenerative diseases suggest that inflammation is not merely a consequence of neurodegeneration but is also an essential factor in this process. Many neurological disorders involve multifaceted interactions between genetics, the environment, and immune responses, making it difficult to pinpoint their exact causes. Future research aims to overcome these hurdles through genetic advances, regenerative medicine, and personalized therapies. Cutting-edge technologies such as artificial intelligence and high-throughput screening are expected to accelerate drug discovery and improve diagnostic accuracy. Increasing collaboration between interdisciplinary fields such as bioinformatics, neuroscience, and immunology will lead to innovative treatment strategies. This comprehensive review discusses the therapeutic effects of enzymes, neurosteroids, and synthetic steroids in different neurodegenerative diseases, particularly AD, PD, ALS, and MS. Potential challenges in the therapeutic use of neurosteroids, such as the limited bioavailability and off-target effects of synthetic steroids, are also discussed, and an up-to-date and comprehensive review of the impact of these steroids on neurodegenerative disorders is presented.}, }
@article {pmid40287045, year = {2025}, author = {Dudzisz, K and Wandzik, I}, title = {Antisense oligonucleotides: A promising advancement in neurodegenerative disease treatment.}, journal = {European journal of pharmacology}, volume = {999}, number = {}, pages = {177644}, doi = {10.1016/j.ejphar.2025.177644}, pmid = {40287045}, issn = {1879-0712}, mesh = {Humans ; *Oligonucleotides, Antisense/therapeutic use ; *Neurodegenerative Diseases/genetics/drug therapy/therapy ; Animals ; Clinical Trials as Topic ; }, abstract = {Antisense oligonucleotides (ASOs) are a class of therapeutics designed to modulate gene expression and have shown promise in the treatment of various neurodegenerative diseases. As of March 2025, four ASO-based therapies have received approval for the treatment of neurodegenerative diseases, including spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS), and hereditary transthyretin amyloidosis (ATTR). These approvals underscore the therapeutic potential of ASOs as effective treatments for neurodegenerative diseases by addressing specific genetic abnormalities. This is best demonstrated by clinical studies in more than a dozen ASOs, which could pave the way for the development of new therapeutics soon. Moreover, the ongoing extended clinical studies, which target presymptomatic carriers, have significant potential to cure familial ALS based on the SOD1 gene mutation. This review provides an update on clinical trials, highlighting promising results and the challenges encountered.}, }
@article {pmid40284554, year = {2025}, author = {Tamai, R and Kiyoura, Y}, title = {Candida Infections: The Role of Saliva in Oral Health-A Narrative Review.}, journal = {Microorganisms}, volume = {13}, number = {4}, pages = {}, pmid = {40284554}, issn = {2076-2607}, support = {21K10233, 23K09511//KAKEN/ ; }, abstract = {Candida species, particularly Candida albicans, are causative agents of oral infections to which immunocompromised patients are especially susceptible. Reduced saliva flow (xerostomia) can lead to Candida overgrowth, as saliva contains antibacterial components such as histatins and β-defensins that inhibit fungal growth and adhesion to the oral mucosa. Candida adheres to host tissues, forms biofilms, and secretes enzymes required for tissue invasion and immune evasion. Secretory asparaginyl proteinases (Saps) and candidalysin, a cytolytic peptide toxin, are vital to Candida virulence, and agglutinin-like sequence (Als) proteins are crucial for adhesion, invasion, and biofilm formation. C. albicans is a risk factor for dental caries and may increase periodontal disease virulence when it coexists with Porphyromonas gingivalis. Candida infections have been suggested to heighten the risk of oral cancer based on a relationship between Candida species and oral squamous cell carcinoma (OSCC) or oral potentially malignant disorder (OPMD). Meanwhile, β-glucan in the Candida cell wall has antitumor effects. In addition, Candida biofilms protect viruses such as herpesviruses and coxsackieviruses. Understanding the intricate interactions between Candida species, host immune responses, and coexisting microbial communities is essential for developing preventive and therapeutic strategies against oral Candida infections, particularly in immunocompromised individuals.}, }
@article {pmid40283578, year = {2025}, author = {Mantle, D and Hargreaves, I}, title = {Coenzyme Q10 and the Blood-Brain Barrier: An Overview.}, journal = {Journal of clinical medicine}, volume = {14}, number = {8}, pages = {}, pmid = {40283578}, issn = {2077-0383}, abstract = {Mitochondrial dysfunction is a common factor known to be involved in the pathogenesis of a number of neurological disorders, including Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis. Given the importance of coenzyme Q10 (CoQ10) in promoting normal mitochondrial function, and the deficiency of CoQ10 reported in such neurological disorders, there is a rationale for investigating the potential therapeutic role of supplementary CoQ10. However, while there is evidence for the efficacy of CoQ10 supplementation in animal models of the above disorders, randomised controlled clinical trials supplementing CoQ10 in PD, AD, or ALS have had disappointing outcomes. This in turn may be a reflection of the current uncertainty as to whether CoQ10 can access the blood-brain barrier in human subjects. In an attempt to further elucidate the disparity in outcomes of such preclinical and clinical studies, in this article we have reviewed evidence from the peer-reviewed literature to establish the ability of CoQ10 to access the brain via the BBB.}, }
@article {pmid40283201, year = {2025}, author = {González-Sánchez, M and Ramírez-Expósito, MJ and Martínez-Martos, JM}, title = {Pathophysiology, Clinical Heterogeneity, and Therapeutic Advances in Amyotrophic Lateral Sclerosis: A Comprehensive Review of Molecular Mechanisms, Diagnostic Challenges, and Multidisciplinary Management Strategies.}, journal = {Life (Basel, Switzerland)}, volume = {15}, number = {4}, pages = {}, pmid = {40283201}, issn = {2075-1729}, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by the progressive degeneration of upper and lower motor neurons, leading to muscle atrophy, paralysis, and respiratory failure. This comprehensive review synthesizes the current knowledge on ALS pathophysiology, clinical heterogeneity, diagnostic frameworks, and evolving therapeutic strategies. Mechanistically, ALS arises from complex interactions between genetic mutations (e.g., in C9orf72, SOD1, TARDBP (TDP-43), and FUS) and dysregulated cellular pathways, including impaired RNA metabolism, protein misfolding, nucleocytoplasmic transport defects, and prion-like propagation of toxic aggregates. Phenotypic heterogeneity, manifesting as bulbar-, spinal-, or respiratory-onset variants, complicates its early diagnosis, which thus necessitates the rigorous application of the revised El Escorial criteria and emerging biomarkers such as neurofilament light chain. Clinically, ALS intersects with frontotemporal dementia (FTD) in up to 50% of the cases, driven by shared TDP-43 pathology and C9orf72 hexanucleotide expansions. Epidemiological studies have revealed a lifetime risk of 1:350, with male predominance (1.5:1) and peak onset between 50 and 70 years. Disease progression varies widely, with a median survival of 2-4 years post-diagnosis, underscoring the urgency for early intervention. Approved therapies, including riluzole (glutamate modulation), edaravone (antioxidant), and tofersen (antisense oligonucleotide), offer modest survival benefits, while dextromethorphan/quinidine alleviates the pseudobulbar affect. Non-pharmacological treatment advances, such as non-invasive ventilation (NIV), prolong survival by 13 months and improve quality of life, particularly in bulb-involved patients. Multidisciplinary care-integrating physical therapy, respiratory support, nutritional management, and cognitive assessments-is critical to addressing motor and non-motor symptoms (e.g., dysphagia, spasticity, sleep disturbances). Emerging therapies show promise in preclinical models. However, challenges persist in translating genetic insights into universally effective treatments. Ethical considerations, including euthanasia and end-of-life decision-making, further highlight the need for patient-centered communication and palliative strategies.}, }
@article {pmid40282367, year = {2025}, author = {Watanabe, Y and Nakagawa, T and Nakagawa, M and Nakayama, K}, title = {The Molecular Intersection of NEK1, C21ORF2, Cyclin F, and VCP in ALS Pathogenesis.}, journal = {Genes}, volume = {16}, number = {4}, pages = {}, pmid = {40282367}, issn = {2073-4425}, support = {23K06367//Japan Society for the Promotion of Science/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *NIMA-Related Kinase 1/genetics/metabolism ; *Valosin Containing Protein/genetics/metabolism ; *Cyclins/genetics/metabolism ; DNA-Binding Proteins/genetics/metabolism ; Animals ; DNA Damage ; Mutation ; DNA Repair ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterized by the progressive degeneration of motor neurons, leading to muscle weakness, paralysis, and death. Although significant progress has been made in understanding ALS, its molecular mechanisms remain complex and multifactorial. This review explores the potential convergent mechanisms underlying ALS pathogenesis, focusing on the roles of key proteins including NEK1, C21ORF2, cyclin F, VCP, and TDP-43. Recent studies suggest that mutations in C21ORF2 lead to the stabilization of NEK1, while cyclin F mutations activate VCP, resulting in TDP-43 aggregation. TDP-43 aggregation, a hallmark of ALS, impairs RNA processing and protein transport, both of which are essential for neuronal function. Furthermore, TDP-43 has emerged as a key player in DNA damage repair, translocating to DNA damage sites and recruiting repair proteins. Given that NEK1, VCP, and cyclin F are also involved in DNA repair, this review examines how these proteins may intersect to disrupt DNA damage repair mechanisms, contributing to ALS progression. Impaired DNA repair and protein homeostasis are suggested to be central downstream mechanisms in ALS pathogenesis. Ultimately, understanding the interplay between these pathways could offer novel insights into ALS and provide potential therapeutic targets. This review aims to highlight the emerging connections between protein aggregation, DNA damage repair, and cellular dysfunction in ALS, fostering a deeper understanding of its molecular basis and potential avenues for intervention.}, }
@article {pmid40281300, year = {2025}, author = {Upadhayay, S and Soni, D and Dhureja, M and Temgire, P and Kumar, V and Arthur, R and Kumar, P}, title = {Role of Fibroblast Growth Factors in Neurological Disorders: Insight into Therapeutic Approaches and Molecular Mechanisms.}, journal = {Molecular neurobiology}, volume = {}, number = {}, pages = {}, pmid = {40281300}, issn = {1559-1182}, abstract = {In the last few decades, the incidence and progression of neurological disorders have consistently increased, which mainly occur due to environmental pollution, genetic abnormalities, and modern lifestyles. Several case reports suggested that these factors enhanced oxidative stress, mitochondrial dysfunction, inflammation, and apoptosis, leading to neurological disease. The pathophysiology of neurological disorders is still not understood, mainly due to the diversity within affected populations. Existing treatment options primarily provide symptomatic relief but frequently come with considerable side effects, including depression, anxiety, and restlessness. Fibroblast growth factors (FGFs) are key signalling molecules regulating various cellular functions, including cell proliferation, differentiation, electrical excitability, and injury responses. Hence, several investigations claimed a relationship between FGFs and neurological disorders, and their findings indicated that they could be used as therapeutic targets for neurological disorders. The FGFs are reported to activate various signalling pathways, including Ras/MAPK/PI3k/Akt, and downregulate the GSK-3β/NF-κB pathways responsible for anti-oxidant, anti-inflammatory, and anti-apoptotic effects. Therefore, researchers are interested in developing novel treatment options for neurological disorders. The emergence of unreported FGFs contributes to our understanding of their involvement in these conditions and encourages further exploration of innovative therapeutic approaches. All the data were obtained from published articles using PubMed, Web of Science, and Scopus databases using the search terms Fibroblast Growth Factor, PD, HD, AD, ALS, signalling pathways, and neurological disorders.}, }
@article {pmid40280464, year = {2025}, author = {Gritsiuta, AI and Reep, G and Parupudi, S and Petrov, RV}, title = {Optimizing the management of anastomotic leaks after esophagectomy: a narrative review of salvage strategies and outcomes.}, journal = {Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract}, volume = {29}, number = {7}, pages = {102069}, doi = {10.1016/j.gassur.2025.102069}, pmid = {40280464}, issn = {1873-4626}, mesh = {Humans ; *Esophagectomy/adverse effects ; *Anastomotic Leak/therapy/etiology ; *Salvage Therapy/methods ; Drainage/methods ; Treatment Outcome ; Nutritional Support ; Anti-Bacterial Agents/therapeutic use ; }, abstract = {BACKGROUND: Anastomotic leaks (ALs) after esophagectomy remain a major postoperative complication, leading to increased morbidity, prolonged hospital stays, and higher mortality. Despite advancements in surgical techniques and perioperative care, AL management lacks standardized protocols. This review aimed to evaluate current salvage strategies, including conservative, endoscopic, and surgical approaches, to optimize outcomes and reduce complications.<br><br>METHODS: A comprehensive literature search was conducted using PubMed, Scopus, Cochrane Library, and Google Scholar databases to identify studies published between 2000 and 2025 on AL management after esophagectomy. Peer-reviewed clinical trials, guidelines, and expert consensus reports were reviewed, focusing on minimally invasive and surgical interventions, patient outcomes, and emerging treatment strategies.<br><br>RESULTS: AL management strategies were classified into 3 primary approaches. Conservative management includes nutritional support, antibiotic therapy, and percutaneous drainage, particularly for contained leaks. Endoscopic interventions, such as self-expanding metal stents and endoscopic vacuum-assisted closure, have shown high success rates, with vacuum-assisted closure achieving superior closure outcomes. Hybrid techniques, including stent-over-sponge and vacuum-assisted closure-stent, are emerging as promising alternatives. Surgical interventions remain the gold standard for severe or refractory leaks with options, including primary repair, esophageal diversion, and delayed conduit reconstruction.<br><br>CONCLUSION: A multidisciplinary approach is crucial for optimizing AL management, incorporating enhanced recovery protocols, early risk assessment, and individualized treatment plans. Endoscopic techniques have reduced the need for surgical revisions, but surgical intervention remains necessary for severe cases. Future research should focus on refining treatment algorithms, integrating novel technologies, and establishing standardized guidelines to improve patient survival and quality of life.}, }
@article {pmid40280282, year = {2025}, author = {Matsuda, KM and Kotani, H and Sato, S and Yoshizaki, A}, title = {Unveiling the hidden syndrome: The enigma of anti-transcobalamin receptor autoantibodies.}, journal = {Immunology letters}, volume = {275}, number = {}, pages = {107028}, doi = {10.1016/j.imlet.2025.107028}, pmid = {40280282}, issn = {1879-0542}, mesh = {Humans ; *Autoantibodies/immunology ; *Autoimmune Diseases/immunology ; Vitamin B 12/therapeutic use ; Animals ; *Vitamin B 12 Deficiency/immunology ; Syndrome ; *Antigens, CD/immunology ; *Receptors, Cell Surface/immunology ; }, abstract = {The transcobalamin receptor (CD320) functions as a critical mediator for vitamin B12 uptake in cells, with emerging evidence linking autoantibodies against CD320 to various autoimmune conditions. Pluvinage et al.'s recent study identified anti-CD320 autoantibodies as a cause of autoimmune vitamin B12 central deficiency, specifically affecting the central nervous system while sparing peripheral nerves. Their findings align with our previous work showing anti-CD320's role in cutaneous arteritis. Both studies identified overlapping CD320 epitopes targeted by autoantibodies and demonstrated the therapeutic efficacy of high-dose vitamin B12 supplementation in mitigating symptoms. Expanding on these findings, we observed anti-CD320 autoantibodies in other inflammatory disorders such as systemic sclerosis, suggesting a broader clinical relevance. The work by Pluvinage et al. and our group supports the concept of an "anti-CD320-associated syndrome," with high-dose B12 supplementation as a promising treatment strategy. Further research is needed to fully elucidate the tissue-specific mechanisms and pathophysiology underlying these autoimmune conditions.}, }
@article {pmid40280271, year = {2025}, author = {Kopalli, SR and Behl, T and Baldaniya, L and Ballal, S and Joshi, KK and Arya, R and Chaturvedi, B and Chauhan, AS and Verma, R and Patel, M and Jain, SK and Wal, A and Gulati, M and Koppula, S}, title = {Neuroadaptation in neurodegenerative diseases: compensatory mechanisms and therapeutic approaches.}, journal = {Progress in neuro-psychopharmacology &amp; biological psychiatry}, volume = {139}, number = {}, pages = {111375}, doi = {10.1016/j.pnpbp.2025.111375}, pmid = {40280271}, issn = {1878-4216}, mesh = {Humans ; *Neurodegenerative Diseases/therapy/physiopathology/metabolism/pathology ; *Neuronal Plasticity/physiology ; Animals ; *Adaptation, Physiological/physiology ; *Brain/physiopathology/pathology/metabolism ; }, abstract = {Progressive neuronal loss is a hallmark of neurodegenerative diseases including Alzheimer's, Parkinson's, Huntington's, and Amyotrophic Lateral Sclerosis (ALS), which cause cognitive and motor impairment. Delaying the onset and course of symptoms is largely dependent on neuroadaptation, the brain's ability to restructure in response to damage. The molecular, cellular, and systemic processes that underlie neuroadaptation are examined in this study. These mechanisms include gliosis, neurogenesis, synaptic plasticity, and changes in neurotrophic factors. Axonal sprouting, dendritic remodelling, and compensatory alterations in neurotransmitter systems are important adaptations observed in NDDs; nevertheless, these processes may shift to maladaptive plasticity, which would aid in the advancement of the illness. Amyloid and tau pathology-induced synaptic alterations in Alzheimer's disease emphasize compensatory network reconfiguration. Dopamine depletion causes a major remodelling of the basal ganglia in Parkinson's disease, and non-dopaminergic systems compensate. Both ALS and Huntington's disease rely on motor circuit rearrangement and transcriptional dysregulation to slow down functional deterioration. Neuroadaptation is, however, constrained by oxidative stress, compromised autophagy, and neuroinflammation, particularly in elderly populations. The goal of emerging therapy strategies is to improve neuroadaptation by pharmacologically modifying neurotrophic factors, neuroinflammation, and synaptic plasticity. Neurostimulation, cognitive training, and physical rehabilitation are instances of non-pharmacological therapies that support neuroplasticity. Restoring compensating systems may be possible with the use of stem cell techniques and new gene treatments. The goal of future research is to combine biomarkers and individualized medicines to maximize neuroadaptive responses and decrease the course of illness. In order to reduce neurodegeneration and enhance patient outcomes, this review highlights the dual function of neuroadaptation in NDDs and its potential as a therapeutic target.}, }
@article {pmid40279084, year = {2025}, author = {Singh, P and Borkar, M and Doshi, G}, title = {Network pharmacology approach to unravel the neuroprotective potential of natural products: a narrative review.}, journal = {Molecular diversity}, volume = {}, number = {}, pages = {}, pmid = {40279084}, issn = {1573-501X}, abstract = {Aging is a slow and irreversible biological process leading to decreased cell and tissue functions with higher risks of multiple age-related diseases, including neurodegenerative diseases. It is widely accepted that aging represents the leading risk factor for neurodegeneration. The pathogenesis of these diseases involves complex interactions of genetic mutations, environmental factors, oxidative stress, neuroinflammation, and mitochondrial dysfunction, which complicate treatment with traditional mono-targeted therapies. Network pharmacology can help identify potential gene or protein targets related to neurodegenerative diseases. Integrating advanced molecular profiling technologies and computer-aided drug design further enhances the potential of network pharmacology, enabling the identification of biomarkers and therapeutic targets, thus paving the way for precision medicine in neurodegenerative diseases. This review article delves into the application of network pharmacology in understanding and treating neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and spinal muscular atrophy. Overall, this article emphasizes the importance of addressing aging as a central factor in developing effective disease-modifying therapies, highlighting how network pharmacology can unravel the complex biological networks associated with aging and pave the way for personalized medical strategies.}, }
@article {pmid40278411, year = {2025}, author = {Di Sarno, A and Romano, F and Arianna, R and Serpico, D and Lavorgna, M and Savastano, S and Colao, A and Di Somma, C}, title = {Lipid Metabolism and Statin Therapy in Neurodegenerative Diseases: An Endocrine View.}, journal = {Metabolites}, volume = {15}, number = {4}, pages = {}, pmid = {40278411}, issn = {2218-1989}, abstract = {Background/aim: A growing body of evidence suggests a link between dyslipidemias and neurodegenerative diseases, highlighting the crucial role of lipid metabolism in the health of the central nervous system. The aim of our work was to provide an update on this topic, with a focus on clinical practice from an endocrinological point of view. Endocrinologists, being experts in the management of dyslipidemias, can play a key role in the prevention and treatment of neurodegenerative conditions, through precocious and effective lipid profile optimization. Methods: The literature was scanned to identify clinical trials and correlation studies on the association between dyslipidemia, statin therapy, and the following neurodegenerative diseases: Alzheimer's disease (AD), Parkisons's disease (PD), Multiple sclerosis (MS), and Amyotrophic lateral sclerosis (ALS). Results: Impaired lipid homeostasis, such as that frequently observed in patients affected by obesity and diabetes, is related to neurodegenerative diseases, such as AD, PD, and other cognitive deficits related to aging. AD and related dementias are now a real priority health problem. In the United States, there are approximately 7 million subjects aged 65 and older living with AD and related dementias, and this number is projected to grow to 12 million in the coming decades. Lipid-lowering therapy with statins is an effective strategy in reducing serum low-density lipoprotein cholesterol to normal range concentrations and, therefore, cardiovascular disease risk; moreover, statins have been reported to have a positive effect on neurodegenerative diseases. Conclusions: Several pieces of research have found inconsistent information following our review. There was no association between statin use and ALS incidence. More positive evidence has emerged regarding statin use and AD/PD. However, further large-scale prospective randomized control trials are required to properly understand this issue.}, }
@article {pmid40273110, year = {2025}, author = {Souza, AA and Silva, STD and Régis, AMP and Aires, DN and Pondofe, KM and Melo, LP and Valentim, RAM and Lindquist, ARR and Macedo, LRD and Ribeiro, TS}, title = {Muscle strengthening in individuals with Amyotrophic Lateral Sclerosis: a systematic review with meta-analyses.}, journal = {PloS one}, volume = {20}, number = {4}, pages = {e0320788}, pmid = {40273110}, issn = {1932-6203}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/rehabilitation/therapy ; *Muscle Strength/physiology ; *Resistance Training/methods ; *Exercise Therapy/methods ; }, abstract = {Despite the observed benefits of properly prescribed exercises for people with Amyotrophic Lateral Sclerosis (ALS), the scarcity of studies and lack of consensus on the effects of muscle-strengthening exercises on this population has a negative impact on their rehabilitation. This study aimed to evaluate the effects of muscle-strengthening interventions in individuals with ALS. This systematic review of intervention studies included clinical trials that performed non-respiratory muscle strengthening in people with ALS compared to non-strengthening interventions, usual care, or placebo. Such studies were obtained from the MEDLINE, EMBASE, Cochrane Library, SPORTDiscus, and Physiotherapy Evidence Database databases, with no language or publication date restrictions. The outcomes considered were peripheral muscle strength, functionality, fatigue, and adverse events. The Physiotherapy Evidence Database scale was used to analyze the risk of bias, while the Grading of Recommendations Assessment, Development and Evaluation system was used to evaluate the quality of the evidence. Searches were conducted in October 2023 and eight studies were included, totaling 296 individuals. Seven of the eight studies showed superiority of the experimental intervention over the control, but this was not supported in the meta-analyses. Small sample size and high heterogeneity in the primary studies contributed significantly to the low quality of the evidence. There was no evidence of the superiority of interventions for muscle strengthening compared to interventions not aimed at strengthening, usual care, or placebo in terms of the outcomes analyzed immediately after the intervention. The quality of the evidence ranged from low to very low. Five of the studies evaluated adverse events, without reporting serious events. Interventions for muscle strengthening did not prove to be more effective when compared to the control group in the short term nor seem to produce serious adverse events. The low quality of the evidence indicates the need for studies with greater methodological rigor in this population, to more assertively assess the impacts of this intervention over the short, medium, and long term.}, }
@article {pmid40272376, year = {2025}, author = {Nguyen, THV and Ferron, F and Murakami, K}, title = {Neurotoxic Implications of Human Coronaviruses in Neurodegenerative Diseases: A Perspective from Amyloid Aggregation.}, journal = {ACS chemical biology}, volume = {20}, number = {5}, pages = {983-992}, doi = {10.1021/acschembio.5c00153}, pmid = {40272376}, issn = {1554-8937}, mesh = {Humans ; *Neurodegenerative Diseases/virology/metabolism ; *Amyloid/metabolism/chemistry ; *Coronavirus/metabolism/pathogenicity ; *Coronavirus Infections/complications/virology ; }, abstract = {Human coronaviruses (HCoVs) include seven species: HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1, MERS-CoV, SARS-CoV-1, and SARS-CoV-2. The last three, classified as Betacoronaviruses, are highly transmissible and have caused severe pandemics. HCoV infections primarily affect the respiratory system, leading to symptoms such as dry cough, fever, and breath shortness, which can progress to acute respiratory failure and death. Beyond respiratory effects, increasing evidence links HCoVs to neurological dysfunction. However, distinguishing direct neural complications from preexisting disorders, particularly in the elderly, remains challenging. This study examines the association between HCoVs and neurodegenerative diseases like Alzheimer disease, Parkinson disease, Lewy body dementia, amyotrophic lateral sclerosis, and Creutzfeldt-Jakob disease. It also presents the long-term neurological effects of HCoV infections and their differential impact across age groups and sexes. A key aspect of this study is the investigation of the sequence and structural similarities between amyloidogenic and HCoV spike proteins, which can provide insights into potential neuropathomechanisms.}, }
@article {pmid40271431, year = {2025}, author = {Rana, A and Katiyar, A and Arun, A and Berrios, JN and Kumar, G}, title = {Natural sulfur compounds in mental health and neurological disorders: insights from observational and intervention studies.}, journal = {Frontiers in nutrition}, volume = {12}, number = {}, pages = {1534000}, pmid = {40271431}, issn = {2296-861X}, abstract = {Over the years, the global disease burden of neurological disorders (NDs) and mental disorders (MDs) has significantly increased, making them one of the most critical concerns and challenges to human health. In pursuit of novel therapies against MD and ND, there has been a growing focus on nutrition and health. Dietary sulfur, primarily derived from various natural sources, plays a crucial role in numerous physiological processes, including brain function. This review offers an overview of the chemical composition of several natural sources of the sulfur-rich substances such as isothiocyanates, sulforaphane, glutathione, taurine, sulfated polysaccharides, allyl sulfides, and sulfur-containing amino acids, all of which have neuroprotective properties. A multitude of studies have documented that consuming foods that are high in sulfur enhances brain function by improving cognitive parameters and reduces the severity of neuropathology by exhibiting antioxidant and anti-inflammatory properties at the molecular level. In addition, the growing role of natural sulfur compounds in repairing endothelial dysfunction, compromising blood-brain barrier and improving cerebral blood flow, are documented here. Furthermore, this review covers the encouraging results of supplementing sulfur-rich diets in many animal models and clinical investigations, along with their molecular targets in MD, such as schizophrenia, depression, anxiety, bipolar disorder, and autism spectrum disorder, and ND, such as Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS), and Multiple Sclerosis (MS). The prospects of natural sulfur compounds show great promise as they have potential applications in nutraceuticals, medicines, and functional foods to enhance brain function and prevent diseases. However, additional research is required to clarify the mechanisms by which it works, enhance its bioavailability, and evaluate its long-term safety for broad use.}, }
@article {pmid40271071, year = {2025}, author = {Luo, H and Wei, S and Fu, S and Han, L}, title = {Role of Achyranthes aspera in neurodegenerative diseases: current evidence and future directions.}, journal = {Frontiers in pharmacology}, volume = {16}, number = {}, pages = {1511011}, pmid = {40271071}, issn = {1663-9812}, abstract = {Neurodegenerative diseases are caused by the progressive degeneration of neurons and/or their myelin sheaths, ultimately leading to cognitive and motor dysfunction. Due to their complex pathogenesis and the limited efficacy of therapeutic drugs, these diseases have attracted significant attention. Achyranthes aspera, belongs to family Amaranthaceae, has been extensively used in the traditional and folk medicines for the treatment of various ailments. Modern research has revealed that Achyranthes aspera possesses various pharmacological effects, including cardiocerebrovascular protection, immune regulation, antioxidation, and anti-aging. Furthermore, the neuroprotective effects of Achyranthes aspera have been confirmed by numerous scientific studies. This review focuses on the primary pharmacological effects and mechanisms of Achyranthes aspera in the prevention and treatment of neurodegenerative diseases, as well as their potential application prospects. This review aims to provide insights into the potential clinical applications and research directions of Achyranthes aspera in neurodegenerative diseases.}, }
@article {pmid40268233, year = {2025}, author = {Basak, B and Holzbaur, ELF}, title = {Mitophagy in Neurons: Mechanisms Regulating Mitochondrial Turnover and Neuronal Homeostasis.}, journal = {Journal of molecular biology}, volume = {437}, number = {18}, pages = {169161}, doi = {10.1016/j.jmb.2025.169161}, pmid = {40268233}, issn = {1089-8638}, mesh = {*Mitophagy ; Humans ; *Neurons/metabolism ; *Homeostasis ; *Mitochondria/metabolism ; Animals ; Ubiquitin-Protein Ligases/metabolism/genetics ; Protein Kinases/metabolism ; *Mitochondrial Turnover ; Parkinson Disease/metabolism ; }, abstract = {Mitochondrial quality control is instrumental in regulating neuronal health and survival. The receptor-mediated clearance of damaged mitochondria by autophagy, known as mitophagy, plays a key role in controlling mitochondrial homeostasis. Mutations in genes that regulate mitophagy are causative for familial forms of neurological disorders including Parkinson's disease (PD) and Amyotrophic lateral sclerosis (ALS). PINK1/Parkin-dependent mitophagy is the best studied mitophagy pathway, while more recent work has brought to light additional mitochondrial quality control mechanisms that operate either in parallel to or independent of PINK1/Parkin mitophagy. Here, we discuss our current understanding of mitophagy mechanisms operating in neurons to govern mitochondrial homeostasis. We also summarize progress in our understanding of the links between mitophagic dysfunction and neurodegeneration, and highlight the potential for therapeutic interventions to maintain mitochondrial health and neuronal function.}, }
@article {pmid40265276, year = {2025}, author = {Mendonça, IP and Peixoto, CA}, title = {The Double-Edged Sword: The Complex Function of Enteric Glial Cells in Neurodegenerative Diseases.}, journal = {Journal of neurochemistry}, volume = {169}, number = {4}, pages = {e70069}, doi = {10.1111/jnc.70069}, pmid = {40265276}, issn = {1471-4159}, support = {CNPq;#301891/2022-2//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; IAM-PROEP# 005-FIO-22//Instituto Aggeu Magalh&#xe3;es/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/pathology/metabolism ; *Neuroglia/metabolism/pathology/physiology ; Animals ; *Enteric Nervous System/pathology/metabolism ; }, abstract = {Over the past two decades, a growing number of studies have been conducted on the role of bidirectional communication through the gut-brain axis in the development of neurodegenerative diseases. These studies were driven by the curious fact that all of these diseases present varying degrees of intestinal involvement included in their wide range of symptoms. A population of cells belonging to the ENS, called enteric glial cells (EGCs), appears to actively participate in this communication between the intestine and the brain, but acting in a dualistic manner, sometimes in reactive gliosis releasing inflammatory mediators, sometimes promoting homeostasis and resilience in the face of inflammatory injuries. To date, the intracellular mechanisms that define the transcriptional profile expressed in EGCs in each situation have not yet been elucidated. This review proposes a discussion on: (1) the complex role of distinct phenotypes of enteric glial cells involved in neurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD) and multiple sclerosis (MS); and (2) innovative strategies such as IDO/TDO inhibitors, Brazil nuts, caffeic acid, polyphenols, among others, that act on EGCs and have the potential to treat neurodegenerative diseases.}, }
@article {pmid40256588, year = {2024}, author = {Ahmady, H and Afrand, M and Motaqi, M and Meftahi, GH}, title = {Utilizing Sertoli Cell Transplantation as a Therapeutic Technique for the Management of Neurodegenerative Diseases.}, journal = {Archives of Razi Institute}, volume = {79}, number = {4}, pages = {701-710}, pmid = {40256588}, issn = {2008-9872}, mesh = {*Neurodegenerative Diseases/therapy ; Humans ; Male ; Animals ; *Sertoli Cells/transplantation ; }, abstract = {Neurodegenerative diseases (NDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD), are defined by aberrant protein accumulation, brain atrophy, and gradual decline of neuronal function. Despite the considerable endeavors devoted to discovering treatments for NDs in recent decades, the demand for efficient therapeutic agents persists. Sertoli cells (SCs) play a crucial role in providing a supportive structure and environment for the development of germ cells. SCs, whether transplanted as xenogeneic or allogeneic cells, present a viable choice for enhancing graft persistence via the release of immunomodulatory and trophic factors, including neurturin (NTN), platelet-derived growth factor, Fas (CD95) ligand (FasL), glial-derived neurotrophic factor, interleukin 1 (IL1), brain-derived neurotrophic factor, interleukin 6 (IL6), transforming growth factors, and vascular growth factor, that protect replaced cells and tissues from the immune system. However, there is currently no cohesive evidence regarding the neuroprotective influence of the transplantation of SCs on NDs. Therefore, this review focuses on assessing stem cells' neuroprotective impact on neurodegenerative diseases in pre-clinical settings and presenting cohesive information. A comprehensive search was conducted between 2000 and 2022. In the identification stage, after a comprehensive search across databases, including Web of Science, Scopus, and PubMed/Medline, 103 papers were obtained. The search conducted in the present study yielded a total of nine relevant papers on the therapeutic effect of the transplantation of SCs on NDs. It was found that the transplantation of SCs exhibits a promising impact on enhancing the symptoms of neurological diseases in rats. The findings highlight the need for multiple standardized pre-clinical trials to find reliable information to confirm the utilization of the transplantation of SCs and the reduction of the symptoms of neurodegenerative diseases.}, }
@article {pmid40254133, year = {2025}, author = {Turner-Ivey, B and Jenkins, DP and Carroll, SL}, title = {Multiple Roles for Neuregulins and Their ERBB Receptors in Neurodegenerative Disease Pathogenesis and Therapy.}, journal = {The American journal of pathology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajpath.2025.03.012}, pmid = {40254133}, issn = {1525-2191}, abstract = {The role that neurotrophins, such as nerve growth factor, play in the pathogenesis of neurodegenerative diseases has long been appreciated. However, the neuregulin (NRG) family of growth factors and/or their v-erb-B2 avian erythroblastic leukemia viral oncogene homolog (ERBB) receptors have also been implicated in the pathogenesis of conditions, such as Alzheimer disease (AD), frontotemporal lobar degeneration (FTLD), and amyotrophic lateral sclerosis (ALS). In this review, we consider i) the structural variability of NRG isoforms generated by alternative RNA splicing, the use of multiple promoters and proteolysis, and the impact that this structural variability has on neuronal and glial physiology during development and adulthood. We discuss ii) the NRG receptors ERBB2, ERBB3, and ERBB4, how activation of each of these receptors further diversifies NRG actions in the central nervous system, and how dementia-related proteins, such as γ-secretase modulate the action of NRGs and their ERBB receptors. We then iii) turn to the abnormalities in NRG and ERBB expression and function evident in human AD and mouse AD models, how these abnormalities affect brain function, and attempts to use NRGs to treat AD. Finally, iv) we discuss NRG effects on the survival and function of neurons relevant to FTLD and ALS, alterations in NRG/ERBB signaling identified in these conditions, and the recent discovery of multiple human pedigrees in which autosomal dominant FTLD/ALS potentially results from point mutations in ERBB4.}, }
@article {pmid40253599, year = {2025}, author = {Malik, M and Bhatti, T and Hodson-Tole, E and Onambele-Pearson, G and Chaouch, A}, title = {Physical activity in amyotrophic lateral sclerosis: a systematic review of the methodologies used to assess a possible association.}, journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration}, volume = {}, number = {}, pages = {1-18}, doi = {10.1080/21678421.2025.2488298}, pmid = {40253599}, issn = {2167-9223}, abstract = {Growing evidence suggests that strenuous physical activity (PA) may be associated with an increased risk of developing Amyotrophic Lateral Sclerosis (ALS), a fatal neurodegenerative disease. However, there are inconsistent findings across studies that may reduce our understanding of any potential associations. We propose that these differences may reflect the tools used to record historical PA. We conducted a systematic review evaluating the risk of developing ALS due to PA. The inclusion criteria were met by 22/113 studies, and an association between increasing PA and ALS was found in 15 studies. Studies that found a positive association were more likely to have longer recall periods and convert data into Metabolic Equivalent of Task values. Studies that did not find an association with increasing PA were more likely to use questionnaires with no validity or reliability data. Questionnaires with validity data all showed at least a moderate correlation of PA compared to objective measures, with reliability ranging from poor to good. Study designs included prospective cohort and case-control, which may also contribute to heterogeneity in findings. This work highlights the need for consensus on the type of questionnaire to use to assess potential associations between PA and ALS.}, }
@article {pmid40252666, year = {2025}, author = {Balendra, R and Sreedharan, J and Hallegger, M and Luisier, R and Lashuel, HA and Gregory, JM and Patani, R}, title = {Amyotrophic lateral sclerosis caused by TARDBP mutations: from genetics to TDP-43 proteinopathy.}, journal = {The Lancet. Neurology}, volume = {24}, number = {5}, pages = {456-470}, doi = {10.1016/S1474-4422(25)00109-7}, pmid = {40252666}, issn = {1474-4465}, support = {/WT_/Wellcome Trust/United Kingdom ; CC0103/CRUK_/Cancer Research UK/United Kingdom ; R01 NS127186/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism ; *DNA-Binding Proteins/genetics/metabolism ; *TDP-43 Proteinopathies/genetics/pathology ; *Mutation/genetics ; }, abstract = {Mutations in the TARDBP gene, which encodes the TDP-43 protein, account for only 3-5% of familial cases of amyotrophic lateral sclerosis and less than 1% of cases that are apparently idiopathic. However, the discovery of neuronal inclusions of TDP-43 as the neuropathological hallmark in the majority of cases of amyotrophic lateral sclerosis has transformed our understanding of the pathomechanisms underlying neurodegeneration. An individual TARDBP mutation can cause phenotypic heterogeneity. Most mutations lie within the C-terminus of the TDP-43 protein. In pathological conditions, TDP-43 is mislocalised from the nucleus to the cytoplasm, where it can be phosphorylated, cleaved, and form insoluble aggregates. This mislocalisation leads to dysfunction of downstream pathways of RNA metabolism, proteostasis, mitochondrial function, oxidative stress, axonal transport, and local translation. Biomarkers for TDP-43 dysfunction and targeted therapies are being developed, justifying cautious optimism for personalised medicine approaches that could rescue the downstream effects of TDP-43 pathology.}, }
@article {pmid40245393, year = {2025}, author = {Musson, LS and Mitic, N and Leigh-Valero, V and Onambele-Pearson, G and Knox, L and Steyn, FJ and Holdom, CJ and Dick, TJ and van Eijk, RP and van Unnik, JW and Botman, LC and Beswick, E and Murray, D and Griffiths, A and McDermott, C and Hobson, E and Chaouch, A and Hodson-Tole, E}, title = {The Use of Digital Devices to Monitor Physical Behavior in Motor Neuron Disease: Systematic Review.}, journal = {Journal of medical Internet research}, volume = {27}, number = {}, pages = {e68479}, pmid = {40245393}, issn = {1438-8871}, mesh = {Humans ; *Exercise ; *Motor Neuron Disease/diagnosis/physiopathology ; *Wearable Electronic Devices ; }, abstract = {BACKGROUND: Motor neuron disease (MND) is a progressive and incurable neurodegenerative disease. The Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) is the primary clinical tool for assessing disease severity and progression in MND. However, despite its widespread use, it does not adequately capture the extent of physical function decline. There is an urgent need for sensitive measures of disease progression that can be used to robustly evaluate new treatments. Measures of physical function derived from digital devices are beginning to be used to assess disease progression. There is value in establishing a consensus approach to standardizing the use of such devices.<br><br>OBJECTIVE: We aimed to explore how digital devices are being used to quantify free-living physical behavior in MND. We evaluated the feasibility and assessed the implications for monitoring physical behavior for future clinical trials and clinical practice.<br><br>METHODS: Systematic searches of 4 databases were performed in October 2023 and June 2024. Peer-reviewed English-language articles (including preprints) that examined how people living with MND used digital devices to assess their free-living physical behavior were included. Study reporting quality was assessed using a 22-item checklist (maximum possible score=44 points).<br><br>RESULTS: In total, 12 articles met the inclusion criteria for data extraction. All studies were longitudinal and observational in design, but data collection, analysis, and reporting protocols varied. Quality assessment scores ranged between 19 and 40 points. Sample sizes ranged between 10 and 376 people living with MND at baseline, declining over the course of the study. Most studies used an accelerometer device worn on the wrist, chest, hip, or ankle. Participants were typically asked to continuously wear devices for 1 to 8 days at 1- to 4-month intervals, with studies running for 12 weeks to 24 months. Some studies asked participants to wear the device continuously for the full duration. Studies derived traditional end points focusing on duration, intensity, and frequency of physical activity or nontraditional end points focusing on features of an individual's movement patterns. The correlation coefficients (r) between physical behavior end points and ALSFRS-R ranged from 0.31 to 0.78. Greater monitoring frequencies and improved end point sensitivity were shown to provide smaller sample size requirements and shorter durations for hypothetical clinical trials. People living with MND found using devices acceptable and reported a low burden. Adherence assessed in 8 (67%) studies was good, ranging from approximately 86% to 96%, with differences evident between wear locations. The perspectives of other end users and implications on clinical practice were not explored.<br><br>CONCLUSIONS: Remote monitoring of free-living physical behavior in MND is in its infancy but has the potential to quantify physical function. It is essential to develop a consensus statement, working toward agreed and standardized methods for data collection, analysis, and reporting.}, }
@article {pmid40244061, year = {2025}, author = {Tseriotis, VS and Liampas, A and Lazaridou, IZ and Karachrysafi, S and Vavougios, GD and Hadjigeorgiou, GM and Papamitsou, T and Kouvelas, D and Arnaoutoglou, M and Pourzitaki, C and Mavridis, T}, title = {Repulsive Guidance Molecule-A as a Therapeutic Target Across Neurological Disorders: An Update.}, journal = {International journal of molecular sciences}, volume = {26}, number = {7}, pages = {}, pmid = {40244061}, issn = {1422-0067}, mesh = {Humans ; Animals ; *Nervous System Diseases/metabolism/drug therapy ; *Nerve Tissue Proteins/metabolism/antagonists &amp; inhibitors/genetics ; *GPI-Linked Proteins/metabolism/antagonists &amp; inhibitors/genetics ; Molecular Targeted Therapy ; Neurodegenerative Diseases/metabolism/drug therapy ; }, abstract = {Repulsive guidance molecule-a (RGMa) has emerged as a significant therapeutic target in a variety of neurological disorders, including neurodegenerative diseases and acute conditions. This review comprehensively examines the multifaceted role of RGMa in central nervous system (CNS) pathologies such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, neuromyelitis optica spectrum disorder, spinal cord injury, stroke, vascular dementia, auditory neuropathy, and epilepsy. The mechanisms through which RGMa contributes to neuroinflammation, neuronal degeneration, and impaired axonal regeneration are herein discussed. Evidence from preclinical studies associate RGMa overexpression with negative outcomes, such as increased neuroinflammation and synaptic loss, while RGMa inhibition, particularly the use of agents like elezanumab, has shown promise in enhancing neuronal survival and functional recovery. RGMa's responses concerning immunomodulation and neurogenesis highlight its potential as a therapeutic avenue. We emphasize RGMa's critical role in CNS pathology and its potential to pave the way for innovative treatment strategies in neurological disorders. While preclinical findings are encouraging so far, further clinical trials are needed to validate the safety and efficacy of RGMa-targeted therapies.}, }
@article {pmid40243699, year = {2025}, author = {Xu, R and Kang, Q and Yang, X and Yi, P and Zhang, R}, title = {Unraveling Molecular Targets for Neurodegenerative Diseases Through Caenorhabditis elegans Models.}, journal = {International journal of molecular sciences}, volume = {26}, number = {7}, pages = {}, pmid = {40243699}, issn = {1422-0067}, support = {32270739//National Natural Science Foundation of China/ ; }, mesh = {*Caenorhabditis elegans/genetics/metabolism ; Animals ; *Neurodegenerative Diseases/metabolism/genetics/drug therapy/pathology ; *Disease Models, Animal ; Humans ; Caenorhabditis elegans Proteins/metabolism/genetics ; }, abstract = {Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and prion disease, represent a group of age-related disorders that pose a growing and formidable challenge to global health. Despite decades of extensive research that has uncovered key genetic factors and biochemical pathways, the precise molecular mechanisms underlying these diseases and effective therapeutic strategies remain elusive. Caenorhabditis elegans (C. elegans) has emerged as a powerful model organism for studying NDDs due to its unique biological features such as genetic tractability, conserved molecular pathways, and ease of high-throughput screening. This model provides an exceptional platform for identifying molecular targets associated with NDDs and developing novel therapeutic interventions. This review highlights the critical role of C. elegans in elucidating the complex molecular mechanisms of human NDDs, with a particular focus on recent advancements and its indispensable contributions to the discovery of molecular targets and therapeutic strategies for these NDDs.}, }
@article {pmid40243463, year = {2025}, author = {Fan, X and Diao, W and Wang, H and Yin, X and Qian, W}, title = {Interferon Regulatory Factors as a Potential Therapeutic Target for Neuroinflammation: A Focus on Alzheimer's Disease.}, journal = {International journal of molecular sciences}, volume = {26}, number = {7}, pages = {}, pmid = {40243463}, issn = {1422-0067}, support = {82473926//National Natural Science Foundation of China/ ; 81872875//National Natural Science Foundation of China/ ; 81170317//National Natural Science Foundation of China/ ; 81473218//National Natural Science Foundation of China/ ; 81503077//National Natural Science Foundation of China/ ; JC2023042//the project of Nantong Natural Science Foundation/ ; }, mesh = {Humans ; *Alzheimer Disease/metabolism/drug therapy/pathology ; Animals ; *Interferon Regulatory Factors/metabolism/genetics ; *Neuroinflammatory Diseases/metabolism/drug therapy ; Signal Transduction ; Inflammation/metabolism ; }, abstract = {Interferon Regulatory Factors (IRFs) are critical modulators of immune and inflammatory responses, yet their roles in Alzheimer's disease (AD) and other neurodegenerative disorders remain incompletely understood. While IRFs are recognized for their regulatory functions in neuroinflammation, microglial activation, and neuronal survival, their dual roles as both drivers of pathological inflammation and mediators of neuroprotective pathways underscore a sophisticated regulatory paradox in neurodegenerative disorders. This review aims to synthesize current evidence on IRF-mediated neuroinflammation in AD and related diseases, focusing on the multifaceted functions of key IRF family members, including IRF1, IRF3, and IRF7. We critically evaluate their divergent roles: IRF1 and IRF3, for instance, exacerbate neuroinflammatory cascades and amyloid-beta (Aβ) pathology in AD, whereas IRF7 may paradoxically suppress inflammation under specific conditions. Additionally, we explore IRF dysregulation in Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, and Huntington's disease, emphasizing shared and distinct mechanisms across neurodegenerative disorders. Restoring IRF balance through genetic manipulation, small-molecule inhibitors, or microbiome-derived modulators could attenuate neuroinflammation, enhance Aβ clearance, and protect neuronal integrity. Ultimately, this work provides a framework for future research to harness IRF signaling pathways in the development of precision therapies for AD and other neurodegenerative diseases.}, }
@article {pmid40234983, year = {2025}, author = {Xie, Q and Li, K and Chen, Y and Li, Y and Jiang, W and Cao, W and Yu, H and Fan, D and Deng, B}, title = {Gene therapy breakthroughs in ALS: a beacon of hope for 20% of ALS patients.}, journal = {Translational neurodegeneration}, volume = {14}, number = {1}, pages = {19}, pmid = {40234983}, issn = {2047-9158}, support = {81901273//National Natural Science Foundation of China/ ; ZCLY24H0903//Natural Science Foundation of Zhejiang Province/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/therapy/genetics ; Humans ; *Genetic Therapy/methods/trends ; Animals ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease that remains incurable. Although the etiologies of ALS are diverse and the precise pathogenic mechanisms are not fully understood, approximately 20% of ALS cases are caused by genetic factors. Therefore, advancing targeted gene therapies holds significant promise, at least for the 20% of ALS patients with genetic etiologies. In this review, we summarize the main strategies and techniques of current ALS gene therapies based on ALS risk genes, and review recent findings from animal studies and clinical trials. Additionally, we highlight ALS-related genes with well-understood pathogenic mechanisms and the potential of numerous emerging gene-targeted therapeutic approaches for ALS.}, }
@article {pmid40234116, year = {2025}, author = {McHale-Owen, H and Faller, KME and Chaytow, H and Gillingwater, TH}, title = {Phosphoglycerate kinase 1 as a therapeutic target in neurological disease.}, journal = {Trends in molecular medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.molmed.2025.03.008}, pmid = {40234116}, issn = {1471-499X}, abstract = {Phosphoglycerate kinase 1 (PGK1) is a highly conserved enzyme that catalyzes the initial ATP-producing step in glycolysis. Improving cellular energy production by increasing PGK1 activity may be beneficial in multiple neurological conditions where cell metabolism is dysregulated, including Parkinson's disease (PD) and motor neuron disease (MND). This review examines recent evidence that suggests increasing PGK1 activity may be beneficial in multiple neurological conditions and discusses the current challenges surrounding the development of PGK1-focused therapies. PGK1 has considerable therapeutic potential, but novel PGK1 activators are needed to maximize the benefit for patients.}, }
@article {pmid40232582, year = {2025}, author = {Mehrnoosh, F and Rezaei, D and Pakmehr, SA and Nataj, PG and Sattar, M and Shadi, M and Ali-Khiavi, P and Zare, F and Hjazi, A and Al-Aouadi, RFA and Sapayev, V and Zargari, F and Alkhathami, AG and Ahmadzadeh, R and Khedmatgozar, M and Hamzehzadeh, S}, title = {The role of Panax ginseng in neurodegenerative disorders: mechanisms, benefits, and future directions.}, journal = {Metabolic brain disease}, volume = {40}, number = {4}, pages = {183}, pmid = {40232582}, issn = {1573-7365}, mesh = {Humans ; *Panax ; *Neurodegenerative Diseases/drug therapy/metabolism ; Animals ; *Ginsenosides/therapeutic use/pharmacology ; *Neuroprotective Agents/therapeutic use/pharmacology ; *Plant Extracts/therapeutic use/pharmacology ; Oxidative Stress/drug effects ; }, abstract = {Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), Multiple sclerosis (MS), and Huntington's disease (HD) represent a growing global health challenge, especially with aging populations. Characterized by progressive neuronal loss, these diseases lead to cognitive, motor, and behavioral impairments, significantly impacting patients' quality of life. Current therapies largely address symptoms without halting disease progression, underscoring the need for innovative, disease-modifying treatments. Ginseng, a traditional herbal medicine with well-known adaptogenic and neuroprotective properties, has gained attention as a potential therapeutic agent for neurodegeneration. Rich in bioactive compounds called ginsenosides, ginseng exhibits antioxidant, anti-inflammatory, and anti-apoptotic effects, making it a promising candidate for addressing the complex pathology of neurodegenerative diseases. Recent studies demonstrate that ginsenosides modulate disease-related processes such as oxidative stress, protein aggregation, mitochondrial dysfunction, and inflammation. In AD models, ginsenosides have been shown to reduce amyloid-beta accumulation and tau hyperphosphorylation, while in PD, they help protect dopaminergic neurons and mitigate motor symptoms. Ginseng's effects in ALS, MS, and HD models include improving motor function, extending neuronal survival, and reducing cellular toxicity. This review provides a comprehensive overview of the neuroprotective mechanisms of ginseng, emphasizing its therapeutic potential across various neurodegenerative diseases and discussing future research directions for its integration into clinical practice.}, }
@article {pmid40222791, year = {2025}, author = {Bhardwaj, I and Singh, S and Ansari, AH and Rai, SP and Singh, D}, title = {Effect of stress on neuronal cell: Morphological to molecular approach.}, journal = {Progress in brain research}, volume = {291}, number = {}, pages = {469-502}, doi = {10.1016/bs.pbr.2025.01.010}, pmid = {40222791}, issn = {1875-7855}, mesh = {Humans ; Animals ; *Neurons/pathology/metabolism/physiology ; *Stress, Psychological/pathology/metabolism ; *Brain/pathology ; }, abstract = {Stress can be characterized as any perceived or actual threat that necessitates compensatory actions to maintain homeostasis. It can alter an organism's behavior over time by permanently altering the composition and functionality of brain circuitry. The amygdala and prefrontal cortex are two interrelated brain regions that have been the focus of initial research on stress and brain structural and functional plasticity, with the hippocampus serving as the entry point for most of this knowledge. Prolonged stress causes significant morphological alterations in important brain regions such as the hippocampus, amygdala, and prefrontal cortex. Memory, learning, and emotional regulation are among the cognitive functions that are adversely affected by these changes, including neuronal shrinkage, dendritic retraction, and synaptic malfunction. Stress perturbs the equilibrium of neurotransmitters, neuronal plasticity, and mitochondrial function at the molecular level. On the other hand, chronic stress negatively impacts physiology and can result in neuropsychiatric diseases. Recent molecular research has linked various epigenetic processes, such as DNA methylation, histone modifications, and noncoding RNAs, to the dysregulation of genes in the impacted brain circuits responsible for the pathophysiology of chronic stress. Numerous disorders, including neurodegenerative diseases (NDDs) including Alzheimer's, amyotrophic lateral sclerosis, Friedreich's ataxia, Huntington's disease, multiple sclerosis, and Parkinson's disease, have been linked to oxidative stress as a possible cause.}, }
@article {pmid40216201, year = {2025}, author = {Cagalinec, M and Mohd, A and Borecka, S and Bultynck, G and Choubey, V and Yanovsky-Dagan, S and Ezer, S and Gasperikova, D and Harel, T and Jurkovicova, D and Kaasik, A and Liévens, JC and Maurice, T and Peviani, M and Richard, EM and Skoda, J and Skopkova, M and Tarot, P and Van Gorp, R and Zvejniece, L and Delprat, B}, title = {Improving mitochondria-associated endoplasmic reticulum membranes integrity as converging therapeutic strategy for rare neurodegenerative diseases and cancer.}, journal = {Biochimica et biophysica acta. Molecular cell research}, volume = {1872}, number = {5}, pages = {119954}, doi = {10.1016/j.bbamcr.2025.119954}, pmid = {40216201}, issn = {1879-2596}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/pathology/therapy/genetics ; *Endoplasmic Reticulum/metabolism/pathology ; *Mitochondria/metabolism/pathology ; *Neoplasms/metabolism/pathology/therapy/genetics ; Animals ; Receptors, sigma/metabolism ; Calcium Signaling ; Sigma-1 Receptor ; *Intracellular Membranes/metabolism ; Unfolded Protein Response ; Mitochondrial Membranes/metabolism ; }, abstract = {Membrane contact sites harbor a distinct set of proteins with varying biological functions, thereby emerging as hubs for localized signaling nanodomains underlying adequate cell function. Here, we will focus on mitochondria-associated endoplasmic reticulum membranes (MAMs), which serve as hotspots for Ca[2+] signaling, redox regulation, lipid exchange, mitochondrial quality and unfolded protein response pathway. A network of MAM-resident proteins contributes to the structural integrity and adequate function of MAMs. Beyond endoplasmic reticulum (ER)-mitochondrial tethering proteins, MAMs contain several multi-protein complexes that mediate the transfer of or are influenced by Ca[2+], reactive oxygen species and lipids. Particularly, IP3 receptors, intracellular Ca[2+]-release channels, and Sigma-1 receptors (S1Rs), ligand-operated chaperones, serve as important platforms that recruit different accessory proteins and intersect with these local signaling processes. Furthermore, many of these proteins are directly implicated in pathophysiological conditions, where their dysregulation or mutation is not only causing diseases such as cancer and neurodegeneration, but also rare genetic diseases, for example familial Parkinson's disease (PINK1, Parkin, DJ-1), familial Amyotrophic lateral sclerosis (TDP43), Wolfram syndrome1/2 (WFS1 and CISD2), Harel-Yoon syndrome (ATAD3A). In this review, we will discuss the current state-of-the-art regarding the molecular components, protein platforms and signaling networks underlying MAM integrity and function in cell function and how their dysregulation impacts MAMs, thereby driving pathogenesis and/or impacting disease burden. We will highlight how these insights can generate novel, potentially therapeutically relevant, strategies to tackle disease outcomes by improving the integrity of MAMs and the signaling processes occurring at these membrane contact sites.}, }
@article {pmid40213632, year = {2025}, author = {Dezawa, M}, title = {Macrophage- and pluripotent-like reparative Muse cells are unique endogenous stem cells distinct from other somatic stem cells.}, journal = {Frontiers in bioengineering and biotechnology}, volume = {13}, number = {}, pages = {1553382}, pmid = {40213632}, issn = {2296-4185}, abstract = {Muse cells are endogenous reparative stem cells with dual characteristics: pluripotent-like and macrophage-like. They can be identified by the pluripotent surface marker stage-specific embryonic antigen-3-positive (SSEA-3 (+)) cells in the bone marrow, peripheral blood, and various organs, including the umbilical cord and amnion. Muse cells can differentiate into ectodermal, endodermal, and mesodermal lineage cells, self-renew, and selectively migrate to damaged sites by sensing one of the universal tissue damage signals, sphingosine-1-phosphate (S1P). At these sites, they phagocytose damaged/apoptotic cells and differentiate into the same cell type as the phagocytosed cells. In this manner, Muse cells replace damaged/apoptotic cells with healthy, functioning cells, thereby repairing tissues. Due to their specific immunosuppressive and immunotolerant mechanism, clinical trials have been conducted for acute myocardial infarction (AMI), subacute ischemic stroke, epidermolysis bullosa, amyotrophic lateral sclerosis (ALS), cervical spinal cord injury, neonatal hypoxic-ischemic encephalopathy (HIE), and COVID-19 acute respiratory distress syndrome. These trials involved the intravenous injection of ∼1.5 × 10[7] donor Muse cells without human leukocyte antigen (HLA) matching or immunosuppressant treatment, and they demonstrated safety and therapeutic efficacy. Thus, donor Muse cell treatment does not require gene manipulation, differentiation induction, or surgical intervention. These unique characteristics distinguish Muse cells from other somatic stem cells, such as mesenchymal stem cells, VSEL stem cells, and marrow-isolated adult multi-lineage inducible (MIAMI) cells.}, }
@article {pmid40209696, year = {2025}, author = {Hawas, Y and Hamad, AA and Meshref, M and Elbehary, M and Mohamed, RG and Elshahat, A and Mabrouk, MA and Nashwan, AJ and Fouda, BH}, title = {Clinical Features, Diagnostic Implications, and Outcomes of Amyotrophic Lateral Sclerosis and Myasthenia Gravis Overlap Syndrome: A Systematic Review.}, journal = {Medical principles and practice : international journal of the Kuwait University, Health Science Centre}, volume = {}, number = {}, pages = {1-11}, pmid = {40209696}, issn = {1423-0151}, abstract = {OBJECTIVE: This review aimed to summarize the current evidence of reported myasthenia gravis (MG) and amyotrophic lateral sclerosis (ALS) overlap syndrome regarding clinical and laboratory features, diagnostic implications, management, outcomes, and comorbid conditions to raise awareness among healthcare providers and aid in proper care provision.<br><br>METHODS: Recently, a few cases of an unusual association between both diseases have been reported. PubMed, Scopus, and Web of Science were searched from inception until May 2024 to identify eligible studies. After the screening and data extraction, 20 studies with 42 cases suffering from ALS and MG were included.<br><br>RESULTS: Forty-two cases were categorized into four groups as follows: the first group had 26 cases with MG onset (age range 26-82 years) preceding ALS (age range 46-83 years). The second group had 9 cases with ALS onset (age range 34-89 years) preceding MG (age range 40-89 years). The third group comprised 5 cases of ALS with positive acetylcholine receptor antibodies but without clinical manifestations of MG. The fourth group involved 2 cases of ALS with initial ocular symptoms that were unresponsive to MG treatments.<br><br>CONCLUSION: The onset of new ptosis or diplopia in ALS patients should prompt clinicians to consider the possibility of a coexisting condition or alternative diagnosis. Additionally, positive acetylcholine receptor antibodies alone are insufficient to diagnose MG if ALS coexists. In patients with ALS, repetitive nerve stimulation tests may be less sensitive for detecting MG. Thus, diagnosing MG in ALS patients should rely on clinical presentation and response to empirical treatment.}, }
@article {pmid40209306, year = {2025}, author = {Meanti, R and Bresciani, E and Rizzi, L and Molteni, L and Coco, S and Omeljaniuk, RJ and Torsello, A}, title = {Cannabinoid Receptor 2 (CB2R) as potential target for the pharmacological treatment of neurodegenerative diseases.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {186}, number = {}, pages = {118044}, doi = {10.1016/j.biopha.2025.118044}, pmid = {40209306}, issn = {1950-6007}, mesh = {Humans ; *Receptor, Cannabinoid, CB2/metabolism/agonists ; *Neurodegenerative Diseases/drug therapy/metabolism ; Animals ; Endocannabinoids/metabolism ; Molecular Targeted Therapy ; Cannabinoid Receptor Agonists/therapeutic use ; }, abstract = {The endocannabinoid system (ECS) is a ubiquitous physiological system that plays a crucial role in maintaining CNS homeostasis and regulating its functions. It includes cannabinoid receptors (CBRs), endogenous cannabinoids (eCBs), and the enzymes responsible for their synthesis and degradation. In recent years, growing evidence has highlighted the therapeutic potential of the ECS and CBRs, in a wide range of severe diseases and pathological conditions, including Alzheimer's and Parkinson's diseases, Amyotrophic Lateral Sclerosis, Multiple Sclerosis, Huntington's Disease, HIV-1 associated neurocognitive disorders, neuropathic pain and migraine. Targeting the cannabinoid type 2 receptor (CB2R) has gained attention due to its ability to (i) mitigate neuroinflammatory responses, (ii) regulate mitochondrial function and (iii) provide trophic support, all without eliciting the psychotropic actions associated with CB1R activation. This review aims to explore the potential of CB2R modulation as a strategy for the prevention and treatment of neurologic disorders, exploring both preclinical and clinical findings.}, }
@article {pmid40205152, year = {2025}, author = {Mohan, M and Mannan, A and Singh, TG}, title = {Unravelling the role of protein kinase R (PKR) in neurodegenerative disease: a review.}, journal = {Molecular biology reports}, volume = {52}, number = {1}, pages = {377}, pmid = {40205152}, issn = {1573-4978}, mesh = {Humans ; *eIF-2 Kinase/metabolism/genetics ; *Neurodegenerative Diseases/metabolism/genetics ; Animals ; Parkinson Disease/metabolism/genetics ; Huntington Disease/genetics/metabolism ; Alzheimer Disease/metabolism/genetics ; Mitochondria/metabolism ; }, abstract = {Protein Kinase R is an essential regulator of many cell activities and belongs to one of the largest and most functionally complex gene families. These are found all over the body, and by adding phosphate groups to the substrate proteins, they regulate their activity and coordinate the action of almost all cellular processes. Recent research has illuminated the involvement of PKR in the pathogenesis of neurodegenerative disorders (NDs), thereby expanding our understanding of intricate molecular mechanisms underlying disease progression. Through their inhibition or activation, they hold potential therapeutic targets for the pathogenesis or protection of NDs. In the case of AD (AD), PKR contributes to the protection or elevation of Aβ accumulation, neuroinflammation, synaptic plasticity alterations, and neuronal excitability. Similarly, in Parkinson's disease (PD), PKR again has a dual role in dopaminergic neuronal loss, gene mutations, and mitochondrial dysfunction via various pathways. Notably, neuronal excitotoxicity, as well as genetic mutations, have been linked to ALS. In Huntington's disease (HD), PKR is associated with decreased or increased mutated genes, striatal neuron degeneration, neuroinflammation, and excitotoxicity. This review emphasizes strategies that target PKR for the treatment of neurodegenerative disorders. Doing so offers valuable insights that can guide future research endeavors and the development of innovative therapeutic approaches.}, }
@article {pmid40202704, year = {2025}, author = {Oyovwi, MO and Chijiokwu, EA and Ben-Azu, B and Atere, AD and Joseph, UG and Ogbutor, UG and Udi, OA}, title = {Potential Roles of Natural Antioxidants in Modulating Neurodegenerative Disease Pathways.}, journal = {Molecular neurobiology}, volume = {62}, number = {8}, pages = {10367-10397}, pmid = {40202704}, issn = {1559-1182}, mesh = {Humans ; *Antioxidants/therapeutic use/pharmacology ; *Neurodegenerative Diseases/drug therapy/metabolism/pathology ; Animals ; Oxidative Stress/drug effects ; Neuroprotective Agents/therapeutic use/pharmacology ; *Signal Transduction/drug effects ; *Biological Products/therapeutic use/pharmacology ; }, abstract = {Neurodegenerative diseases, including Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis, are increasingly prevalent among aging populations. Oxidative stress contributes to these diseases, leading to cellular damage and neuronal death. Natural antioxidants are being explored as preventive measures. This study aims to assess the effectiveness of natural antioxidants in delaying the onset or progression of neurodegenerative diseases by identifying their specific mechanisms of action. A comprehensive review of existing literature was conducted, focusing on studies that examine the role of natural antioxidants in neuroprotection. Key natural antioxidants, including flavonoids, polyphenls, vitamins C and E, and omega-3 fatty acids, were reviewed and analyzed for their bioavailability, mechanisms of action, and outcomes in both in vitro and in vivo studies. Additionally, clinical trials involving human subjects were considered to provide insights into the translational implications of antioxidant consumption. The findings suggest that several natural antioxidants exhibit neuroprotective properties by modulating oxidative stress, reducing inflammation, and promoting neuronal survival. For instance, flavonoids such as quercetin and resveratrol have shown promise in enhancing cognitive function and mitigating the pathophysiological alterations associated with neurodegeneration. In clinical studies, higher intakes of dietary antioxidants were correlated with a reduced risk of developing neurodegenerative disorders. Natural antioxidants offer potential for preventing neurodegenerative diseases by counteracting oxidative stress and maintaining cellular integrity. Overall, our report recommends that further research is needed to optimize dosages and understand their long-term benefits.}, }
@article {pmid40198473, year = {2025}, author = {Seok, HY}, title = {Critical issues in the use of edaravone for the treatment of amyotrophic lateral sclerosis.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {46}, number = {8}, pages = {3427-3430}, pmid = {40198473}, issn = {1590-3478}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy ; Humans ; *Edaravone/therapeutic use ; *Neuroprotective Agents/therapeutic use ; *Free Radical Scavengers/therapeutic use ; Disease Progression ; Riluzole/therapeutic use ; }, abstract = {Edaravone, along with riluzole, is a key treatment for amyotrophic lateral sclerosis (ALS), with evidence supporting its efficacy in slowing disease progression, particularly in patients with early-stage ALS. Despite its approval and increasing clinical use, several critical questions about its use remain unanswered: Can edaravone be effective as monotherapy? Is it beneficial for patients who fall outside the inclusion criteria of pivotal trials? What is the optimal duration of treatment as ALS progresses? In addition, does edaravone provide clinical benefit to patients with familial ALS? Answering these questions is essential to optimize the use of edaravone in clinical practice and to further our understanding of its role in the treatment of ALS. This review synthesizes the current evidence to address these questions and identifies areas that require further investigation.}, }
@article {pmid40196899, year = {2025}, author = {Li, S and Pandat, T and Chi, B and Moon, D and Mas, M}, title = {Management Approaches to Spastic Gait Disorders.}, journal = {Muscle &amp; nerve}, volume = {72}, number = {2}, pages = {179-200}, doi = {10.1002/mus.28402}, pmid = {40196899}, issn = {1097-4598}, mesh = {Humans ; *Gait Disorders, Neurologic/therapy/etiology/diagnosis/physiopathology ; *Muscle Spasticity/therapy/complications/physiopathology/diagnosis ; *Disease Management ; }, abstract = {Spastic gait presents clinically as the net mechanical consequence of neurological impairments of spasticity, weakness, and abnormal synergies and their interactions with the ground reaction force in patients with upper motor neuron syndromes and with some neuromuscular diseases. It is critical to differentiate whether the primary problem is weakness or spasticity, thus better understanding different phenotypes of spastic gait disorders. Pelvic girdle abnormality plays a pivotal role in determining the clinical presentation of gait disorders, since it determines the body vector and compensatory kinetic chain reactions in the knee and ankle joints. Knee joint abnormality can be a mechanical compensation for hip and/or ankle and foot abnormality. Diagnostic nerve blocks and instrumented gait analysis may be needed for diagnosing the underlying problems and developing an individualized plan of care. A wide spectrum of treatment options has been used to manage spastic gait disorders. Some are in early and investigational stages, such as neuromodulation modalities, while others are well-developed, such as therapeutic exercise, ankle-foot orthoses, botulinum toxin treatment, and surgical interventions. Physicians and other healthcare providers who manage spastic gait disorders should be familiar with these treatment options and should employ appropriate interventions concurrently rather than serially. The most effective treatments can be selected based on careful evaluation, inputs from patients, family, and therapists, along with appropriate goal setting. Treatment plans need to be re-evaluated for effectiveness, relevance, and in concordance with disease progress. This is particularly important for patients with progressive neuromuscular diseases such as amyotrophic lateral sclerosis.}, }
@article {pmid40193512, year = {2025}, author = {Heidelburg, K and Sipior, C and King, J and Cueto Brito, M and Fredrick, S}, title = {A systematic review of cultural adaptations to social emotional learning interventions for PreK-12th grade Black students.}, journal = {School psychology (Washington, D.C.)}, volume = {40}, number = {2}, pages = {121-132}, doi = {10.1037/spq0000676}, pmid = {40193512}, issn = {2578-4226}, mesh = {Humans ; *Black or African American/psychology ; Adolescent ; Child ; *Social Learning ; *Students/psychology ; *Emotions ; Schools ; }, abstract = {Due to the lack of culturally responsive social-emotional learning (SEL) interventions and the negative implications of discipline disproportionality of Black students in schools, there is a dire need to develop and implement SEL interventions that promote racial equity and align with the specific cultural needs of Black youth. This systematic review explores cultural adaptations used in SEL interventions for Black PreK-12 students and their associated outcomes. A total of 15 studies with 339 Black/African American students ranging from 8 to 15 years old were included. Each study used at least four or more culturally adapted elements outlined in Bernal et al.'s (1995) Ecological Validity Framework, and every study utilized content and method adaptation elements to meet the needs of Black students. Outcomes associated with cultural adaptation SEL interventions for Black students included positive changes in racial/ethnic identity and increases in skill acquisition and performance across various social, emotional, and behavioral domains. Findings from the current review expand the research on evidence-based, culturally responsive SEL interventions for Black students and highlight the positive outcomes associated with cultural adaptations of SEL interventions for Black students. (PsycInfo Database Record (c) 2025 APA, all rights reserved).}, }
@article {pmid40192904, year = {2025}, author = {Kodirov, SA}, title = {Comparison of Superoxide Dismutase Activity at the Cell, Organ, and Whole-Body Levels.}, journal = {Cell biochemistry and biophysics}, volume = {}, number = {}, pages = {}, pmid = {40192904}, issn = {1559-0283}, abstract = {Superoxide dismutase (SOD) can be considered an antitoxic metalloenzyme that facilitates the production of oxygen and hydrogen peroxide from superoxide anions. Four classes have been identified depending on selective binding of metals, namely Cu,Zn-SOD, Fe-SOD, Mn-SOD, and Ni-SOD. The established isoforms are SOD1, SOD2, and SOD3 in various cells and tissues of eukaryotes. The relatively newer type Ni-SOD binds nickel and is observed in bacteria, including the genus Streptomyces. The Fe-SOD and Mn-SOD are also present in bacteria. Cu,Zn superoxide dismutase (SOD1) activity correlates with various pathophysiological states of organs. SOD2 binds manganese (Mn) and is located in the mitochondria. The SOD3, similar to the SOD1, binds copper and zinc, which are also expressed in the brain. The assay relies on several methods, including the enzyme activities, expression, field potential, and patch-clamp electrophysiology. The effects of SOD activity are emphasized at organ and whole-body levels depending on animal models. The antioxidant properties and behavior of SOD are compared based on responses among females and males to diet and toxic substances. However, in humans with amyotrophic lateral sclerosis (ALS), the mean SOD activity in both erythrocytes and muscles was comparable to controls. The detailed comparisons between the catalase and SOD activities are one of the aspects of this review. Also, modulation of excitability and synaptic plasticity in neurons by SOD is highlighted.}, }
@article {pmid40189519, year = {2025}, author = {Tseng, PT and Zeng, BY and Hsu, CW and Hung, CM and Carvalho, AF and Stubbs, B and Chen, YW and Chen, TY and Lei, WT and Chen, JJ and Su, KP and Shiue, YL and Liang, CS}, title = {The pharmacodynamics-based prophylactic benefits of GLP-1 receptor agonists and SGLT2 inhibitors on neurodegenerative diseases: evidence from a network meta-analysis.}, journal = {BMC medicine}, volume = {23}, number = {1}, pages = {197}, pmid = {40189519}, issn = {1741-7015}, mesh = {Humans ; *Glucagon-Like Peptide-1 Receptor Agonists/pharmacology/therapeutic use ; Hypoglycemic Agents/pharmacology/therapeutic use ; *Neurodegenerative Diseases/prevention &amp; control/drug therapy ; Randomized Controlled Trials as Topic ; *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/pharmacology ; }, abstract = {BACKGROUND: Glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors represent a new generation of antihyperglycemic agents that operate through mechanisms distinct from conventional diabetes treatments. Beyond their metabolic effects, these medications have demonstrated neuroprotective properties in preclinical studies. While clinical trials have explored their therapeutic potential in established neurodegenerative conditions, their role in disease prevention remains unclear. We conducted a network meta-analysis (NMA) to comprehensively evaluate the prophylactic benefits of these agents across multiple neurodegenerative diseases and identify the most promising preventive strategies.<br><br>METHODS: We systematically searched PubMed, Embase, ClinicalKey, Cochrane CENTRAL, ProQuest, ScienceDirect, Web of Science, and ClinicalTrials.gov through October 24th, 2024, for randomized controlled trials (RCTs) of GLP-1 receptor agonists or SGLT2 inhibitors. Our primary outcome was the incidence of seven major neurodegenerative diseases: Parkinson's disease, Alzheimer's disease, Lewy body dementia, multiple sclerosis, amyotrophic lateral sclerosis, frontotemporal dementia, and Huntington's disease. Secondary outcomes included safety profiles assessed through dropout rates. We performed a frequentist-based NMA and evaluated risk of bias with Risk of Bias tool. The main result of the primary outcome in the current study would be re-affirmed via sensitivity test with Bayesian-based NMA.<br><br>RESULTS: Our analysis encompassed 22 RCTs involving 138,282 participants (mean age 64.8&#xa0;years, 36.4% female). Among all investigated medications, only dapagliflozin demonstrated significant prophylactic benefits, specifically in preventing Parkinson's disease (odds ratio&#x2009;=&#x2009;0.28, 95%&#xa0;confidence intervals&#x2009;=&#x2009;0.09 to 0.93) compared to controls. Neither GLP-1 receptor agonists nor other SGLT2 inhibitors showed significant preventive effects for any of the investigated neurodegenerative conditions. Drop-out rates were comparable across all treatments.<br><br>CONCLUSIONS: This comprehensive NMA reveals a novel and specific prophylactic effect of dapagliflozin against Parkinson's disease, representing a potential breakthrough in preventive neurology. The specificity of dapagliflozin's protective effect to Parkinson's disease might rely on its highly selective inhibition to SGLT2. These findings provide important direction for future research and could inform preventive strategies for populations at risk of Parkinson's disease.<br><br>TRIAL REGISTRATION: PROSPERO CRD42021252381.}, }
@article {pmid40188980, year = {2025}, author = {Chong, ZZ and Souayah, N}, title = {Pathogenic TDP-43 in amyotrophic lateral sclerosis.}, journal = {Drug discovery today}, volume = {30}, number = {5}, pages = {104351}, doi = {10.1016/j.drudis.2025.104351}, pmid = {40188980}, issn = {1878-5832}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *DNA-Binding Proteins/genetics/metabolism ; Animals ; Mutation ; Protein Processing, Post-Translational ; }, abstract = {The aberrant expression of the transactive response DNA-binding protein of 43 kDa (TDP-43) has been closely associated with amyotrophic lateral sclerosis (ALS). Cytoplasmic inclusions containing TDP-43 can be found in the brain and spinal cord in up to 97% of ALS cases. Mutations in the TARDBP gene promote the nuclear export of TDP-43, increase cytoplasmic aggregation, and predispose TDP-43 to post-translational modifications. Cleavage of TDP-43 and the resulting C- and N-terminal fragments also contribute to the development of ALS. Cellularly, the resulting impairment of autophagy and mitochondria aggravates cellular damage and neurodegeneration. Given the contribution of pathogenic TDP-43 to the development of ALS, elucidating the mechanisms related to TDP-43 will facilitate finding therapeutic targets for the disease.}, }
@article {pmid40188375, year = {2025}, author = {Prajapati, JL and Dhurandhar, Y and Singh, AP and Gupta, DK and Baghel, VS and Kushwaha, U and Namdeo, KP}, title = {Redox chemical delivery system: an innovative strategy for the treatment of neurodegenerative diseases.}, journal = {Expert opinion on drug delivery}, volume = {22}, number = {6}, pages = {805-822}, doi = {10.1080/17425247.2025.2489558}, pmid = {40188375}, issn = {1744-7593}, mesh = {Humans ; *Drug Delivery Systems ; *Neurodegenerative Diseases/drug therapy/physiopathology ; Oxidation-Reduction ; Blood-Brain Barrier/metabolism ; Animals ; *Central Nervous System Agents/administration &amp; dosage/pharmacokinetics ; Brain/metabolism ; }, abstract = {INTRODUCTION: It is anticipated that the prevalence of illnesses affecting the central nervous system (CNS) will rise significantly due to longer lifespans and changing demography. Age-related decline in brain function and neuronal death are features of neurodegenerative disorders, such as Parkinson's disease, Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis, which provide formidable treatment challenges. Because most therapeutic drugs cannot across the blood-brain barrier (BBB) to reach the brain, there are still few treatment alternatives available despite a great deal of research.<br><br>AREAS COVERED: This study explores the role of redox chemical delivery systems in CNS drug delivery and addresses challenges associated with neurodegenerative disease (ND). Redox Chemical Delivery System offers a promising approach to enhancing leveraging redox reactions that facilitate the transport of therapeutic agents across the BBB. Through the optimization of medication delivery pathways to the brain, this technology has the potential to greatly improve the treatment of ND.<br><br>EXPERT OPINION: As our understanding of the biological underpinnings of ND deepens, the potential for effective interventions increases. Refining drug delivery strategies, such as RCDS, is essential for advancing CNS therapies from research to clinical practice. These advancements could transform the management of ND, improving both treatment efficacy and patient outcomes.}, }
@article {pmid40187044, year = {2025}, author = {Fu, Y and Zhang, J and Qin, R and Ren, Y and Zhou, T and Han, B and Liu, B}, title = {Activating autophagy to eliminate toxic protein aggregates with small molecules in neurodegenerative diseases.}, journal = {Pharmacological reviews}, volume = {77}, number = {3}, pages = {100053}, doi = {10.1016/j.pharmr.2025.100053}, pmid = {40187044}, issn = {1521-0081}, mesh = {Humans ; *Autophagy/drug effects ; *Neurodegenerative Diseases/drug therapy/metabolism/pathology ; Animals ; *Protein Aggregates/drug effects ; *Protein Aggregation, Pathological/drug therapy/metabolism ; }, abstract = {Neurodegenerative diseases (NDs), such as Alzheimer disease, Parkinson disease, Huntington disease, amyotrophic lateral sclerosis, and frontotemporal dementia, are well known to pose formidable challenges for their treatment due to their intricate pathogenesis and substantial variability among patients, including differences in environmental exposures and genetic predispositions. One of the defining characteristics of NDs is widely reported to be the buildup of misfolded proteins. For example, Alzheimer disease is marked by amyloid beta and hyperphosphorylated Tau aggregates, whereas Parkinson disease exhibits α-synuclein aggregates. Amyotrophic lateral sclerosis and frontotemporal dementia exhibit TAR DNA-binding protein 43, superoxide dismutase 1, and fused-in sarcoma protein aggregates, and Huntington disease involves mutant huntingtin and polyglutamine aggregates. These misfolded proteins are the key biomarkers of NDs and also serve as potential therapeutic targets, as they can be addressed through autophagy, a process that removes excess cellular inclusions to maintain homeostasis. Various forms of autophagy, including macroautophagy, chaperone-mediated autophagy, and microautophagy, hold a promise in eliminating toxic proteins implicated in NDs. In this review, we focus on elucidating the regulatory connections between autophagy and toxic proteins in NDs, summarizing the cause of the aggregates, exploring their impact on autophagy mechanisms, and discussing how autophagy can regulate toxic protein aggregation. Moreover, we underscore the activation of autophagy as a potential therapeutic strategy across different NDs and small molecules capable of activating autophagy pathways, such as rapamycin targeting the mTOR pathway to clear α-synuclein and Sertraline targeting the AMPK/mTOR/RPS6KB1 pathway to clear Tau, to further illustrate their potential in NDs' therapeutic intervention. Together, these findings would provide new insights into current research trends and propose small-molecule drugs targeting autophagy as promising potential strategies for the future ND therapies. SIGNIFICANCE STATEMENT: This review provides an in-depth overview of the potential of activating autophagy to eliminate toxic protein aggregates in the treatment of neurodegenerative diseases. It also elucidates the fascinating interrelationships between toxic proteins and the process of autophagy of "chasing and escaping" phenomenon. Moreover, the review further discusses the progress utilizing small molecules to activate autophagy to improve the efficacy of therapies for neurodegenerative diseases by removing toxic protein aggregates.}, }
@article {pmid40185982, year = {2025}, author = {Cummings, JL and Teunissen, CE and Fiske, BK and Le Ber, I and Wildsmith, KR and Schöll, M and Dunn, B and Scheltens, P}, title = {Biomarker-guided decision making in clinical drug development for neurodegenerative disorders.}, journal = {Nature reviews. Drug discovery}, volume = {24}, number = {8}, pages = {589-609}, doi = {10.1038/s41573-025-01165-w}, pmid = {40185982}, issn = {1474-1784}, mesh = {Humans ; *Biomarkers/metabolism/blood ; *Drug Development/methods ; *Neurodegenerative Diseases/drug therapy/diagnosis ; Clinical Trials as Topic/methods ; Animals ; Alzheimer Disease/drug therapy ; }, abstract = {Neurodegenerative disorders are characterized by complex neurobiological changes that are reflected in biomarker alterations detectable in blood, cerebrospinal fluid (CSF) and with brain imaging. As accessible proxies for processes that are difficult to measure, biomarkers are tools that hold increasingly important roles in drug development and clinical trial decision making. In the past few years, biomarkers have been the basis for accelerated approval of new therapies for Alzheimer disease and amyotrophic lateral sclerosis as surrogate end points reasonably likely to predict clinical benefit.Blood-based biomarkers are emerging for Alzheimer disease and other neurodegenerative disorders (for example, Parkinson disease, frontotemporal dementia), and some biomarkers may be informative across multiple disease states. Collection of CSF provides access to biomarkers not available in plasma, including markers of synaptic dysfunction and neuroinflammation. Molecular imaging is identifying an increasing array of targets, including amyloid plaques, neurofibrillary tangles, inflammation, mitochondrial dysfunction and synaptic density. In this Review, we consider how biomarkers can be implemented in clinical trials depending on their context of use, including providing information on disease risk and/or susceptibility, diagnosis, prognosis, pharmacodynamic outcomes, monitoring, prediction of response to therapy and safety. Informed choice of increasingly available biomarkers and rational deployment in clinical trials support drug development decision making and de-risk the drug development process for neurodegenerative disorders.}, }
@article {pmid40185536, year = {2025}, author = {Uzgiris, AJ and Ladic, LA and Pfister, SX}, title = {Advances in neurofilament light chain analysis.}, journal = {Advances in clinical chemistry}, volume = {126}, number = {}, pages = {31-71}, doi = {10.1016/bs.acc.2025.01.006}, pmid = {40185536}, issn = {2162-9471}, mesh = {*Neurofilament Proteins/analysis ; Humans ; Biomarkers/analysis ; *Nervous System Diseases/diagnosis/metabolism ; }, abstract = {This chapter provides a comprehensive summary of clinical laboratory testing for neurofilament light chain (NfL) in neurologic disease. A primer on the NfL structure and function is presented with its potential use as a biomarker. The most widely utilized methods for NfL in biologic samples are highlighted and examined. Limitations of current knowledge are considered, as are outstanding questions related to dissemination and standardization of testing. Herein we focus on methods available today and those in development for clinical use. In the final section, a broad vision is presented of how NfL may be utilized in the future to improve diagnosis and treatment of neurologic diseases as well as for maintaining health.}, }
@article {pmid40184864, year = {2025}, author = {Deloncle, R and Guillard, O and Pineau, A}, title = {Copper in human health: From COVID 19 to neurodegenerative diseases.}, journal = {Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)}, volume = {89}, number = {}, pages = {127636}, doi = {10.1016/j.jtemb.2025.127636}, pmid = {40184864}, issn = {1878-3252}, mesh = {*Copper/metabolism ; Humans ; *Neurodegenerative Diseases/metabolism ; *COVID-19/metabolism ; Animals ; SARS-CoV-2 ; Brain/metabolism ; }, abstract = {Copper (Cu) exists in two oxidation states Cu+I and Cu+II yielding formation of enzymes involved in biological processes. In higher concentrations, by oxidative process and ROS production, Cu is toxic towards plants, humans and animals livers as observed in Wilson disease or sheep scrapie. Fighting according to the Fenton reaction against bacteria and viruses, has been proposed as a mean of combatting nosocomial diseases and complementary to COVID19 vaccination. In humans, Cu is stocked in liver, muscle or bound to brain protein as ß-APP, tau-protein, α-synuclein, ubiquitin or prion which present antioxidant properties when Cu-bonded. In abnormal ß-sheet conformation, they can trigger neurodegenerative diseases such as Alzheimer(AD), Parkinson(PD) and ALS. In these diseases, blood copper increase correlated with brain copper decrease has been described. In AD, abnormal D-serine has been detected in blood and cerebrospinal fluid. D-glutamate and D-alanine blood levels have been found in AD and could also be controlled with Cu and ceruloplasmin in a possible disease screening test. This abnormal D-conformation might result from epimerization of physiologically L-conformation brain peptides into protease-resistant D-enantiomers. This has previously been experimentally demonstrated for Bovine Spongiform Encephalopathy in a free Cu reductive medium with UV-induced free radicals. The Cu brain protective effect against free radicals was restored with cupric addition in oxidizing medium. Cupric supplementation in the brain, might restore Cu protection and slow down neurodegenerative processes. To lower side effects, Cu amino-acid complexes able to cross the blood brain barrier might be suggested for a Cu transfer to the brain.}, }
@article {pmid40181571, year = {2025}, author = {Yoganathan, K and Dharmadasa, T and Northall, A and Talbot, K and Thompson, AG and Turner, MR}, title = {Asymmetry in amyotrophic lateral sclerosis: Clinical, neuroimaging and histological observations.}, journal = {Brain : a journal of neurology}, volume = {148}, number = {8}, pages = {2605-2615}, pmid = {40181571}, issn = {1460-2156}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology/physiopathology/diagnostic imaging ; *Neuroimaging/methods ; *Brain/pathology/diagnostic imaging ; Disease Progression ; Spinal Cord/pathology/diagnostic imaging ; *Functional Laterality/physiology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of the motor system marked by significant phenotypic heterogeneity. Motor symptoms in the limbs consistently emerge focally and asymmetrically and, whilst variable, the pattern of regional progression related to the balance of clinical upper and lower motor neuron signs, upper versus lower limb onset and hand dominance to some extent. The neurobiological mechanisms and pathological correlates for this lateralized onset and non-random progression are uncertain. Cerebral neuroimaging studies have commonly reported structural and functional asymmetries in ALS, but the limited analysis of the pre-symptomatic phase has limited their implications. Post-mortem study of spinal cord provided strong evidence for focal pathology at symptom onset in ALS. Histopathological staging of molecular pathology in post-mortem tissue lacks clinical correlation and an ordered, sequential temporal progression in life cannot be assumed. The development of integrated brain and cord MRI holds the hope of deepening understanding of the relationship between focal symptomatology and histopathological progression. This review considers the nature and implications of asymmetry in ALS across clinical, neuroimaging and post-mortem histopathology, highlighting the current gaps in knowledge and the need for a broader investigative framework.}, }
@article {pmid40181198, year = {2025}, author = {Manolopoulos, A and Yao, PJ and Kapogiannis, D}, title = {Extracellular vesicles: translational research and applications in neurology.}, journal = {Nature reviews. Neurology}, volume = {21}, number = {5}, pages = {265-282}, pmid = {40181198}, issn = {1759-4766}, mesh = {Humans ; *Extracellular Vesicles/metabolism ; *Translational Research, Biomedical/methods ; Biomarkers/metabolism ; *Nervous System Diseases/therapy/diagnosis/metabolism ; Animals ; *Neurology/methods/trends ; }, abstract = {Over the past few decades, extensive basic, translational and clinical research has been devoted to deciphering the physiological and pathogenic roles of extracellular vesicles (EVs) in the nervous system. The presence of brain cell-derived EVs in the blood, carrying diverse cargoes, has enabled the development of predictive, diagnostic, prognostic, disease-monitoring and treatment-response biomarkers for various neurological disorders. In this Review, we consider how EV biomarkers can bring us closer to understanding the complex pathogenesis of neurological disorders such as Alzheimer disease, Parkinson disease, stroke, traumatic brain injury, amyotrophic lateral sclerosis and multiple sclerosis. We describe how translational research on EVs might unfold bidirectionally, proceeding from basic to clinical studies but also in the opposite direction, with biomarker findings in the clinic leading to novel hypotheses that can be tested in the laboratory. We demonstrate the potential value of EVs across all stages of the therapeutic development pipeline, from identifying therapeutic targets to the use of EVs as reporters in model systems and biomarkers in clinical research. Finally, we discuss how the cargo and physicochemical properties of naturally occurring and custom-engineered EVs can be leveraged as novel treatments and vehicles for drug delivery, potentially revolutionizing neurotherapeutics.}, }
@article {pmid40180687, year = {2025}, author = {Ms, S and Banerjee, S and D'Mello, SR and Dastidar, SG}, title = {Amyotrophic Lateral Sclerosis: Focus on Cytoplasmic Trafficking and Proteostasis.}, journal = {Molecular neurobiology}, volume = {62}, number = {8}, pages = {10091-10117}, pmid = {40180687}, issn = {1559-1182}, support = {SAN No: 102/IFD/SAN/2549/2019-20//DBT RLS/ ; CRG/2022/005004//Science and Engineering Research Board/ ; LBRN//Louisiana Biomedical Research Network/ ; IIRPIG-2023-0001508//Indian Council of Medical Research/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/pathology ; Humans ; *Proteostasis/physiology ; Animals ; *Cytoplasm/metabolism ; Endoplasmic Reticulum Stress ; Endoplasmic Reticulum/metabolism ; Golgi Apparatus/metabolism ; Protein Transport/physiology ; Motor Neurons/metabolism/pathology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive and fatal motor neuron disease characterized by the pathological loss of upper and lower motor neurons. Whereas most ALS cases are caused by a combination of environmental factors and genetic susceptibility, in a relatively small proportion of cases, the disorder results from mutations in genes that are inherited. Defects in several different cellular mechanisms and processes contribute to the selective loss of motor neurons (MNs) in ALS. Prominent among these is the accumulation of aggregates of misfolded proteins or peptides which are toxic to motor neurons. These accumulating aggregates stress the ability of the endoplasmic reticulum (ER) to function normally, cause defects in the transport of proteins between the ER and Golgi, and impair the transport of RNA, proteins, and organelles, such as mitochondria, within axons and dendrites, all of which contribute to the degeneration of MNs. Although dysfunction of a variety of cellular processes combines towards the pathogenesis of ALS, in this review, we focus on recent advances concerning the involvement of defective ER stress, vesicular transport between the ER and Golgi, and axonal transport.}, }
@article {pmid40178484, year = {2025}, author = {Gao, Y and Lu, Y and Chen, R and Zhao, S and Liu, J and Zhang, S and Bai, X and Zhang, J}, title = {Skin pathology in ALS: Diagnostic implications and biomarker potential.}, journal = {Biomolecules &amp; biomedicine}, volume = {}, number = {}, pages = {}, doi = {10.17305/bb.2025.12100}, pmid = {40178484}, issn = {2831-090X}, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of motor neurons in the spinal cord and brain, resulting in motor deficits and muscle atrophy. Approximately 5-10% of ALS patients are familial (fALS), while the rest are sporadic (sALS). Currently, early diagnosis of ALS cannot be achieved based on clinical manifestations and electromyography due to the lack of effective and easily available biomarkers. The skin and central nervous system (CNS) share the same embryonic origin. Several skin biomarkers have been found in many neurodegenerative diseases, such as abnormal deposition of pathological α-synuclein (α-Syn) in Parkinson's disease. Thus, molecular changes in the skin associated with ALS-specific pathological events could readily be detected and become biomarkers for ALS through skin testing. Here, we summarize the literature on pathological changes in the skin of ALS patients and animal models, including structural abnormalities of the skin, reduced density of skin nerve fibers, abnormal protein aggregation, altered mitochondrial morphology and function, and dysregulation of skin inflammation, which may be useful for early diagnosis and monitoring of ALS progression.}, }
@article {pmid40178423, year = {2025}, author = {Cheong, WSC and Au, XYJ and Lim, MY and Fu, EW and Li, H and Pua, U and Soon, YQA and Gan, YJ}, title = {The efficacy and safety of radiofrequency ablation in papillary thyroid carcinoma: A systematic review and meta-analysis.}, journal = {Annals of the Academy of Medicine, Singapore}, volume = {54}, number = {3}, pages = {170-177}, doi = {10.47102/annals-acadmedsg.2024241}, pmid = {40178423}, issn = {2972-4066}, mesh = {Humans ; *Radiofrequency Ablation/adverse effects/methods ; *Thyroid Cancer, Papillary/surgery ; *Thyroid Neoplasms/surgery ; Treatment Outcome ; Postoperative Complications/epidemiology/etiology ; }, abstract = {INTRODUCTION: Radiofrequency ablation (RFA) avoids the complications of general anaesthesia, reduces length of hospitalisation and reduces morbidity from surgery. As such, it is a strong alternative treatment for patients with comorbidities who are not surgical candidates. However, to our knowledge, there have only been 1 systematic review and 3 combined systematic review and meta-analyses on this topic to date. This systematic review and meta-analysis seeks to evaluate the efficacy and safety of RFA in the treatment of papillary thyroid carcinoma (PTC) with longer follow-up durations.<br><br>METHOD: PubMed, Embase and Cochrane databases were searched for relevant studies published from 1990 to 2021; 13 studies with a total of 1366 patients were included. The Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines and Sandelowski et al.'s approach1 to "negotiated consensual validation" were used to achieve consensus on the final list of articles to be included. All authors then assessed each study using a rating scheme modified from the Oxford Centre for Evidence-Based Medicine.<br><br>RESULTS: Pooled volume reduction rates (VRRs) from 1 to 48 months after RFA, complete disappearance rates (CDR) and complications were assessed. Pooled mean VRRs were 96.59 (95% confidence interval [CI] 91.05-102.13, I2=0%) at 12 months2-6 and 99.31 (95% CI 93.74-104.88, I2=not applicable) at 48 months.2,5 Five studies showed an eventual CDR of 100%.2,4,7-9 No life-threatening complications were recorded. The most common complications included pain, transient voice hoarseness, fever and less commonly, first-degree burn.<br><br>CONCLUSION: RFA may be an effective and safe alternative to treating PTC. Larger clinical trials with longer follow-up are needed to further evaluate the effectiveness of RFA in treating PTC.}, }
@article {pmid40169538, year = {2025}, author = {Iyer, KA and Tenchov, R and Sasso, JM and Ralhan, K and Jotshi, J and Polshakov, D and Maind, A and Zhou, QA}, title = {Rare Diseases, Spotlighting Amyotrophic Lateral Sclerosis, Huntington's Disease, and Myasthenia Gravis: Insights from Landscape Analysis of Current Research.}, journal = {Biochemistry}, volume = {64}, number = {8}, pages = {1698-1719}, pmid = {40169538}, issn = {1520-4995}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/therapy/pathology/metabolism ; *Myasthenia Gravis/genetics/therapy/pathology/metabolism ; *Rare Diseases/genetics/therapy ; *Huntington Disease/genetics/therapy/pathology/metabolism ; Animals ; }, abstract = {Rare diseases are a diverse group of disorders that, despite each individual condition's rarity, collectively affect a significant portion of the global population. Currently approximately 10,000 rare diseases exist globally, with 80% of these diseases being identified as having genetic origins. In this Review, we examine data from the CAS Content Collection to summarize scientific progress in the area of rare diseases. We examine the publication landscape in the area in an effort to provide insights into current advances and developments. We then discuss the evolution of key concepts in the field, genetic associations, as well as the major technologies and development pipelines of rare disease treatments. We focus our attention on three specific rare diseases: (i) amyotrophic lateral sclerosis, a terminal neurodegenerative disease affecting the central nervous system resulting in progressive loss of motor neurons that control voluntary muscles; (ii) Huntington's disease, another terminal neurodegenerative disease that causes progressive degeneration of nerve cells in the brain, with a wide impact on a person's functional abilities; and (iii) myasthenia gravis, a chronic autoimmune synaptopathy leading to skeletal muscle weakness. While the pathogenesis of these rare diseases is being elucidated, there is neither a cure nor preventative treatment available, only symptomatic treatment. The objective of the paper is to provide a broad overview of the evolving landscape of current knowledge on rare diseases and specifically on the biology and genetics of the three spotlighted diseases, to outline challenges and evaluate growth opportunities, an aim to further efforts in solving the remaining challenges.}, }
@article {pmid40169452, year = {2025}, author = {Hou, X and Jiang, J and Deng, M}, title = {Exploring epigenetic modifications as potential biomarkers and therapeutic targets in amyotrophic lateral sclerosis.}, journal = {Journal of neurology}, volume = {272}, number = {4}, pages = {304}, pmid = {40169452}, issn = {1432-1459}, support = {82273915//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/therapy/metabolism/diagnosis ; *Epigenesis, Genetic ; Biomarkers/metabolism ; DNA Methylation ; Animals ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder and the most common motor neuron disease. Whole-genome sequencing has identified many novel ALS-associated genes, but genetics alone cannot fully explain the onset of ALS and an effective treatment is still lacking. Moreover, we need more biomarkers for accurate diagnosis and assessment of disease prognosis. Epigenetics, which includes DNA methylation and hydroxymethylation, histone modifications, chromatin remodeling, and non-coding RNAs, influences gene transcription and expression by affecting chromatin accessibility and transcription factor binding without altering genetic information. These processes play a role in the onset and progression of ALS. Epigenetic targets can serve as potential biomarkers and more importantly, the reversibility of epigenetic changes supports their potential role as versatile therapeutic targets in ALS. This review summarized the alterations in different epigenetic modulations in ALS. Additionally, given the close association between aberrant metabolic profiles characterized by hypoxia and high glycolytic metabolism in ALS and epigenetic changes, we also integrate epigenetics with metabolomics. Finally, we discuss the application of therapies based on epigenetic mechanisms in ALS. Our data integration helps to identify potential diagnostic and prognostic biomarkers and support the development of new effective therapies.}, }
@article {pmid40165691, year = {2025}, author = {Bunce, B and Apostolopoulou, E and Andres, SM and Choy, AP and Requena-I-Mora, M and Brockington, D}, title = {A social network analysis of an epistemic community studying neoliberal conservation.}, journal = {Conservation biology : the journal of the Society for Conservation Biology}, volume = {39}, number = {2}, pages = {e70001}, pmid = {40165691}, issn = {1523-1739}, support = {//Women for Africa Foundation/ ; //Mar&#xed;a de Maeztu, Spanish Ministry of Science and Innovation/ ; ERC/ERC_/European Research Council/International ; CONDJUST/ERC_/European Research Council/International ; 101054259/ERC_/European Research Council/International ; }, mesh = {*Conservation of Natural Resources ; *Social Network Analysis ; *Politics ; Cooperative Behavior ; Knowledge ; }, abstract = {Researchers typically operate in epistemic communities: groups that share common approaches to research agendas and sociopolitical action and define areas of debate. Although productive in their own spheres, a lack of understanding among these communities can undermine scientific progress. Thus, analyzing epistemic communities is important for understanding the politics of knowledge production. Social network analysis sheds light on these dynamics by mapping the collaborative networks that shape academic output. We used 255 publications examined in Apostolopoulou et al.'s review of neoliberal conservation literature and 2135 additional publications in a social network analysis. We compiled a coauthorship network for 318 authors and found a dispersed and polycentric network with low connectivity and relatively small clusters of scholars collaborating within tightly knit groups. Although the structure is conducive to innovation and diversity, building new connections among dispersed coauthor groups could enrich knowledge sharing to drive novel approaches. We identified central actors in building collaborations among communities and communicating ideas across the network. We considered actor attributes, such as gender and geographic location, alongside centrality measures. We found that seventy percent of the 20 authors with the highest betweenness centrality were men, and only one male author was affiliated to an institution in the Global South. Our analysis of thematic clusters in the literature highlighted the spatial patchiness and partialness of the literature across different subfields. Scholars should undertake more work on identified themes in currently excluded geographic regions through effective interdisciplinary collaborations and with local communities of research and practice and grassroots movements. There is a need to strengthen the field's intellectual diversity and to have a deeper engagement with issues of class, gender, and race. This would allow neoliberal conservation to reimagine conservation in ways that are not only environmentally sustainable, but also socially just.}, }
@article {pmid40164145, year = {2025}, author = {Furze, C and Newall, J and Nickbakht, M and Dawes, P and Ching, TYC and Sharma, M}, title = {A systematic review of barriers and facilitators for ethnically diverse communities in accessing adult and paediatric hearing services.}, journal = {International journal of audiology}, volume = {}, number = {}, pages = {1-11}, doi = {10.1080/14992027.2025.2477755}, pmid = {40164145}, issn = {1708-8186}, abstract = {OBJECTIVE: To conduct a systematic review of identified barriers and facilitators for ethnically diverse adults and children in accessing hearing health services.<br><br>DESIGN: Searches were performed in electronic databases MEDLINE, EMBASE, CINAHL, Pychinfo, LLBA, and Scopus. The Strengthening of Reporting of Observational Studies in Epidemiology and Standards for Reporting Qualitative Research were used to assess quality of articles. Barriers and facilitators for ethnically diverse adults and children to access hearing services were summarised descriptively using Levesque et&#xa0;al.'s conceptual framework of access to healthcare.<br><br>STUDY SAMPLE: 25 articles met the inclusion criteria.<br><br>RESULTS: Barriers and facilitators were identified for every domain of Levesque's framework for ethnically diverse adults, children, and their families. Personal barriers included health literacy, health beliefs, and stigma. Environmental barriers included language, limited cultural and interpreter training for clinicians, time constraints in appointments, direct and indirect costs. Facilitators included availability of translated and/or simplified information, cultural responsiveness training, outreach programs, and community health workers to engage with ethnically diverse communities.<br><br>CONCLUSION: With increasingly multicultural societies globally, there is an increased need to provide culturally responsive care and accessible hearing health services. Understanding current barriers and facilitators to accessibility would facilitate global sustainable development goals around reduced inequality, health, and wellbeing.}, }
@article {pmid40163151, year = {2025}, author = {Wadan, AS and Shaaban, AH and El-Sadek, MZ and Mostafa, SA and Moshref, AS and El-Hussein, A and Ellakwa, DE and Mehanny, SS}, title = {Mitochondrial-based therapies for neurodegenerative diseases: a review of the current literature.}, journal = {Naunyn-Schmiedeberg's archives of pharmacology}, volume = {}, number = {}, pages = {}, pmid = {40163151}, issn = {1432-1912}, abstract = {Neurodegenerative disorders present significant challenges to modern medicine because of their complex etiology, pathogenesis, and progressive nature, which complicate practical treatment approaches. Mitochondrial dysfunction is an important contributor to the pathophysiology of various neurodegenerative illnesses, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). This review paper examines the current literature highlighting the multifaceted functions of mitochondria, including energy production, calcium signaling, apoptosis regulation, mitochondrial biogenesis, mitochondrial dynamics, axonal transport, endoplasmic reticulum-mitochondrial interactions, mitophagy, mitochondrial proteostasis, and their crucial involvement in neuronal health. The literature emphasizes the increasing recognition of mitochondrial dysfunction as a critical factor in the progression of neurodegenerative disorders, marking a shift from traditional symptom management to innovative mitochondrial-based therapies. By discussing mitochondrial mechanisms, including mitochondrial quality control (MQC) processes and the impact of oxidative stress, this review highlights the need for novel therapeutic strategies to restore mitochondrial function, protect neuronal connections and integrity, and slow disease progression. This comprehensive review aims to provide insights into potential interventions that could transform the treatment landscape for neurodegenerative diseases, addressing symptoms and underlying pathophysiological changes.}, }
@article {pmid40161216, year = {2025}, author = {Scarcella, S and Brambilla, L and Quetti, L and Rizzuti, M and Melzi, V and Galli, N and Sali, L and Costamagna, G and Comi, GP and Corti, S and Gagliardi, D}, title = {Unveiling amyotrophic lateral sclerosis complexity: insights from proteomics, metabolomics and microbiomics.}, journal = {Brain communications}, volume = {7}, number = {2}, pages = {fcaf114}, pmid = {40161216}, issn = {2632-1297}, abstract = {Amyotrophic lateral sclerosis is the most common motor neuron disease and manifests as a clinically and genetically heterogeneous neurodegenerative disorder mainly affecting the motor systems. To date, despite promising results and accumulating knowledge on the pathomechanisms of amyotrophic lateral sclerosis, a specific disease-modifying treatment is still not available. In vitro and in vivo disease models coupled with multiomics techniques have helped elucidate the pathomechanisms underlying this disease. In particular, omics approaches are powerful tools for identifying new potential disease biomarkers that may be particularly useful for diagnosis, prognosis and assessment of treatment response. In turn, these findings could support physicians in stratifying patients into clinically relevant subgroups for the identification of the best therapeutic targets. Here, we provide a comprehensive review of the most relevant literature highlighting the importance of proteomics approaches in determining the role of pathogenic misfolded/aggregated proteins and the molecular mechanisms involved in the pathogenesis and progression of amyotrophic lateral sclerosis. In addition, we explored new findings arising from metabolomic and lipidomic studies, which can aid to elucidate the intricate metabolic alterations underlying amyotrophic lateral sclerosis pathology. Moreover, we integrated these insights with microbiomics data, providing a thorough understanding of the interplay between metabolic dysregulation and microbial dynamics in disease progression. Indeed, a greater integration of these multiomics data could lead to a deeper understanding of disease mechanisms, supporting the development of specific therapies for amyotrophic lateral sclerosis.}, }
@article {pmid40160105, year = {2025}, author = {Malloy, E and Corrie, S and Cushen-Brewster, N}, title = {What is the current state of the research literature examining the impact of the motor neurone disease journey on the couple's relationship? A scoping review.}, journal = {Palliative &amp; supportive care}, volume = {23}, number = {}, pages = {e85}, doi = {10.1017/S1478951524002141}, pmid = {40160105}, issn = {1478-9523}, mesh = {Humans ; *Motor Neuron Disease/psychology/complications ; *Spouses/psychology ; Qualitative Research ; Interpersonal Relations ; Male ; Female ; Adaptation, Psychological ; }, abstract = {BACKGROUND: Motor neurone disease (MND) results in complex and disabling symptoms that give rise to significant and challenging care needs. While much of the care required is typically provided by the partner of the individual who has been diagnosed with MND, there are few studies that have investigated the impact of MND on the couple's relationship.<br><br>OBJECTIVES: To establish the current state of the research literature examining the impact of MND on the couple's relationship.<br><br>METHODS: A scoping review was undertaken with thematic analysis used to synthesize the data.<br><br>RESULTS: The scoping review identified 15 studies that were thematically analyzed to identify prominent themes. The following 5 themes were identified: adjusting to new roles; changes in communication and values; spouse well-being and health; and changes to social relationships and intimacy changes.<br><br>SIGNIFICANCE OF RESULTS: This scoping review highlighted the impact of the MND trajectory on the couple's relationship overall and on key areas of couple communication and functioning. These areas can be used to guide the development of interventions and services that are tailored to the needs of couple relationships. Further understanding of the factors impacting the couple's relationship on the MND journey and how to navigate these factors is critically warranted.}, }
@article {pmid40153582, year = {2024}, author = {Norata, D and Capone, F and Motolese, F and Marano, M and Rossi, M and Calandrelli, R and Sacchetti, M and Mantelli, F and Di Lazzaro, V and Pilato, F}, title = {1953-2023. Seventy Years of the Nerve Growth Factor: A Potential Novel Treatment in Neurological Diseases?.}, journal = {Aging and disease}, volume = {16}, number = {4}, pages = {2293-2314}, pmid = {40153582}, issn = {2152-5250}, mesh = {Humans ; *Nerve Growth Factor/therapeutic use ; Animals ; *Nervous System Diseases/therapy/drug therapy ; History, 20th Century ; History, 21st Century ; }, abstract = {Rita Levi-Montalcini's 1953 discovery of nerve growth factor (NGF) in mouse sarcoma tumors marked a groundbreaking moment in neuroscience. NGF, a key signaling molecule, became the first identified neurotrophic factor, influencing the growth, differentiation, and survival of neurons in both peripheral and central nervous systems. NGF and related neurotrophic factors hold therapeutic potential for various neurological disorders, such as Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, amyotrophic lateral sclerosis, spinal cord injuries, neuropathies, traumatic brain injuries, and stroke. However, despite promising in vitro studies and animal models findings, NGF efficacy in patients remains unproven. Indeed, its use as a therapeutic agent faces challenges in delivery and clinical translation. This review delves into these challenges, exploring ongoing research on refined delivery methods, dosages, and safety profiles. Innovative strategies, including molecular mimicking, combination therapies, gene therapy, and coupling with neuromodulation techniques like transcranial magnetic stimulation and vagal nerve stimulation, are discussed. Incorporating nerve growth factor (NGF) into a comprehensive strategy may prove beneficial, particularly in non-neurodegenerative conditions such as stroke, trauma, and neuropathies. In these instances, NGF holds promise for promoting tissue regeneration and repair. Challenges persist in addressing the complexity of neurodegenerative pathologies for a combined therapeutic approach.}, }
@article {pmid40149536, year = {2025}, author = {Kleinerova, J and Chipika, RH and Tan, EL and Yunusova, Y and Marchand-Pauvert, V and Kassubek, J and Pradat, PF and Bede, P}, title = {Sensory Dysfunction in ALS and Other Motor Neuron Diseases: Clinical Relevance, Histopathology, Neurophysiology, and Insights from Neuroimaging.}, journal = {Biomedicines}, volume = {13}, number = {3}, pages = {}, pmid = {40149536}, issn = {2227-9059}, support = {JPND-Cofund-2-2019-1 &amp; HRB EIA-2017-019//HRB/ ; }, abstract = {Background: The clinical profiles of MNDs are dominated by inexorable motor decline, but subclinical proprioceptive, nociceptive and somatosensory deficits may also exacerbate mobility, dexterity, and bulbar function. While extra-motor pathology and frontotemporal involvement are widely recognised in motor neuron diseases (MNDs), reports of sensory involvement are conflicting. The potential contribution of sensory deficits to clinical disability is not firmly established and the spectrum of sensory manifestations is poorly characterised. Methods: A systematic review was conducted to examine the clinical, neuroimaging, electrophysiology and neuropathology evidence for sensory dysfunction in MND phenotypes. Results: In ALS, paraesthesia, pain, proprioceptive deficits and taste alterations are sporadically reported and there is also compelling electrophysiological, histological and imaging evidence of sensory network alterations. Gait impairment, impaired dexterity, and poor balance in ALS are likely to be multifactorial, with extrapyramidal, cerebellar, proprioceptive and vestibular deficits at play. Human imaging studies and animal models also confirm dorsal column-medial lemniscus pathway involvement as part of the disease process. Sensory symptoms are relatively common in spinal and bulbar muscular atrophy (SBMA) and Hereditary Spastic Paraplegia (HSP), but are inconsistently reported in primary lateral sclerosis (PLS) and in post-poliomyelitis syndrome (PPS). Conclusions: Establishing the prevalence and nature of sensory dysfunction across the spectrum of MNDs has a dual clinical and academic relevance. From a clinical perspective, subtle sensory deficits are likely to impact the disability profile and care needs of patients with MND. From an academic standpoint, sensory networks may be ideally suited to evaluate propagation patterns and the involvement of subcortical grey matter structures. Our review suggests that sensory dysfunction is an important albeit under-recognised facet of MND.}, }
@article {pmid40148980, year = {2025}, author = {Harerimana, A and Mchunu, G and Pillay, JD}, title = {Menstrual hygiene management among girls and women refugees in Africa: a scoping review.}, journal = {Conflict and health}, volume = {19}, number = {1}, pages = {20}, pmid = {40148980}, issn = {1752-1505}, abstract = {BACKGROUND: Menstrual Hygiene Management (MHM) presents a significant public health challenge for refugee women and girls in Africa. Displaced populations often lack access to menstrual products, adequate Water, Sanitation, and Hygiene (WASH) infrastructure, as well as comprehensive menstrual health education.<br><br>AIM: This scoping review aimed to understand the state of MHM, identify key challenges, and evaluate existing interventions among refugee women and girls in Africa.<br><br>METHODS: Employing Levac et al.'s framework, the review analysed evidence from databases like CINAHL, Emcare, PubMed, Scopus, and Web of Science, focusing on studies published between 2014 and 2024. Sixteen articles met the inclusion criteria, and both numerical summaries and descriptive analyses were conducted.<br><br>RESULTS: Refugee women and girls often lack access to both disposable and reusable menstrual products, resorting to unhygienic alternatives such as clothing, leaves, and paper. Inadequate WASH facilities restrict safe and private spaces for menstrual management. Cultural stigma and taboos surrounding menstruation contribute to social exclusion and school absenteeism among girls. The interventions included distributing dignity kits, enhancing WASH infrastructure, and providing menstrual health education; however, they were inconsistently implemented due to resource limitations and cultural obstacles.<br><br>CONCLUSION: This study highlights the urgent need for sustainable menstrual health solutions in refugee settings. Without access to necessary products, WASH facilities, and stigma-free education, women and girls risk exclusion, health issues, and interrupted education. Addressing these barriers requires consistent, well-resourced interventions that integrate cultural sensitivity to ensure dignity and long-term impact.}, }
@article {pmid40148057, year = {2025}, author = {De Marchi, F and Spinelli, EG and Bendotti, C}, title = {Neuroglia in neurodegeneration: Amyotrophic lateral sclerosis and frontotemporal dementia.}, journal = {Handbook of clinical neurology}, volume = {210}, number = {}, pages = {45-67}, doi = {10.1016/B978-0-443-19102-2.00004-1}, pmid = {40148057}, issn = {0072-9752}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology ; *Frontotemporal Dementia/pathology ; *Neuroglia/pathology/metabolism ; Animals ; }, abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are devastating neurodegenerative diseases sharing significant pathologic and genetic overlap, leading to consider these diseases as a continuum in the spectrum of their pathologic features. Although FTD compromises only specific brain districts, while ALS involves both the nervous system and the skeletal muscles, several neurocentric mechanisms are in common between ALS and FTD. Also, recent research has revealed the significant involvement of nonneuronal cells, particularly glial cells such as astrocytes, oligodendrocytes, microglia, and peripheral immune cells, in disease pathology. This chapter aims to provide an extensive overview of the current understanding of the role of glia in the onset and advancement of ALS and FTD, highlighting the recent implications in terms of prognosis and future treatment options.}, }
@article {pmid40143051, year = {2025}, author = {Zou, Y and Zhang, J and Chen, L and Xu, Q and Yao, S and Chen, H}, title = {Targeting Neuroinflammation in Central Nervous System Diseases by Oral Delivery of Lipid Nanoparticles.}, journal = {Pharmaceutics}, volume = {17}, number = {3}, pages = {}, pmid = {40143051}, issn = {1999-4923}, support = {82100892//Hong Chen/ ; 82300929//Jing Zhang/ ; }, abstract = {Neuroinflammation within the central nervous system (CNS) is a primary characteristic of CNS diseases, such as Parkinson's disease, Alzheimer's disease (AD), amyotrophic lateral sclerosis, and mental disorders. The excessive activation of immune cells results in the massive release of pro-inflammatory cytokines, which subsequently induce neuronal death and accelerate the progression of neurodegeneration. Therefore, mitigating excessive neuroinflammation has emerged as a promising strategy for the treatment of CNS diseases. Despite advancements in drug discovery and the development of novel therapeutics, the effective delivery of these agents to the CNS remains a serious challenge due to the restrictive nature of the blood-brain barrier (BBB). This underscores the need to develop a novel drug delivery system. Recent studies have identified oral lipid nanoparticles (LNPs) as a promising approach to efficiently deliver drugs across the BBB and treat neurological diseases. This review aims to comprehensively summarize the recent advancements in the development of LNPs designed for the controlled delivery and therapeutic modulation of CNS diseases through oral administration. Furthermore, this review addresses the mechanisms by which these LNPs overcome biological barriers and evaluate their clinical implications and therapeutic efficacy in the context of oral drug delivery systems. Specifically, it focuses on LNP formulations that facilitate oral administration, exploring their potential to enhance bioavailability, improve targeting precision, and alleviate or manage the symptoms associated with a range of CNS diseases.}, }
@article {pmid40141996, year = {2025}, author = {Kodama, TS and Furuita, K and Kojima, C}, title = {Beyond Static Tethering at Membrane Contact Sites: Structural Dynamics and Functional Implications of VAP Proteins.}, journal = {Molecules (Basel, Switzerland)}, volume = {30}, number = {6}, pages = {}, pmid = {40141996}, issn = {1420-3049}, support = {JP22H05536, JP22K19184, JP23H02416, and JP23K18030//Ministry of Education, Culture, Sports, Science and Technology/ ; NMR Platform//Ministry of Education, Culture, Sports, Science and Technology/ ; CR-24-05//Institute for Protein Research, Osaka University/ ; JP24ama121001//Japan Agency for Medical Research and Development/ ; }, mesh = {Humans ; *Vesicular Transport Proteins/metabolism/chemistry/genetics ; Animals ; *Cell Membrane/metabolism ; }, abstract = {The membranes surrounding the eukaryotic cell and its organelles are continuously invaginating, budding, and undergoing membrane fusion-fission events, which enable them to perform functions not found in prokaryotic cells. In addition, organelles come into close contact with each other at membrane contact sites (MCSs), which involve many types of proteins, and which regulate the signaling and transport of various molecules. Vesicle-associated membrane protein (VAMP)-associated protein (VAP) is an important factor involved in the tethering and contact of various organelles at MCSs in almost all eukaryotes and has attracted attention for its association with various diseases, mainly neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). However, the detailed mechanism of its functional expression remains unclear. In this review, we quantitatively discuss the structural dynamics of the entire molecule, including intrinsically disordered regions and intramolecular and intermolecular interactions, focusing on the vertebrate VAP paralogs VAPA and VAPB. Molecular phylogenetic and biophysical considerations are the basis of the work.}, }
@article {pmid40141987, year = {2025}, author = {Russo, A and Putaggio, S and Tellone, E and Calderaro, A and Cirmi, S and Laganà, G and Ficarra, S and Barreca, D and Patanè, GT}, title = {Emerging Ferroptosis Involvement in Amyotrophic Lateral Sclerosis Pathogenesis: Neuroprotective Activity of Polyphenols.}, journal = {Molecules (Basel, Switzerland)}, volume = {30}, number = {6}, pages = {}, pmid = {40141987}, issn = {1420-3049}, mesh = {*Ferroptosis/drug effects ; Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/metabolism/pathology/etiology ; *Neuroprotective Agents/pharmacology/therapeutic use ; *Polyphenols/pharmacology/therapeutic use ; Animals ; Reactive Oxygen Species/metabolism ; Lipid Peroxidation/drug effects ; Mitochondria/metabolism/drug effects ; Oxidative Stress/drug effects ; Iron/metabolism ; }, abstract = {Neurodegenerative diseases are a group of diseases that share common features, such as the generation of misfolded protein deposits and increased oxidative stress. Among them, amyotrophic lateral sclerosis (ALS), whose pathogenesis is still not entirely clear, is a complex neurodegenerative disease linked both to gene mutations affecting different proteins, such as superoxide dismutase 1, Tar DNA binding protein 43, Chromosome 9 open frame 72, and Fused in Sarcoma, and to altered iron homeostasis, mitochondrial dysfunction, oxidative stress, and impaired glutamate metabolism. The purpose of this review is to highlight the molecular targets common to ALS and ferroptosis. Indeed, many pathways implicated in the disease are hallmarks of ferroptosis, a recently discovered type of iron-dependent programmed cell death characterized by increased reactive oxygen species (ROS) and lipid peroxidation. Iron accumulation results in mitochondrial dysfunction and increased levels of ROS, lipid peroxidation, and ferroptosis triggers; in addition, the inhibition of the Xc[-] system results in reduced cystine levels and glutamate accumulation, leading to excitotoxicity and the inhibition of GPx4 synthesis. These results highlight the potential involvement of ferroptosis in ALS, providing new molecular and biochemical targets that could be exploited in the treatment of the disease using polyphenols.}, }
@article {pmid40141149, year = {2025}, author = {Zheng, MY and Luo, LZ}, title = {The Role of IL-17A in Mediating Inflammatory Responses and Progression of Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {26}, number = {6}, pages = {}, pmid = {40141149}, issn = {1422-0067}, support = {No. 2023D022//the Fujian Provincial Natural Science Foundation/ ; No. 3502Z202473076//the Science and Technology Program of Xiamen City/ ; No. 2019-WJ-30//the Fujian Province Health Education Joint Research Project/ ; }, mesh = {Humans ; *Interleukin-17/metabolism ; *Neurodegenerative Diseases/metabolism/pathology/immunology ; Animals ; *Inflammation/metabolism/pathology ; Signal Transduction ; Disease Progression ; Blood-Brain Barrier/metabolism ; }, abstract = {IL-17A has been implicated as a critical pro-inflammatory cytokine in the pathogenesis of autoimmune and neurodegenerative disorders. Emerging evidence indicates its capacity to activate microglial cells and astrocytes, subsequently inducing the production of inflammatory mediators that exacerbate neuronal injury and functional impairment. Clinical observations have revealed a demonstrated association between IL-17A concentrations and blood-brain barrier (BBB) dysfunction, creating a pathological feedback loop that amplifies neuro-inflammatory responses. Recent advances highlight the cytokine's critical involvement in neurodegenerative disorders through multiple molecular pathways. Therapeutic interventions utilizing monoclonal antibodies (mAbs) against IL-17A or its cognate receptor (IL-17R) have shown promising clinical potential. This review systematically examines the IL-17A-mediated neuro-inflammatory cascades; the mechanistic contributions to neurodegenerative pathology in the established disease models including multiple sclerosis, Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis; and current therapeutic strategies targeting the IL-17A signaling pathways. The analysis provides novel perspectives on optimizing cytokine-directed therapies while identifying the key challenges and research priorities for translational applications in neurodegeneration.}, }
@article {pmid40138119, year = {2025}, author = {Ali, N and Sayeed, U and Shahid, SMA and Akhtar, S and Khan, MKA}, title = {Molecular mechanisms and biomarkers in neurodegenerative disorders: a comprehensive review.}, journal = {Molecular biology reports}, volume = {52}, number = {1}, pages = {337}, pmid = {40138119}, issn = {1573-4978}, mesh = {Humans ; *Biomarkers/metabolism/cerebrospinal fluid ; *Neurodegenerative Diseases/metabolism/genetics/diagnosis ; Amyloid beta-Peptides/metabolism/cerebrospinal fluid ; alpha-Synuclein/metabolism/cerebrospinal fluid ; Parkinson Disease/metabolism/genetics ; tau Proteins/metabolism/cerebrospinal fluid ; Alzheimer Disease/metabolism/genetics ; Huntington Disease/genetics/metabolism ; Amyotrophic Lateral Sclerosis/metabolism/genetics ; Dopamine Plasma Membrane Transport Proteins/metabolism ; }, abstract = {Neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS), and Huntington's disease (HD), are significant global health challenges, owing to their profound impact on cognitive, motor, and behavioral functions. The etiology and progression of these disorders are influenced by a complex interplay of environmental factors and genetic predispositions with specific genetic markers, such as mutations in the APOE and HTT genes, which play pivotal roles. Current therapeutic interventions predominantly focus on symptom management; however, emerging strategies, including gene therapies, anti-amyloid agents, and neuroprotective approaches, are designed to directly target the underlying disease mechanisms. Advances in biomarker discovery and imaging methodologies have emerged as essential tools for early diagnosis and monitoring of therapeutic efficacy in these disorders. In the context of AD, cerebrospinal fluid (CSF) amyloid-beta (Aβ) and tau levels, along with positron emission tomography (PET) imaging, are well-established biomarkers. Similarly, CSF alpha-synuclein and dopamine transporter (DAT) imaging have been employed as diagnostic tools for PD. Moreover, emerging biomarkers, such as blood-based tau and the Aβ42/40 ratio for AD, as well as the neurofilament light chain (NfL) for ALS and PD, hold promise for enhancing early diagnostic accuracy and facilitating the longitudinal assessment of disease progression. This study comprehensively examined the molecular mechanisms underlying these neurodegenerative disorders, focusing on amyloid-beta plaque deposition and tau protein aggregation in AD, alpha-synuclein misfolding in PD, and aberrant protein aggregation in ALS and HD, thereby contributing to a deeper understanding of the pathophysiological basis of these disorders.}, }
@article {pmid40137505, year = {2025}, author = {Calderón-Garcidueñas, L and González-Maciel, A and Reynoso-Robles, R and Cejudo-Ruiz, FR and Silva-Pereyra, HG and Gorzalski, A and Torres-Jardón, R}, title = {Alzheimer's, Parkinson's, Frontotemporal Lobar Degeneration, and Amyotrophic Lateral Sclerosis Start in Pediatric Ages: Ultrafine Particulate Matter and Industrial Nanoparticles Are Key in the Early-Onset Neurodegeneration: Time to Invest in Preventive Medicine.}, journal = {Toxics}, volume = {13}, number = {3}, pages = {}, pmid = {40137505}, issn = {2305-6304}, abstract = {Billions of people are exposed to fine particulate matter (PM2.5) levels above the USEPA's annual standard of 9 μg/m[3]. Common emission sources are anthropogenic, producing complex aerosolized toxins. Ultrafine particulate matter (UFPM) and industrial nanoparticles (NPs) have major detrimental effects on the brain, but the USA does not measure UFPM on a routine basis. This review focuses on the development and progression of common neurodegenerative diseases, as diagnosed through neuropathology, among young residents in Metropolitan Mexico City (MMC). MMC is one of the most polluted megacities in the world, with a population of 22 million residents, many of whom are unaware of the brain effects caused by their polluted atmosphere. Fatal neurodegenerative diseases (such as Alzheimer's and Parkinson's) that begin in childhood in populations living in air polluted environments are preventable. We conclude that UFPM/NPs are capable of disrupting neural homeostasis and give rise to relentless neurodegenerative processes throughout the entire life of the highly exposed population in MMC. The paradigm of reaching old age to have neurodegeneration is no longer supported. Neurodegenerative changes start early in pediatric ages and are irreversible. It is time to invest in preventive medicine.}, }
@article {pmid40137226, year = {2025}, author = {Stella, R and Bertoli, A and Lopreiato, R and Peggion, C}, title = {A Twist in Yeast: New Perspectives for Studying TDP-43 Proteinopathies in S. cerevisiae.}, journal = {Journal of fungi (Basel, Switzerland)}, volume = {11}, number = {3}, pages = {}, pmid = {40137226}, issn = {2309-608X}, abstract = {TAR DNA-binding protein 43 kDa (TDP-43) proteinopathies are a group of neurodegenerative diseases (NDs) characterized by the abnormal accumulation of the TDP-43 protein in neurons and glial cells. These proteinopathies are associated with several NDs, including amyotrophic lateral sclerosis, frontotemporal lobar degeneration, and some forms of Alzheimer's disease. Yeast models have proven valuable in ND research due to their simplicity, genetic tractability, and the conservation of many cellular processes shared with higher eukaryotes. For several decades, Saccharomyces cerevisiae has been used as a model organism to study the behavior and toxicity of TDP-43, facilitating the identification of genes and pathways that either exacerbate or mitigate its toxic effects. This review will discuss evidence showing that yeast models of TDP-43 exhibit defects in proteostasis, mitochondrial function, autophagy, and RNA metabolism, which are key features of TDP-43-related NDs. Additionally, we will explore how modulating proteins involved in these processes reduce TDP-43 toxicity, aiding in restoring normal TDP-43 function or preventing its pathological aggregation. These findings highlight potential therapeutic targets for the treatment of TDP-43-related diseases.}, }
@article {pmid40136670, year = {2025}, author = {Bond, S and Saxena, S and Sierra-Delgado, JA}, title = {Microglia in ALS: Insights into Mechanisms and Therapeutic Potential.}, journal = {Cells}, volume = {14}, number = {6}, pages = {}, pmid = {40136670}, issn = {2073-4409}, support = {//Rare Village/ ; //Radala Foundation/ ; //University of Missouri- Columbia, School of Medicine/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/therapy/pathology/immunology ; Humans ; *Microglia/pathology/metabolism ; Animals ; Motor Neurons/pathology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the loss of motor neurons, leading to escalating muscle weakness, atrophy, and eventually paralysis. While neurons are the most visibly affected, emerging data highlight microglia-the brain's resident immune cells-as key contributors to disease onset and progression. Rather than existing in a simple beneficial or harmful duality, microglia can adopt multiple functional states shaped by internal and external factors, including those in ALS. Collectively, these disease-specific forms are called disease-associated microglia (DAM). Research using rodent models, patient-derived cells, and human postmortem tissue shows that microglia can transition into DAM phenotypes, driving inflammation and neuronal injury. However, these cells can also fulfill protective roles under certain conditions, revealing their adaptable nature. This review explores recent discoveries regarding the multifaceted behavior of microglia in ALS, highlights important findings that link these immune cells to motor neuron deterioration, and discusses emerging therapies-some already used in clinical trials-that aim to recalibrate microglial functions and potentially slow disease progression.}, }
@article {pmid40136528, year = {2025}, author = {Chen, X and Wang, Y and Zhang, Y and Li, X and Zhang, L and Gao, S and Zhang, C}, title = {Neural Excitatory/Inhibitory Imbalance in Motor Aging: From Genetic Mechanisms to Therapeutic Challenges.}, journal = {Biology}, volume = {14}, number = {3}, pages = {}, pmid = {40136528}, issn = {2079-7737}, support = {C2406001//the Shenzhen Medical Research Fund/ ; 2024TJCR023//the Tongji Hospital High Quality Clinical Research Fund/ ; 32020103007//the Major International (Regional) Joint Research Project/ ; 2022YFA1206000//the National Key Research and Development Program of China/ ; 32371189, 32300984//the National Natural Science Foundation of China/ ; }, abstract = {Neural excitatory/inhibitory (E/I) imbalance plays a pivotal role in the aging process. However, despite its significant impact, the role of E/I imbalance in motor dysfunction and neurodegenerative diseases has not received sufficient attention. This review explores the mechanisms underlying motor aging through the lens of E/I balance, emphasizing genetic and molecular factors that contribute to this imbalance (such as SCN2A, CACNA1C, GABRB3, GRIN2A, SYT, BDNF…). Key regulatory genes, including REST, vps-34, and STXBP1, are examined for their roles in modulating synaptic activity and neuronal function during aging. With insights drawn from ALS, we discuss how disruptions in E/I balance contribute to the pathophysiology of age-related motor dysfunction. The genes discussed above exhibit a certain association with age-related motor neuron diseases (like ALS), a relationship that had not been previously recognized. Innovative genetic therapies, such as gene editing technology and optogenetic manipulation, are emerging as promising tools for restoring E/I balance, offering hope for ameliorating motor deficits in aging. This review explores the potential of these technologies to intervene in aging-related motor diseases, despite challenges in their direct application to human conditions.}, }
@article {pmid40133096, year = {2025}, author = {Shenouda, M and McKeever, PM and Robertson, J}, title = {The long and the short of TDP-43.}, journal = {Trends in neurosciences}, volume = {48}, number = {5}, pages = {313-314}, doi = {10.1016/j.tins.2025.03.003}, pmid = {40133096}, issn = {1878-108X}, mesh = {Humans ; *DNA-Binding Proteins/metabolism/genetics ; Animals ; Protein Isoforms/metabolism/genetics ; }, abstract = {In a recent study, Dykstra and colleagues show that shortened TAR DNA Binding Protein 43 (sTDP-43) isoforms are generated as by-products of TDP-43 autoregulation. sTDP-43 levels are regulated through nonsense-mediated decay and proteasomal and autophagic degradation, and elicit toxicity through dominant negative effects on TDP-43 splicing activity. These results identify mechanisms contributing to sTDP-43 accumulation and toxicity in disease.}, }
@article {pmid40132732, year = {2025}, author = {He, Y and Zheng, Q and Zhifang, Z and Xiaofeng, N and Shenggen, W and Xue, M and Zheng, C and Liu, Z}, title = {When COVID-19 meets diabetes: A bibliometric analysis.}, journal = {Diabetes research and clinical practice}, volume = {223}, number = {}, pages = {112118}, doi = {10.1016/j.diabres.2025.112118}, pmid = {40132732}, issn = {1872-8227}, mesh = {*COVID-19/epidemiology/complications ; Humans ; *Bibliometrics ; *Diabetes Mellitus/epidemiology ; SARS-CoV-2 ; }, abstract = {Coronavirus disease 2019 (COVID-19) survivors are concerned about the likelihood of developing further diseases. This study examines the global trends in scientific research on diabetes associated with COVID-19 from several perspectives. Bibliometric analyses are used to undertake a scientific review of the literature. The Web of Science Core Collection (WoSCC) database was used to acquire bibliographic information on diabetes related to COVID-19 from Jan 2020 to Dec. 2023. The visual map was built via advanced CiteSpace 6.2.R6. 7,348 papers were found. Khunti Kamlesh and Rizzo-Manfredi are the most well-known high-yield authors in this area, and the top ten authors collaborate extensively. Most of these papers came from universities. Harvard Medical School has the most publications, followed by Wuhan University and Huazhong University of Science and Technology. China and the United States are the countries with the most publications. Angiotensin-converting enzymes, chronic disease, intensive care unit, viral infection, and gestational diabetes mellitus were scored 0-11, 2, 3, and 4, respectively. Zhou et al.'s work on this topic, which appeared in the prominent medical journal The Lancet, was cited 1,366 times, highlighting its importance. "clinical characteristics," "diabetes mellitus," "metabolic syndrome," and "angiotensin-converting enzyme" were used as keywords for reference co-citation and clustering data identify. Over the last four years, related investigations have focused primarily on observing clinical aspects. This report is important for developing treatment strategies, directing future research, and guiding clinical practice.}, }
@article {pmid40132681, year = {2025}, author = {Wang, Z and Yang, C and Wang, X and Lyu, W and Liao, H and Liu, X and Liu, H and Zhang, J and Shen, H and Zhang, L and Wang, H}, title = {Decoding stress granules dynamics: Implications for neurodegenerative disease.}, journal = {Progress in neurobiology}, volume = {248}, number = {}, pages = {102758}, doi = {10.1016/j.pneurobio.2025.102758}, pmid = {40132681}, issn = {1873-5118}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism ; Animals ; *Stress Granules/metabolism ; }, abstract = {Stress granules (SGs) are membrane-less cytoplasmic structures formed by cells in response to external stress, primarily composed of mRNA and proteins. The dynamic properties of their assembly, maintenance, and disassembly play crucial roles in cellular homeostasis. Recent studies have increasingly revealed that aberrations in SGs dynamics are closely related to the pathogenesis of various neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This review summarizes the latest research progress on SGs dynamics in neurodegenerative diseases. It begins with an overview of the basic biological characteristics of SGs and their functions in neurons, followed by an in-depth exploration of the mechanisms and regulatory pathways of SGs dynamics. The review then summarizes potential therapeutic strategies targeting SGs dynamics abnormalities, particularly through small molecule drugs to modulate SGs formation and disassembly, aiming to delay or halt the progression of neurodegenerative diseases. The review also highlights the application prospects of these interventions in treating neurodegenerative diseases. Finally, the review introduces current techniques used to study SGs dynamics, discussing their advantages, limitations, and future development possibilities. This review aims to provide researchers with a comprehensive perspective to advance the understanding and clinical application of SGs dynamics in the field of neurodegenerative diseases.}, }
@article {pmid40131291, year = {2025}, author = {Penn, J and McAleer, R and Ziegler, C and Cheskes, S and Nolan, B and von Vopelius-Feldt, J}, title = {Effectiveness of Prehospital Critical Care Scene Response for Major Trauma: A Systematic Review.}, journal = {Prehospital emergency care}, volume = {}, number = {}, pages = {1-14}, doi = {10.1080/10903127.2025.2483978}, pmid = {40131291}, issn = {1545-0066}, abstract = {OBJECTIVES: Major trauma is a leading cause of morbidity and mortality worldwide. It is unclear if the addition of a critical care response unit (CCRU) with capabilities comparable to hospital emergency departments might improve outcomes following major trauma, when added to Basic or Advanced Life Support (BLS/ALS) prehospital care. This systematic review describes the evidence for a CCRU scene response model for major trauma.<br><br>METHODS: We searched Medline (Ovid), Embase (Ovid), Cochrane Central Register of Controlled Trials (Ovid), CINAHL (EBSCOhost), Science Citation Index Expanded (Web of Science), Conference Proceedings Citation Index - Science (Web of Science), LILACS (Latin American and Caribbean Health Sciences Literature) for relevant publications from 2003 to 2024. We included any study that compared CCRU and BLS/ALS care at the scene of major trauma, reported patient-focused outcomes, and utilized statistical methods to reduce bias and confounding. The risk of bias was assessed by two independent reviewers, using the ROBINS-I tool. Based on our a priori knowledge of the literature, a narrative analysis was chosen. The review was prospectively registered (PROSPERO ID CRD42023490668).<br><br>RESULTS: The search yielded 5243 unique records, of which 26 retrospective cohort studies and one randomized controlled trial met inclusion criteria. Sample sizes ranged from 308 to 153,729 patients. Eighteen of the 27 included studies showed associations between CCRUs and improved survival following trauma, which appear to be more consistently found in more critically injured and adult patients, as well as those suffering traumatic cardiac arrest. The remaining nine studies showed no significant difference in outcomes between CCRU and BLS/ALS care. Most studies demonstrated critical or severe risks of bias.<br><br>CONCLUSIONS: Current evidence examining CCRU scene response for major trauma suggests potential benefits in severely injury patients but is limited by overall low quality. Further high-quality research is required to confirm the benefits from CCRU scene response for major trauma.}, }
@article {pmid40130694, year = {2025}, author = {Burke, KM and Arulanandam, V and Scirocco, E and Royse, T and Hall, S and Weber, H and Arnold, J and Pathak, P and Walsh, C and Paganoni, S}, title = {Assistive Technology in ALS: A Scoping Review of Devices for Limb, Trunk, and Neck Weakness.}, journal = {American journal of physical medicine &amp; rehabilitation}, volume = {104}, number = {8}, pages = {e115-e124}, pmid = {40130694}, issn = {1537-7385}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/rehabilitation/physiopathology ; *Self-Help Devices ; *Muscle Weakness/rehabilitation/etiology/physiopathology ; Activities of Daily Living ; Torso/physiopathology ; }, abstract = {Amyotrophic lateral sclerosis is a progressive neurodegenerative disease affecting upper and lower motor neurons that control voluntary muscles. With no known cure, clinical care is focused on symptom management to maximize function and quality of life. Assistive technology plays a crucial role and enables some restoration of movement and function despite disease progression. This scoping review assesses the effectiveness of assistive technologies tested in people living with amyotrophic lateral sclerosis, specifically those designed to compensate for upper and lower extremity, trunk, and cervical muscle weakness. A comprehensive search was conducted across PubMed, CINAHL, ERIC, and Google Scholar and through citation chasing. We included 26 articles that tested an assistive device on at least one person living with amyotrophic lateral sclerosis and evaluated the device's effectiveness in restoring movement or providing stabilization to support functional mobility or activities of daily living. Most studies were pilot feasibility or usability trials, with small numbers of amyotrophic lateral sclerosis participants. The devices showed various benefits, including improved range of motion, function, and participation in daily activities. This review highlights the potential for assistive devices to enhance function in people living with amyotrophic lateral sclerosis and underscores the need for comprehensive studies involving larger cohorts of individuals at different stages of amyotrophic lateral sclerosis.}, }
@article {pmid40128823, year = {2025}, author = {Zhang, W and Huang, C and Yao, H and Yang, S and Jiapaer, Z and Song, J and Wang, X}, title = {Retrotransposon: an insight into neurological disorders from perspectives of neurodevelopment and aging.}, journal = {Translational neurodegeneration}, volume = {14}, number = {1}, pages = {14}, pmid = {40128823}, issn = {2047-9158}, support = {2023TSYCCX0051//Tianshan Talent Training Program/ ; }, mesh = {Humans ; *Retroelements/genetics ; *Aging/genetics ; *Nervous System Diseases/genetics ; Animals ; }, abstract = {Neurological disorders present considerable challenges in diagnosis and treatment due to their complex and diverse etiology. Retrotransposons are a type of mobile genetic element that are increasingly revealed to play a role in these diseases. This review provides a detailed overview of recent developments in the study of retrotransposons in neurodevelopment, neuroaging, and neurological diseases. Retrotransposons, including long interspersed nuclear elements-1, Alu, SINE-VNTR-Alu, and endogenous retrovirus, play important regulatory roles in the development and aging of the nervous system. They have also been implicated in the pathological processes of several neurological diseases, including Alzheimer's disease, X-linked dystonia-parkinsonism, amyotrophic lateral sclerosis, autism spectrum disorder, and schizophrenia. Retrotransposons provide a new perspective for understanding the molecular mechanisms underlying neurological diseases and provide insights into diagnostic and therapeutic strategies of these diseases.}, }
@article {pmid40126301, year = {2025}, author = {Sohn, J and Rochester, E and Oluyase, AO}, title = {Features of COPD That Lead to Stigmatisation and Its Consequences: A Framework Synthesis.}, journal = {COPD}, volume = {22}, number = {1}, pages = {2476435}, doi = {10.1080/15412555.2025.2476435}, pmid = {40126301}, issn = {1541-2563}, mesh = {Humans ; *Pulmonary Disease, Chronic Obstructive/psychology ; *Social Stigma ; Smoking/psychology ; Patient Acceptance of Health Care/psychology ; Qualitative Research ; Social Isolation ; }, abstract = {COPD is a highly stigmatised condition. To develop effective measures to reduce COPD-related stigma, it is important to understand patients' experiences and identify contributing factors. This systematic review explores qualitative evidence regarding the features of COPD leading to stigmatisation and how it can potentially influence health outcomes. Electronic databases were searched to identify primary qualitative studies focussing on stigma-related experiences of adults with COPD, published between January 1988 to August 2024. Data were synthesised using framework synthesis. Twenty-nine studies with 427 participants were included in this review. Findings fit well into six themes identified from Jones et al.'s framework of stigma dimensions and provide rich description. Smoking habit was not the only factor of stigma but also factors that contributed to disability of individuals. Patients experience COPD-related stigma mainly from themselves and healthcare professionals. Potential consequences of stigma identified are mental distress, isolation, reduced help-seeking behaviour and non-compliance to management. Collective effort by society and healthcare systems will be necessary to alleviate the stigma associated with chronic symptoms and smoking behaviour of COPD and to promote the benefit of pulmonary rehabilitation and available mental health support.}, }
@article {pmid40122623, year = {2025}, author = {Ghanizada, H and Nedergaard, M}, title = {The glymphatic system.}, journal = {Handbook of clinical neurology}, volume = {209}, number = {}, pages = {161-170}, doi = {10.1016/B978-0-443-19104-6.00006-1}, pmid = {40122623}, issn = {0072-9752}, mesh = {Humans ; *Glymphatic System/metabolism/physiology ; Animals ; *Neurodegenerative Diseases ; *Brain/metabolism ; }, abstract = {The glymphatic system, a brain-wide network-supporting cerebrospinal fluid (CSF) and interstitial fluid (ISF) exchange, is essential for removing metabolic waste from the brain. This system's proper functioning is crucial for maintaining neural health and preventing the accumulation of harmful substances that can lead to neurodegenerative diseases. This chapter explores the glymphatic system's mechanisms, its dysfunction in various neurologic disorders, and potential therapeutic strategies. Recent discoveries reveal the glymphatic system's involvement in aging, sleep, cerebral edema, and conditions, such as Alzheimer, Parkinson, Huntington diseases, amyotrophic lateral sclerosis, small vessel disease, hydrocephalus, migraine, stroke, traumatic brain injury, and psychiatric disorders, where impaired waste clearance contributes to disease pathogenesis. Moreover, therapeutic interventions targeting glymphatic dysfunction present promising avenues for mitigating the effects of neurodegenerative diseases. The chapter underscores the potential of integrating glymphatic research into broader clinical practices, offering new strategies for disease management and prevention.}, }
@article {pmid40122396, year = {2025}, author = {Cao, Y and Xu, Y and Cao, M and Chen, N and Zeng, Q and Lai, MKP and Fan, D and Sethi, G and Cao, Y}, title = {Fluid-based biomarkers for neurodegenerative diseases.}, journal = {Ageing research reviews}, volume = {108}, number = {}, pages = {102739}, doi = {10.1016/j.arr.2025.102739}, pmid = {40122396}, issn = {1872-9649}, mesh = {Humans ; *Biomarkers/cerebrospinal fluid/blood/metabolism ; *Neurodegenerative Diseases/diagnosis/blood/cerebrospinal fluid/metabolism ; Amyloid beta-Peptides/blood ; tau Proteins/blood ; }, abstract = {Neurodegenerative diseases, such as Alzheimer's Disease (AD), Multiple Sclerosis (MS), Parkinson's Disease (PD), and Amyotrophic Lateral Sclerosis (ALS) are increasingly prevalent as global populations age. Fluid biomarkers, derived from cerebrospinal fluid (CSF), blood, saliva, urine, and exosomes, offer a promising solution for early diagnosis, prognosis, and disease monitoring. These biomarkers can reflect critical pathological processes like amyloid-beta (Aβ) deposition, tau protein hyperphosphorylation, α-syn misfolding, TDP-43 mislocalization and aggregation, and neuronal damage, enabling detection long before clinical symptoms emerge. Recent advances in blood-based biomarkers, particularly plasma Aβ, phosphorylated tau, and TDP-43, have shown diagnostic accuracy equivalent to CSF biomarkers, offering more accessible testing options. This review discusses the current challenges in fluid biomarker research, including variability, standardization, and sensitivity issues, and explores how combining multiple biomarkers with clinical symptoms improves diagnostic reliability. Ethical considerations, future directions involving extracellular vehicles (EVs), and the integration of artificial intelligence (AI) are also highlighted. Continued research efforts will be key to overcoming these obstacles, enabling fluid biomarkers to become crucial tools in personalized medicine for neurodegenerative diseases.}, }
@article {pmid40120962, year = {2025}, author = {Zhang, X and Wang, J and Zhang, J and Jiang, C and Liu, X and Wang, S and Zhang, Z and Rastegar-Kashkooli, Y and Dialameh, F and Peng, Q and Tao, J and Ding, R and Wang, J and Cheng, N and Wang, M and Wang, F and Li, N and Xing, N and Chen, X and Fan, X and Wang, J and Wang, J}, title = {Humanized rodent models of neurodegenerative diseases and other brain disorders.}, journal = {Neuroscience and biobehavioral reviews}, volume = {172}, number = {}, pages = {106112}, doi = {10.1016/j.neubiorev.2025.106112}, pmid = {40120962}, issn = {1873-7528}, mesh = {Animals ; *Disease Models, Animal ; Humans ; *Neurodegenerative Diseases/genetics/pathology/physiopathology ; *Brain Diseases ; Rodentia ; }, abstract = {Central Nervous System (CNS) diseases significantly affect human health. However, replicating the onset, progression, and pathology of these diseases in rodents is challenging. To address this issue, researchers have developed humanized animal models. These models introduce human genes or cells into rodents. As a result, rodents become more suitable for studying human CNS diseases and their therapies in vivo. This review explores the preparation protocols, pathological and behavioral characteristics, benefits, significance, and limitations of humanized rodent models in researching various CNS diseases, particularly Alzheimer's disease, Parkinson's disease, Huntington's disease, Amyotrophic lateral sclerosis, glial cells-related CNS diseases, N-methyl-D-aspartic acid receptor encephalitis, and others. Humanized rodent models have expanded the opportunities for in vivo exploration of human neurodegenerative diseases, other brain disorders, and their treatments. We can enhance translational research on CNS disorders by developing, investigating, and utilizing these models.}, }
@article {pmid40119776, year = {2025}, author = {Pesti, B and Langa, X and Kumpesa, N and Valdeolivas, A and Sultan, M and Rottenberg, S and Hahn, K}, title = {Mini Review: Spatial Transcriptomics to Decode the Central Nervous System.}, journal = {Toxicologic pathology}, volume = {53}, number = {4}, pages = {397-402}, doi = {10.1177/01926233251325204}, pmid = {40119776}, issn = {1533-1601}, mesh = {Humans ; Animals ; *Transcriptome ; *Central Nervous System/metabolism ; *Gene Expression Profiling/methods ; Neurodegenerative Diseases/genetics ; }, abstract = {Spatial transcriptomics (ST) is revolutionizing our understanding of the central nervous system (CNS) by providing spatially resolved gene expression data. This mini review explores the impact of ST on CNS research, particularly in neurodegenerative diseases like Alzheimer's, Parkinson's, multiple sclerosis, and amyotrophic lateral sclerosis. We describe two foundational ST methods: sequencing-based and imaging-based. Key studies are reviewed highlighting the power of ST data sets to map transcriptomes to disease-specific histomorphology, elucidate molecular mechanisms of regional and cellular vulnerability, integrate single-cell data with tissue mapping, and reveal receptor-ligand interactions. Despite current challenges like data interpretation and resolution limits, ST holds promise for identifying novel drug targets, evaluating their therapeutic potential, and bridging gaps between animal models and human studies to advance development of CNS-targeting compounds.}, }
@article {pmid40118328, year = {2025}, author = {Mansour, HM and El-Khatib, AS}, title = {Oligonucleotide-based therapeutics for neurodegenerative disorders: Focus on antisense oligonucleotides.}, journal = {European journal of pharmacology}, volume = {998}, number = {}, pages = {177529}, doi = {10.1016/j.ejphar.2025.177529}, pmid = {40118328}, issn = {1879-0712}, mesh = {Humans ; *Oligonucleotides, Antisense/therapeutic use/chemistry ; *Neurodegenerative Diseases/drug therapy/genetics/therapy ; Animals ; }, abstract = {Antisense oligonucleotides (ASOs) specifically bind to target RNA sequences and regulate protein expression through various mechanisms. ASOs are a promising therapeutic approach for treating neurodegenerative diseases. The ASO field is a growing area of drug development that focuses on targeting the root cause of diseases at the RNA level, providing a promising alternative to therapies that target downstream processes. Addressing challenges related to off-target effects and inadequate biological activity is essential to successfully develop ASO-based therapies. Researchers have investigated various chemical modifications and delivery strategies to overcome these challenges. This review discusses oligonucleotide-based therapies, particularly ASOs. We discuss the chemical modifications and mechanisms of action of ASOs. Additionally, we recap the results of preclinical and clinical studies testing different ASOs in various neurodegenerative disorders, including spinal muscular atrophy, Huntington's disease, amyotrophic lateral sclerosis, Alzheimer's disease, and Parkinson's disease. In conclusion, ASO drugs show promise as a therapeutic option for treating neurodegenerative diseases.}, }
@article {pmid40116286, year = {2025}, author = {Cleverley, K and Salman, S and Davies, J and Ewing, L and McCann, E and Sainsbury, K and Gray, M and Lau, CKY and Lipsitz, O and Prompiengchai, S}, title = {Frameworks Used to Engage Postsecondary Students in Campus Mental Health Research: A Scoping Review.}, journal = {Health expectations : an international journal of public participation in health care and health policy}, volume = {28}, number = {2}, pages = {e70144}, pmid = {40116286}, issn = {1369-7625}, support = {//This research was supported by a grant from the Connaught Global Challenge Award at the University of Toronto awarded to K.C./ ; }, mesh = {Humans ; *Students/psychology ; *Mental Health ; Universities ; }, abstract = {BACKGROUND: There is an increasing prevalence of mental health concerns reported among postsecondary students (PSS) and growing demands for care on campuses around the world, as such there is an urgent need for research and innovations in PSS mental health that engages PSS. However, best practices and guidelines for facilitating PSS engagement in research is lacking. To address this gap, we undertook this review to explore frameworks used for engaging with PSS in research focused on PSS mental health.<br><br>METHODS: A scoping review of the academic literature was conducted. Frameworks used to engage PSS in mental health research were identified and categorized using the taxonomy of patient and public engagement by Greenhalgh et al. A list of barriers and facilitators to engaging with PSS was also identified and reported.<br><br>RESULTS: Of the articles assessed for full-text screening (n&#x2009;=&#x2009;167), 26 journal articles were included. Frameworks used for engaging PSS in mental health research were classified into one of the three categories from Greenhalgh et al.'s taxonomy: study-focused (n&#x2009;=&#x2009;14), partnership-focused (n&#x2009;=&#x2009;9) and power-focused (n&#x2009;=&#x2009;3). No relevant frameworks were found for two categories: priority- and report-focused. Seven documents reported relational or process-related barriers and/or facilitators to engaging with PSS. Based on these findings, recommendations were drafted with PSS advisors on how to implement an engagement framework in PSS mental health research.<br><br>CONCLUSIONS: We identified existing practices outlined within frameworks used to engage PSS and barriers and facilitators to engage with PSS in mental health research. Based on the review findings and PSS advisors recommendations, a need for developing a comprehensive engagement framework specific to the PSS context was identified.<br><br>The research team led consultations with a PSS advisory group for this review. Student advisors were actively engaged in data analysis, which included categorizing and drafting of recommendations, and the preparation of this manuscript.}, }
@article {pmid40114110, year = {2025}, author = {Anderson, T and Mitchell, G and Prue, G and McLaughlin, S and Graham-Wisener, L}, title = {The psychosocial impact of pancreatic cancer on caregivers: a scoping review.}, journal = {BMC cancer}, volume = {25}, number = {1}, pages = {511}, pmid = {40114110}, issn = {1471-2407}, mesh = {Humans ; *Caregivers/psychology ; *Pancreatic Neoplasms/psychology/therapy ; Quality of Life ; *Stress, Psychological/psychology ; }, abstract = {BACKGROUND: Family caregivers are essential members of the care team of someone with pancreatic cancer, supporting their physical and psychological needs. Caregivers are often unprepared for this which may cause substantial psychosocial impact. This may be exacerbated by the short life-expectancy and rapid deterioration associated with pancreatic cancer. A scoping review was conducted to identify, from the existing literature, what is currently known about the psychosocial impact of pancreatic cancer on caregivers across the disease trajectory.<br><br>METHODS: A Joanna Briggs Institute (JBI) mixed methods scoping review was conducted across four databases (CINAHL, EMBASE, MEDLINE, PsycINFO). All identified citations were uploaded to Covidence, and were screened independently by two reviewers. Data were extracted and synthesised following a deductive approach guided by 'The Cancer Family Caregiving Experience' model (Fletcher et al., 2012).<br><br>RESULTS: 42 studies were included: 22 qualitative, 15 quantitative, 5 mixed methods. Results of the included studies were collated into the proposed constructs of Fletcher et al.'s (2012) model: primary stressors, secondary stressors, appraisal, cognitive-behavioural responses, health and wellbeing outcomes, as well as the influence of disease trajectory and contextual factors. The literature highlighted pancreatic cancer caregivers experienced stress related to caregiving activities, disruptions in their daily life and family relationships, high levels of unmet need, and poorer quality of life compared to other cancer caregivers. They were also at increased risk for various psychiatric disorders and reported a persistent lack of support which exacerbated the psychosocial impact.<br><br>CONCLUSIONS: Pancreatic cancer caregivers experience negative psychosocial impacts, exacerbated by the disease's trajectory. Feelings of a lack of support were reflected throughout the included literature and emphasise the need for future research into how pancreatic cancer caregivers may be best supported, and sign-posted to existing support, to minimise the substantial psychosocial impact they may experience.}, }
@article {pmid40110864, year = {2025}, author = {Kornhaber, R and Mc Kittrick, A and Rossiter, R and Cleary, M}, title = {Pain Experiences in Adult Burn Survivors During Rehabilitation and Recovery: A Qualitative Systematic Review.}, journal = {Journal of burn care &amp; research : official publication of the American Burn Association}, volume = {46}, number = {4}, pages = {818-832}, pmid = {40110864}, issn = {1559-0488}, support = {//2023 Charles Sturt University Faculty of Science/ ; //Health New Staff Research Establishment Scheme/ ; }, mesh = {Humans ; *Burns/rehabilitation/psychology/complications ; *Survivors/psychology ; Qualitative Research ; Adult ; *Pain/psychology/etiology ; }, abstract = {Despite advancements in burn care, pain persists despite multidisciplinary management efforts. This review aimed to synthesize the qualitative research that explored the impact of pain on burn survivors' rehabilitation and recovery. In September 2023, PubMed, Cumulative Index of Nursing and Allied Health Literature, and Scopus were searched for peer-reviewed published research in English. Nineteen articles from 17 studies met the inclusion criteria. The review used Thomas and Harden's thematic synthesis framework for qualitative research evidence. Two descriptors of pain were described, physical and psychological pain. Pain in burn survivors, both physical and psychological, was complex, intertwined, and dynamic across 3 stages: before, during, and after interventions. This was found to closely align with Cleary et al.'s trauma-informed model of care in burn settings, which emphasizes a 3-stage process, underlining that pain is not static but evolves and fluctuates, necessitating adaptive and person-centered burn care and post-treatment mental health support. Adopting a Trauma-Informed Care (TIC) approach in burn injury settings is crucial. Individuals postburn encounter varying degrees of physical and psychological pain, which for some remains persistent. Using patient-reported measures throughout recovery deepens the understanding of burn survivors' pain, respecting their personal experiences and insights. It is essential to conduct future longitudinal research and push for a burn-specific qualitative pain assessment to address these complex needs effectively.}, }
@article {pmid40109277, year = {2025}, author = {Ding, XY and Habimana, JD and Li, ZY}, title = {The role of DPP6 dysregulation in neuropathology: from synaptic regulation to disease mechanisms.}, journal = {Frontiers in cellular neuroscience}, volume = {19}, number = {}, pages = {1547495}, pmid = {40109277}, issn = {1662-5102}, abstract = {As a transmembrane protein, DPP6 modulates the function and properties of ion channels, playing a crucial role in various tissues, particularly in the brain. DPP6 interacts with potassium channel Kv4.2 (KCND2), enhancing its membrane expression and channel kinetics. Potassium ion channels are critical in progressing action potential formation and synaptic plasticity. Therefore, dysfunction of DPP6 can lead to significant health consequences. Abnormal DPP6 expression has been identified in several diseases, such as amyotrophic lateral sclerosis (ALS), autism spectrum disorder (ASD), spinal bulbar muscular atrophy (SBMA), and idiopathic ventricular fibrillation. Recent research has indicated a connection between DPP6 and Alzheimer's disease as well. The most common symptoms resulting from DPP6 dysregulation are mental deficiency and muscle wastage. Notably, these symptoms do not always occur at the same time. Besides genetic factors, environmental factors also undoubtedly play a role in diseases related to DPP6 dysregulation. However, it remains unclear how the expression of DPP6 gets regulated. This review aims to summarize the associations between DPP6 and neurological diseases, offering insights as well as proposing hypotheses to elucidate the underlying mechanisms of DPP6 dysregulation.}, }
@article {pmid40097762, year = {2025}, author = {Nabakhteh, S and Lotfi, A and Afsartaha, A and Khodadadi, ES and Abdolghaderi, S and Mohammadpour, M and Shokri, Y and Kiani, P and Ehtiati, S and Khakshournia, S and Khatami, SH}, title = {Nutritional Interventions in Amyotrophic Lateral Sclerosis: From Ketogenic Diet and Neuroprotective Nutrients to the Microbiota-Gut-Brain Axis Regulation.}, journal = {Molecular neurobiology}, volume = {62}, number = {7}, pages = {9216-9239}, pmid = {40097762}, issn = {1559-1182}, mesh = {*Amyotrophic Lateral Sclerosis/diet therapy/microbiology ; Humans ; *Diet, Ketogenic/methods ; *Gastrointestinal Microbiome/physiology ; *Neuroprotective Agents/therapeutic use/pharmacology ; Animals ; *Brain/metabolism ; *Nutrients/therapeutic use ; *Neuroprotection ; *Brain-Gut Axis/physiology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease with significant challenges in diagnosis and treatment. Recent research has highlighted the complex nature of ALS, encompassing behavioral impairments in addition to its neurological manifestations. While several medications have been approved to slow disease progression, ongoing research is focused on identifying new therapeutic targets. The current review focuses on emerging therapeutic strategies and personalized approaches aimed at improving patient outcomes. Recent advancements highlight the importance of targeting additional pathways such as mitochondrial dysfunction and neuroinflammation to develop more effective treatments. Personalized medicine, including genetic testing and biomarkers, is proving valuable in stratifying patients and tailoring treatment options. Complementary therapies, such as nutritional interventions like the ketogenic diet and microbiome modulation, also show promise. This review emphasizes the need for a multidisciplinary approach that integrates early diagnosis, targeted treatments, and supportive care to address the multisystemic nature of ALS and improve the quality of life for patients.}, }
@article {pmid40097438, year = {2025}, author = {Ayyadurai, VAS and Deonikar, P and Kamm, RD}, title = {A molecular systems architecture of neuromuscular junction in amyotrophic lateral sclerosis.}, journal = {NPJ systems biology and applications}, volume = {11}, number = {1}, pages = {27}, pmid = {40097438}, issn = {2056-7189}, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/pathology/physiopathology ; Humans ; *Neuromuscular Junction/metabolism/pathology/physiopathology ; Motor Neurons/metabolism/pathology ; Animals ; Schwann Cells/metabolism ; Muscle, Skeletal/pathology/metabolism ; }, abstract = {A molecular systems architecture is presented for the neuromuscular junction (NMJ) in order to provide a framework for organizing complexity of biomolecular interactions in amyotrophic lateral sclerosis (ALS) using a systematic literature review process. ALS is a fatal motor neuron disease characterized by progressive degeneration of the upper and lower motor neurons that supply voluntary muscles. The neuromuscular junction contains cells such as upper and lower motor neurons, skeletal muscle cells, astrocytes, microglia, Schwann cells, and endothelial cells, which are implicated in pathogenesis of ALS. This molecular systems architecture provides a multi-layered understanding of the intra- and inter-cellular interactions in the ALS neuromuscular junction microenvironment, and may be utilized for target identification, discovery of single and combination therapeutics, and clinical strategies to treat ALS.}, }
@article {pmid40095345, year = {2025}, author = {Dehghani, S and Ocakcı, O and Hatipoglu, PT and Özalp, VC and Tevlek, A}, title = {Exosomes as Biomarkers and Therapeutic Agents in Neurodegenerative Diseases: Current Insights and Future Directions.}, journal = {Molecular neurobiology}, volume = {62}, number = {7}, pages = {9190-9215}, pmid = {40095345}, issn = {1559-1182}, mesh = {*Exosomes/metabolism ; Humans ; *Neurodegenerative Diseases/therapy/diagnosis/metabolism/drug therapy ; *Biomarkers/metabolism ; Animals ; Blood-Brain Barrier/metabolism ; Drug Delivery Systems ; }, abstract = {Neurodegenerative diseases (NDs) like Alzheimer's, Parkinson's, and ALS rank among the most challenging global health issues, marked by substantial obstacles in early diagnosis and effective treatment. Current diagnostic techniques frequently demonstrate inadequate sensitivity and specificity, whilst conventional treatment strategies encounter challenges related to restricted bioavailability and insufficient blood-brain barrier (BBB) permeability. Recently, exosomes-nanoscale vesicles packed with proteins, RNAs, and lipids-have emerged as promising agents with the potential to reshape diagnostic and therapeutic approaches to these diseases. Unlike conventional drug carriers, they naturally traverse the BBB and can deliver bioactive molecules to affected neural cells. Their molecular cargo can influence cell signaling, reduce neuroinflammation, and potentially slow neurodegenerative progression. Moreover, exosomes serve as non-invasive biomarkers, enabling early and precise diagnosis while allowing real-time disease monitoring. Additionally, engineered exosomes, loaded with therapeutic molecules, enhance this capability by targeting diseased neurons and overcoming conventional treatment barriers. By offering enhanced specificity, reduced immunogenicity, and an ability to bypass physiological limitations, exosome-based strategies present a transformative advantage over existing diagnostic and therapeutic approaches. This review examines the multifaceted role of exosomes in NDDs, emphasizing their diagnostic capabilities, intrinsic therapeutic functions, and transformative potential as advanced treatment vehicles.}, }
@article {pmid40091916, year = {2025}, author = {Ansari, U and Wen, J and Karabala, M and Syed, B and Abed, I and Razick, DI and Lui, F}, title = {Analysis of Respiratory Muscle Strength Training in Amyotrophic Lateral Sclerosis (ALS) Patients: A Systematic Review.}, journal = {Cureus}, volume = {17}, number = {2}, pages = {e78903}, pmid = {40091916}, issn = {2168-8184}, abstract = {Respiratory muscle weakness is a significant contributor to morbidity and mortality in amyotrophic lateral sclerosis (ALS) patients. Respiratory muscle strength training (RMST) has emerged as a potential therapeutic approach to mitigate respiratory muscle weakness in ALS. Still, its efficacy and safety remain unclear due to conflicting evidence and methodological heterogeneity in existing studies. A systematic review was conducted across three databases (PubMed (United States National Library of Medicine, Bethesda, MD, USA), Embase (Elsevier, Amsterdam, Netherlands), and Cochrane Library (Cochrane, Alberta, Canada)) following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to assess the effectiveness of RMST in ALS patients. Eligible studies included comparative studies for RMST, focusing on outcomes such as maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), forced vital capacity (FVC), and ALS Functional Rating Scale (ALSFRS-R). Quality assessment was performed using the Cochrane Risk of Bias tool. This study included six studies, including 183 patients with a mean age of 58.0 years (49.6 to 63.2) and a mean follow-up time of 21.2 weeks (eight to 52). The average mean difference for ALSFRS-R (three studies), MIP (three studies), MEP (three studies), and FVC (two studies) were 2.062 (0.04 to 5.3), 2.285 (-8.145 to 10.8), 19.435 (10.86 to 21.7), and 7.23 (3.6 to 10.86), respectively. Complications related to RMST were poorly reported across studies. Secondary outcomes, such as depression scores, blood oxygen levels, and heart rate variability, showed promising trends but lacked consistency. Despite positive findings on respiratory muscle strength, RMST's efficacy in ALS management remains inconclusive. Challenges include methodological heterogeneity, limited sample sizes, and inadequate reporting of complications. Future research should focus on standardized protocols, larger sample sizes, longer follow-ups, and comprehensive assessment of adverse effects to clarify the role of RMST in ALS treatment.}, }
@article {pmid40090808, year = {2025}, author = {Rosina, M and Scaricamazza, S and Fenili, G and Nesci, V and Valle, C and Ferri, A and Paronetto, MP}, title = {Hidden players in the metabolic vulnerabilities of amyotrophic lateral sclerosis.}, journal = {Trends in endocrinology and metabolism: TEM}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tem.2025.02.004}, pmid = {40090808}, issn = {1879-3061}, abstract = {Amyotrophic lateral sclerosis (ALS) is a complex and rapidly progressive motor neuron disorder with a fatal outcome. Despite the remarkable progress in understanding ALS pathophysiology, which has significantly contributed to clinical trial design, ALS remains a rapidly disabling and life-shortening condition. The non-motor neuron features of ALS, including nutritional status, energy expenditure, and metabolic imbalance, are increasingly gaining attention. Indeed, the bioenergetic failure and mitochondrial dysfunction of patients with ALS impact not only the high energy-demanding motor neurons but also organs and brain areas long considered irrelevant to the disease. As such, here we discuss how considering energy balance in ALS is reshaping research on this disease, opening the path to novel targetable opportunities for its treatment.}, }
@article {pmid40089090, year = {2025}, author = {Men, J and Wang, X and Zhou, Y and Huang, Y and Zheng, Y and Wang, Y and Yang, S and Chen, N and Yan, N and Duan, X}, title = {Neurodegenerative diseases: Epigenetic regulatory mechanisms and therapeutic potential.}, journal = {Cellular signalling}, volume = {131}, number = {}, pages = {111715}, doi = {10.1016/j.cellsig.2025.111715}, pmid = {40089090}, issn = {1873-3913}, mesh = {Humans ; *Epigenesis, Genetic ; *Neurodegenerative Diseases/genetics/therapy/pathology ; DNA Methylation ; Animals ; Histones/metabolism ; RNA, Untranslated/genetics/metabolism ; Chromatin Assembly and Disassembly ; }, abstract = {Neurodegenerative diseases (NDDs) are a class of diseases in which the progressive loss of subtype-specific neurons leads to dysfunction. NDDs include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), among others. Previous studies have demonstrated that the pathogenesis of NDDs involves various mechanisms, including genetic factors, oxidative stress, apoptosis, and the immune response. Recent studies have shown that epigenetic regulation mediates the interactions between DNA methylation, chromatin remodeling, histone modification, and non-coding RNAs, thus affecting gene transcription. A growing body of research links epigenetic modifications to crucial pathways involved in the occurrence and development of NDDs. Epigenetics has also been found to regulate and maintain nervous system function, and its imbalance is closely related to the occurrence and development of NDDs. The present review summarizes focuses on the role of epigenetic modifications in the pathogenesis of NDDs and provides an overview of the key genes regulated by DNA methylation, histone modification, and non-coding RNAs in NDDs. Further, the current research status of epigenetics in NDDs is summarized and the potential application of epigenetics in the clinical diagnosis and treatment of NDDs is discussed.}, }
@article {pmid40086112, year = {2025}, author = {Liampas, I and Veltsista, D and Germeni, A and Batzikosta, P and Michou, E and Kefalopoulou, Z and Chroni, E}, title = {F waves in amyotrophic lateral sclerosis: A systematic review and meta-analysis.}, journal = {Neurophysiologie clinique = Clinical neurophysiology}, volume = {55}, number = {4}, pages = {103061}, doi = {10.1016/j.neucli.2025.103061}, pmid = {40086112}, issn = {1769-7131}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnosis ; *Neural Conduction/physiology ; Ulnar Nerve/physiopathology ; Electromyography ; Muscle, Skeletal/physiopathology ; }, abstract = {OBJECTIVE: This systematic review and meta-analysis aimed to determine the pattern of F-wave abnormalities and their potential utility in the early diagnosis of amyotrophic lateral sclerosis (ALS).<br><br>METHODS: Medline and Embase were thoroughly searched. We primarily emphasized F-wave recordings from the abductor digiti minimi, following stimulation of the ulnar nerve at the wrist. Data from case-control studies involving individuals with ALS versus healthy controls (HC) or other well-defined patient groups were reviewed and -if appropriate- quantitatively synthesized.<br><br>RESULTS: Twenty-nine studies were included in this systematic review and 17 of them in the analytic part. The pattern of F-abnormalities in ALS compared to HC was as follows: decreased persistence (MD=20.25 %,15.67-24.84 %), mildly prolonged minimum latency (MD=1.59msec,1.11-2.06msec), increased maximum amplitude (MD=196&#x3bc;V,106-287&#x3bc;V) and elevated Index total Freps (MD=33.9 %,26.0-41.8 %). Affected limbs (with substantial weakness in clinical examination and/or muscle wasting and/or abnormal nerve conduction studies) exhibited more marked abnormalities in persistence, minimum latency, and Index total Freps, whereas abnormalities in these parameters were very mild in clinically unaffected limbs. More prominent increases in maximum amplitude accompanied pyramidal dysfunction. Of note, isolated upper motor neuron (UMN) disorders exhibited a comparable increase in Index total Freps without a decrease in persistence.<br><br>CONCLUSIONS: The pattern of F wave abnormalities may raise suspicion of involvement of the under-study lower motor neuron (LMN) pool in ALS. These findings may identify LMN dysfunction even at a preclinical stage and prompt extensive electromyographic investigations. UMN involvement may to some extent differentiate the profile of F wave abnormalities in ALS.}, }
@article {pmid40084393, year = {2025}, author = {Helmold, B and Nathaniel, G and Barkhaus, P and Bertorini, T and Bromberg, M and Brown, A and Carter, GT and Chang, V and Crayle, J and Denson, K and Glass, J and Heiman-Patterson, T and Hobson, E and Jackson, C and Jhooty, S and Mallon, E and Maragakis, N and Cadavid, JM and Mcdermott, C and Pattee, G and Pierce, K and Wang, O and Wicks, P and Bedlack, R}, title = {ALSUntangled #78: Zinc.}, journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration}, volume = {26}, number = {5-6}, pages = {599-603}, doi = {10.1080/21678421.2025.2476688}, pmid = {40084393}, issn = {2167-9223}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/diet therapy ; Humans ; *Zinc/therapeutic use/administration &amp; dosage ; *Dietary Supplements ; Animals ; Disease Progression ; }, abstract = {ALSUntangled reviews alternative and off-label treatments for people living with amyotrophic lateral sclerosis (PALS). In this review, we assess the utilization of dietary zinc supplements for modulating ALS pathology and progression. Studies in mouse models of ALS have demonstrated that high-dose zinc supplementation may be harmful, but moderate doses could potentially be beneficial. Clinical data is limited, and only one trial has explored zinc supplementation within PALS. This study reported potential benefits in slowing ALS progression but lacked statistical analyses and failed to report quantitative evidence. Numerous case reports from individual patients at varying doses have demonstrated no benefit. Zinc supplements at moderate doses are generally low cost and not associated with severe complications, but further research is required to determine the safety and efficacy of zinc supplementation within PALS. Therefore, we cannot at this time, endorse zinc supplementation to slow ALS progression.}, }
@article {pmid40080233, year = {2025}, author = {Aydın, &#x15e; and Özdemir, S and Adıgüzel, A}, title = {The Potential of cfDNA as Biomarker: Opportunities and Challenges for Neurodegenerative Diseases.}, journal = {Journal of molecular neuroscience : MN}, volume = {75}, number = {1}, pages = {34}, pmid = {40080233}, issn = {1559-1166}, mesh = {Humans ; Biomarkers/blood ; *Neurodegenerative Diseases/diagnosis/genetics/blood ; *Cell-Free Nucleic Acids/blood/metabolism ; Animals ; }, abstract = {Neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS), are characterized by the progressive and gradual degeneration of neurons. The prevalence and rates of these disorders rise significantly with age. As life spans continue to increase in many countries, the number of cases is expected to grow in the foreseeable future. Early and precise diagnosis, along with appropriate surveillance, continues to pose a challenge. The high heterogeneity of neurodegenerative diseases calls for more accurate and definitive biomarkers to improve clinical therapy. Cell-free DNA (cfDNA), including fragmented DNA released into bodily fluids via apoptosis, necrosis, or active secretion, has emerged as a promising non-invasive diagnostic tool for various disorders including neurodegenerative diseases. cfDNA can serve as an indicator of ongoing cellular damage and mortality, including neuronal loss, and may provide valuable insights into disease processes, progression, and therapeutic responses. This review will first cover the key aspects of cfDNA and then examine recent advances in its potential use as a biomarker for neurodegenerative disorders.}, }
@article {pmid40077653, year = {2025}, author = {de Carvalho Vilar, MD and Coutinho, KMD and de Lima Vale, SH and Dourado Junior, MET and de Medeiros, GCBS and Piuvezam, G and Brandao-Neto, J and Leite-Lais, L}, title = {Evidence-Based Nutritional Recommendations for Maintaining or Restoring Nutritional Status in Patients with Amyotrophic Lateral Sclerosis: A Systematic Review.}, journal = {Nutrients}, volume = {17}, number = {5}, pages = {}, pmid = {40077653}, issn = {2072-6643}, support = {grant number 302298/2017-7 (Jose Brandao-Neto)//National Council for Scientific and Technological Development/ ; TED 132/2018//Ministry of Health (Brazil) - Laboratory of Technological Innovation in Health from the Federal University of Rio Grande do Norte - LAIS/UFRN/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diet therapy/therapy/physiopathology/complications ; *Nutritional Status ; Evidence-Based Medicine ; Nutrition Assessment ; Quality of Life ; Deglutition Disorders/etiology ; Dietary Supplements ; *Nutritional Support ; *Nutrition Therapy ; Practice Guidelines as Topic ; Gastrostomy ; }, abstract = {Background/Objectives: This study is a systematic review of guidelines that aims to synthesize evidence-based recommendations to support appropriate nutritional management for patients with amyotrophic lateral sclerosis (ALS). Methods: PubMed/MEDLINE, Embase, Scopus, SciELO, Web of Science, LILACS, ScienceDirect, and Google Scholar were searched for records published up to July 2024. Clinical practice guidelines addressing any aspect of nutritional intervention in ALS were included. No language or country of publication restrictions were applied. Data extraction was performed by two independent reviewers. The methodological quality of the reports was assessed using the AGREE II instrument. Discrepancies were resolved by consensus. Results: The findings and main recommendations were summarized narratively. A total of 837 records were identified, and 11 were included in this review. The overall AGREE II scores for the included studies ranged from 3 to 7. The summary of nutritional recommendations was organized into topics: (1) dysphagia, (2) nutritional assessment, (3) energy, (4) protein, (5) supplementation, and (6) percutaneous endoscopic gastrostomy (PEG). This review summarizes relevant and updated nutritional recommendations to maintain or restore the nutritional status of patients with ALS, contributing to their quality of life and survival time. Conclusions: These nutritional recommendations will help health professionals and caregivers to implement and standardize nutritional care according to evidence-based practice in ALS. PROSPERO registration number CRD42021233088.}, }
@article {pmid40075376, year = {2025}, author = {Bourke, L and Conway, C and Abdalla, ME}, title = {Mentorship in surgical training; a systematic scoping review to inform a mentorship framework for ophthalmology trainees.}, journal = {BMC medical education}, volume = {25}, number = {1}, pages = {373}, pmid = {40075376}, issn = {1472-6920}, mesh = {Humans ; *Ophthalmology/education ; *Mentors ; Clinical Competence ; }, abstract = {BACKGROUND: Mentorship plays a vital role in surgical training. In the field of ophthalmology, effective mentorship is particularly critical due to the specialised nature of surgeries and the need for comprehensive skill development. However, the landscape of mentorship remains underexplored. Understanding key characteristics and components of effective mentorship is essential for optimising training and ensuring the success of future generations of surgeons. This scoping review aims to analyse existing literature on mentorship in surgical training and to employ Levac et al.'s enhanced methodological framework to construct a conceptual framework for a bespoke mentorship programme tailored to the needs of ophthalmology trainees.<br><br>METHODS: The search strategy adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and included relevant databases such as MEDLINE, Scopus, CINAHL Complete, ERIC, EMBASE, and the Cochrane Library. Selection criteria encompassed studies exploring mentorship experiences, perceptions, and outcomes across all surgical training domains. A two-step screening process was employed, followed by thematic analysis using Braun and Clarke's approach. The Medical Education Research Study Quality Instrument (MERSQI) assessed study quality.<br><br>RESULTS: Of the 81 identified articles, 24 were included in the review, with an average MERSQI score of 11.65. Studies comprised randomised controlled trials, systematic reviews, cohort, cross-sectional studies, and reviews. The thematic analysis identified five domains: (1) mentorship and burnout; (2) surgical skill and performance; (3) career paths and professional development; (4) diversity promotion; and (5) work-life balance.<br><br>CONCLUSIONS: This review underscores the significance of mentorship in surgical training and proposes a conceptual framework tailored to ophthalmology trainees. By synthesising existing literature and through author engagement with relevant training bodies, the study contributes to the development of an imminent mentoring programme, aiming to enhance surgical training outcomes and foster trainee well-being and professional growth.}, }
@article {pmid40074390, year = {2025}, author = {Cappa, SF}, title = {Hemispheric asymmetry in neurodegenerative diseases.}, journal = {Handbook of clinical neurology}, volume = {208}, number = {}, pages = {101-112}, doi = {10.1016/B978-0-443-15646-5.00009-9}, pmid = {40074390}, issn = {0072-9752}, mesh = {Humans ; *Neurodegenerative Diseases/pathology/physiopathology ; *Functional Laterality/physiology ; *Brain/pathology ; }, abstract = {Hemispheric asymmetry in pathologic involvement is frequently observed in neurodegenerative disorders (NDD) and is responsible for differences in cognitive and motor clinical manifestations in individual patients. While asymmetry is modest in typical Alzheimer disease (AD), atypical AD presentations with prominent language impairment [logopenic/phonologic variant of primary progressive aphasia (L/Phv-PPA)] are associated with prevalent involvement of the language-dominant hemisphere. Similarly, in the frontotemporal dementia-amyotrophic lateral sclerosis (FTD-ALS) spectrum, the semantic (Sv) and nonfluent/agrammatic (Nf/Av) variants of PPA are due to asymmetric pathology involving the language-dominant hemisphere. A reversed (typically right-sided) pattern of asymmetry is often found in conditions associated with prominent disorders of behavior and social cognition (i.e., behavioral variant of frontotemporal degeneration-Bv FTD). Asymmetry is generally modest and less consistent in NDD with prevalent motor manifestations, such as Parkinson disease (PD). Overall, the pattern of hemispheric involvement reflects the network-specific selectivity of NDD and is compatible with the spreading of pathology along connection pathways.}, }
@article {pmid40072076, year = {2025}, author = {Calvo, B and Schembri-Wismayer, P and Durán-Alonso, MB}, title = {Age-Related Neurodegenerative Diseases: A Stem Cell's Perspective.}, journal = {Cells}, volume = {14}, number = {5}, pages = {}, pmid = {40072076}, issn = {2073-4409}, mesh = {Humans ; *Neurodegenerative Diseases/pathology/therapy ; *Aging/pathology ; *Stem Cells/metabolism ; Animals ; }, abstract = {Neurodegenerative diseases encompass a number of very heterogeneous disorders, primarily characterized by neuronal loss and a concomitant decline in neurological function. Examples of this type of clinical condition are Alzheimer's Disease, Parkinson's Disease, Huntington's Disease and Amyotrophic Lateral Sclerosis. Age has been identified as a major risk in the etiology of these disorders, which explains their increased incidence in developed countries. Unfortunately, despite continued and intensive efforts, no cure has yet been found for any of these diseases; reliable markers that allow for an early diagnosis of the disease and the identification of key molecular events leading to disease onset and progression are lacking. Altered adult neurogenesis appears to precede the appearance of severe symptoms. Given the scarcity of human samples and the considerable differences with model species, increasingly complex human stem-cell-based models are being developed. These are shedding light on the molecular alterations that contribute to disease development, facilitating the identification of new clinical targets and providing a screening platform for the testing of candidate drugs. Moreover, the secretome and other promising features of these cell types are being explored, to use them as replacement cells of high plasticity or as co-adjuvant therapy in combinatorial treatments.}, }
@article {pmid40069959, year = {2025}, author = {Chiò, A and Foucher, J and Gwathmey, KG and Ingre, C}, title = {Minimum clinically important difference for drug effectiveness in an area of patient-oriented therapeutic goals in amyotrophic lateral sclerosis.}, journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration}, volume = {26}, number = {5-6}, pages = {389-398}, doi = {10.1080/21678421.2025.2475893}, pmid = {40069959}, issn = {2167-9223}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/diagnosis ; Humans ; *Minimal Clinically Important Difference ; Randomized Controlled Trials as Topic ; Treatment Outcome ; Quality of Life ; }, abstract = {Objective: In this review, we will examine the more common endpoints incorporated in randomized controlled trials (RCTs) and their strength of evidence, focusing on the definition of what constitutes a clinically meaningful change. We will also reflect on the perspective of patients and their families regarding the design of RCTs in amyotrophic lateral sclerosis (ALS). Methods: Authors performed a scoping review of the literature around clinical meaningfulness in the ALS field and the minimum clinically important difference to deem a treatment effective. Results: The use of survival as an RCT endpoint, as well as the ALS functional rating scale-revised slope, has been criticized, and their relevance for patients remains debated. Biomarkers are promising alternatives as surrogate endpoints, but currently, only cerebrospinal fluid and plasma neurofilaments have emerged as reliable and sensitive biomarkers of disease progression. Incorporating patients' preferences and priorities for their care when treatments are selected is important to minimize the burden of care and limit the potential harms of overtreatment. Patients' interest in and acceptance of a new therapy is also determined by its impact on their quality of life. Discussion and conclusion: While scientifically sound trials must be conducted, this must be balanced with patient expectations of limiting trial burden, duration and placebo usage. An important approach in uniting these diverging needs is the inclusion of people with ALS and their organizations to advise in the design and execution of clinical trials, facilitating the design of RCTs more focused on patients' expectations while retaining a high scientific rigor.}, }
@article {pmid40065552, year = {2025}, author = {Shibata, N and Kataoka, I and Okamura, Y and Murakami, K and Kato, Y and Yamamoto, T and Masui, K}, title = {Implications for soluble iron accumulation, oxidative stress, and glial glutamate release in motor neuron death associated with sporadic amyotrophic lateral sclerosis.}, journal = {Neuropathology : official journal of the Japanese Society of Neuropathology}, volume = {45}, number = {3}, pages = {177-201}, pmid = {40065552}, issn = {1440-1789}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology/metabolism ; *Oxidative Stress/physiology ; *Iron/metabolism ; *Glutamic Acid/metabolism ; *Motor Neurons/metabolism/pathology ; Male ; Female ; Middle Aged ; Aged ; Spinal Cord/metabolism/pathology ; *Neuroglia/metabolism/pathology ; Cell Death/physiology ; Microglia/metabolism ; Animals ; Astrocytes/metabolism ; Aged, 80 and over ; }, abstract = {Oxidative stress in sporadic amyotrophic lateral sclerosis (ALS) has been evidenced by accumulation of oxidatively modified products of nucleic acids, lipids, sugars, and proteins in the motor neuron system of brains and spinal cords obtained at autopsy from the patients. We recently demonstrated soluble iron accumulation in activated microglia of sporadic ALS spinal cords. This finding could indicate that iron-mediated Fenton reaction is most likely to be responsible for oxidative stress associated with this disease. The excitatory amino acid neurotoxicity hypothesis for sporadic ALS has been proposed based on increased glutamate and aspartate concentrations in cerebrospinal fluid from the patients. Initially, the increase in extracellular excitatory amino acid levels was considered to reflect excessive release from the axon terminal of upper motor neurons. However, it is a question of whether the damaged upper motor neurons continue releasing glutamate even in advanced stage of this disease. To address this issue, we hypothesized that glial cells might be a glutamate release source. Our immunohistochemical analysis on autopsied human spinal cords revealed that ferritin, hepcidin, ferroportin, aconitase 1, tumor necrosis factor-α (TNF-α), TNF-α-converting enzyme (TACE), and glutaminase-C (GAC) were expressed mainly in microglia and that cystine/glutamate antiporter (xCT) was expressed mainly in astrocytes. We next performed cell culture experiments. Cultured microglia treated with soluble iron over-released glutamate and TNF-α via aconitase 1 and TACE, respectively. Cultured microglia treated with TNF-α over-released glutamate via GAC. Cultured microglia treated with hepcidin, of which expression is known to be upregulated by TNF-α, showed downregulated expression of ferroportin. Cultured astrocytes treated with hydrogen peroxide over-released glutamate via xCT. These observations provide in vivo and in vitro evidence that microglia and astrocytes are glutamate suppliers in response to soluble iron overload and oxidative stress, respectively, in sporadic ALS.}, }
@article {pmid40060160, year = {2025}, author = {Mangalindan, KE and Wyatt, TR and Brown, KR and Shapiro, M and Maggio, LA}, title = {Investigating the Road to Equity: A Scoping Review of Solutions to Mitigate Implicit Bias in Assessment within Medical Education.}, journal = {Perspectives on medical education}, volume = {14}, number = {1}, pages = {92-106}, pmid = {40060160}, issn = {2212-277X}, mesh = {Humans ; *Education, Medical/methods/standards ; *Bias, Implicit ; *Educational Measurement/methods/standards ; }, abstract = {INTRODUCTION: In medical education, assessments have high-stakes implications. Yet, assessments are rife with unconscious bias, which contributes to inequitable social structures. Implicit bias in assessment must be addressed because medical educators use assessments to guide learning and promote development of physicians' careers. In this scoping review, the authors map the literature on implicit bias in assessment, as it applies to: 1) the types of implicit bias addressed, 2) the targets and types of interventions studied or proposed, and 3) how publications describe intervention efficacy.<br><br>METHODS: The authors conducted a scoping review of the literature on interventions to mitigate implicit bias that was published between January 2010 and August 2023. Author pairs independently screened articles for inclusion and extracted data. Discrepancies were resolved with discussion and consensus. Qualitative and quantitative analysis was informed by Anderson et al's three assessment orientations: fairness, assessment for inclusion (AfI), and justice.<br><br>RESULTS: 7,831 articles were identified; 54 articles were included. The majority (n = 37; 69%) of articles focus on implicit bias toward those underrepresented in medicine. Interventions to mitigate implicit bias were targeted toward admissions and applications, faculty training, recruitment, summative assessments, and evaluation templates. Interventions had fairness (n = 43; 96%) and AfI (n = 22; 49%) orientations; no articles used a justice-orientation. For the sub-set of research studies (n = 40), almost all (n = 34; 85%) examined a single program/institution.<br><br>DISCUSSION: This scoping review showed that more work is necessary to address different types of implicit biases, move scholarship beyond single-institution studies, refine existing interventions, and evaluate how efficacy is defined.}, }
@article {pmid40057669, year = {2025}, author = {Hatcher, H and Stankeviciute, S and Learn, C and Qu, AX}, title = {Regulatory, Translational, and Operational Considerations for the Incorporation of Biomarkers in Drug Development.}, journal = {Therapeutic innovation &amp; regulatory science}, volume = {59}, number = {3}, pages = {519-526}, pmid = {40057669}, issn = {2168-4804}, mesh = {*Drug Development/legislation &amp; jurisprudence ; Humans ; *Biomarkers ; United States ; United States Food and Drug Administration ; Drug Approval ; }, abstract = {BACKGROUND: Biomarkers are an integral component in the drug development paradigm. According to the US Food and Drug Administration (FDA), a biomarker is "a defined characteristic that is measured as an indicator of normal biological processes, pathogenic processes, or biological responses to an exposure or intervention, including therapeutic intervention" (FDA-NIH Biomarker Working Group. BEST (Biomarkers, EndpointS, and other Tools) Resource [Internet]. Silver Spring (MD): Food and Drug Administration (US); 2016-. Glossary. 2016 [Updated 2021 Nov 29, cited 2024 Apr 14]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK338448/ Co-published by National Institutes of Health (US), Bethesda (MD)). The European Medicines Agency (EMA) defines a biomarker as "an objective and quantifiable measure of a physiological process, pathological process or response to a treatment (excluding measurements of how an individual feels or functions" European Medicines Agency (EMA). Biomaker. 2020a. Available from: https://www.ema.europa.eu/en/glossary-terms/biomarker#:~:text=Biomarker-,Biomarker,an%20individual%20feels%20or%20functions . Several clinical biomarkers are well-documented and have been used routinely for decades in health care settings and have long been accepted as valid endpoints for drug approval (for example, blood pressure measurement as a biomarker for cardiovascular health) (European Medicines Agency (EMA). Assessment report, TAGRISSO. 2016. Available from: https://www.ema.europa.eu/en/documents/assessment-report/tagrisso-epar-public-assessment-report_en.pdf . Accessed 15 Apr 2024). Recently, novel biomarkers have been identified and validated to accelerate developing innovative therapies indicated for serious human diseases, for example targeted/immune therapies of cancer (Chen in Med Drug Discov 21:100174, 2024). As indicators of the efficacy of new pharmacological treatments or therapeutic interventions, biomarkers can improve clinical trial efficacy and reduce uncertainty in regulatory decision making (Bakker et al. in Clin Pharmacol Ther 112:69-80, 2022; Califf in Exp Biol Med 243:213-221, 2018; Parker et al. in Cancer Med 10:1955-1963, 2021).<br><br>METHODOLOGY: This article describes case studies of recent drug approvals that successfully leveraged validated and non-validated biomarkers (i.e., tofersen for the neurodegenerative disease amyotrophic lateral sclerosis (ALS) in adults; and osimertinib for treatment of patients with metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer (NSCLC)).<br><br>CONCLUSIONS: Best practices for biomarker selection and strategies for health authority biomarker qualification programs are presented along with an overview of current limitations and challenges to optimizing biomarker applications along the drug development continuum from regulatory, translational, and operational perspectives.}, }
@article {pmid40056503, year = {2025}, author = {Zhan, A and Zhong, K and Zhang, K}, title = {Novel subcellular regulatory mechanisms of protein homeostasis and its implications in amyotrophic lateral sclerosis.}, journal = {Biochemical and biophysical research communications}, volume = {756}, number = {}, pages = {151582}, doi = {10.1016/j.bbrc.2025.151582}, pmid = {40056503}, issn = {1090-2104}, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/pathology ; Humans ; *Proteostasis ; Animals ; Homeostasis ; Mitochondria/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron degenerative disorder. Protein aggregates induce various forms of neuronal dysfunction and represent pathological hallmarks in ALS patients. Reducing protein aggregates could be a promising therapeutic strategy for ALS. While most studies have focused on cytoplasmic protein homeostasis, neurons adaptively reduce aggregates across subcellular compartments during stress through previously uncharacterized mechanisms. Here, we summarize novel compartment-specific proteostatic mechanisms: (1) the ERAD/RESET pathways, (2) HSPs-mediated nuclear sequestration, (3) mitochondrial aggregate import (MAGIC), (4) neurite-localized UPS/autophagosome and NMP, and (5) exopher-mediated extracellular disposal. These mechanisms collectively ensure cellular stress adaptation and provide novel therapeutic targets for ALS treatment.}, }
@article {pmid40046336, year = {2025}, author = {Öztürk, MM and Emgård, J and García-Revilla, J and Fernández-Calle, R and Yang, Y and Deierborg, T and Roos, TT}, title = {The role of microglia in the prion-like transmission of protein aggregates in neurodegeneration.}, journal = {Brain communications}, volume = {7}, number = {2}, pages = {fcaf087}, pmid = {40046336}, issn = {2632-1297}, abstract = {Numerous neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis share a neuropathological hallmark: aberrant protein aggregation in the CNS. Microglia, the brain's innate immune cells, also play a pivotal role in the pathogenesis of these disorders. Multiple studies indicate that these pathological aggregates can propagate throughout the brain in a prion-like manner. A protein/peptide that adopts a prion-like conformation can induce homologous proteins to misfold into a prion-like conformation through templated seeding, enabling cell-to-cell spread and accelerating protein aggregation throughout the brain. Two important questions in the prion-like paradigm are where the prion-like misfolding occurs and how the prion-like aggregates are spread throughout the CNS. Here, we review the role of microglia and associated inflammation in the prion-like spread of pathologically aggregated proteins/peptides in Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. A growing body of evidence suggests that microglia can internalize prion-like proteins and transport them to neighbouring neurons and other glial cells. Microglia may also influence the potential seeding of proteins in neurons and induce inflammatory pathways in their microenvironment. This review aims to broaden the understanding of the role of microglia in the prion-like spread of protein aggregation.}, }
@article {pmid40045432, year = {2025}, author = {Blair, K and Martinez-Serra, R and Gosset, P and Martín-Guerrero, SM and Mórotz, GM and Atherton, J and Mitchell, JC and Markovinovic, A and Miller, CCJ}, title = {Structural and functional studies of the VAPB-PTPIP51 ER-mitochondria tethering proteins in neurodegenerative diseases.}, journal = {Acta neuropathologica communications}, volume = {13}, number = {1}, pages = {49}, pmid = {40045432}, issn = {2051-5960}, support = {MR/X021858/1//UK Research and Innovation/ ; }, mesh = {Humans ; *Endoplasmic Reticulum/metabolism ; *Mitochondria/metabolism ; *Neurodegenerative Diseases/metabolism/pathology ; Animals ; *Mitochondrial Proteins/metabolism ; *Vesicular Transport Proteins/metabolism/chemistry ; Signal Transduction/physiology ; Protein Tyrosine Phosphatases ; }, abstract = {Signaling between the endoplasmic reticulum (ER) and mitochondria regulates many of the seemingly disparate physiological functions that are damaged in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). A number of studies have now demonstrated that ER-mitochondria signaling is perturbed in these diseases and there is evidence that this may be a driving mechanism in disease onset and progression. VAPB and PTPIP51 are ER-mitochondria tethering proteins; VAPB is an ER protein and PTPIP51 is an outer mitochondrial membrane protein and the two proteins interact to enable inter-organelle signaling. The VAPB-PTPIP51 interaction is disrupted in Alzheimer's disease, Parkinson's disease, FTD and ALS. Here we review the roles of VAPB and PTPIP51 in ER-mitochondria signaling and the mechanisms by which neurodegenerative disease insults may disrupt the VAPB-PTPIP51 interaction.}, }
@article {pmid40041912, year = {2025}, author = {Dash, UC and Bhol, NK and Swain, SK and Samal, RR and Nayak, PK and Raina, V and Panda, SK and Kerry, RG and Duttaroy, AK and Jena, AB}, title = {Oxidative stress and inflammation in the pathogenesis of neurological disorders: Mechanisms and implications.}, journal = {Acta pharmaceutica Sinica. B}, volume = {15}, number = {1}, pages = {15-34}, pmid = {40041912}, issn = {2211-3835}, abstract = {Neuroprotection is a proactive approach to safeguarding the nervous system, including the brain, spinal cord, and peripheral nerves, by preventing or limiting damage to nerve cells and other components. It primarily defends the central nervous system against injury from acute and progressive neurodegenerative disorders. Oxidative stress, an imbalance between the body's natural defense mechanisms and the generation of reactive oxygen species, is crucial in developing neurological disorders. Due to its high metabolic rate and oxygen consumption, the brain is particularly vulnerable to oxidative stress. Excessive ROS damages the essential biomolecules, leading to cellular malfunction and neurodegeneration. Several neurological disorders, including Alzheimer's, Parkinson's, Amyotrophic lateral sclerosis, multiple sclerosis, and ischemic stroke, are associated with oxidative stress. Understanding the impact of oxidative stress in these conditions is crucial for developing new treatment methods. Researchers are exploring using antioxidants and other molecules to mitigate oxidative stress, aiming to prevent or slow down the progression of brain diseases. By understanding the intricate interplay between oxidative stress and neurological disorders, scientists hope to pave the way for innovative therapeutic and preventive approaches, ultimately improving individuals' living standards.}, }
@article {pmid40038221, year = {2025}, author = {Mustafa, F and Mittal, S and Garg, D and Agarwal, A and Garg, A and Gupta, BK and Soneja, M and Srivastava, AK}, title = {HIV associated motor neuron disease (MND): A case series with systematic review of literature.}, journal = {Journal of neurovirology}, volume = {31}, number = {1}, pages = {1-15}, pmid = {40038221}, issn = {1538-2443}, mesh = {Humans ; *HIV Infections/drug therapy/complications/virology ; Male ; Middle Aged ; *Amyotrophic Lateral Sclerosis/virology/drug therapy/diagnostic imaging/pathology ; Female ; Adult ; *Motor Neuron Disease/virology/drug therapy ; Viral Load ; CD4 Lymphocyte Count ; Anti-HIV Agents/therapeutic use ; }, abstract = {Human immunodeficiency virus (HIV) associated motor neuron disease (MND) is very rare. HIV infection can cause an MND-like syndrome due to central nervous system (CNS) involvement de novo or during antiretroviral therapy (ART) due to CNS escape. We present two cases: one with a classic amyotrophic lateral sclerosis (ALS) phenotype, which was the manifestation of symptomatic CNS escape from ART, and the second with a primary lateral sclerosis (PLS) phenotype associated with underlying HIV infection. A systematic review of published literature of people living with HIV (PLHIV) who developed ALS/ MND was conducted using the PubMed, Embase, and Lilacs databases. A total of 91 cases were found, 89 of which were obtained from 37 articles, and two were included from our own case series. In patients with HIV-associated MND, 63 patients reviewed had a classic ALS phenotype followed by progressive muscular atrophy variant (12), progressive bulbar palsy (8), PLS (7) and bulbar onset ALS (1). Neuroimaging, electrophysiology, cerebrospinal fluid (CSF) analysis, CSF and serum HIV viral load, and CD4 count investigations were used for diagnosis. Following the initiation or modification of antiretroviral therapy (ART), approximately 70% exhibited an improvement or a stable disease course. HIV-associated MND is a rare condition that can occur in both ART-naive individuals and those on treatment. A proportion of cases (~ 70%) show improvement with ART. Accurate diagnosis requires the exclusion of opportunistic infections, which remains a critical yet challenging aspect of managing this condition.}, }
@article {pmid40037468, year = {2025}, author = {Peck, A and Dadi, A and Yavarow, Z and Alfano, LN and Anderson, D and Arkin, MR and Chou, TF and D'Ambrosio, ES and Diaz-Manera, J and Dudley, JP and Elder, AG and Ghoshal, N and Hart, CE and Hart, MM and Huryn, DM and Johnson, AE and Jones, KB and Kimonis, V and Kiskinis, E and Lee, EB and Lloyd, TE and Mapstone, M and Martin, A and Meyer, H and Mozaffar, T and Onyike, CU and Pfeffer, G and Pindon, A and Raman, M and Richard, I and Rubinsztein, DC and Schiava, M and Schütz, AK and Shen, PS and Southworth, DR and Staffaroni, AM and Taralio-Gravovac, M and Weihl, CC and Yao, Q and Ye, Y and Peck, N}, title = {2024 VCP International Conference: Exploring multi-disciplinary approaches from basic science of valosin containing protein, an AAA+ ATPase protein, to the therapeutic advancement for VCP-associated multisystem proteinopathy.}, journal = {Neurobiology of disease}, volume = {207}, number = {}, pages = {106861}, pmid = {40037468}, issn = {1095-953X}, support = {R01 CA293084/CA/NCI NIH HHS/United States ; R21 NS123631/NS/NINDS NIH HHS/United States ; Z99 DK999999/ImNIH/Intramural NIH HHS/United States ; }, mesh = {*Valosin Containing Protein/genetics/metabolism ; Humans ; Frontotemporal Dementia/genetics ; Animals ; Osteitis Deformans/genetics ; Myositis, Inclusion Body/genetics ; Congresses as Topic ; }, abstract = {Valosin-containing protein (VCP/p97) is a ubiquitously expressed AAA+ ATPase associated with numerous protein-protein interactions and critical cellular functions including protein degradation and clearance, mitochondrial homeostasis, DNA repair and replication, cell cycle regulation, endoplasmic reticulum-associated degradation, and lysosomal functions including autophagy and apoptosis. Autosomal-dominant missense mutations in the VCP gene may result in VCP-associated multisystem proteinopathy (VCP-MSP), a rare degenerative disorder linked to heterogeneous phenotypes including inclusion body myopathy (IBM) with Paget's disease of bone (PDB) and frontotemporal dementia (FTD) or IBMPFD, amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), parkinsonism, Charcot-Marie Tooth disease (CMT), and spastic paraplegia. The complexity of VCP-MSP makes collaboration among stakeholders essential and necessitates a multi-disciplinary approach. The 2024 VCP International Conference was hosted at Caltech between February 22 and 25. Co-organized by Cure VCP Disease and Dr. Tsui-Fen Chou, the meeting aimed to center the patient as a research partner, harmonize diverse stakeholder engagement, and bridge the gap between basic and clinical neuroscience as it relates to VCP-MSP. Over 100 multi-disciplinary experts attended, ranging from basic scientists to clinicians to patient advocates. Attendees discussed genetics and clinical presentation, cellular and molecular mechanisms underlying disease, therapeutic approaches, and strategies for future VCP research. The conference included three roundtable discussions, 29 scientific presentations, 32 scientific posters, nine patient and caregiver posters, and a closing discussion forum. The following conference proceedings summarize these sessions, highlighting both the identified gaps in knowledge and the significant strides made towards understanding and treating VCP diseases.}, }
@article {pmid40036368, year = {2025}, author = {Ervilha Pereira, P and De Bleecker, JL and Bogaert, E and Dermaut, B}, title = {Myopathic aggregation-prone variants in the TDP-43 prion-like domain: genetics paving the way.}, journal = {Brain : a journal of neurology}, volume = {148}, number = {6}, pages = {1876-1887}, doi = {10.1093/brain/awaf076}, pmid = {40036368}, issn = {1460-2156}, support = {3G0H8318//Research Foundation Flanders/ ; G0AC724N//Research Foundation Flanders/ ; //Funds W. Pyleman and Cremers-Opdebeeck/ ; 2023-J1141680-231086//King Baudouin Foundation/ ; 01N10319//Ghent University Special Research Fund/ ; //Ghent University Fund/ ; }, mesh = {Humans ; *DNA-Binding Proteins/genetics/metabolism ; *TDP-43 Proteinopathies/genetics/pathology ; Animals ; *Muscular Diseases/genetics/pathology ; *Prions/genetics/metabolism ; Amyotrophic Lateral Sclerosis/genetics ; }, abstract = {While neuropathological and genetic studies have established the crucial involvement of TDP-43 proteinopathy in the pathogenesis of amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and related neurodegenerative disorders, multiple studies have described the presence of TDP-43 inclusions in muscular disorders, including inclusion body myositis but also other related rimmed vacuole myopathies. In addition, TAR DNA-binding protein-43 (TDP-43) has been reported to be essential in normal muscle physiology as it is implicated in the formation of so-called amyloid-like myogranules during normal muscle regeneration after injury. However, genetic evidence supporting a primary role for TDP-43 proteinopathy in muscle disease has been missing. In the present review we highlight recent landmark discoveries linking novel pathogenic TDP-43 variants [p.(W385IfsX10) and p.(G376V)] within the prion-like domain with unusual aggregation-propensity and muscle rather than neuronal pathology. We discuss these studies in the context of known TDP-43-related pathways in ALS/FTD pathogenesis and show how they challenge some widely accepted views such as ALS as a pure neurogenic presynaptic neuromuscular disease and the direct correlation between TDP-43 aggregation-propensity and neurotoxicity. Finally, we discuss TDP-43 as part of a growing list of RNA-binding proteins including hnRNPA2B1 and hnRNPA1 as genetic causes of myopathies and relate this to the idea of 'multisystem proteinopathy'.}, }
@article {pmid40035928, year = {2025}, author = {Amos, J and Moase, J and Sladeczek, IE}, title = {A scoping review of school-based expressive writing implementation reporting practices: missed opportunities and new research directions.}, journal = {Discover mental health}, volume = {5}, number = {1}, pages = {27}, pmid = {40035928}, issn = {2731-4383}, abstract = {BACKGROUND: Expressive writing (EW) interventions are an effective, flexible, and cost-efficient option for mental health promotion, making them ideally suited for resource-limited school settings. However, the effectiveness of EW interventions varies greatly across studies, which may be partly explained by how EW interventions are implemented. As school-based EW interventions become increasingly popular and more widely used, rigorous reporting of implementation can help advance this emerging field by informing how variation in implementation across studies influences intervention outcomes.<br><br>PURPOSE: The purpose of this scoping review was to evaluate the implementation reporting practices of EW interventions in school settings as they can profoundly impact EW effectiveness.<br><br>METHODS: The present scoping review assessed the current state of fidelity of implementation (implementation) reporting in the school-based EW literature and identified areas where more rigorous reporting is needed. Out of an initial sample of 367 studies, 19 were eligible for inclusion in the review. Data were analyzed for critical issues and themes derived from Cargo et al.'s (2015) Checklist for Implementation (Ch-IMP).<br><br>RESULTS: Overall, the results of this scoping review indicate that researchers who implement EW in school settings have not consistently assessed key implementation domains such as dose received and fidelity.<br><br>CONCLUSIONS: To address this problem, the present review adds a unique contribution to the literature by identifying how rigorous reporting of implementation can strengthen the evidence base for school-based EW interventions. Specifically, researchers can support the use of EW interventions in schools through increased implementation reporting to better understand how variability in fidelity of implementation affects treatment outcomes.}, }
@article {pmid40033997, year = {2025}, author = {Poulsen, NS and Kraglund, LR and Vissing, J}, title = {Physical training of wheelchair users with neuromuscular disorders: A systematic review.}, journal = {Journal of neuromuscular diseases}, volume = {12}, number = {3}, pages = {330-341}, doi = {10.1177/22143602241313114}, pmid = {40033997}, issn = {2214-3602}, mesh = {Humans ; *Wheelchairs ; *Neuromuscular Diseases/rehabilitation ; *Exercise Therapy/methods ; }, abstract = {OBJECTIVE: Wheelchair users with neuromuscular disorders have symptoms related to the disease and complications to the sedentary lifestyle, such as constipation and lower back pain. Physical training might be beneficial. This systematic review investigates the potential benefits and harms of physical training for wheelchair users with neuromuscular disorders.<br><br>METHODS: We systematically searched PubMed including studies published until July 2024.<br><br>INCLUSION CRITERIA: 1) participants with a neuromuscular disorder, 2) at least 60% of participants in a study were wheelchair users, 3) physical training and its effects were investigated, 4) studies were prospective, and 5) English language was used. Non-peer-reviewed articles were excluded. Search results were screened by title, abstract, and full text. Two independent authors assessed the quality with the Downs and Black Quality Index.<br><br>RESULTS: We included 14 studies of 140 patients from 5 types of neuromuscular disorders (Duchenne muscular atrophy, spinal muscular atrophy, limb-girdle muscular atrophy, facioscapulohumeral muscular dystrophy, and amyotrophic lateral sclerosis). The mean quality was low (16/32) due to flaws in study design, selection bias, and power. Even though many were of low quality and lacked descriptions of adverse events, they all showed positive effects. Most studies investigated physical training of mastication or respiration with improvements in both. Other findings were improvements in endurance, extremity strength, and range of motion.<br><br>CONCLUSIONS: Physical training of wheelchair users with neuromuscular disorders is not well investigated. Physical training seems safe and beneficial, but training of respiratory and masticatory muscles is the only well-documented exercise modality that can be advised in patients with Duchenne Muscular Dystrophy or Duchenne Muscular Dystrophy/Spinal Muscular Atrophy, respectively. Larger, high-quality trials, including other neuromuscular disorders, are needed to assess the effects and adverse events of physical training.}, }
@article {pmid40032118, year = {2025}, author = {Dang, M and Wu, L and Zhang, X}, title = {Structural insights and milestones in TDP-43 research: A comprehensive review of its pathological and therapeutic advances.}, journal = {International journal of biological macromolecules}, volume = {306}, number = {Pt 3}, pages = {141677}, doi = {10.1016/j.ijbiomac.2025.141677}, pmid = {40032118}, issn = {1879-0003}, mesh = {Humans ; *DNA-Binding Proteins/chemistry/metabolism/genetics ; Animals ; *Neurodegenerative Diseases/metabolism/pathology/genetics/therapy ; Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; }, abstract = {Transactive response (TAR) DNA-binding protein 43 (TDP-43) is a critical RNA/DNA-binding protein involved in various cellular processes, including RNA splicing, transcription regulation, and RNA stability. Mislocalization and aggregation of TDP-43 in the cytoplasm are key features of the pathogenesis of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimer's disease (AD). This review provides a comprehensive retrospective and prospective analysis of TDP-43 research, highlighting structural insights, significant milestones, and the evolving understanding of its physiological and pathological functions. We delineate five major stages in TDP-43 research, from its initial discovery as a pathological hallmark in neurodegeneration to the recent advances in understanding its liquid-liquid phase separation (LLPS) behavior and interactions with cellular processes. Furthermore, we assess therapeutic strategies targeting TDP-43 pathology, categorizing approaches into direct and indirect interventions, alongside modulating aberrant TDP-43 LLPS. We propose that future research will focus on three critical areas: targeting TDP-43 structural polymorphisms for disease-specific therapeutics, exploring dual temporal-spatial modulation of TDP-43, and advancing nano-therapy. More importantly, we emphasize the importance of understanding TDP-43's functional repertoire at the mesoscale, which bridges its molecular functions with broader cellular processes. This review offers a foundational framework for advancing TDP-43 research and therapeutic development.}, }
@article {pmid40029926, year = {2025}, author = {Panda, P and Mohanty, S and Gouda, SR and Baral, TC and Mohanty, A and Nayak, J and Mohapatra, R}, title = {Advanced strategies for enhancing the neuroprotective potential of curcumin: delivery systems and mechanistic insights in neurodegenerative disorders.}, journal = {Nutritional neuroscience}, volume = {28}, number = {9}, pages = {1151-1176}, doi = {10.1080/1028415X.2025.2472773}, pmid = {40029926}, issn = {1476-8305}, mesh = {*Curcumin/administration &amp; dosage/pharmacokinetics/pharmacology/therapeutic use ; Humans ; *Neuroprotective Agents/administration &amp; dosage/pharmacokinetics/pharmacology/therapeutic use ; *Neurodegenerative Diseases/drug therapy/metabolism ; Animals ; Oxidative Stress/drug effects ; *Drug Delivery Systems ; Blood-Brain Barrier/metabolism/drug effects ; Biological Availability ; }, abstract = {Background: Curcumin, a polyphenolic compound derived from Curcuma longa, exhibits significant neuroprotective potential due to its diverse pharmacological properties.Objective: This review explores curcumin's role in modulating key pathological mechanisms underlying neurodegenerative disorders such as Alzheimer's, Parkinson's diseases, Amyotrophic Lateral Sclerosis, Huntington's Disease and Prion Disease.Methods: A comprehensive analysis of curcumin's molecular interactions, including its effects on amyloid-beta (Aβ) aggregation, tau hyperphosphorylation, neuroinflammation, oxidative stress, and metal-induced neurotoxicity, was conducted. Additionally, strategies to overcome its low bioavailability and blood-brain barrier (BBB) permeability were evaluated.Results: Curcumin inhibits Aβ aggregation and promotes disaggregation, reducing amyloid plaque formation in Alzheimer's disease. It modulates glial cell activity, attenuating neuroinflammation and fostering a neuroprotective environment. By interacting with tau proteins, curcumin prevents hyperphosphorylation and neurofibrillary tangle formation. As a potent antioxidant, it scavenges reactive oxygen species, mitigating oxidative stress-related neuronal damage. Its metal-chelating properties further diminish neurotoxicity by sequestering iron and copper ions. Despite its limited bioavailability and BBB permeability, curcumin's therapeutic efficacy can be enhanced using nanocarriers such as nanoparticles, liposomes, and micelles, which improve solubility, stability, and brain penetration.Conclusion: Curcumin's multifaceted neuroprotective mechanisms make it a promising candidate for preventing or slowing neurodegenerative disease progression. Advanced drug delivery systems hold potential for overcoming its pharmacokinetic limitations, paving the way for future clinical applications.}, }
@article {pmid40029669, year = {2025}, author = {Carroll, E and Scaber, J and Huber, KVM and Brennan, PE and Thompson, AG and Turner, MR and Talbot, K}, title = {Drug repurposing in amyotrophic lateral sclerosis (ALS).}, journal = {Expert opinion on drug discovery}, volume = {20}, number = {4}, pages = {447-464}, pmid = {40029669}, issn = {1746-045X}, mesh = {*Drug Repositioning/methods ; *Amyotrophic Lateral Sclerosis/drug therapy/physiopathology ; Humans ; Animals ; Drug Discovery/methods ; Translational Research, Biomedical/methods ; }, abstract = {INTRODUCTION: Identifying treatments that can alter the natural history of amyotrophic lateral sclerosis (ALS) is challenging. For years, drug discovery in ALS has relied upon traditional approaches with limited success. Drug repurposing, where clinically approved drugs are reevaluated for other indications, offers an alternative strategy that overcomes some of the challenges associated with de novo drug discovery.<br><br>AREAS COVERED: In this review, the authors discuss the challenge of drug discovery in ALS and examine the potential of drug repurposing for the identification of new effective treatments. The authors consider a range of approaches, from screening in experimental models to computational approaches, and outline some general principles for preclinical and clinical research to help bridge the translational gap. Literature was reviewed from original publications, press releases and clinical trials.<br><br>EXPERT OPINION: Despite remaining challenges, drug repurposing offers the opportunity to improve therapeutic options for ALS patients. Nevertheless, stringent preclinical research will be necessary to identify the most promising compounds together with innovative experimental medicine studies to bridge the translational gap. The authors further highlight the importance of combining expertise across academia, industry and wider stakeholders, which will be key in the successful delivery of repurposed therapies to the clinic.}, }
@article {pmid40025745, year = {2025}, author = {Norén, L and Bergström, M and Wallander, L}, title = {Coming to Terms with Risk Factors for Intimate Partner Violence Perpetration: A Scoping Review.}, journal = {Journal of evidence-based social work (2019)}, volume = {22}, number = {4}, pages = {469-498}, doi = {10.1080/26408066.2025.2469670}, pmid = {40025745}, issn = {2640-8074}, mesh = {Humans ; *Intimate Partner Violence/statistics &amp; numerical data/prevention &amp; control/psychology ; Risk Factors ; Female ; Male ; }, abstract = {PURPOSE: Intimate partner violence (IPV) is a global issue requiring a thorough understanding of risk factors to inform prevention strategies. This study applies Kraemer et al.'s (2005) categorization system to classify risk factors for IPV perpetration, addressing two research questions: 1) What variables or attributes are commonly employed to assess the risks associated with IPV perpetration, and how can these be thematized? 2) Which non-correlates, correlates, fixed markers, variable markers, and causal risk factors related to IPV perpetration are identified and examined in the existing literature?<br><br>MATERIAL AND METHODS: A scoping review of 62 publications on risk factors for IPV perpetration in married- and cohabiting couples was conducted. Risk factors were categorized using Kraemer et al.'s (2005) system.<br><br>RESULTS: The risk factors were classified into eight themes based on their shared characteristics. All variables fit Kraemer et al.'s categorization system. The majority showed correlational relationships. Fixed markers appeared in two themes, while variable markers appeared in six themes, however publications on these were limited. No causal risk factors were found.<br><br>DISCUSSION: The risk categorization system by Kraemer et al. enhances understanding of IPV perpetration risk factors. Priority areas for preventing IPV include reducing the risk of experiencing violence in childhood and ensuring access to higher education. More longitudinal research is needed for the remaining categories to establish temporal relationships.<br><br>CONCLUSION: The study highlights the value of Kraemer et al.'s categorization system for distinguishing correlation from causality in IPV risk factors, advancing prevention efforts. Important areas for preventive measures were targeted.}, }
@article {pmid40024955, year = {2025}, author = {Masood, S and Almas, MS and Hassan, SSU and Tahira, S and Fiaz, MH and Minhas, UEA and Zafar, HMQ and Masood, M}, title = {Safety and efficacy of arimoclomol in amyotrophic lateral sclerosis: a systematic review and meta-analysis.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {46}, number = {7}, pages = {2985-2994}, pmid = {40024955}, issn = {1590-3478}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; Randomized Controlled Trials as Topic ; *Neuroprotective Agents/adverse effects/therapeutic use ; Treatment Outcome ; Hydroxylamines ; }, abstract = {OBJECTIVES: Amyotrophic Lateral Sclerosis (ALS) is a debilitating motor neuron disorder characterized by muscle weakness, atrophy, and spasticity. This meta-analysis aims to assess the safety and efficacy of Arimoclomol in patients with ALS.<br><br>METHOD: A comprehensive literature search was conducted on 3 databases to discover articles published up to August 2024. Included studies were randomized controlled trials (RCTs). Data was analysed using Review Manager (v5.4). Cochrane Risk of Bias-2 (RoB-2) was adopted to assess the quality of RCTs.<br><br>RESULTS: A total of 359 patients were analysed, with 239 individuals in the Arimoclomol group and 120 individuals in the placebo group. The pooled analysis of the primary outcome, change in Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score from baseline, did not demonstrate a statistically significant difference favoring the Arimoclomol group (MD&#x2009;=&#x2009;0.4495; 95% CI: -0.39, 1.27; p&#x2009;=&#x2009;0.30). Similarly, secondary outcomes, including the Combined Assessment of Function and Survival (CAFS) rank score (MD&#x2009;=&#x2009;1.00; 95% CI: -2.68, 4.67; p&#x2009;=&#x2009;0.60), increase in transaminases (RR&#x2009;=&#x2009;1.05; 95% CI: 0.19, 5.70; p&#x2009;=&#x2009;0.95), mortality rate (RR&#x2009;=&#x2009;0.86; 95% CI: 0.55, 1.34; p&#x2009;=&#x2009;0.50), and adverse events (RR&#x2009;=&#x2009;0.86; 95% CI: 0.55, 1.34; p&#x2009;=&#x2009;0.50), showed no statistically significant differences between the groups.<br><br>CONCLUSION: This study does not conclusively demonstrate that Arimoclomol has beneficial effects on ALS patients' physical functionality but shows promise for safety. Further clinical trials are needed to explore the neuroprotective effects of Arimoclomol in the treatment of ALS.}, }
@article {pmid40022581, year = {2025}, author = {Galvin, M and Heverin, M and Mac Domhnaill, &#xc9; and Mcfarlane, R and Meldrum, D and Murray, D and Bolger, A and Connelly, J and Flynn, K and Fox, E and Gibbons, F and Hederman, L and Impey, S and O'Keefe, I and O'Meara, C and McKibben, D and Nicholson, M and Stephens, G and Van Dijk, J and Van Den Berg, L and Hardiman, O}, title = {Challenges and solutions to complex data governance issues in cross-national, cross-sectoral, multidisciplinary real world health research: a descriptive overview.}, journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration}, volume = {26}, number = {sup1}, pages = {1-7}, doi = {10.1080/21678421.2024.2428927}, pmid = {40022581}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/epidemiology ; *Biomedical Research ; *Precision Medicine ; Europe ; *Data Management ; }, abstract = {Real-world clinical data is generated during clinical engagements. The collection and further processing and mining of clinical information requires consents and navigation of necessary and important data governance processes. PRECISION ALS is an academic industry programme that collects, collates and analyses clinical and para-clinical data from patients with ALS across 10 European sites. The infrastructure of PRECISION ALS represents a complex interplay of the clinical, governance, and technical frameworks. Incorporation of infrastructural and operational measures enables sophisticated cross-national, cross-sectoral and cross disciplinary health research. PRECISION ALS has established a range of domain expertise, technologies, governance and clinical data management practices that can be applied throughout the life cycle of patient data from generation, collation, delivery and secure storage for advanced analytics. PRECISION ALS is designed to move the field of ALS research to a true Precision Medicine based approach toward new and more effective therapeutics.}, }
@article {pmid40017539, year = {2025}, author = {Mengistu, DY and Terribili, M and Pellacani, C and Ciapponi, L and Marzullo, M}, title = {Epigenetic regulation of TDP-43: potential implications for amyotrophic lateral sclerosis.}, journal = {Frontiers in molecular medicine}, volume = {5}, number = {}, pages = {1530719}, pmid = {40017539}, issn = {2674-0095}, abstract = {Amyotrophic lateral sclerosis (ALS) is a multifactorial neurodegenerative disease characterized by the progressive degeneration of motor neurons. One of the key pathogenic factors implicated in ALS is TDP-43 (TAR DNA-binding protein 43), an RNA-binding protein encoded by the TARDBP gene. Under normal physiological conditions, TDP-43 predominantly resides in the nucleus, where it plays a critical role in regulating gene expression, alternative splicing, RNA transport, and stability. In ALS, TDP-43 undergoes pathological mislocalization from the nucleus to the cytoplasm, disrupting its normal function and contributing to disease progression. The nuclear loss of TDP-43 leads to widespread dysregulation of RNA metabolism. Moreover, mislocalized TDP-43 aggregates in the cytoplasm, acquires toxic properties that sequester essential RNA molecules and proteins. Importantly, deviations in TDP-43 levels, whether excessive or reduced, can lead to cellular dysfunction, and contribute to disease progression, highlighting the delicate balance required for neuronal health. Emerging evidence suggests that epigenetic mechanisms may play a crucial role in regulating TARDBP expression and, consequently, TDP-43 cellular levels. Epigenetic modifications such as DNA methylation, histone modifications, and non-coding RNAs are increasingly recognized as modulators of gene expression and cellular function in neurodegenerative diseases, including ALS. Dysregulation of these processes could contribute to aberrant TARDBP expression, amplifying TDP-43-associated pathologies. This review explores and summarizes the recent findings on how specific epigenetic modifications influence TDP-43 expression and discusses their possible implications for disease progression.}, }
@article {pmid40012994, year = {2025}, author = {Sabetta, E and Ferrari, D and Massimo, L and Kõks, S}, title = {Tandem repeat expansions and copy number variations as risk factors and diagnostic tools for amyotrophic lateral sclerosis.}, journal = {Frontiers in neurology}, volume = {16}, number = {}, pages = {1522445}, pmid = {40012994}, issn = {1664-2295}, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder leading to upper and lower motoneurons degeneration. Although several mechanisms potentially involved in disease development have been identified, its pathogenesis is not fully understood. From the patient side, ALS diagnosis, still based on clinical criteria, can be difficult and may take up to 1 year. More than 30 genes have been associated to genetically inherited ALS, among which four (C9ORF72, SOD1, TARDBP and FUS) would explain around 60-70% of cases. However, familial ALS represents only 5-10% of ALS cases while the remaining are sporadic, with genetics explaining 6-10% of such cases only. In this context, short tandem repeats (STRs) expansions, have recently been found in clinically diagnosed ALS patients. In this review, we discuss the recent discoveries on ALS associated STRs and their potential as biomarkers as well as prognosis and therapy targets.}, }
@article {pmid40012862, year = {2024}, author = {Tang, MB and Liu, YX and Hu, ZW and Luo, HY and Zhang, S and Shi, CH and Xu, YM}, title = {Study insights in the role of PGC-1α in neurological diseases: mechanisms and therapeutic potential.}, journal = {Frontiers in aging neuroscience}, volume = {16}, number = {}, pages = {1454735}, pmid = {40012862}, issn = {1663-4365}, abstract = {Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), which is highly expressed in the central nervous system, is known to be involved in the regulation of mitochondrial biosynthesis, metabolic regulation, neuroinflammation, autophagy, and oxidative stress. This knowledge indicates a potential role of PGC-1α in a wide range of functions associated with neurological diseases. There is emerging evidence indicating a protective role of PGC-1α in the pathogenesis of several neurological diseases. As such, a deeper and broader understanding of PGC-1α and its role in neurological diseases is urgently needed. The present review provides a relatively complete overview of the current knowledge on PGC-1α, including its functions in different types of neurons, basic structural characteristics, and its interacting transcription factors. Furthermore, we present the role of PGC-1α in the pathogenesis of various neurological diseases, such as intracerebral hemorrhage, ischemic stroke, Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis, Huntington's disease, and other PolyQ diseases. Importantly, we discuss some compounds or drug-targeting strategies that have been studied to ameliorate the pathology of these neurological diseases and introduce the possible mechanistic pathways. Based on the available studies, we propose that targeting PGC-1α could serve as a promising novel therapeutic strategy for one or more neurological diseases.}, }
@article {pmid40012856, year = {2025}, author = {Minkels, C and van der Kamp, J and de Vries, R and Beek, PJ}, title = {Learning how to swim in 5- to 12-year-old children: a scoping review of evidence-based motor learning methods.}, journal = {Frontiers in sports and active living}, volume = {7}, number = {}, pages = {1505301}, pmid = {40012856}, issn = {2624-9367}, abstract = {BACKGROUND: Swimming is widely acknowledged for its safety and health benefits. Across the world children are receiving swimming lessons in which a variety of learning methods are employed. However, little is known about the effectiveness of those methods, and a comprehensive overview of pertinent research is lacking. Such an overview is needed for both researchers and instructors seeking to improve swimming skill acquisition in children.<br><br>OBJECTIVE: This scoping review aims to provide an overview of studies examining the effectiveness of motor learning methods for the acquisition of swimming skills by 5- to 12-year-old children, including an evaluation of their theoretical underpinnings, methodological quality, and core findings.<br><br>METHODS: This scoping review adhered to the PRISMA guidelines and followed Tricco et al.'s framework for conducting and reporting scoping reviews. Five bibliographic databases were systematically searched. Peer-reviewed studies in all languages published before 2025 were considered. Studies focusing on children with water-related fear were included. Gray literature, non-peer-reviewed studies and studies on specific groups (e.g., young, competitive swimmers or children with disabilities), or cognitive/motivational outcomes were excluded. Review selection and characterization were performed by three independent reviewers using pretested forms.<br><br>RESULTS: A total of 23 studies were included, which were classified into three main categories: traditional motor learning methods (n&#x2009;=&#x2009;4), contemporary methods (n&#x2009;=&#x2009;1), and atheoretical methods (n&#x2009;=&#x2009;18). Traditional methods focused on video-based instruction and feedback (n&#x2009;=&#x2009;4). Contemporary methods involved a single study on a non-linear swimming program (n&#x2009;=&#x2009;1). Atheoretical methods were further classified into learn-to-swim programs (n&#x2009;=&#x2009;12), learning environments (n&#x2009;=&#x2009;3), and assistive devices (n&#x2009;=&#x2009;3). Most studies (87%) reported a positive effect of the motor learning method under investigation during practice. However, significant methodological limitations were identified. Specifically, 87% of studies did not incorporate retention or transfer tests, 35% lacked control or comparison groups, and 48% did not provide detailed descriptions of the investigated intervention(s). Additionally, 83% of studies were not explicitly grounded in theoretical frameworks, except for the video-based studies and the study on a non-linear swimming program.<br><br>CONCLUSION: The literature on this topic is scarce, generally atheoretical and of questionable methodological quality. Addressing these shortcomings in future research will improve the evidence-base for the effectiveness of theoretically inspired learning methods for the acquisition of swimming skills in children, and their long-term retention and transfer, which in turn might result in evidence-based innovations in swimming lessons.<br><br>PRISMA (RRID:SCR_018721).}, }
@article {pmid40012679, year = {2025}, author = {Glashutter, M and Wijesinghe, P and Matsubara, JA}, title = {TDP-43 as a potential retinal biomarker for neurodegenerative diseases.}, journal = {Frontiers in neuroscience}, volume = {19}, number = {}, pages = {1533045}, pmid = {40012679}, issn = {1662-4548}, abstract = {TDP-43 proteinopathies are a spectrum of neurodegenerative diseases (NDDs) characterized by the pathological cytoplasmic aggregation of the TDP-43 protein. These include amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), Alzheimer's disease (AD), chronic traumatic encephalopathy (CTE), and others. TDP-43 in the eye shows promise as a biomarker for these NDDs. Several studies have identified cytoplasmic TDP-43 inclusions in retinal layers of donors with ALS, FTLD, AD, CTE, and other conditions using immunohistochemistry. Our findings suggest that pathological aggregates of TDP-43 in the human retina are most prevalent in FTLD-TDP, ALS, and CTE, suggesting these diseases may provide the most reliable context for studying the potential of TDP-43 as a retinal biomarker. Animal model studies have been pivotal in exploring TDP-43's roles in the retina, including its nuclear and cytoplasmic localization, RNA binding properties, and interactions with other proteins. Despite these advances, more research is needed to develop therapeutic strategies. A major limitation of human autopsy studies is the lack of corresponding brain pathology assessments to confirm TDP-43 proteinopathy diagnosis and staging. Other limitations include small sample sizes, lack of antemortem eye pathology and clinical histories, and limited comparisons across multiple NDDs. Future directions for the TDP-43 as a retinal biomarker for NDDs include retinal tracers, hyperspectral imaging, oculomics, and machine learning development.}, }
@article {pmid40012174, year = {2025}, author = {Rajamanickam, G and Hu, Z and Liao, P}, title = {Targeting the TRPM4 Channel for Neurologic Diseases: Opportunity and Challenge.}, journal = {The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry}, volume = {}, number = {}, pages = {10738584251318979}, doi = {10.1177/10738584251318979}, pmid = {40012174}, issn = {1089-4098}, abstract = {As a monovalent cation channel, the transient receptor potential melastatin 4 (TRPM4) channel is a unique member of the transient receptor potential family. Abnormal TRPM4 activity has been identified in various neurologic disorders, such as stroke, spinal cord injury, traumatic brain injury, multiple sclerosis, amyotrophic lateral sclerosis, pathologic pain, and epilepsy. Following brain hypoxia/ischemia and inflammation, TRPM4 up-regulation and enhanced activity contribute to the cell death of neurons, vascular endothelial cells, and astrocytes. Enhanced ionic influx via TRPM4 leads to cell volume increase and oncosis. Depolarization of membrane potential following TRPM4 activation and interaction between TRPM4 and N-methyl-d-aspartate receptors exacerbate excitotoxicity during hypoxia. Importantly, TRPM4 expression and activity remain low in healthy neurons, making it an ideal drug target. Current approaches to inhibit or modulate the TRPM4 channel have various limitations that hamper the interpretation of TRPM4 physiology in the nervous system and potentially hinder their translation into therapy. In this review, we discuss the pathophysiologic roles of TRPM4 and the different inhibitors that modulate TRPM4 activity for potential treatment of neurologic diseases.}, }
@article {pmid40009859, year = {2025}, author = {Chung, J and Lim, F}, title = {Effect of Nurse Residency Programs on New Graduate Nurses Entering the Critical Care Setting: An Integrative Review.}, journal = {Critical care nursing quarterly}, volume = {48}, number = {2}, pages = {120-142}, pmid = {40009859}, issn = {1550-5111}, mesh = {Humans ; *Clinical Competence ; Preceptorship ; *Critical Care Nursing/education ; *Internship, Nonmedical ; *Critical Care ; }, abstract = {The transition period from undergraduate nursing education to professional practice is a time of uncertainty and great difficulty for new graduate nurses (NGNs). Nurse residency programs (NRPs) provide structured education, simulation-based learning, and preceptorship to ease the transition. Although its effect on improving retention of NGNs is well established in the literature, the effect on clinical competency has not been documented as well. The purpose of this integrative review is to appraise the available literature and synthesize the evidence that demonstrates the effect of NRPs on clinical competency of NGNs entering the critical care setting. Inclusion criteria were quantitative and qualitative studies, peer-reviewed studies published after 2004 and in English, identified through a systematic literature search using the CINAHL database. Critical appraisal of the articles was completed using Law et al's Critical Review Form. Eight articles (4 quantitative, 3 mixed method, and 1 qualitative study) met the inclusion criteria. The themes identified were common tools used to assess the efficacy of NRPs, improved clinical competency of NGNs, improved self-confidence, improved retention rates, and peer support among NGNs. Implications for nursing education and practice include applying evidence-based NRPs, incorporating simulation, enhancing sustainability, and reducing NRP variability through accreditation.}, }
@article {pmid40009238, year = {2025}, author = {Ruffo, P and Traynor, BJ and Conforti, FL}, title = {Advancements in genetic research and RNA therapy strategies for amyotrophic lateral sclerosis (ALS): current progress and future prospects.}, journal = {Journal of neurology}, volume = {272}, number = {3}, pages = {233}, pmid = {40009238}, issn = {1432-1459}, support = {ZIA AG000933/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/therapy ; *Genetic Therapy/methods/trends ; Animals ; }, abstract = {This review explores the intricate landscape of neurodegenerative disease research, focusing on Amyotrophic Lateral Sclerosis (ALS) and the intersection of genetics and RNA biology to investigate the causative pathogenetic basis of this fatal disease. ALS is a severe neurodegenerative disease characterized by the progressive loss of motor neurons, leading to muscle weakness and paralysis. Despite significant research advances, the exact cause of ALS remains largely unknown. Thanks to the application of next-generation sequencing (NGS) approaches, it was possible to highlight the fundamental role of rare variants with large effect sizes and involvement of portions of non-coding RNA, providing valuable information on risk prediction, diagnosis, and treatment of age-related diseases, such as ALS. Genetic research has provided valuable insights into the pathophysiology of ALS, leading to the development of targeted therapies such as antisense oligonucleotides (ASOs). Regulatory agencies in several countries are evaluating the commercialization of Qalsody (Tofersen) for SOD1-associated ALS, highlighting the potential of gene-targeted therapies. Furthermore, the emerging significance of microRNAs (miRNAs) and long RNAs are of great interest. MiRNAs have emerged as promising biomarkers for diagnosing ALS and monitoring disease progression. Understanding the role of lncRNAs in the pathogenesis of ALS opens new avenues for therapeutic intervention. However, challenges remain in delivering RNA-based therapeutics to the central nervous system. Advances in genetic screening and personalized medicine hold promise for improving the management of ALS. Ongoing clinical trials use genomic approaches for patient stratification and drug targeting. Further research into the role of non-coding RNAs in the pathogenesis of ALS and their potential as therapeutic targets is crucial to the development of effective treatments for this devastating disease.}, }
@article {pmid40006958, year = {2025}, author = {Mielcarska, MB and Rouse, BT}, title = {Viruses and the Brain-A Relationship Prone to Trouble.}, journal = {Viruses}, volume = {17}, number = {2}, pages = {}, pmid = {40006958}, issn = {1999-4915}, mesh = {Humans ; *Brain/virology ; *Viruses/pathogenicity ; Animals ; *Virus Diseases/virology/complications ; Neurodegenerative Diseases/virology ; Antiviral Agents/therapeutic use ; *Central Nervous System Viral Diseases/virology ; }, abstract = {Neurological disorders, some of which are associated with viral infections, are growing due to the aging and expanding population. Despite strong defenses of the central nervous system, some viruses have evolved ways to breach them, which often result in dire consequences. In this review, we recount the various ways by which different viruses can enter the CNS, and we describe the consequences of such invasions. Consequences may manifest as acute disease, such as encephalitis, meningitis, or result in long-term effects, such as neuromuscular dysfunction, as occurs in poliomyelitis. We discuss evidence for viral involvement in the causation of well-known chronic neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, as well as vascular dementia in the elderly. We also describe the approaches currently available to control a few of the neural viral infections. These include antivirals that are effective against human immunodeficiency virus and herpes simplex virus, as well as vaccines valuable for controlling rabies virus, poliomyelitis virus, and some flavivirus infections. There is an urgent need to better understand, at a molecular level, how viruses contribute to acute and, especially, chronic neurological diseases and to develop more precise and effective vaccines and therapies.}, }
@article {pmid40004464, year = {2025}, author = {Liu, Z and Song, SY}, title = {Genomic and Transcriptomic Approaches Advance the Diagnosis and Prognosis of Neurodegenerative Diseases.}, journal = {Genes}, volume = {16}, number = {2}, pages = {}, pmid = {40004464}, issn = {2073-4425}, mesh = {Humans ; *Neurodegenerative Diseases/genetics/diagnosis ; Prognosis ; *Transcriptome/genetics ; *Genomics/methods ; Genome-Wide Association Study ; Gene Expression Profiling/methods ; Parkinson Disease/genetics/diagnosis ; }, abstract = {Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), represent a growing societal challenge due to their irreversible progression and significant impact on patients, caregivers, and healthcare systems. Despite advances in clinical and imaging-based diagnostics, these diseases are often detected at advanced stages, limiting the effectiveness of therapeutic interventions. Recent breakthroughs in genomic and transcriptomic technologies, including whole-genome sequencing, single-cell RNA sequencing (scRNA-seq), and CRISPR-based screens, have revolutionized the field, offering new avenues for early diagnosis and personalized prognosis. Genomic approaches have elucidated disease-specific genetic risk factors and molecular pathways, while transcriptomic studies have identified stage-specific biomarkers that correlate with disease progression and severity. Furthermore, genome-wide association studies (GWAS), polygenic risk scores (PRS), and spatial transcriptomics are enabling the stratification of patients based on their risk profiles and prognostic trajectories. Advances in functional genomics have uncovered actionable targets, such as ATXN2 in ALS and TREM2 in AD, paving the way for tailored therapeutic strategies. Despite these achievements, challenges remain in translating genomic discoveries into clinical practice due to disease heterogeneity and the complexity of neurodegenerative pathophysiology. Future integration of genetic technologies holds promise for transforming diagnostic and prognostic paradigms, offering hope for improved patient outcomes and precision medicine approaches.}, }
@article {pmid40004056, year = {2025}, author = {Yan, B and Suen, MC and Xu, N and Lu, C and Liu, C and Zhu, G}, title = {G-Quadruplex Structures Formed by Human Telomere and C9orf72 GGGGCC Repeats.}, journal = {International journal of molecular sciences}, volume = {26}, number = {4}, pages = {}, pmid = {40004056}, issn = {1422-0067}, support = {32071188//National Scientific Foundation of China/ ; 16101120, 161011121, AoE/M-403-16, AoE/M-401/20//Research Grants Council of the Hong Kong Special Administrative Region, China/ ; BGF.2023.019//Hong Kong University of Science and Technology, China/ ; 2021A1515220104//Guangdong Basic and Applied Basic Research Foundation, China/ ; 32301012//Young Scientists Fund of the National Natural Science Foundation of China/ ; }, mesh = {Humans ; *G-Quadruplexes ; *Telomere/genetics/chemistry ; *C9orf72 Protein/genetics/chemistry ; Amyotrophic Lateral Sclerosis/genetics ; *DNA Repeat Expansion ; Frontotemporal Dementia/genetics ; }, abstract = {G-quadruplexes (G4s) are unique nucleic acid structures composed of guanine-rich (G-rich) sequences that can form diverse topologies based on the arrangement of their four strands. G4s have attracted attention for their potential roles in various biological processes and human diseases. In this review, we focus on the G4 structures formed by human telomeric sequences, (GGGTTA)n, and the hexanucleotide repeat expansion, (GGGGCC)n, in the first intron region of the chromosome 9 open reading frame 72 (C9orf72) gene, highlighting their structural diversity and biological significance. Human telomeric G4s play crucial roles in telomere retention and gene regulation. In particular, we provide an in-depth summary of known telomeric G4s and focus on our recently discovered chair-type conformation, which exhibits distinct folding patterns. The chair-type G4s represent a novel folding pattern with unique characteristics, expanding our knowledge of telomeric G4 structural diversity and potential biological functions. Specifically, we emphasize the G4s formed by the (GGGGCC)n sequence of the C9orf72 gene, which represents the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The thorough structural analysis in this review advances our comprehension of the disease mechanism and provides valuable insights into developing targeted therapeutic strategies in ALS/FTD.}, }
@article {pmid40002740, year = {2025}, author = {Meng, K and Jia, H and Hou, X and Zhu, Z and Lu, Y and Feng, Y and Feng, J and Xia, Y and Tan, R and Cui, F and Yuan, J}, title = {Mitochondrial Dysfunction in Neurodegenerative Diseases: Mechanisms and Corresponding Therapeutic Strategies.}, journal = {Biomedicines}, volume = {13}, number = {2}, pages = {}, pmid = {40002740}, issn = {2227-9059}, support = {600791001//the Research Start-up Fund of Jining Medical University/ ; JYHL2021MS13//Research Fund for Lin He's Academician Workstation of New Medicine and Clinical Translation in Jining Medical University/ ; 81700055//the National Natural Science Foundation of China/ ; Grant No. D2016021//Outstanding Talent Research Funding of Xuzhou Medical University/ ; BK20160229//Natural Science Foundation of Jiangsu Province/ ; tsqn201909147//Taishan Scholars Program of Shandong Province/ ; G2Y-kJS-SD-2023-097//Co-construction of Science and Technology Projects by the Science and Technology Department of the State Administration of Traditional Chinese Medicine/ ; }, abstract = {Neurodegenerative disease (ND) refers to the progressive loss and morphological abnormalities of neurons in the central nervous system (CNS) or peripheral nervous system (PNS). Examples of neurodegenerative diseases include Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Recent studies have shown that mitochondria play a broad role in cell signaling, immune response, and metabolic regulation. For example, mitochondrial dysfunction is closely associated with the onset and progression of a variety of diseases, including ND, cardiovascular diseases, diabetes, and cancer. The dysfunction of energy metabolism, imbalance of mitochondrial dynamics, or abnormal mitophagy can lead to the imbalance of mitochondrial homeostasis, which can induce pathological reactions such as oxidative stress, apoptosis, and inflammation, damage the nervous system, and participate in the occurrence and development of degenerative nervous system diseases such as AD, PD, and ALS. In this paper, the latest research progress of this subject is detailed. The mechanisms of oxidative stress, mitochondrial homeostasis, and mitophagy-mediated ND are reviewed from the perspectives of β-amyloid (Aβ) accumulation, dopamine neuron damage, and superoxide dismutase 1 (SOD1) mutation. Based on the mechanism research, new ideas and methods for the treatment and prevention of ND are proposed.}, }
@article {pmid40002527, year = {2025}, author = {Eisen, A and Kiernan, MC}, title = {The Neonatal Microbiome: Implications for Amyotrophic Lateral Sclerosis and Other Neurodegenerations.}, journal = {Brain sciences}, volume = {15}, number = {2}, pages = {}, pmid = {40002527}, issn = {2076-3425}, abstract = {Most brain development occurs in the "first 1000 days", a critical period from conception to a child's second birthday. Critical brain processes that occur during this time include synaptogenesis, myelination, neural pruning, and the formation of functioning neuronal circuits. Perturbations during the first 1000 days likely contribute to later-life neurodegenerative disease, including sporadic amyotrophic lateral sclerosis (ALS). Neurodevelopment is determined by many events, including the maturation and colonization of the infant microbiome and its metabolites, specifically neurotransmitters, immune modulators, vitamins, and short-chain fatty acids. Successful microbiome maturation and gut-brain axis function depend on maternal factors (stress and exposure to toxins during pregnancy), mode of delivery, quality of the postnatal environment, diet after weaning from breast milk, and nutritional deficiencies. While the neonatal microbiome is highly plastic, it remains prone to dysbiosis which, once established, may persist into adulthood, thereby inducing the development of chronic inflammation and abnormal excitatory/inhibitory balance, resulting in neural excitation. Both are recognized as key pathophysiological processes in the development of ALS.}, }
@article {pmid40002468, year = {2025}, author = {Dawoody Nejad, L and Pioro, EP}, title = {Modeling ALS with Patient-Derived iPSCs: Recent Advances and Future Potentials.}, journal = {Brain sciences}, volume = {15}, number = {2}, pages = {}, pmid = {40002468}, issn = {2076-3425}, abstract = {Amyotrophic lateral sclerosis (ALS) is a terminal complex neurodegenerative disease, with 10-15% of cases being familial and the majority being sporadic with no known cause. There are no animal models for the 85-90% of sporadic ALS cases. More creative, sophisticated models of ALS disease are required to unravel the mysteries of this complicated disease. While ALS patients urgently require new medications and treatments, suitable preclinical in vitro models for drug screening are lacking. Therefore, human-derived induced pluripotent stem cell (hiPSC) technology offers the opportunity to model diverse and unreachable cell types in a culture dish. In this review, we focus on recent hiPSC-derived ALS neuronal and non-neuronal models to examine the research progress of current ALS 2D monocultures, co-cultures, and more complex 3D-model organoids. Despite the challenges inherent to hiPSC-based models, their application to preclinical drug studies is enormous.}, }
@article {pmid40002444, year = {2025}, author = {Okoh, C and Mayall, L and Makin, SM and Chen, C and Zarotti, N}, title = {Non-Pharmacological Interventions for Caregivers of People with Motor Neurone Disease: A Scoping Review of Psychosocial Outcomes.}, journal = {Brain sciences}, volume = {15}, number = {2}, pages = {}, pmid = {40002444}, issn = {2076-3425}, abstract = {Objective: Caregivers of individuals with motor neurone disease (MND) face a wide range of psychosocial difficulties. To address these, non-pharmacological interventions have been trialled, showing promising results. However, no clear characterisation of the breadth of psychosocial constructs examined by the interventions is currently available, resulting in the lack of a core outcome set (COS). The present review explored the types of psychosocial outcomes investigated in studies that adopted non-pharmacological interventions with caregivers of people with MND. Methods: A scoping review was conducted across four major databases (Academic Search Ultimate, CINAHL, PsycINFO, and MEDLINE) from inception to the 1 March 2024. Results: From an initial return of 4802 citations, 10 were considered eligible for inclusion. A total of 10 main psychosocial outcomes were identified: anxiety and depression, psychological distress, resilience, caregiver burden, caregiver preparedness, self-efficacy, quality of life, spiritual wellbeing, and mindfulness. Conclusions: Caregiver burden and symptoms of anxiety and depression represent pivotal outcomes, but caution is advised with regard to caregiver burden's potential multidimensional structure. Psychological distress and quality of life are also commonly investigated, but clearer consensus is needed on their conceptualisation. There is a paucity of studies characterising important psychosocial outcomes such as resilience, problem-solving, self-efficacy, and mindfulness, while no investigations are available for relevant outcomes such as coping, isolation, and loneliness. Further research is warranted to address these gaps to improve our insight into non-pharmacological support for MND caregivers and ultimately lead to the development of a core psychosocial outcome set in this population.}, }
@article {pmid40001529, year = {2025}, author = {Onu, CJ and Adu, M and Chakkour, M and Kumar, V and Greenberg, ML}, title = {Inositol Phosphates and Synthesizing Enzymes: Implications in Neurodegenerative Disorders.}, journal = {Biomolecules}, volume = {15}, number = {2}, pages = {}, pmid = {40001529}, issn = {2218-273X}, support = {R01 GM125082/GM/NIGMS NIH HHS/United States ; R35 GM149271/GM/NIGMS NIH HHS/United States ; GM149271/GF/NIH HHS/United States ; GM125082/GF/NIH HHS/United States ; }, mesh = {Humans ; *Inositol Phosphates/metabolism ; *Neurodegenerative Diseases/metabolism/enzymology ; Animals ; Inositol/metabolism ; Signal Transduction ; }, abstract = {Inositol is a vital sugar molecule involved in numerous signaling pathways required for cellular homeostasis and cell survival. Myo-inositol and its phospho-derivatives, inositol phosphates (IPs), are the most prevalent forms of inositol found in living cells. They are involved in regulating ion channels, metabolic flux, stress response, and other key biological processes. While emerging research has highlighted the significant roles of inositol phosphates in immunity, cancer, and metabolic diseases, there is a lack of comprehensive reviews on their roles in psychiatric and neurological disorders. This review aims to fill that gap by analyzing the existing literature on the importance of inositol phosphates in severe psychiatric and neurological conditions such as Parkinson's disease, Alzheimer's disease, bipolar disorder, amyotrophic lateral sclerosis, schizophrenia, and Huntington's disease, underscoring the potential to pave the way for new treatment regimens for these debilitating disorders targeting inositol pathways.}, }
@article {pmid40001370, year = {2025}, author = {Silva Ortíz, YL and de Sousa, TC and Kruklis, NE and Galeano García, P and Brango-Vanegas, J and Soller Ramada, MH and Franco, OL}, title = {The Role of Amphibian AMPs Against Oxidative Stress and Related Diseases.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {14}, number = {2}, pages = {}, pmid = {40001370}, issn = {2079-6382}, abstract = {Amphibians use their skin as an effective defense mechanism against predators and microorganisms. Specialized glands produce antimicrobial peptides (AMPs) that possess antioxidant properties, effectively reducing reactive oxygen species (ROS) levels. These peptides are promising candidates for treating diseases associated with oxidative stress (OS) and redox imbalance, including neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), as well as age-related conditions, like cardiovascular diseases and cancer. This review highlights the multifaceted roles of AMPs and antioxidant peptides (AOPs) in amphibians, emphasizing their protective capabilities against oxidative damage. They scavenge ROS, activate antioxidant enzyme systems, and inhibit cellular damage. AOPs often share structural characteristics with AMPs, suggesting a potential evolutionary connection and similar biosynthetic pathways. Peptides such as brevinin-1FL and Cath-KP demonstrate neuroprotective effects, indicating their therapeutic potential in managing oxidative stress-related diseases. The antioxidant properties of amphibian-derived peptides pave the way for novel therapeutic developments. However, a deeper understanding of the molecular mechanisms underlying these peptides and their interactions with oxidative stress is essential to addressing ROS-related diseases and advancing therapeutic strategies in clinical practice.}, }
@article {pmid40000618, year = {2025}, author = {Ru, Q and Li, Y and Zhang, X and Chen, L and Wu, Y and Min, J and Wang, F}, title = {Iron homeostasis and ferroptosis in muscle diseases and disorders: mechanisms and therapeutic prospects.}, journal = {Bone research}, volume = {13}, number = {1}, pages = {27}, pmid = {40000618}, issn = {2095-4700}, support = {82071970//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82072506//National Natural Science Foundation of China (National Science Foundation of China)/ ; 31970689//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32330047//National Natural Science Foundation of China (National Science Foundation of China)/ ; 2024AFB971//Natural Science Foundation of Hubei Province (Hubei Provincial Natural Science Foundation)/ ; }, mesh = {Humans ; *Ferroptosis/physiology ; *Iron/metabolism ; *Homeostasis ; *Muscular Diseases/metabolism/pathology/therapy ; Animals ; Muscle, Skeletal/metabolism ; }, abstract = {The muscular system plays a critical role in the human body by governing skeletal movement, cardiovascular function, and the activities of digestive organs. Additionally, muscle tissues serve an endocrine function by secreting myogenic cytokines, thereby regulating metabolism throughout the entire body. Maintaining muscle function requires iron homeostasis. Recent studies suggest that disruptions in iron metabolism and ferroptosis, a form of iron-dependent cell death, are essential contributors to the progression of a wide range of muscle diseases and disorders, including sarcopenia, cardiomyopathy, and amyotrophic lateral sclerosis. Thus, a comprehensive overview of the mechanisms regulating iron metabolism and ferroptosis in these conditions is crucial for identifying potential therapeutic targets and developing new strategies for disease treatment and/or prevention. This review aims to summarize recent advances in understanding the molecular mechanisms underlying ferroptosis in the context of muscle injury, as well as associated muscle diseases and disorders. Moreover, we discuss potential targets within the ferroptosis pathway and possible strategies for managing muscle disorders. Finally, we shed new light on current limitations and future prospects for therapeutic interventions targeting ferroptosis.}, }
@article {pmid39998997, year = {2025}, author = {García-Casanova, PH and Vázquez-Costa, JF}, title = {Advances in the early diagnosis of amyotrophic lateral sclerosis.}, journal = {Expert review of neurotherapeutics}, volume = {25}, number = {4}, pages = {415-425}, doi = {10.1080/14737175.2025.2471556}, pmid = {39998997}, issn = {1744-8360}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; *Early Diagnosis ; Biomarkers ; Disease Progression ; Delayed Diagnosis ; }, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease. Despite rapid disease progression, diagnostic delay of 10-16 months persists, influenced by disease-specific factors and healthcare systems. Reducing it is crucial for early intervention, multidisciplinary care planning, and patient participation in clinical trials.<br><br>AREAS COVERED: The authors review relevant studies identified through PubMed from 1990 to 2024. The article explores factors contributing to diagnostic delay, the importance of early diagnosis, and strategies for improvement, including the role of diagnostic criteria and biomarkers.<br><br>EXPERT OPINION: Diagnosis of ALS remains clinical, with clinical expertise as the main modifiable factor in the diagnostic delay. Some biomarkers may be useful to speed up diagnosis at an earlier stage of the disease and in patients with atypical presentations or co-morbidities. However, the use of biomarkers for ALS diagnosis in clinical practice is far from being established and poses considerable challenges, including the lack of disease-specific biomarkers and the potential for delayed results. Until disease-specific biomarkers become available, early referral to ALS specialists, together with physician education programs, will remain the main tools to reduce diagnostic delay in the next years.}, }
@article {pmid39997929, year = {2025}, author = {Newell, ME and Aravindan, A and Babbrah, A and Halden, RU}, title = {Epigenetic Biomarkers Driven by Environmental Toxins Associated with Alzheimer's Disease, Parkinson's Disease, and Amyotrophic Lateral Sclerosis in the United States: A Systematic Review.}, journal = {Toxics}, volume = {13}, number = {2}, pages = {}, pmid = {39997929}, issn = {2305-6304}, support = {GF000000002135//Glen Swette Memorial Fund/ ; }, abstract = {Environmental toxins and epigenetic changes have been linked to neurodegenerative diseases, including Alzheimer's Disease (AD), Parkinson's Disease (PD), and amyotrophic lateral sclerosis (ALS). This paper aimed to (i) identify environmental toxins associated with AD, PD, and ALS, (ii) locate potential industrial sources of toxins in the United States (U.S.), and (iii) assess epigenetic changes driven by exposure to toxins reported by patients. Environmental factors and epigenetic biomarkers of neurodegeneration were compiled from 69 studies in the literature using Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) and geographic information system approaches. Some 127 environmental toxins have been associated or putatively associated with AD, PD, or ALS, with four toxic metals (As, Cd, Mn, and Hg) common to all three of these neurodegenerative diseases. Environmental toxins associated with epigenetic changes (e.g., DNA methylation) in patients include air pollutants, metals, and organic chemicals (e.g., pesticides, mycotoxins, and cyanotoxins). Geographic analysis showed that study locations (e.g., U.S., Europe, and East Asia) were selected by researchers based on convenience of access rather than exposure risk and disease prevalence. We conclude that several toxins and epigenetic markers shared among neurodegenerative diseases could serve as attractive future targets guiding environmental quality improvements and aiding in early disease detection.}, }
@article {pmid39996748, year = {2025}, author = {Yang, HM}, title = {Mitochondrial Dysfunction in Neurodegenerative Diseases.}, journal = {Cells}, volume = {14}, number = {4}, pages = {}, pmid = {39996748}, issn = {2073-4409}, support = {2020R1A2C1011311//National Research Foundation of Korea/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/pathology ; *Mitochondria/metabolism/pathology ; Animals ; Oxidative Stress ; Mitophagy ; Reactive Oxygen Species/metabolism ; }, abstract = {Mitochondrial dysfunction represents a pivotal characteristic of numerous neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. These conditions, distinguished by unique clinical and pathological features, exhibit shared pathways leading to neuronal damage, all of which are closely associated with mitochondrial dysfunction. The high metabolic requirements of neurons make even minor mitochondrial deficiencies highly impactful, driving oxidative stress, energy deficits, and aberrant protein processing. Growing evidence from genetic, biochemical, and cellular investigations associates impaired electron transport chain activity and disrupted quality-control mechanisms, such as mitophagy, with the initial phases of disease progression. Furthermore, the overproduction of reactive oxygen species and persistent neuroinflammation can establish feedforward cycles that exacerbate neuronal deterioration. Recent clinical research has increasingly focused on interventions aimed at enhancing mitochondrial resilience-through antioxidants, small molecules that modulate the balance of mitochondrial fusion and fission, or gene-based therapeutic strategies. Concurrently, initiatives to identify dependable mitochondrial biomarkers seek to detect pathological changes prior to the manifestation of overt symptoms. By integrating the current body of knowledge, this review emphasizes the critical role of preserving mitochondrial homeostasis as a viable therapeutic approach. It also addresses the complexities of translating these findings into clinical practice and underscores the potential of innovative strategies designed to delay or potentially halt neurodegenerative processes.}, }
@article {pmid39996130, year = {2025}, author = {Dilliott, AA and Costanzo, MC and Bandres-Ciga, S and Blauwendraat, C and Casey, B and Hoang, Q and Iwaki, H and Jang, D and Kim, JJ and Leonard, HL and Levine, KS and Makarious, M and Nguyen, TT and Rouleau, GA and Singleton, AB and Smadbeck, P and Solle, J and Vitale, D and Nalls, M and Flannick, J and Burtt, NP and Farhan, SMK}, title = {The Neurodegenerative Disease Knowledge Portal: Propelling Discovery Through the Sharing of Neurodegenerative Disease Genomic Resources.}, journal = {Neurology. Genetics}, volume = {11}, number = {2}, pages = {e200246}, pmid = {39996130}, issn = {2376-7839}, abstract = {Although large-scale genetic association studies have proven useful for the delineation of neurodegenerative disease processes, we still lack a full understanding of the pathologic mechanisms of these diseases, resulting in few appropriate treatment options and diagnostic challenges. To mitigate these gaps, the Neurodegenerative Disease Knowledge Portal (NDKP) was created as an open-science initiative with the aim to aggregate, enable analysis, and display all available genomic datasets of neurodegenerative disease, while protecting the integrity and confidentiality of the underlying datasets. The portal contains 218 genomic datasets, including genotyping and sequencing studies, of individuals across 10 different phenotypic groups, including neurologic conditions such as Alzheimer disease, amyotrophic lateral sclerosis, Lewy body dementia, and Parkinson disease. In addition to securely hosting large genomic datasets, the NDKP provides accessible workflows and tools to effectively use the datasets and assist in the facilitation of customized genomic analyses. Here, we summarize the genomic datasets currently included within the portal, the bioinformatics processing of the datasets, and the variety of phenotypes captured. We also present example use cases of the various user interfaces and integrated analytic tools to demonstrate their extensive utility in enabling the extraction of high-quality results at the source, for both genomics experts and those in other disciplines. Overall, the NDKP promotes open science and collaboration, maximizing the potential for discovery from the large-scale datasets researchers and consortia are expending immense resources to produce and resulting in reproducible conclusions to improve diagnostic and therapeutic care for patients with neurodegenerative disease.}, }
@article {pmid39995125, year = {2025}, author = {Kalinin, AP and Zubkova, ES and Menshikov, MY and Parfyonova, YV}, title = {ISR Modulators in Neurological Diseases.}, journal = {Current neuropharmacology}, volume = {23}, number = {10}, pages = {1184-1214}, pmid = {39995125}, issn = {1875-6190}, support = {23-15-00539//Russian Science Foundation, RSF/ ; }, mesh = {Humans ; *Nervous System Diseases/metabolism/drug therapy ; Animals ; *Signal Transduction/drug effects/physiology ; *Stress, Physiological/physiology/drug effects ; }, abstract = {The dysfunction of different cells lies in the pathogenesis of neurological diseases and is usually associated with cellular stress. Various stressors trigger the integrated stress response (ISR) signaling, whose highly conserved mechanism is primarily aimed at protecting a stress-exposed cell to cope as safely as possible with such stressful conditions. On the contrary, if a cell is unable to cope with excessive stress, the ISR can induce apoptosis. The ISR mechanism, whose main stage is the inhibition of translation machinery in favor of the synthesis of specific proteins, including the transcription factors ATF3, ATF4, CEBPA, and CEBPB, which function only as dimers and determine the uniqueness of the ISR response in each individual case, thus ensures different outcomes of the ISR. Inhibition of global protein synthesis is achieved through phosphorylation of eIF2α by PERK, HRI, PKR, or GCN2. To date, a number of compounds have been developed that modulate the ISR, including activators and inhibitors of the abovementioned ISR kinases as well as modulators of p-eIF2α dephosphorylation. They target different ISR stages, allowing a broad ISR modulation strategy. At the same time, there are no drugs that are both exceptionally safe and effective for the treatment of several neurological diseases, so there is an urgent need for new approaches to the treatment of these disorders. In this review, we represent ISR signaling as an important participant in the pathogenesis of neurological diseases. We also describe how various ISR modulators may become a part of future therapies for these diseases.}, }
@article {pmid39995102, year = {2025}, author = {Perdikakis, M and Papadimitrakis, D and Floros, N and Tzavellas, E and Piperi, C and Gargalionis, AN and Papavassiliou, AG}, title = {Diagnostic role of circulating cell-free DNA in schizophrenia and neuro-degenerative disorders.}, journal = {Biomarkers in medicine}, volume = {19}, number = {5}, pages = {165-176}, pmid = {39995102}, issn = {1752-0371}, mesh = {Humans ; *Cell-Free Nucleic Acids/blood ; *Schizophrenia/diagnosis/blood/genetics ; *Neurodegenerative Diseases/diagnosis/blood/genetics ; Biomarkers/blood ; }, abstract = {Over the past few years, circulating cell-free DNA (cfDNA) research has grown exponentially. Several studies have associated the release of cfDNA in the bloodstream, cerebrospinal fluid, and other body fluids with increased apoptosis and cell death. Therefore, their possible use as biomarkers for cancer and other diseases has emerged. The diagnosis of pathological entities such as schizophrenia and neurodegenerative diseases involves many challenges and requires ruling out conditions with similar symptoms. In this context, cfDNA could serve as a valuable diagnostic biomarker. This study encompasses the recent bibliography and research regarding the utilization of circulating cfDNA for diagnostic purposes in schizophrenia, Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, and Huntington's disease. This minimally invasive method has provided important evidence regarding the diagnosis of the aforementioned diseases although further research is necessary.}, }
@article {pmid39995075, year = {2025}, author = {Manco, C and Righi, D and Primiano, G and Romano, A and Luigetti, M and Leonardi, L and De Stefano, N and Plantone, D}, title = {Peripherin, A New Promising Biomarker in Neurological Disorders.}, journal = {The European journal of neuroscience}, volume = {61}, number = {4}, pages = {e70030}, pmid = {39995075}, issn = {1460-9568}, mesh = {Humans ; *Peripherins/metabolism/genetics/blood ; Biomarkers/metabolism/blood ; Animals ; *Nervous System Diseases/metabolism/diagnosis ; }, abstract = {Peripherin is a class III intermediate filament protein that has recently gained attention as a potential biomarker for axonal damage in the peripheral nervous system. This review examines peripherin gene expression, protein structure, and its functions in both healthy and diseased states. Peripherin is predominantly expressed in the peripheral nervous system, especially in motor and sensory neurons, and plays a critical role in neurite growth, stability, and axonal transport during myelination. Its expression is regulated by various cytokines and undergoes several post-transcriptional modifications. Peripherin interacts with multiple proteins, including neurofilaments and kinases, influencing cytoskeletal dynamics and neuronal functions. The review also explores peripherin involvement in several neurological disorders, such as Amyotrophic Lateral Sclerosis, where its abnormal expression and aggregation contribute to disease pathology. Additionally, peripherin has been linked to polyneuropathies, traumatic axonal injury, and diabetic neuropathy, suggesting its broader relevance as a biomarker in these conditions. The potential of peripherin as a biomarker is further supported by recent studies using ultrasensitive detection methods, which have identified elevated peripherin levels in the serum of patients with neurological diseases. Despite the promising findings, the application of peripherin as a biomarker in clinical settings remains limited, primarily due to challenges in its detection and the need for further validation in diverse patient populations. Future research directions include the development of more sensitive assays and the exploration of peripherin's role in non-neuronal tissues, which may expand its diagnostic and therapeutic potential.}, }
@article {pmid39994160, year = {2025}, author = {Dubey, PR and Kaur, G and Shukla, R}, title = {Nano-mediated Management of Metal Toxicity-induced Neurodegeneration: A Critical Review.}, journal = {Molecular neurobiology}, volume = {62}, number = {7}, pages = {8400-8419}, pmid = {39994160}, issn = {1559-1182}, mesh = {Humans ; Animals ; *Neurodegenerative Diseases/chemically induced/therapy ; *Metals, Heavy/toxicity ; *Nanotechnology/methods ; *Nanoparticles/therapeutic use ; Oxidative Stress/drug effects ; Drug Delivery Systems/methods ; }, abstract = {Heavy metals, omnipresent in the environment, though imperative in trace quantities for human physiology, become a serious health hazard due to their toxicity. Copper, arsenic, lead, iron, and mercury are some examples of the heavy metals responsible for oxidative stress, which is one of the primary factors behind neurodegenerative diseases like Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis. Neurodegeneration is caused by toxicity due to environmental exposure to these toxic substances or genetic variation. Conventional therapies, relying on chelation and antioxidants, suffer from the broader perspective of metal removal in a non-selective manner and poor targeting of the brain. In this respect, treatments based on nanotechnology that employ nanoparticles such as dendrimers, micelles, and liposomes constitute a promising interest in enhancing drug delivery with minimal neurotoxicity. The present review outlines the heavy metals responsible for neurodegenerative diseases, their pathophysiology, management strategies available at present, and the scope of nanotechnology intervention in overcoming shortcomings of conventional therapies. The genetic influence of heavy metals on neurological health is also part of this article.}, }
@article {pmid39987392, year = {2025}, author = {Liu, Y and Xiang, J and Gong, H and Yu, T and Gao, M and Huang, Y}, title = {The Regulation of TDP-43 Structure and Phase Transitions: A Review.}, journal = {The protein journal}, volume = {44}, number = {2}, pages = {113-132}, pmid = {39987392}, issn = {1875-8355}, support = {22477022//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *DNA-Binding Proteins/chemistry/metabolism/genetics ; Phase Transition ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; *Frontotemporal Dementia/metabolism/genetics/pathology ; Animals ; Protein Processing, Post-Translational ; }, abstract = {The transactive response DNA binding protein 43 (TDP-43) is an RNA/DNA-binding protein that is involved in a number of cellular functions, including RNA processing and alternative splicing, RNA transport and translation, and stress granule assembly. It has attracted significant attention for being the primary component of cytoplasmic inclusions in patients with amyotrophic lateral sclerosis or frontotemporal dementia. Mounting evidence suggests that both cytoplasmic aggregation of TDP-43 and loss of nuclear TDP-43 function contribute to TDP-43 pathology. Furthermore, recent studies have demonstrated that TDP-43 is an important component of many constitutive or stress-induced biomolecular condensates. Dysregulation or liquid-to-gel transition of TDP-43 condensates can lead to alterations in TDP-43 function and the formation of TDP-43 amyloid fibrils. In this review, we summarize recent research progress on the structural characterization of TDP-43 and the TDP-43 phase transition. In particular, the roles that disease-associated genetic mutations, post-translational modifications, and extrinsic stressors play in the transitions among TDP-43 monomers, liquid condensates, solid condensates, and fibrils are discussed. Finally, we discuss the effectiveness of available regulators of TDP-43 phase separation and aggregation. Understanding the underlying mechanisms that drive the pathological transformation of TDP-43 could help develop therapeutic strategies for TDP-43 pathology.}, }
@article {pmid39987285, year = {2025}, author = {Fang, M and Zhou, Y and He, K and Lu, Y and Tao, F and Huang, H}, title = {Glucose Metabolic Reprogramming in Microglia: Implications for Neurodegenerative Diseases and Targeted Therapy.}, journal = {Molecular neurobiology}, volume = {62}, number = {7}, pages = {8204-8221}, pmid = {39987285}, issn = {1559-1182}, support = {82204651//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Microglia/metabolism/drug effects ; *Neurodegenerative Diseases/metabolism/drug therapy/pathology/therapy ; *Glucose/metabolism ; Animals ; *Molecular Targeted Therapy ; Glycolysis ; Metabolic Reprogramming ; }, abstract = {As intrinsic immune cells in the central nervous system, microglia play a crucial role in maintaining brain homeostasis. Microglia can transition from homeostasis to various responsive states in reaction to different external stimuli, undergoing corresponding alterations in glucose metabolism. In neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS), microglial glucose metabolic reprogramming is widespread. This reprogramming leads to changes in microglial function, exacerbating neuroinflammation and the accumulation of pathological products, thereby driving the progression of neurodegeneration. This review summarizes the specific alterations in glucose metabolism within microglia in AD, PD, ALS, and MS, as well as the corresponding treatments aimed at reprogramming glucose metabolism. Compounds that inhibit key glycolytic enzymes like hexokinase 2 (HK2) and pyruvate kinase M2 (PKM2), or activate regulators of energy metabolism such as AMP-activated protein kinase (AMPK), have shown significant potential in the treatment of various neurodegenerative diseases. However, current research faces numerous challenges, including side effects and blood-brain barrier (BBB) penetration of compounds. Screening relevant drugs from natural products, especially flavonoids, is a reliable approach. On the one hand, longtime herbal medical practices provide a certain degree of assurance regarding clinical safety, and their chemical properties contribute to effective BBB permeability. On the other hand, the concurrent anti-tumor and anti-neuroinflammatory activities of flavonoids suggest that regulation of glucose metabolism reprogramming might be a potential common mechanism of action. Notably, considering the dynamic nature of microglial metabolism, there is an urgent need to develop technologies for real-time monitoring of glucose metabolism processes, which would significantly advance research in this field.}, }
@article {pmid39986312, year = {2025}, author = {Mizielinska, S and Hautbergue, GM and Gendron, TF and van Blitterswijk, M and Hardiman, O and Ravits, J and Isaacs, AM and Rademakers, R}, title = {Amyotrophic lateral sclerosis caused by hexanucleotide repeat expansions in C9orf72: from genetics to therapeutics.}, journal = {The Lancet. Neurology}, volume = {24}, number = {3}, pages = {261-274}, pmid = {39986312}, issn = {1474-4465}, support = {U19 AG063911/AG/NIA NIH HHS/United States ; P01 NS084974/NS/NINDS NIH HHS/United States ; P30 AG062677/AG/NIA NIH HHS/United States ; UG3 NS103870/NS/NINDS NIH HHS/United States ; RF1 NS123052/NS/NINDS NIH HHS/United States ; R01 NS117461/NS/NINDS NIH HHS/United States ; R01 NS121125/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/therapy/diagnosis ; C9orf72 Protein/genetics ; *DNA Repeat Expansion/genetics ; }, abstract = {GGGGCC repeat expansions in C9orf72 are a common genetic cause of amyotrophic lateral sclerosis in people of European ancestry; however, substantial variability in the penetrance of the mutation, age at disease onset, and clinical presentation can complicate diagnosis and prognosis. The repeat expansion is bidirectionally transcribed in the sense and antisense directions into repetitive RNAs and translated into dipeptide repeat proteins, and both accumulate in the cortex, cerebellum, and the spinal cord. Furthermore, neuropathological aggregates of phosphorylated TDP-43 are observed in motor cortex and other cortical regions, and in the spinal cord of patients at autopsy. C9orf72 repeat expansions can also cause frontotemporal dementia. The GGGGCC repeat induces a complex interplay of loss-of-function and gain-of-function pathological mechanisms. Clinical trials using antisense oligonucleotides to target the GGGGCC repeat RNA have not been successful, potentially because they only target a single gain-of-function mechanism. Novel therapeutic approaches targeting the DNA repeat expansion, multiple repeat-derived RNA species, or downstream targets of TDP-43 dysfunction are, however, on the horizon, together with the development of diagnostic and prognostic biomarkers.}, }
@article {pmid39985812, year = {2025}, author = {Filippi, M and Ghirelli, A and Spinelli, EG and Agosta, F}, title = {A comprehensive update on neuroimaging endpoints in amyotrophic lateral sclerosis.}, journal = {Expert review of neurotherapeutics}, volume = {25}, number = {4}, pages = {397-413}, doi = {10.1080/14737175.2025.2470324}, pmid = {39985812}, issn = {1744-8360}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/physiopathology/therapy ; *Neuroimaging/methods ; Magnetic Resonance Imaging/methods ; Positron-Emission Tomography/methods ; Disease Progression ; Biomarkers ; }, abstract = {INTRODUCTION: There are currently few treatments approved for amyotrophic lateral sclerosis (ALS). Additionally, there remains a significant unmet need for reliable, standardized biomarkers to assess endpoints in clinical trials. Magnetic resonance imaging (MRI)- and positron emission tomography (PET)-derived metrics could help in patient selection and stratification, shortening trial duration and reducing costs.<br><br>AREAS COVERED: This review focuses on the potential use of neuroimaging endpoints in the context of ALS therapeutic trials, providing insights on structural and functional neuroimaging, plexus and muscle alterations, glial involvement and neuroinflammation, envisioning how these surrogates of disease progression could be implemented in clinical trials. A PubMed search covering the past 15&#x2009;years was performed.<br><br>EXPERT OPINION: Neuroimaging is essential in understanding ALS pathophysiology, aiding in disease progression tracking and evaluating therapeutic interventions. High costs, limited accessibility, lack of standardization, and patient tolerability limit their use in routine ALS care. Addressing these obstacles is essential for fully harnessing neuroimaging potential in improving diagnostics and treatment in ALS.}, }
@article {pmid39978484, year = {2025}, author = {Hülsmeier, AJ}, title = {Glycosphingolipids in neurodegeneration - Molecular mechanisms, cellular roles, and therapeutic perspectives.}, journal = {Neurobiology of disease}, volume = {207}, number = {}, pages = {106851}, doi = {10.1016/j.nbd.2025.106851}, pmid = {39978484}, issn = {1095-953X}, mesh = {Humans ; *Glycosphingolipids/metabolism ; *Neurodegenerative Diseases/metabolism/pathology/therapy ; Animals ; }, abstract = {Neurodegenerative diseases, including Alzheimer's (AD), Parkinson's (PD), Huntington's (HD), and amyotrophic lateral sclerosis (ALS), are characterized by progressive neuronal loss and pose significant global health challenges. Glycosphingolipids (GSLs), critical components of neuronal membranes, regulate signal transduction, membrane organization, neuroinflammation, and lipid raft functionality. This review explores GSL roles in neural development, differentiation, and neurogenesis, along with their dysregulation in neurodegenerative diseases. Aberrations in GSL metabolism drive key pathological features such as protein aggregation, neuroinflammation, and impaired signaling. Specific GSLs, such as GM1, GD3, and GM3, influence amyloid-beta aggregation in AD, α-synuclein stability in PD, and mutant huntingtin toxicity in HD. Therapeutic strategies targeting GSL metabolism, such as GM1 supplementation and enzyme modulation, have demonstrated potential to mitigate disease progression. Further studies using advanced lipidomics and glycomics may support biomarker identification and therapeutic advancements. This work aims to highlight the translational potential of GSL research for diagnosing and managing devastating neurodegenerative conditions.}, }
@article {pmid39977838, year = {2025}, author = {Chang, JH and Tschannen, D}, title = {An Integrative Review of Quality Improvement Competence and Engagement Among Frontline Nurses.}, journal = {Journal of nursing care quality}, volume = {40}, number = {2}, pages = {173-180}, pmid = {39977838}, issn = {1550-5065}, mesh = {Humans ; *Quality Improvement ; *Clinical Competence/standards ; Leadership ; *Nursing Staff, Hospital ; }, abstract = {BACKGROUND: Nurses providing direct care have firsthand knowledge of gaps in practice and thus must actively engage in quality improvement (QI) to enhance patient outcomes.<br><br>PURPOSE: This integrative review evaluated QI competence and engagement among frontline nurses.<br><br>METHODS: Using Souza et al's 6-step framework, literature on QI engagement and competence was synthesized using a rigorous search strategy and quality assessment.<br><br>RESULTS: Sixteen studies revealed generally low QI engagement and competence. Factors such as education, experience, and role influenced engagement, with higher levels of education and experience linked to higher QI involvement. Nurse leaders had higher engagement, underscoring the need for strong leadership in creating a culture of improvement.<br><br>CONCLUSIONS: Successful and sustainable QI programs and supportive environments enhance QI engagement and competence among frontline nurses.}, }
@article {pmid39969752, year = {2025}, author = {Liao, D and Zhang, Y and Li, S and Tang, H and Bai, X}, title = {miRNAs in neurodegenerative diseases: from target screening to precision therapy.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {46}, number = {6}, pages = {2393-2399}, pmid = {39969752}, issn = {1590-3478}, support = {NO.2022-CXTD-05//Sichuan Province Science and Technology Support Program/ ; }, mesh = {Humans ; *MicroRNAs/metabolism/genetics ; *Neurodegenerative Diseases/therapy/genetics/diagnosis/metabolism ; Animals ; *Precision Medicine/methods ; }, abstract = {miRNAs are critical for different disease development processes, including cell growth, signaling, apoptosis, cancer and neurodegenerative diseases. It has been shown that altered miRNA levels are associated with reactive oxygen species (ROS) formation and mitochondrial dysfunction. While mitochondrial dysfunction and ROS formation occur in many neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis, amyotrophic lateral sclerosis, miRNAs have the potential to be diagnostic biomarkers and therapeutic targets with a high degree of specificity, which is highly relevant in neurodegenerative pathologies.This paper gives a general summary of the current expression of miRNAs in neurodegenerative diseases, including miRNAs up-regulated or down-regulated in a variety of diseases, as well as the associated factors of influence. miRNAs are more like a double-edged sword, their multi-targeted role has brought light to many diseases for which there are currently no clear therapeutic options, but at the same time, their low specificity and possible side effects on the whole body should not be ignored, therefore However, at the same time, its low specificity and possible side effects on the whole body should not be ignored, therefore, more attention should be paid to the development of miRNA therapy in terms of its high efficiency, the use of carriers, and the clarification of side effects.}, }
@article {pmid39969664, year = {2025}, author = {Irdianto, SA and Dwiranti, A and Bowolaksono, A}, title = {Extrachromosomal circular DNA: a double-edged sword in cancer progression and age-related diseases.}, journal = {Human cell}, volume = {38}, number = {2}, pages = {58}, pmid = {39969664}, issn = {1749-0774}, support = {NKB-888/UN2.RST/HKP.05.00/2024//Kementerian Riset Teknologi Dan Pendidikan Tinggi Republik Indonesia/ ; }, mesh = {Humans ; *Neoplasms/genetics/therapy/pathology ; *DNA, Circular/genetics/physiology ; Disease Progression ; *Diabetes Mellitus, Type 2/genetics ; *Aging/genetics ; *Amyotrophic Lateral Sclerosis/genetics ; Werner Syndrome/genetics ; Genomic Instability/genetics ; }, abstract = {Extrachromosomal circular DNA (eccDNA) is a fascinating form of genetic material found outside the usual chromosomal DNA in eukaryotic cells, including humans. Since its discovery in the 1960s, eccDNA has been linked to critical roles in cancer progression and age-related diseases. This review thoroughly explores eccDNA, covering its types, how it forms, and its significant impact on diseases, particularly cancer. EccDNA, especially in its extrachromosomal DNA (ecDNA) form, contributes to the genetic diversity of tumour cells, helping them evolve quickly and resist treatments. Beyond cancer, eccDNA is also connected to age-related conditions like Werner syndrome, amyotrophic lateral sclerosis (ALS), and type 2 diabetes mellitus (T2DM), where it may affect genomic stability and disease development. The potential of eccDNA as a biomarker for predicting disease outcomes and as a target for new treatments is also highlighted. This review aims to deepen our understanding of eccDNA and inspire further research into its roles in human health and disease, paving the way for innovative diagnostic and therapeutic approaches.}, }
@article {pmid39965449, year = {2025}, author = {Awasthi, S and Tiwari, PC and Awasthi, S and Dwivedi, A and Srivastava, S}, title = {Mechanistic role of proteins and peptides in Management of Neurodegenerative Disorders.}, journal = {Neuropeptides}, volume = {110}, number = {}, pages = {102505}, doi = {10.1016/j.npep.2025.102505}, pmid = {39965449}, issn = {1532-2785}, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Peptides/therapeutic use/metabolism ; Animals ; *Proteins/therapeutic use/metabolism ; }, abstract = {Proteins and peptides have emerged as significant contributors in the management of neurodegenerative disorders due to their diverse biological functions. These biomolecules influence various cellular processes, including cellular repair, inflammation reduction, and neuronal survival, which are crucial for mitigating the effects of diseases such as Alzheimer's, Parkinson's, and Amyotrophic Lateral Sclerosis (ALS). By interacting with specific cellular receptors, proteins and peptides like neurotrophic factors, cytokines, and enzyme inhibitors promote neurogenesis, reduce oxidative stress, and enhance synaptic plasticity. Nevertheless, till certain limitations and challenges do exist to deliver these fragile therapeutic bioactives. Moreover, targeted delivery systems, such as nanoparticles and biomolecular carriers, are being developed to improve the bioavailability and specificity of these protein-based therapeutics, ensuring efficient crossing of the blood-brain barrier. This review explores the mechanistic pathways through which these biomolecules act, emphasizing their potential to modify disease progression and improve the quality of life in patients with neurodegenerative conditions. Overall, proteins and peptides are not only seen as promising therapeutic agents but also as foundational tools in advancing personalized medicine in the field of neurodegenerative disorders.}, }
@article {pmid39963928, year = {2025}, author = {Lomas, C and Dubey, RC and Perez-Alvarez, G and Lopez Hernandez, Y and Atmar, A and Arias, AY and Vashist, A and Aggarwal, S and Manickam, P and Lakshmana, MK and Vashist, A}, title = {Recent advances in nanotherapeutics for HIV-associated neurocognitive disorders and substance use disorders.}, journal = {Nanomedicine (London, England)}, volume = {20}, number = {6}, pages = {603-619}, pmid = {39963928}, issn = {1748-6963}, support = {R01 DA049657/DA/NIDA NIH HHS/United States ; R03 AG087475/AG/NIA NIH HHS/United States ; U01 ES033265/ES/NIEHS NIH HHS/United States ; }, mesh = {Humans ; *Substance-Related Disorders/drug therapy/therapy ; Blood-Brain Barrier/metabolism ; *Nanomedicine/methods ; *HIV Infections/complications/drug therapy ; *Nanoparticles/chemistry/therapeutic use ; Animals ; *Neurocognitive Disorders/drug therapy ; *AIDS Dementia Complex/drug therapy ; }, abstract = {Substance use disorders (SUD) and HIV-associated neurocognitive disorders (HAND) work synergistically as a significant cause of cognitive decline in adults and adolescents globally. Current therapies continue to be limited due to difficulties crossing the blood-brain barrier (BBB) leading to limited precision and effectiveness, neurotoxicity, and lack of co-treatment options for both HAND and SUD. Nanoparticle-based therapeutics have several advantages over conventional therapies including more precise targeting, the ability to cross the BBB, and high biocompatibility which decreases toxicity and optimizes sustainability. These advantages extend to other neurological disorders such as Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS). This review summarizes recent advances in nanotechnology for application to HAND, SUD, and co-treatment, as well as other neurological disorders. This review also highlights the potential challenges these therapies face in clinical translation and long-term safety.}, }
@article {pmid39958595, year = {2025}, author = {Arnold, WD and Majithia, K}, title = {Triumphs, Trials, and Future Considerations in Genetic Therapies for Hereditary Neuromuscular Diseases.}, journal = {Missouri medicine}, volume = {122}, number = {1}, pages = {46-52}, pmid = {39958595}, issn = {0026-6620}, mesh = {Humans ; *Genetic Therapy/methods/trends ; *Neuromuscular Diseases/therapy/genetics ; Muscular Dystrophy, Duchenne/therapy/genetics ; Amyotrophic Lateral Sclerosis/therapy/genetics ; Muscular Atrophy, Spinal/therapy/genetics ; Precision Medicine/methods ; }, abstract = {Neuromuscular diseases include conditions that affect the spinal motor neurons, peripheral nerves, neuromuscular junctions, and muscles, and they can result from acquired and inherited causes. The number of genetic therapies targeting the inherited causes of neuromuscular diseases has surged in the last decade. This review aims to highlight the current state of genetic therapies within the framework of precision medicine, focusing on the achievements and the gaps that remain. A major emphasis is on spinal muscular atrophy, Duchenne muscular dystrophy, and amyotrophic lateral sclerosis, as these neuromuscular diseases have seen tremendous recent advancements. We will also discuss the future considerations necessary to accelerate the development of next-generation genetic therapies and enhance therapeutic outcomes for patients with neuromuscular diseases.}, }
@article {pmid39958442, year = {2025}, author = {Ozbey, D and Saribas, S and Kocazeybek, B}, title = {Gut microbiota in Crohn's disease pathogenesis.}, journal = {World journal of gastroenterology}, volume = {31}, number = {6}, pages = {101266}, pmid = {39958442}, issn = {2219-2840}, mesh = {Humans ; Colon/microbiology/pathology/immunology ; *Crohn Disease/therapy/microbiology/immunology/pathology ; Dysbiosis/therapy ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/immunology ; Ileum/microbiology/pathology/immunology ; Intestinal Mucosa/microbiology/pathology/immunology ; Treatment Outcome ; }, abstract = {Inflammatory bowel diseases (IBDs) are classified into two distinct types based on the area and severity of inflammation: Crohn's disease (CD) and ulcerative colitis. In CD, gut bacteria can infiltrate mesenteric fat, causing expansion known as creeping fat, which may limit bacterial spread and inflammation but can promote fibrosis. The gut bacteria composition varies depending on whether the colon or ileum is affected. Fecal microbiota transplantation (FMT) transfers feces from a healthy donor to restore gut microbiota balance, often used in IBD patients to reduce inflammation and promote mucosal repair. The use of FMT for CD remains uncertain, with insufficient evidence to fully endorse it as a definitive treatment. While some studies suggest it may improve symptoms, questions about the duration of these improvements and the need for repeated treatments persist. There is a pressing need for methods that provide long-term benefits, as highlighted by Wu et al's research.}, }
@article {pmid39955147, year = {2025}, author = {Robinson, J and Abrams, R and Price, O and Barley, E}, title = {Tools used to measure the therapeutic relationship between staff and service users in adult mental health care: A scoping review.}, journal = {Archives of psychiatric nursing}, volume = {54}, number = {}, pages = {73-83}, doi = {10.1016/j.apnu.2025.01.007}, pmid = {39955147}, issn = {1532-8228}, mesh = {Humans ; *Mental Health Services ; Adult ; *Mental Disorders/therapy ; *Professional-Patient Relations ; }, abstract = {BACKGROUND: Therapeutic relationships are key to both service user recovery and the safety of staff and service users in adult mental health care. However, staff over-involvement (crossing professional boundaries including sexual and emotional exploitation) and under-involvement (staff disinterest, avoidance or neglect) is often a cause for concern within mental health care. Little is known about measuring and assessing over / under involvement. This scoping review provides a broad understanding of existing tools used to measure this in adult mental health care.<br><br>OBJECTIVE: To explore what measures are used, and the characteristics of the identified measures, to understand the therapeutic relationship between staff and adult service users in mental health care settings.<br><br>DESIGN: Scoping review.<br><br>SETTING(S): Adult mental health settings.<br><br>PARTICIPANTS: Service users and staff.<br><br>METHODS: This review is guided by Levac et al.'s six stage methodology of scoping review frameworks. The reporting of this review has been guided by the PRISMA-ScR.<br><br>RESULTS: Of 2863 papers found, 23 were eligible for inclusion. The papers identified 14 scales. No tool specifically measured over- or under- involvement. Finally, data indicates that scales should be specific to their intended setting as the nature of therapeutic relationships may vary by setting.<br><br>CONCLUSIONS: Definitions of therapeutic relationships and over- and under-involvement relevant to different settings are needed. There is a need to develop setting-specific scales to measure therapeutic involvement and definitions for over- and under- involvement. This would enhance care provided to service users and encourage staff members to challenge their own boundary setting practices.<br><br>REGISTRATION: https://osf.io/93dxp/.}, }
@article {pmid39954969, year = {2025}, author = {Utami, KH and Morimoto, S and Mitsukura, Y and Okano, H}, title = {The roles of intrinsically disordered proteins in neurodegeneration.}, journal = {Biochimica et biophysica acta. General subjects}, volume = {1869}, number = {4}, pages = {130772}, doi = {10.1016/j.bbagen.2025.130772}, pmid = {39954969}, issn = {1872-8006}, mesh = {Humans ; *Intrinsically Disordered Proteins/metabolism ; *Neurodegenerative Diseases/metabolism/pathology ; Animals ; Proteostasis ; Autophagy ; alpha-Synuclein/metabolism ; Proteasome Endopeptidase Complex/metabolism ; }, abstract = {Neurodegenerative diseases such as Amyotrophic Lateral Sclerosis, Alzheimer's disease, Parkinson's disease, and Huntington's disease share a common pathological hallmark: the accumulation of misfolded proteins, particularly involving intrinsically disordered proteins (IDPs) like TDP-43, FUS, Tau, α-synuclein, and Huntingtin. These proteins undergo pathological aggregation, forming toxic inclusions that disrupt cellular function. The dysregulation of proteostasis mechanisms, including the ubiquitin-proteasome system (UPS), ubiquitin-independent proteasome system (UIPS), autophagy, and molecular chaperones, exacerbates these proteinopathies by failing to clear misfolded proteins effectively. Emerging therapeutic strategies aim to restore proteostasis through proteasome activators, autophagy enhancers, and chaperone-based interventions to prevent the toxic accumulation of IDPs. Additionally, understanding liquid-liquid phase separation (LLPS) and its role in stress granule dynamics offers novel insights into how aberrant phase transitions contribute to neurodegeneration. By targeting the molecular pathways involved in IDP aggregation and proteostasis regulation, and better understanding the specificity of each component, research in this area will pave the way for innovative therapeutic approaches to combat these neurodegenerative diseases. This review discusses the molecular mechanisms underpinning IDP pathology, highlights recent advancements in drug discovery, and explores the potential of targeting proteostasis machinery to develop effective therapies.}, }
@article {pmid39954940, year = {2025}, author = {Satao, KS and Doshi, GM}, title = {Intercellular communication via exosomes: A new paradigm in the pathophysiology of neurodegenerative disorders.}, journal = {Life sciences}, volume = {365}, number = {}, pages = {123468}, doi = {10.1016/j.lfs.2025.123468}, pmid = {39954940}, issn = {1879-0631}, mesh = {Humans ; *Exosomes/metabolism/physiology ; *Neurodegenerative Diseases/physiopathology/metabolism/pathology ; *Cell Communication/physiology ; Animals ; }, abstract = {Neurodegenerative disorders are one of the leading causes of death and disability and pose a great economic burden on healthcare systems. Generally, these neurodegenerative disorders have a progressive deterioration in neural function and structure, and deposition of misfolded proteins commonly occurs, such as amyloid-β in AD and α-synuclein in PD. However, there exists a special class of exosomes, which acts like a transmitter and enhances communication between cells. The present review discusses the significant role of exosomes in neurodegenerative diseases, with a focus on Amyotrophic lateral Sclerosis (ALS), AD, PD, and Huntington's disease (HD). In this review, the biogenesis of exosomes is discussed from multivesicular bodies and onwards to their release into the extracellular environment. The present review focuses on recent data concerning the possible use of modified exosomes as ND therapy. Indeed, future work is needed to explain the processes driving exosome biogenesis and cargo selection, while opening new routes by the use of exosome-based therapeutics in neurodegenerative disease diagnosis and treatment.}, }
@article {pmid39952329, year = {2025}, author = {Ji, Y and Jiang, Q and Chen, B and Chen, X and Li, A and Shen, D and Shen, Y and Liu, H and Qian, X and Yao, X and Sun, H}, title = {Endoplasmic reticulum stress and unfolded protein response: Roles in skeletal muscle atrophy.}, journal = {Biochemical pharmacology}, volume = {234}, number = {}, pages = {116799}, doi = {10.1016/j.bcp.2025.116799}, pmid = {39952329}, issn = {1873-2968}, mesh = {*Unfolded Protein Response/physiology/drug effects ; Humans ; *Endoplasmic Reticulum Stress/physiology/drug effects ; *Muscular Atrophy/metabolism/pathology ; Animals ; *Muscle, Skeletal/metabolism/pathology/drug effects ; }, abstract = {Skeletal muscle atrophy is commonly present in various pathological states, posing a huge burden on society and patients. Increased protein hydrolysis, decreased protein synthesis, inflammatory response, oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress (ERS) and unfolded protein response (UPR) are all important molecular mechanisms involved in the occurrence and development of skeletal muscle atrophy. The potential mechanisms of ERS and UPR in skeletal muscle atrophy are extremely complex and have not yet been fully elucidated. This article elucidates the molecular mechanisms of ERS and UPR, and discusses their effects on different types of muscle atrophy (muscle atrophy caused by disuse, cachexia, chronic kidney disease (CKD), diabetes mellitus (DM), amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), spinal and bulbar muscular atrophy (SBMA), aging, sarcopenia, obesity, and starvation), and explores the preventive and therapeutic strategies targeting ERS and UPR in skeletal muscle atrophy, including inhibitor therapy and drug therapy. This review aims to emphasize the importance of endoplasmic reticulum (ER) in maintaining skeletal muscle homeostasis, which helps us further understand the molecular mechanisms of skeletal muscle atrophy and provides new ideas and insights for the development of effective therapeutic drugs and preventive measures for skeletal muscle atrophy.}, }
@article {pmid39944166, year = {2025}, author = {Islam, S and Noorani, A and Sun, Y and Michikawa, M and Zou, K}, title = {Multi-functional role of apolipoprotein E in neurodegenerative diseases.}, journal = {Frontiers in aging neuroscience}, volume = {17}, number = {}, pages = {1535280}, pmid = {39944166}, issn = {1663-4365}, abstract = {Genetic diversity in the apolipoprotein E (ApoE) gene has been identified as the major susceptibility genetic risk factor for sporadic Alzheimer's disease (SAD). Specifically, the ApoEε4 allele is a significant risk factor for SAD, while ApoEε2 allele provides protection compared to the more common ApoEε3 allele. This review discusses the role of the ApoE in AD and other neurodegenerative disorders. ApoE, a cholesterol transport protein, influences several pathways involved in neurodegeneration, particularly in AD. Beyond its established role in amyloid β-protein (Aβ) metabolism and deposition, ApoE also impacts tau pathology, neurodegeneration, and the microglial response to AD. The review aims to provide an updated overview of ApoE's diverse roles, emphasizing its involvement in Aβ clearance through ApoE receptors. It also covers ApoE's influence in other neurodegenerative diseases like Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), Huntington's disease (HD), vascular dementia (VD), and multiple sclerosis (MS). New research highlights the interaction between ApoE and presenilin (PS), suggesting connections between familial AD (FAD) and SAD. The review also explores protective effects of ApoE mutations against AD and ApoE4-induced tauopathy, neurodegeneration, and neuroinflammation. The insights from this comprehensive update could indeed lead to new therapeutic strategies for neurodegenerative diseases.}, }
@article {pmid39942798, year = {2025}, author = {Długosz, A and Błaszak, B and Czarnecki, D and Szulc, J}, title = {Mechanism of Action and Therapeutic Potential of Xanthohumol in Prevention of Selected Neurodegenerative Diseases.}, journal = {Molecules (Basel, Switzerland)}, volume = {30}, number = {3}, pages = {}, pmid = {39942798}, issn = {1420-3049}, mesh = {*Propiophenones/pharmacology/therapeutic use/chemistry ; *Flavonoids/pharmacology/therapeutic use/chemistry ; Humans ; *Neurodegenerative Diseases/drug therapy/prevention &amp; control/metabolism ; Animals ; Antioxidants/pharmacology/therapeutic use/chemistry ; *Neuroprotective Agents/pharmacology/therapeutic use/chemistry ; Parkinson Disease/drug therapy ; Alzheimer Disease/drug therapy/metabolism ; Humulus/chemistry ; }, abstract = {Xanthohumol (XN), a bioactive plant flavonoid, is an antioxidant, and as such, it exhibits numerous beneficial properties, including anti-inflammatory, antimicrobial, and antioxidative effects. The main dietary source of XN is beer, where it is introduced through hops. Although the concentration of XN in beer is low, the large quantities of hop-related post-production waste present an opportunity to extract XN residues for technological or pharmaceutical purposes. The presented study focuses on the role of XN in the prevention of neurodegenerative diseases, analyzing its effect at a molecular level and including its signal transduction and metabolism. The paper brings up XN's mechanism of action, potential effects, and experimental and clinical studies on Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Additionally, challenges and future research directions on XN, including its bioavailability, safety, and tolerance, have been discussed.}, }
@article {pmid39941101, year = {2025}, author = {Orywal, K and Socha, K and Iwaniuk, P and Kaczyński, P and Farhan, JA and Zoń, W and Łozowicka, B and Perkowski, M and Mroczko, B}, title = {Vitamins in the Prevention and Support Therapy of Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {26}, number = {3}, pages = {}, pmid = {39941101}, issn = {1422-0067}, support = {NdS/551580/2022/2022//Polish Ministry of Education and Science/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/prevention &amp; control/drug therapy ; *Vitamins/therapeutic use/pharmacology ; Animals ; Parkinson Disease/prevention &amp; control ; Dietary Supplements ; Neuroprotective Agents/therapeutic use ; Oxidative Stress/drug effects ; }, abstract = {Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS), which are a consequence of the progressive loss of neuronal function and structure, cause significant cognitive impairment. The incidence of these diseases in the world's population is constantly increasing as a result of an aging population. Although genetic and environmental factors are most often mentioned as the pathogenetic factors of these diseases, increasing evidence points to the important role of proper nutrition in the prevention and support of the treatment of these disorders. A healthy, balanced diet can mitigate the risks associated with the risk factors mentioned above and slow the progression of the disease by reducing oxidative stress and inflammation. Vitamins B, D, E, C, K, and A have been shown to support cognitive functions and protect the nervous system. This review demonstrates the importance of vitamins in preventing and supporting the therapy of neurodegenerative diseases. Information regarding the health-promoting properties of these vitamins must be effectively communicated to consumers seeking to protect their health, particularly in the context of neurodegenerative diseases. Consequently, this review also examines the authorized health claims under EU food law related to these vitamins, assessing their role in promoting awareness of the vitamins' potential benefits for neuroprotection and the management of neurodegenerative diseases.}, }
@article {pmid39941012, year = {2025}, author = {Sonkodi, B}, title = {PIEZO2 Proton Affinity and Availability May Also Regulate Mechanical Pain Sensitivity, Drive Central Sensitization and Neurodegeneration.}, journal = {International journal of molecular sciences}, volume = {26}, number = {3}, pages = {}, pmid = {39941012}, issn = {1422-0067}, mesh = {Humans ; *Ion Channels/metabolism/genetics ; Animals ; *Protons ; *Pain/metabolism ; Motor Neurons/metabolism ; *Central Nervous System Sensitization ; *Neurodegenerative Diseases/metabolism ; }, abstract = {The current opinion manuscript posits that not only Piezo2 voltage block, but also proton affinity and availability in relation to Piezo2, a mechanically gated ion channel, may count in the mediation of pain and its sensitivity. Moreover, this paper argues that autonomously acquired Piezo2 channelopathy on somatosensory terminals is likely the initiating peripheral impaired input source that drives the central sensitization of spinal nociceptive neurons on the chronic path as being the autonomous pain generator. In parallel, impaired proprioception and the resultant progressive deficit in neuromuscular junctions of motoneurons might be initiated on the chronic path by the impairment of the proton-based ultrafast proprioceptive feedback to motoneurons due to disconnection through vesicular glutamate transporter 1. The irreversible form of this autonomously acquired Piezo2 ion channel microdamage, in association with genetic predisposition and/or environmental risk factors, is suggested to lead to progressive motoneuron death in addition to loss of pain sensation in amyotrophic lateral sclerosis. Furthermore, the impairment of the proton-based ultrafast long-range oscillatory synchronization to the hippocampus through vesicular glutamate transporter 2 may gain further importance in pain modulation and formation on the chronic path. Overall, this novel, unaccounted Piezo2-initiated protonic extrafast signaling, including both the protonic ultrafast proprioceptive and the rapid nociceptive ones, within the nervous system seems to be essential in order to maintain life. Hence, its microdamage promotes neurodegeneration and accelerates aging, while the complete loss of it is incompatible with life sustainment, as is proposed in amyotrophic lateral sclerosis.}, }
@article {pmid39940966, year = {2025}, author = {Jamerlan, AM and Shim, KH and Sharma, N and An, SSA}, title = {Multimer Detection System: A Universal Assay System for Differentiating Protein Oligomers from Monomers.}, journal = {International journal of molecular sciences}, volume = {26}, number = {3}, pages = {}, pmid = {39940966}, issn = {1422-0067}, support = {RS-2023-00251396//National Research Foundation of Korea/ ; 2021R1A6A1A03038996//National Research Foundation of Korea/ ; }, mesh = {Humans ; alpha-Synuclein/metabolism ; *Protein Multimerization ; *Neurodegenerative Diseases/metabolism ; Protein Aggregates ; tau Proteins/metabolism ; Amyloid beta-Peptides/metabolism ; *Protein Aggregation, Pathological/metabolism ; DNA-Binding Proteins/metabolism ; }, abstract = {Depositions of protein aggregates are typical pathological hallmarks of various neurodegenerative diseases (NDs). For example, amyloid-beta (Aβ) and tau aggregates are present in the brain and plasma of patients with Alzheimer's disease (AD); α-synuclein in Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA); mutant huntingtin protein (Htt) in Huntington's disease (HD); and DNA-binding protein 43 kD (TDP-43) in amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and limbic-predominant age-related TDP-43 encephalopathy (LATE). The same misfolded proteins can be present in multiple diseases in the form of mixed proteinopathies. Since there is no cure for all these diseases, understanding the mechanisms of protein aggregation becomes imperative in modern medicine, especially for developing diagnostics and therapeutics. A Multimer Detection System (MDS) was designed to distinguish and quantify the multimeric/oligomeric forms from the monomeric form of aggregated proteins. As the unique epitope of the monomer is already occupied by capturing or detecting antibodies, the aggregated proteins with multiple epitopes would be accessible to both capturing and detecting antibodies simultaneously, and signals will be generated from the oligomers rather than the monomers. Hence, MDS could present a simple solution for measuring various conformations of aggregated proteins with high sensitivity and specificity, which may help to explore diagnostic and treatment strategies for developing anti-aggregation therapeutics.}, }
@article {pmid39938752, year = {2025}, author = {Zhu, Y and Tian, M and Lu, S and Qin, Y and Zhao, T and Shi, H and Li, Z and Qin, D}, title = {The antioxidant role of aromatic plant extracts in managing neurodegenerative diseases: A comprehensive review.}, journal = {Brain research bulletin}, volume = {222}, number = {}, pages = {111253}, doi = {10.1016/j.brainresbull.2025.111253}, pmid = {39938752}, issn = {1873-2747}, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Antioxidants/pharmacology/therapeutic use ; *Plant Extracts/pharmacology/therapeutic use ; Oxidative Stress/drug effects ; Animals ; Polyphenols/pharmacology/therapeutic use ; }, abstract = {Neurodegenerative diseases (NDDs) are a class of cognitive and motor disorders including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Amyotrophic Lateral Sclerosis (ALS), and others. They are caused by lesions in cells and tissues of the central nervous system, resulting in corresponding dysfunctions and consequent decline in cognitive and motor functions. Neural tissues are extremely vulnerable to oxidative stress, which plays critical biological roles in NDDs. Aromatic compounds are found extensively in natural plants and have substantial effects of anti-oxidative stress damage, which not only have a wide range of research applications in cosmetics, foods, etc., but are also frequently utilized in the treatment of various central nervous system diseases. This review summarizes the relevant oxidative stress mechanisms in NDDs (AD, PD, HD, and ALS) and reviews aromatic compounds such as polyphenols, terpenoids, and flavonoids that can be used in the management of neurodegenerative diseases, as well as their specific mechanisms of antioxidant action. This review will serve as a reference for future experimental studies on neurodegenerative illnesses while also offering fresh insights into clinical therapy.}, }
@article {pmid39936266, year = {2025}, author = {Denton, TT and Carter, GT and Goddard, M and Weiss, J and Weeks, DL and Weydt, P and Russo, EB and Weiss, MD}, title = {Amyotrophic Lateral Sclerosis, the Endocannabinoid System, and Exogenous Cannabinoids: Current State and Clinical Implications.}, journal = {Muscle &amp; nerve}, volume = {72}, number = {1}, pages = {7-14}, doi = {10.1002/mus.28359}, pmid = {39936266}, issn = {1097-4598}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/metabolism ; Humans ; Animals ; *Cannabinoids/therapeutic use/pharmacology ; *Endocannabinoids/metabolism/therapeutic use ; Mice ; }, abstract = {A unifying mechanistic cause for amyotrophic lateral sclerosis (ALS) remains uncertain. Multiple pathophysiological processes appear to occur simultaneously. Cannabinoids, including delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD), cannabigerol (CBG), and others found in cannabis, and cannabis extracts (CEs), appear to have activity in these pathogenic pathways, which have led to increasing interest in cannabinoids as therapeutic agents for ALS. The use of cannabinoids as a treatment strategy is substantiated by preclinical evidence suggesting a role for the endocannabinoid system (ECS) in ALS and other neurodegenerative disorders. Preclinical data indicate that cannabis and CEs have powerful antioxidative, anti-inflammatory, and neuroprotective effects in the SOD1 [G93A] mouse model of ALS. The use of CEs in SOD1 [G93A] murine models has been shown to prolong neuronal cell survival, which leads to delayed onset of the disease state, and slows progression of the disease. Although research in humans remains limited, a few studies suggest that cannabis and CBD, in humans, provide benefits for both motor symptoms, including rigidity, cramps, and fasciculations, and non-motor symptoms including sleep quality, pain, emotional state, quality of life, and depression. There remains a need for further, well-designed clinical trials to validate further the use of an individual cannabinoid, or a combination of cannabinoids, as a disease-modifying therapy for ALS.}, }
@article {pmid39935463, year = {2025}, author = {van Genugten, CR and Thong, MSY and van Ballegooijen, W and Kleiboer, AM and Spruijt-Metz, D and Smit, AC and Sprangers, MAG and Terhorst, Y and Riper, H}, title = {Beyond the current state of just-in-time adaptive interventions in mental health: a qualitative systematic review.}, journal = {Frontiers in digital health}, volume = {7}, number = {}, pages = {1460167}, pmid = {39935463}, issn = {2673-253X}, abstract = {BACKGROUND: Just-In-Time Adaptive Interventions (JITAIs) are interventions designed to deliver timely tailored support by adjusting to changes in users' internal states and external contexts. To accomplish this, JITAIs often apply complex analytic techniques, such as machine learning or Bayesian algorithms to real- or near-time data acquired from smartphones and other sensors. Given the idiosyncratic, dynamic, and context dependent nature of mental health symptoms, JITAIs hold promise for mental health. However, the development of JITAIs is still in the early stages and is complex due to the multifactorial nature of JITAIs. Considering this complexity, Nahum-Shani et al. developed a conceptual framework for developing and testing JITAIs for health-related problems. This review evaluates the current state of JITAIs in the field of mental health including their alignment with Nahum-Shani et al.'s framework.<br><br>METHODS: Nine databases were systematically searched in August 2023. Protocol or empirical studies self-identifying their intervention as a "JITAI" targeting mental health were included in the qualitative synthesis if they were published in peer-reviewed journals and written in English.<br><br>RESULTS: Of the 1,419 records initially screened, 9 papers reporting on 5 JITAIs were included (sample size range: 5 to an expected 264). Two JITAIs were for bulimia nervosa, one for depression, one for insomnia, and one for maternal prenatal stress. Although most core components of Nahum-Shani's et al.'s framework were incorporated in the JITAIs, essential elements (e.g., adaptivity and receptivity) within the core components were missing and the core components were only partly substantiated by empirical evidence (e.g., interventions were supported, but the decision rules and points were not). Complex analytical techniques such as data from passive monitoring of individuals' states and contexts were hardly used. Regarding the current state of studies, initial findings on usability, feasibility, and effectiveness appear positive.<br><br>CONCLUSIONS: JITAIs for mental health are still in their early stages of development, with opportunities for improvement in both development and testing. For future development, it is recommended that developers utilize complex analytical techniques that can handle real-or near-time data such as machine learning, passive monitoring, and conduct further research into empirical-based decision rules and points for optimization in terms of enhanced effectiveness and user-engagement.}, }
@article {pmid39934874, year = {2025}, author = {Prananto, K and Cahyadi, S and Lubis, FY and Hinduan, ZR}, title = {Perceived teacher support and student engagement among higher education students - a systematic literature review.}, journal = {BMC psychology}, volume = {13}, number = {1}, pages = {112}, pmid = {39934874}, issn = {2050-7283}, mesh = {Humans ; *Students/psychology ; *Motivation ; *Social Support ; *School Teachers/psychology ; *Academic Success ; Self Efficacy ; Universities ; }, abstract = {BACKGROUND: Research on student engagement has garnered significant interest from educators and practitioners because of its direct impact on academic success and achievement. Engaged students tend to perform better academically and exhibit fewer undesirable study behaviors, thereby enhancing academic outcomes.<br><br>OBJECTIVE: This systematic literature review consolidates research on the impact of perceived teacher support on student engagement in higher education. This study emphasizes the association between teacher support in improving students' academic performance, motivation, and retention. Furthermore, the review explores key theoretical frameworks, such as self-determination theory and social cognitive theory, alongside methodological tools such as measurement instruments and statistical analyses. The goal is to equip psychologists and educational researchers with insights into the relevant frameworks, tools, and methods for advancing future studies within the context of higher education.<br><br>METHODS: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. We conducted a comprehensive search for academic studies published in English within databases such as APA PsycNet, Scopus, ERIC, EBSCOHost, ProQuest, and PubMed to identify eligible studies published between 2014 and 2024.<br><br>RESULTS: A review of 13 selected articles revealed that both students' personal characteristics and school environment factors mediate and moderate the relationship between perceived teacher support and student engagement. The students' personal characteristics factors include self-efficacy, the fulfillment of psychological needs, and motivation, whereas school environment factors involve the learning environment and the quality of teacher-student and peer relationships. Our findings show a lack of studies prior to 2020, with most research conducted in China and limited contributions from Malaysia and Vietnam. The reviewed articles predominantly used cross-sectional quantitative designs and self-report questionnaires, employing statistical methods like path analysis and structural equation modeling. Theoretical frameworks on student engagement mostly followed Fredricks et al.'s model, while teacher support theories varied, with three main patterns identified: direct influence, mediation through basic psychological needs, and social cognitive perspectives. This review emphasizes the crucial role of teacher support in enhancing student engagement in higher education and urges further exploration in this under-researched area.<br><br>CONCLUSION: In conclusion, this review underscores the significant role of teacher support in enhancing student engagement in higher education. It highlights key theoretical frameworks and research methodologies, offering valuable insights for future studies aimed at advancing teacher support and student engagement in this context.}, }
@article {pmid39933444, year = {2025}, author = {Rob, M and Yousef, M and Lakshmanan, AP and Mahboob, A and Terranegra, A and Chaari, A}, title = {Microbial signatures and therapeutic strategies in neurodegenerative diseases.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {184}, number = {}, pages = {117905}, doi = {10.1016/j.biopha.2025.117905}, pmid = {39933444}, issn = {1950-6007}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Neurodegenerative Diseases/microbiology/therapy/metabolism ; Animals ; Dysbiosis ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Metabolome ; }, abstract = {Neurodegenerative diseases (NDs), including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS), arise from complex interactions between genetic factors, environmental exposures, and aging. Additionally, gut dysbiosis has been linked to systemic inflammation and neurodegeneration. Advances in microbiome and metabolome profiling techniques have provided deeper insights into how alterations in gut microbiota and dietary patterns affect metabolic pathways and contribute to the progression of NDs. This review explores the profiles of gut microbiome and metabolome derived biomarkers and their roles in NDs. Across phyla, families, and genera, we identified 55 microbial alterations in PD, 24 in AD, 4 in ALS, and 17 in MS. Some notable results include an increase in Akkermansia in PD, AD, and MS and a decrease in short-chain fatty acids (SCFAs) in PD and AD. We examined the effects of probiotics, prebiotics, fecal microbiota transplants (FMT), sleep, exercise, and diet on the microbiota, all of which contributed to delayed onset and alleviation of symptoms. Further, artificial intelligence (AI) and machine learning (ML) algorithms applied to omics data have been crucial in identifying novel therapeutic targets, diagnosing and predicting prognosis, and enabling personalized medicine using microbiota-modulating therapies in NDs patients.}, }
@article {pmid39933302, year = {2025}, author = {Li, H and Qiao, Z and Xiao, X and Cao, X and Li, Z and Liu, M and Jiao, Q and Chen, X and Du, X and Jiang, H}, title = {G protein-coupled receptors: A golden key to the treasure-trove of neurodegenerative diseases.}, journal = {Clinical nutrition (Edinburgh, Scotland)}, volume = {46}, number = {}, pages = {155-168}, doi = {10.1016/j.clnu.2025.01.032}, pmid = {39933302}, issn = {1532-1983}, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Receptors, G-Protein-Coupled/metabolism ; Signal Transduction ; Animals ; }, abstract = {G protein-coupled receptors (GPCRs) are a class of transmembrane proteins that distribute in various organs extensively. They can regulate physiological functions such as perception, neurotransmission and endocrinology through the synergies of signaling pathways. At present, Food and Drug Administration (FDA) have approved more than 500 drugs targeting GPCRs to treat a variety of conditions, including neurological diseases, gastrointestinal diseases and tumors. Conformational diversity and dynamic changes make GPCRs a star target for the treatment of neurodegenerative diseases. Moreover, GPCRs can also open biased signaling pathways for G protein and β-arrestin, which has unique functional selectivity and the possibility of overcoming side effects. Some studies believe that biased drugs will be the mainstream direction of drug innovation in the future. To disclose the essential role and research process of GPCRs in neurodegenerative diseases, we firstly reviewed several pivotal GPCRs and their mediated signaling pathways in Alzheimer's disease (AD), Parkinson's disease (PD) and Amyotrophic lateral sclerosis (ALS). Then we focused on the biased signaling pathway of GPCRs in these diseases. Finally, we updated the GPCR drugs under research for the treatment of neurodegenerative diseases in the clinical trials or approval. This review could provide valuable targets for precision therapy to cope with the dysfunction of neurodegenerative diseases in the future.}, }
@article {pmid39929585, year = {2025}, author = {Huang, M and Stremlau, M and Zavras, J and Zivko, C and Thomas, AG and Pietri, P and Machairaki, V and Slusher, BS}, title = {Neutral sphingomyelinase 2: A promising drug target for CNS disease.}, journal = {Advances in pharmacology (San Diego, Calif.)}, volume = {102}, number = {}, pages = {65-101}, pmid = {39929585}, issn = {1557-8925}, support = {P30 MH075673/MH/NIMH NIH HHS/United States ; R01 AG063831/AG/NIA NIH HHS/United States ; R01 AG084728/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Sphingomyelin Phosphodiesterase/metabolism/antagonists &amp; inhibitors ; Animals ; *Central Nervous System Diseases/drug therapy/enzymology/metabolism ; *Enzyme Inhibitors/pharmacology/therapeutic use ; }, abstract = {Neutral sphingomyelinase 2 (nSMase2), encoded by the SMPD3 gene, is a pivotal enzyme in sphingolipid metabolism, hydrolyzing sphingomyelin to produce ceramide, a bioactive lipid involved in apoptosis, inflammation, membrane structure, and extracellular vesicle (EV) biogenesis. nSMase2 is abundantly expressed in the central nervous system (CNS), particularly in neurons, and its dysregulation is implicated in pathologies such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), prion diseases, and neuroviral diseases. In this review, we discuss the critical role of nSMase2 in the CNS and its involvement in neurological as well as non-neurological diseases. We explore the enzyme's functions in sphingolipid metabolism, its regulatory mechanisms, and the implications of its dysregulation in disease pathogenesis. The chapter highlights the therapeutic potential of pharmacologically targeting nSMase2 with small molecule inhibitors and emphasizes the need for further research to optimize inhibitor specificity and efficacy for clinical applications. By understanding the multifaceted roles of nSMase2, we aim to provide insights into novel therapeutic strategies for treating complex diseases associated with its dysregulation.}, }
@article {pmid39929580, year = {2025}, author = {Matheoudakis, K and O'Connor, JJ}, title = {Modulatory and protective effects of prolyl hydroxylase domain inhibitors in the central nervous system.}, journal = {Advances in pharmacology (San Diego, Calif.)}, volume = {102}, number = {}, pages = {211-235}, doi = {10.1016/bs.apha.2024.10.006}, pmid = {39929580}, issn = {1557-8925}, mesh = {Humans ; Animals ; *Prolyl-Hydroxylase Inhibitors/pharmacology/therapeutic use ; *Neuroprotective Agents/pharmacology/therapeutic use ; *Central Nervous System/drug effects/metabolism ; }, abstract = {Oxygen is essential for all mammalian species, with complex organs such as the brain requiring a large and steady supply to function. During times of low or inadequate oxygen supply (hypoxia), adaptation is required in order to continue to function. Hypoxia inducible factors (HIF) are transcription factors which are activated during hypoxia and upregulate protective genes. Normally, when oxygen levels are sufficient (normoxia) HIFs are degraded by oxygen sensing prolyl hydroxylase domain proteins (PHD), but during hypoxia PHDs no longer exert influence on HIFs allowing their activation. Given that PHDs regulate the activity of HIFs, their pharmacological inhibition through PHD inhibitors (PHDIs) is believed to be the basis of their neuroprotective benefits. This review discusses some of the potential therapeutic benefits of PHDIs in a number of neurological disorders which see hypoxia as a major pathophysiological mechanism. These include stroke, Parkinson's disease, and amyotrophic lateral sclerosis. We also explore the potential neuroprotective benefits and limitations of PHDIs in a variety of disorders in the central nervous system (CNS). Additionally, the activation of HIFs by PHDIs can have modulatory effects on CNS functions such as neurotransmission and synaptic plasticity, mechanisms critical to cognitive processes such as learning and memory.}, }
@article {pmid39928236, year = {2025}, author = {Kaspute, G and Ramanavicius, A and Prentice, U}, title = {Natural drug delivery systems for the treatment of neurodegenerative diseases.}, journal = {Molecular biology reports}, volume = {52}, number = {1}, pages = {217}, pmid = {39928236}, issn = {1573-4978}, support = {S-MIP-24-111//Research Council of Lithuania (LMTLT)/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy ; *Drug Delivery Systems/methods ; Blood-Brain Barrier/metabolism/drug effects ; Animals ; *Biological Products/therapeutic use/administration &amp; dosage ; Nanoparticles/chemistry ; Liposomes ; Anti-Inflammatory Agents ; Biological Availability ; }, abstract = {Today, herbal drugs are prominent in the pharmaceutical industry due to their well-known therapeutic and side effects. Plant-based compounds often face limitations such as poor solubility, low bioavailability, and instability in physiological environments, restricting their therapeutic efficacy and delivery. Nanotechnology-based solutions, including nanoparticle formulations and advanced delivery systems like liposomes and transfersomes, address these issues by enhancing solubility, stability, bioavailability, and targeted delivery, thereby optimizing the therapeutic potential of phytoactive compounds. Neuroinflammation can be a cause of neurodegenerative disorders such as Alzheimer's and Parkinson's diseases, or amyotrophic lateral sclerosis. Consequently, there is a need for the optimal delivery of a pharmacological anti-inflammatory agents to the CNS. Thus, the non-invasive administration of a stable compound at a therapeutic concentration is needed to assure molecule crossing through the blood-brain barrier. Natural resources have more structural diversity and novelty than synthetic compounds, e.g. plant-derived drug products have higher molecular weights, incorporate more oxygen atoms, and are more complex. As a result, plant-derived products have unique features which can be used to effectively modulate neuroinflammation. Therefore, this review aims to identify herbal molecules capable of targeting neuroinflammation and present novel strategies for their efficient delivery.}, }
@article {pmid39924298, year = {2025}, author = {Malouin-Lachance, A and Capolupo, J and Laplante, C and Hudon, A}, title = {Does the Digital Therapeutic Alliance Exist? Integrative Review.}, journal = {JMIR mental health}, volume = {12}, number = {}, pages = {e69294}, pmid = {39924298}, issn = {2368-7959}, mesh = {Humans ; *Digital Health ; *Mental Disorders/therapy ; *Artificial Intelligence ; *Psychotherapy/methods ; *Therapeutic Alliance ; }, abstract = {BACKGROUND: Mental health disorders significantly impact global populations, prompting the rise of digital mental health interventions, such as artificial intelligence (AI)-powered chatbots, to address gaps in access to care. This review explores the potential for a "digital therapeutic alliance (DTA)," emphasizing empathy, engagement, and alignment with traditional therapeutic principles to enhance user outcomes.<br><br>OBJECTIVE: The primary objective of this review was to identify key concepts underlying the DTA in AI-driven psychotherapeutic interventions for mental health. The secondary objective was to propose an initial definition of the DTA based on these identified concepts.<br><br>METHODS: The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) for scoping reviews and Tavares de Souza's integrative review methodology were followed, encompassing systematic literature searches in Medline, Web of Science, PsycNet, and Google Scholar. Data from eligible studies were extracted and analyzed using Horvath et al's conceptual framework on a therapeutic alliance, focusing on goal alignment, task agreement, and the therapeutic bond, with quality assessed using the Newcastle-Ottawa Scale and Cochrane Risk of Bias Tool.<br><br>RESULTS: A total of 28 studies were identified from an initial pool of 1294 articles after excluding duplicates and ineligible studies. These studies informed the development of a conceptual framework for a DTA, encompassing key elements such as goal alignment, task agreement, therapeutic bond, user engagement, and the facilitators and barriers affecting therapeutic outcomes. The interventions primarily focused on AI-powered chatbots, digital psychotherapy, and other digital tools.<br><br>CONCLUSIONS: The findings of this integrative review provide a foundational framework for the concept of a DTA and report its potential to replicate key therapeutic mechanisms such as empathy, trust, and collaboration in AI-driven psychotherapeutic tools. While the DTA shows promise in enhancing accessibility and engagement in mental health care, further research and innovation are needed to address challenges such as personalization, ethical concerns, and long-term impact.}, }
@article {pmid39923277, year = {2025}, author = {Hall, S and Koslouski, JB and Richter, CG and Chafouleas, SM}, title = {Measures of emotional well-being for individuals with intellectual disabilities: A scoping review of reviews.}, journal = {Research in developmental disabilities}, volume = {158}, number = {}, pages = {104940}, pmid = {39923277}, issn = {1873-3379}, support = {U24 AT011281/AT/NCCIH NIH HHS/United States ; }, mesh = {Humans ; *Intellectual Disability/psychology ; *Quality of Life/psychology ; *Emotions ; }, abstract = {OBJECTIVE: This scoping review of reviews examines how one facet of quality of life, emotional well-being (EWB), has been assessed for individuals with intellectual disabilities (ID), including the characteristics of measures that have been designed, adapted, or administered to individuals in this population.<br><br>METHODS: Following established practices for scoping reviews, we searched the ERIC, APA Psych Info, and Academic Search Premier databases in November 2022 for review articles that included measures of EWB that had been designed, adapted, or administered to individuals with ID. Following PRISMA guidelines, we conducted independent double coding at the title and abstract and full text review stages. From each included review article, we extracted the review's purpose, EWB-related construct of interest, and EWB-related measure names and authors. We then located each measure and coded its items using Park et al.'s (2023) definition of EWB. We also coded the "non-EWB" domains assessed by these measures. We used the PRISMA Extension for Scoping Reviews (PRISMA-Scr) checklist to structure our manuscript.<br><br>RESULTS: The scoping review identified 10 review articles that included 14 unique measures of EWB. Each of these measures included at least 1 item (M = 2.8) that assessed EWB. Quality of life was the most common EWB-related construct specified by review articles. Measures frequently assessed additional constructs beyond EWB, including self-determination, interpersonal relations, physical well-being, and material well-being.<br><br>CONCLUSIONS: In measures designed or adapted for individuals with ID, EWB is often included as a subcomponent of quality of life. Because of EWB's link to positive social, emotional, behavioral, and health outcomes, research is needed to identify the most salient components of EWB for individuals with ID. This would allow for measures and interventions to be developed to promote EWB in this population.<br><br>WHAT THIS PAPER ADDS: This study provides a scoping review of available measures of EWB that have been designed, adapted, or administered to individuals with ID. Study findings detail the characteristics of these measures, highlighting gaps in available EWB measures for children and adolescents with ID. We also found that emotional well-being is frequently assessed as a component of a broader construct (e.g., quality of life) using a small number of items. This suggests a need and opportunity for growth in further understanding emotional well-being assessment in individuals with ID.}, }
@article {pmid39922366, year = {2025}, author = {Kopalli, SR and Behl, T and Kyada, A and Rekha, MM and Kundlas, M and Rani, P and Nathiya, D and Satyam Naidu, K and Gulati, M and Bhise, M and Gupta, P and Wal, P and Fareed, M and Ramniwas, S and Koppula, S and Gasmi, A}, title = {Synaptic plasticity and neuroprotection: The molecular impact of flavonoids on neurodegenerative disease progression.}, journal = {Neuroscience}, volume = {569}, number = {}, pages = {161-183}, doi = {10.1016/j.neuroscience.2025.02.007}, pmid = {39922366}, issn = {1873-7544}, mesh = {Humans ; *Neuronal Plasticity/drug effects/physiology ; *Flavonoids/pharmacology/therapeutic use ; Animals ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Neuroprotective Agents/pharmacology/therapeutic use ; *Neuroprotection/drug effects/physiology ; Signal Transduction/drug effects ; Disease Progression ; }, abstract = {Flavonoids are a broad family of polyphenolic chemicals that are present in a wide variety of fruits, vegetables, and medicinal plants. Because of their neuroprotective qualities, flavonoids have attracted a lot of interest. The potential of flavonoids to control synaptic plasticity-a crucial process underlying memory, learning, and cognitive function-is becoming more and more clear. Dysregulation of synaptic plasticity is a feature of neurodegenerative diseases such as amyotrophic lateral sclerosis (0.4 %), Parkinson's (1-2 %), Alzheimer's (5-7 %), and Huntington's ((0.2 %)). This review discusses the molecular mechanisms via which flavonoids influence synaptic plasticity as well as their therapeutic potential in neurodegenerative diseases. Flavonoids modulate key signaling pathways such as MAPK/ERK and PI3K/Akt/mTOR to support neuroprotection, synaptic plasticity, and neuronal health, while also influencing neurotrophic factors (BDNF, NGF) and their receptors (TrkB, TrkA). They regulate neurotransmitter receptors like GABA, AMPA, and NMDA to balance excitatory and inhibitory transmission, and exert antioxidant effects via the Nrf2-ARE pathway and anti-inflammatory actions by inhibiting NF-κB signaling, highlighting their potential for treating neurodegenerative diseases. These varied reactions support the preservation of synapse function and neuronal integrity in the face of neurodegenerative insults. Flavonoids can reduce the symptoms of neurodegeneration, prevent synaptic loss, and enhance cognitive function, according to experimental studies. However, there are still obstacles to using these findings in clinical settings, such as limited bioavailability and the need for consistent dose. The focus of future research should be on improving flavonoid delivery systems and combining them with conventional medications.}, }
@article {pmid39915896, year = {2025}, author = {Wassef, K and Ma, K and Durieux, BN and Brown, TL and Paladino, J and Thorne, S and Sanders, JJ}, title = {Measuring the quality of patient-provider relationships in serious illness: A scoping review.}, journal = {Palliative medicine}, volume = {39}, number = {3}, pages = {332-345}, pmid = {39915896}, issn = {1477-030X}, mesh = {Humans ; *Critical Illness/psychology ; *Professional-Patient Relations ; Male ; Female ; *Quality of Health Care/standards ; *Physician-Patient Relations ; Middle Aged ; }, abstract = {BACKGROUND: People affected by serious illness face several threats to their well-being: physical symptoms, psychological distress, disrupted social relations, and spiritual/existential crises. Relationships with clinicians provide a form of structured support that promotes shared decision-making and adaptive stress coping. Measuring relationship quality may improve quality assessment and patient care outcomes. However, researchers and those promoting quality improvement lack clear guidance on measuring this.<br><br>AIM: To identify and assess items from valid measures of patient-provider relationship quality in serious illness settings for guiding quality assessment.<br><br>DESIGN: Scoping review.<br><br>DATA SOURCES: We identified peer-reviewed, English-language articles published from 1990 to 2023 in CINAHL, Embase, and PubMed. Eligible articles described the validation of measures assessing healthcare experiences of patient populations characterized by serious illness. We used Clarke et al.'s theory of relationship quality to assess relationship-focused items.<br><br>RESULTS: From 3868 screened articles, we identified 101 publications describing 47 valid measures used in serious illness settings. Measures assessed patients and other caregivers. We determined that 597 of 2238 items (26.7%) related to relationships. Most measures (n&#x2009;=&#x2009;46) included items related to engaging the patient as a whole person. Measures evaluated how providers promote information exchange (n&#x2009;=&#x2009;35), foster therapeutic alliance (n&#x2009;=&#x2009;35), recognize and respond to emotion (n&#x2009;=&#x2009;27), and include patients in care-related decisions (n&#x2009;=&#x2009;23). Few instruments (n&#x2009;=&#x2009;9) assessed patient self-management and navigation.<br><br>CONCLUSIONS: Measures include items that assess patient-provider relationship quality in serious illness settings. Researchers may consider these for evaluating and improving relationship quality, a patient-centered care and research outcome.}, }
@article {pmid39910731, year = {2025}, author = {Singh, S and Khan, S and Khan, S and Ansari, O and Malhotra, N and Shukla, SK and Narang, J}, title = {Muscle Matters: Transforming Amyotrophic Lateral Sclerosis Diagnostics with Next-Gen Biosensors and Smart Detection.}, journal = {ACS chemical neuroscience}, volume = {16}, number = {4}, pages = {563-587}, doi = {10.1021/acschemneuro.4c00664}, pmid = {39910731}, issn = {1948-7193}, mesh = {*Amyotrophic Lateral Sclerosis/diagnosis/physiopathology/genetics ; Humans ; *Biosensing Techniques/methods ; Biomarkers ; Electromyography/methods ; Motor Neurons ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that primarily targets the motor system, causing patients' speech and swallowing ability to rapidly deteriorate. Although ALS is usually classified into familial and sporadic forms, diagnosing it can be extremely difficult due to the absence of definitive biomarkers, often resulting in delays in diagnosis. Current diagnostic practices rely heavily on clinical assessments that indicate damage to both upper motor neurons (UMNs) and lower motor neurons (LMNs). This includes comprehensive physical examinations, electromyography (EMG) to assess neuromuscular function, and the exclusion of other similar conditions such as cervical spondylotic myelopathy, multifocal motor neuropathy, and Kennedy's disease through appropriate diagnostic procedures. The urgent need for specific biomarkers is critical for timely diagnosis and therapeutic advancements in ALS management. While many recent developments in research have not yet translated into direct patient benefits, the recognition of ALS as a complex disease is beginning to influence clinical practice significantly. Optimal management strategies emphasize on symptom control and improving the quality of life for patients within a holistic healthcare framework. This review provides a comprehensive overview of ALS, delving into its pathophysiology, clinical symptoms, and the latest advancements in detection methods that utilize traditional approaches, innovative biosensors, and smart diagnostic technologies. It discusses various treatment options available for ALS while exploring future developments that may enhance patient screening and improve clinical outcomes. By integrating assessments into the underlying mechanisms of the disease with cutting-edge diagnostic approaches, this review aims to contribute meaningfully to ongoing efforts to optimize ALS management and therapeutic strategies, ultimately improving patient care and outcomes.}, }
@article {pmid39908735, year = {2025}, author = {Ghannam, IAY and Hassan, RM and Abdel-Maksoud, MS}, title = {Peroxisome proliferator-activated receptors (PPARs) agonists as promising neurotherapeutics.}, journal = {Bioorganic chemistry}, volume = {156}, number = {}, pages = {108226}, doi = {10.1016/j.bioorg.2025.108226}, pmid = {39908735}, issn = {1090-2120}, mesh = {Humans ; *Peroxisome Proliferator-Activated Receptors/agonists/metabolism ; *Neurodegenerative Diseases/drug therapy ; Animals ; *Neuroprotective Agents/pharmacology/chemistry/chemical synthesis/therapeutic use ; Molecular Structure ; }, abstract = {Neurodegenerative disorders are characterized by a continuous neurons loss resulting in a wide range of pathogenesis affecting the motor impairment. Several strategies are outlined for therapeutics of synthetic and natural PPARs agonists in some neurological disorders; Parkinson's disease (PD), Alzheimer's disease (AD), Multiple sclerosis (MS), Amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD). The aim of this review is to provide a recent update of the previously reported studies, and reviews dealing with the medicinal chemistry of PPARs and their agonists, and to highlight the outstanding advances in the development of both synthetic compounds including; PPARα agonists (fibrates), PPARγ agonists (thiazolidindiones), and PPARβ/δ agonists either as sole or dual acting PPAR full or pan agonists, in addition to the natural phytochemicals; acids, cannabinoids, and flavonoids for their different neuroprotection effects in the previously mentioned neurodegenerative disorders (PD, AD, MS, ALS, and HD). Moreover, this review reports the diverse pre-clinical and clinical studies of PPARs agonists in the neurodegenerative diseases via cellular, and animal models and human.}, }
@article {pmid39908264, year = {2025}, author = {Hobert, MA and Helle, N and Siebert, C and Eisenhauer, A and Gledhill, M and Maetzler, W}, title = {Exploiting the Fractionation of Stable Isotopes in Biochemical Processes for Medical Diagnosis: A Narrative Review.}, journal = {Aging and disease}, volume = {}, number = {}, pages = {}, doi = {10.14336/AD.2024.1577}, pmid = {39908264}, issn = {2152-5250}, abstract = {Analysis of isotope distributions plays a crucial role in medical diagnostics. While radioactive and radiogenic isotopes - those that undergo or result from radioactive decay - are widely used, stable isotopes are less commonly applied despite their significant diagnostic potential. For example, calcium isotope ratio analysis is already commercially utilized for calcium loss and the early diagnosis of osteoporosis. Additionally, analyses of iron, copper, and zinc isotope ratios have been explored in various conditions, including hemochromatosis, Wilson's disease, cancer, Alzheimer's disease, and amyotrophic lateral sclerosis. Altered isotope ratios in these diseases are thought to reflect pathophysiologically relevant processes, making them promising biomarkers. This review provides a comprehensive overview of the current and potential applications of stable isotope analysis in medicine.}, }
@article {pmid39907139, year = {2025}, author = {Matera, AG}, title = {Chaperone dysfunction in motor neuron disease: new insights from studies of the SMN complex.}, journal = {Genetics}, volume = {229}, number = {3}, pages = {}, pmid = {39907139}, issn = {1943-2631}, support = {R35 GM136435/GM/NIGMS NIH HHS/United States ; //USA National Institutes of Health/ ; }, mesh = {Humans ; Muscular Atrophy, Spinal/genetics/metabolism ; Amyotrophic Lateral Sclerosis/genetics/metabolism ; *SMN Complex Proteins/metabolism/genetics ; *Molecular Chaperones/metabolism/genetics ; Animals ; *Motor Neuron Disease/genetics/metabolism ; Motor Neurons/metabolism ; }, abstract = {Spinal muscular atrophy and amyotrophic lateral sclerosis are devastating neurodegenerative diseases characterized by motor neuron loss. Although these 2 disorders have distinct genetic origins, recent studies suggest that they share common etiological mechanisms rooted in proteostatic dysfunction. At the heart of this emerging understanding is the survival motor neuron (SMN) complex.}, }
@article {pmid39901378, year = {2025}, author = {San Gil, R and Walker, AK}, title = {Unlocking Disease-Modifying Treatments for TDP-43-Mediated Neurodegeneration.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {47}, number = {4}, pages = {e202400257}, pmid = {39901378}, issn = {1521-1878}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics/therapy ; *DNA-Binding Proteins/metabolism/genetics ; *Frontotemporal Dementia/metabolism/pathology/genetics/therapy ; Animals ; *Neurodegenerative Diseases/metabolism ; }, abstract = {Neurons degenerate in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), causing progressive and inevitably fatal neurological decline. The best therapeutic strategies target underlying disease mediators, but after decades of intensive research, the causes of these neurodegenerative diseases remain elusive. Recently, coordinated activities of large consortia, increasing open access to large datasets, new methods such as cryo-transmission electron microscopy, and advancements in high-resolution omics technologies have offered new insights into the biology of disease that bring us closer to understanding mechanisms of neurodegeneration. In particular, improved understanding of the roles of the key pathological protein TAR DNA binding protein 43 (TDP-43) in disease has revealed intriguing new opportunities that provide hope for better diagnostic tools and effective treatments for ALS and FTD.}, }
@article {pmid39901141, year = {2025}, author = {O'Connor, H and Meloncelli, N and Wilkinson, SA and Scott, AM and Vincze, L and Rushton, A and Dawson, S and Hollis, J and Whiteoak, B and Gauci, S and de Jersey, S}, title = {Effective dietary interventions during pregnancy: a systematic review and meta-analysis of behavior change techniques to promote healthy eating.}, journal = {BMC pregnancy and childbirth}, volume = {25}, number = {1}, pages = {112}, pmid = {39901141}, issn = {1471-2393}, mesh = {Humans ; Female ; Pregnancy ; *Diet, Healthy/methods ; *Behavior Therapy/methods ; Randomized Controlled Trials as Topic ; *Prenatal Care/methods ; *Health Promotion/methods ; Feeding Behavior ; }, abstract = {Improving dietary intake during pregnancy can mitigate adverse consequences for women and their children. The effective techniques and features for supporting and sustaining dietary change during pregnancy and postpartum are minimally reported. The primary aims of this systematic review and meta-analysis were to summarise the effectiveness of dietary interventions for pregnant woman, identify which behaviour change techniques (BCTs) and intervention features were most frequently used and determine which were most effective at improving dietary intake. Six databases were searched to identify randomised control trials (RCTs) reporting on dietary intake in pregnant women over the age of sixteen, with an active intervention group compared to a control group receiving usual care or less intensive interventions. The Cochrane Risk of Bias Tool 1 was used to assess study validity. BCTs were coded by two authors using Michie et al.'s BCT taxonomy V1. A random effect model assessed intervention effects on indices of dietary quality and food groups (fruit, vegetables, grains and cereals, meat, and dairy) in relation to the use of BCTs and intervention features. Thirty- seven RCTs met the inclusion criteria. High heterogeneity was observed across intervention characteristics and measures of fidelity. Only half of the available BCTs were used, with eleven used once. The BCT category Reward and threat was successful in improving dietary quality and vegetable intake, whilst 'Action planning' (1.4) from the category Goals and planning significantly improved dietary quality. Interventions delivered by a nutrition professional and those that included group sessions improved dietary quality more than those delivered by other health professionals, research staff, or application-delivered interventions and delivered via other modalities. Future dietary interventions during pregnancy should incorporate and report on BCTs used in the intervention. Successful design elements for improving antenatal dietary intake may include multimodal interventions delivered by nutrition professionals and the use of Rewards and Goal setting.}, }
@article {pmid39899435, year = {2025}, author = {Blake, J and Peryer, G and Dance, R and Parke, S and Aryankhesal, A and Farquhar, M}, title = {How can healthcare professionals work with families to address misaligned expectations of recovery in brain injury rehabilitation? A scoping review.}, journal = {Brain injury}, volume = {39}, number = {7}, pages = {551-564}, doi = {10.1080/02699052.2025.2450603}, pmid = {39899435}, issn = {1362-301X}, mesh = {Humans ; *Brain Injuries/rehabilitation/psychology ; *Health Personnel/psychology ; *Family/psychology ; *Professional-Family Relations ; Recovery of Function ; }, abstract = {INTRODUCTION: Most survivors of severe acquired brain injuries will have significant long-term disability. During inpatient rehabilitation, families often have expectations of recovery that do not match healthcare professional opinion. This impacts on patient care, service processes, professional-family relations, and wellbeing. This review aimed to understand how family expectations are managed in this setting, and to explore potential areas of improvement.<br><br>METHOD: A scoping review was conducted by searching CINAHL, Medline, EMBASE and Web of Science. Krieger et al's 'Conceptual Building Blocks' provided a framework to analyze the data using a 'best fit' framework synthesis approach.<br><br>RESULTS: Twenty-one papers were included in the review. Six sub-themes within three overarching themes were generated, which explored recommendations for effective expectation management. The sub-themes within the 'staff behaviors' theme were 'appropriate information provision,' 'open communication' and 'prioritize family.' Sub-themes within 'system behaviors' were 'cultural change' and 'increased resource.' 'Rehabilitation as a shared process' was the third theme.<br><br>DISCUSSION: Misaligned expectations of recovery appear to reflect a range of unmet family needs related to their position within the healthcare hierarchy, professional-family communication, and their involvement in rehabilitation processes. Early identification of family and healthcare professional expectations alongside regular review may prevent misunderstanding and conflict.}, }
@article {pmid39898689, year = {2025}, author = {Farrell, S and Mills, TA and Lavender, DT}, title = {Exploring parental knowledge, care-seeking, and support strategies for neonatal illness: an integrative review of the African Great Lakes region.}, journal = {Global health action}, volume = {18}, number = {1}, pages = {2450137}, pmid = {39898689}, issn = {1654-9880}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; *Health Knowledge, Attitudes, Practice ; *Parents/psychology ; Infant, Newborn ; *Patient Acceptance of Health Care ; Africa South of the Sahara ; *Infant, Newborn, Diseases/therapy ; Female ; Socioeconomic Factors ; }, abstract = {BACKGROUND: Sub-Saharan Africa shoulders much of the global burden of neonatal mortality. Quality postnatal care is often lacking due to availability, accessibility, mistrust of health systems, and socio-economic barriers, yet delays in care-seeking contribute to avoidable neonatal deaths. Research highlights the urgent need for improved health education about neonatal illness; however, contextual factors are rarely considered, and few interventions have been implemented.<br><br>OBJECTIVES: To critically examine the literature on parents' knowledge of neonatal illness and care-seeking behaviour and evaluate interventions supporting parental understanding in sub-Saharan African Great Lakes countries.<br><br>METHODS: Systematic searches were conducted in CINAHL, MEDLINE, Global Health, the Cochrane Library, and thesis repositories. Studies meeting inclusion criteria were critically analysed using Whittemore and Knafl's framework, and quality was assessed with Hawker et al.'s tool, following PRISMA guidelines.<br><br>RESULTS: Seventy studies (48 quantitative, 14 qualitative, eight mixed methods) were reviewed. The first theme, "poor knowledge of neonatal illness", showed parents struggled to recognise illness, with knowledge affected by maternity and socio-economic factors. The second theme, "sub-optimal healthcare-seeking behaviour", highlighted delayed care-seeking due to cultural, social, and economic factors. Finally, "strategies to support parents' understanding" emphasised the roles of community workers, health education phone calls, SMS, and videos, and neonatal monitoring systems.<br><br>CONCLUSIONS: Parental knowledge of neonatal illness is generally low, and care-seeking is influenced by beliefs, trust in healthcare, and logistical challenges. While community health workers and multi-media interventions appear effective, health education efforts must address contextual barriers and beliefs to improve recognition and care-seeking for neonatal illness.}, }
@article {pmid39897290, year = {2025}, author = {McBenedict, B and Hauwanga, WN and Nezam, U and Ko Oo, A and Eapi, S and Pradhan, S and Dang, NB and Cher, PW and Orsini, MA and Lima Pessôa, B}, title = {Amyotrophic Lateral Sclerosis (ALS) Type 8: A Narrative Review.}, journal = {Cureus}, volume = {17}, number = {1}, pages = {e76717}, pmid = {39897290}, issn = {2168-8184}, abstract = {Amyotrophic lateral sclerosis type 8 (ALS8) is a rare familial subtype of ALS caused by mutations in the vesicle-associated membrane protein-associated protein B (VAPB) gene, particularly the p.P56S mutation. It is distinguished by slower disease progression and an earlier onset compared to sporadic ALS forms, along with unique clinical features such as severe cramping, fasciculations, postural tremors, and cognitive and behavioral impairments. Although current pharmacological options, such as riluzole, edaravone, and sodium phenylbutyrate/taurursodiol, provide modest benefits, they fail to address the underlying genetic mechanisms of ALS8. Emerging gene therapies, RNA-based interventions, and stem cell approaches hold promise for precision-targeted treatments but face challenges in clinical application. Symptom management strategies, including respiratory, nutritional, and psychological support, are crucial for improving patient outcomes and quality of life. Despite significant progress in understanding the genetic and molecular pathogenesis of ALS8, its rarity, phenotypic variability, and limited clinical data pose challenges to therapeutic advancements. This narrative review highlights current therapeutic strategies, the unique clinical trajectory of ALS8, and potential pathways for innovative, subtype-specific interventions, emphasizing the need for multidisciplinary and targeted approaches to optimize care for this distinct ALS subtype.}, }
@article {pmid39894843, year = {2025}, author = {Chen, L and Shen, Q and Liu, Y and Zhang, Y and Sun, L and Ma, X and Song, N and Xie, J}, title = {Homeostasis and metabolism of iron and other metal ions in neurodegenerative diseases.}, journal = {Signal transduction and targeted therapy}, volume = {10}, number = {1}, pages = {31}, pmid = {39894843}, issn = {2059-3635}, support = {32471049//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32170984//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32200802//National Natural Science Foundation of China (National Science Foundation of China)/ ; ZR2020YQ23//Natural Science Foundation of Shandong Province (Shandong Provincial Natural Science Foundation)/ ; ZR2024MC153//Natural Science Foundation of Shandong Province (Shandong Provincial Natural Science Foundation)/ ; }, mesh = {Humans ; *Iron/metabolism ; *Neurodegenerative Diseases/metabolism/drug therapy/pathology/genetics ; *Homeostasis ; Zinc/metabolism ; Copper/metabolism ; Animals ; Parkinson Disease/metabolism/genetics/drug therapy/pathology ; Alzheimer Disease/metabolism/genetics/drug therapy/pathology ; Manganese/metabolism ; Oxidative Stress ; Chelating Agents/therapeutic use ; }, abstract = {As essential micronutrients, metal ions such as iron, manganese, copper, and zinc, are required for a wide range of physiological processes in the brain. However, an imbalance in metal ions, whether excessive or insufficient, is detrimental and can contribute to neuronal death through oxidative stress, ferroptosis, cuproptosis, cell senescence, or neuroinflammation. These processes have been found to be involved in the pathological mechanisms of neurodegenerative diseases. In this review, the research history and milestone events of studying metal ions, including iron, manganese, copper, and zinc in neurodegenerative diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD), will be introduced. Then, the upstream regulators, downstream effector, and crosstalk of mental ions under both physiologic and pathologic conditions will be summarized. Finally, the therapeutic effects of metal ion chelators, such as clioquinol, quercetin, curcumin, coumarin, and their derivatives for the treatment of neurodegenerative diseases will be discussed. Additionally, the promising results and limitations observed in clinical trials of these metal ion chelators will also be addressed. This review will not only provide a comprehensive understanding of the role of metal ions in disease development but also offer perspectives on their modulation for the prevention or treatment of neurodegenerative diseases.}, }
@article {pmid39889542, year = {2025}, author = {Albrecht, F and Kvist, A and Franzén, E}, title = {Resting-state functional near-infrared spectroscopy in neurodegenerative diseases - A systematic review.}, journal = {NeuroImage. Clinical}, volume = {45}, number = {}, pages = {103733}, pmid = {39889542}, issn = {2213-1582}, mesh = {Humans ; Spectroscopy, Near-Infrared/methods ; *Neurodegenerative Diseases/diagnostic imaging/physiopathology ; *Brain/diagnostic imaging/physiopathology ; Rest/physiology ; *Functional Neuroimaging/methods ; }, abstract = {OBJECTIVE: To systematically review and summarize alterations found in resting-state activity as measured via functional near-infrared spectroscopy (fNIRS) in neurodegenerative diseases.<br><br>BACKGROUND: fNIRS is a novel and emerging neuroimaging method suitable for a variety of study designs. Resting-state is the measure of brain activity in the absence of a task, which has been investigated for yielding information about neurodegenerative diseases, mainly using magnetic resonance imaging. We aimed to systematically review the usage of resting-state fNIRS (rsfNIRS) in neurodegenerative diseases.<br><br>INCLUSION CRITERIA: Studies investigating people diagnosed with a neurodegenerative disease and resting-state activity obtained with fNIRS using at least two channels.<br><br>METHODS: We searched three databases for publications. After the screening, 16 studies were included in the systematic review. The quality of the studies was assessed, and data were extracted. Data were qualitatively synthesized and in the case of at least 10 similar studies, a meta-analysis was planned.<br><br>RESULTS: Most studies investigated Mild cognitive impairment (50%), followed by Alzheimer's disease (25%). Other neurodegenerative diseases encompassed Parkinson's disease, Multiple sclerosis, and Amyotrophic lateral sclerosis. All studies reported oxygenated hemoglobin. Still, studies were heterogeneous in terms of study design, measurement duration, fNIRS device, montage, pre-processing, and analyses. A meta-analysis was not considered possible due to this heterogeneity.<br><br>CONCLUSION: rsfNIRS shows promise in neurodegenerative disease, as most studies have observed resting-state alterations when compared to healthy controls. However, inconsistencies across studies limit data comparison and meta-analysis. Hence, we strongly advocate the application of fNIRS reporting guidelines and the establishment of rsfNIRS-specific guidelines. This will ensure reliable and comparable results in future research.}, }
@article {pmid39880333, year = {2025}, author = {Izrael, M and Chebath, J and Molakandov, K and Revel, M}, title = {Clinical perspective on pluripotent stem cells derived cell therapies for the treatment of neurodegenerative diseases.}, journal = {Advanced drug delivery reviews}, volume = {218}, number = {}, pages = {115525}, doi = {10.1016/j.addr.2025.115525}, pmid = {39880333}, issn = {1872-8294}, mesh = {Humans ; *Neurodegenerative Diseases/therapy ; *Pluripotent Stem Cells/transplantation/cytology ; Animals ; *Cell- and Tissue-Based Therapy/methods ; *Stem Cell Transplantation/methods ; Clinical Trials as Topic ; }, abstract = {Self-renewal capacity and potential to differentiate into almost any cell type of the human body makes pluripotent stem cells a valuable starting material for manufacturing of clinical grade cell therapies. Neurodegenerative diseases are characterized by gradual loss of structure or function of neurons, often leading to neuronal death. This results in gradual decline of cognitive, motor, and physiological functions due to the degeneration of the central nervous systems. Over the past two decades, comprehensive preclinical efficacy (proof-of-concept) and safety studies have led to the initiation of First-in-Human phase I-II clinical trials for a range of neurodegenerative diseases. In this review, we explore the fundamentals and challenges of neural-cell therapies derived from pluripotent stem cells for treating neurodegenerative diseases. Additionally, we highlight key preclinical investigations that paved the way for regulatory approvals of these trials. Furthermore, we provide an overview on progress and status of clinical trials done so far in treating neurodegenerative diseases such as spinal cord injury (SCI), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), as well as advances in retina diseases such as Stargardt disease (a.k.a fundus flavimaculatus), retinitis pigmentosa (RP) and age-related macular degeneration (AMD). These trials will pave the way for the development of new cell-based therapies targeting additional neurological conditions, including Alzheimer's disease and epilepsy.}, }
@article {pmid39879721, year = {2025}, author = {Derevyanko, A and Tao, T and Allen, NJ}, title = {Common alterations to astrocytes across neurodegenerative disorders.}, journal = {Current opinion in neurobiology}, volume = {90}, number = {}, pages = {102970}, doi = {10.1016/j.conb.2025.102970}, pmid = {39879721}, issn = {1873-6882}, mesh = {Humans ; *Astrocytes/metabolism/pathology/immunology ; *Neurodegenerative Diseases/pathology/metabolism/immunology ; Animals ; *Brain/pathology/metabolism ; }, abstract = {Astrocytes perform multiple functions in the nervous system, many of which are altered in neurodegenerative disorders. In this review, we explore shared astrocytic alterations across neurodegenerative disorders, including Alzheimer's disease, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, and frontotemporal lobe degeneration. Assessing recent datasets of single-nucleus RNA-sequencing of human brains, a theme emerges of common alterations in astrocyte state across disorders including in neuroinflammation, synaptic organization, metabolic support, and the cellular stress response. Immune pathways are upregulated by astrocytes across disorders and may exacerbate neurodegeneration. Dysregulated expression of synaptogenic factors could contribute to synaptic loss, while compromised metabolic support affects neuronal homeostasis. On the other hand, upregulated responses to cellular stress may represent a protective response of astrocytes and thus mitigate pathology. Understanding these shared responses offers insights into disease progression and provides potential therapeutic targets for various neurodegenerative disorders.}, }
@article {pmid39876814, year = {2025}, author = {Papadopoulou, M and Stefanou, MI and Fanouraki, S and Moschovos, C and Bakola, E and Salakou, S and Zouvelou, V and Papadimas, GK and Tsivgoulis, G}, title = {Motor neuron diseases are not exclusively motor; the SSR paradigm.}, journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration}, volume = {26}, number = {5-6}, pages = {399-408}, doi = {10.1080/21678421.2025.2458694}, pmid = {39876814}, issn = {2167-9223}, mesh = {Humans ; *Motor Neuron Disease/physiopathology/diagnosis/complications ; *Galvanic Skin Response/physiology ; *Autonomic Nervous System Diseases/diagnosis/physiopathology/etiology ; }, abstract = {Motor Neuron Diseases (MNDs), familial and sporadic, are progressive neurodegenerative disorders that, for an extended period in the past, were considered purely motor disorders. During the course of the disease, however, some patients exhibit concomitant non-motor signs; thus, MNDs are currently perceived as multisystem disorders. Assessment of non-motor symptoms is usually performed clinically, although laboratory tests can also be routinely used to objectively evaluate these symptoms. Sympathetic Skin Response (SSR) is an example of a neurophysiological test that has been used in cases of Amyotrophic Lateral Sclerosis, Spinal Muscular Atrophy, and Monomelic Atrophy, mostly to assess Autonomic Nervous System (ANS) disorders. Dysautonomia affects quality of life and life expectancy, as it is involved in cardiovascular events and incidents of sudden death. SSR abnormalities are present even in subclinical involvement of the ANS in MNDs. In this review, we present published research examining SSR findings in various MNDs, and discuss the correlation of SSR findings with clinical symptoms and disease severity, as well as the potential sources of abnormal findings. The aim of this study is to raise clinician awareness of autonomic dysfunction in MNDs and present the benefits of SSR examination in patient care.}, }
@article {pmid39872677, year = {2025}, author = {Pulst, SM}, title = {Spinocerebellar Ataxia Type 2: A Review and Personal Perspective.}, journal = {Neurology. Genetics}, volume = {11}, number = {1}, pages = {e200225}, pmid = {39872677}, issn = {2376-7839}, support = {R35 NS127253/NS/NINDS NIH HHS/United States ; }, abstract = {Spinocerebellar ataxias (SCAs) are dominantly inherited diseases that lead to neurodegeneration in the cerebellum and other parts of the nervous system. This review examines the progress that has been made in SCA2 from its initial clinical description to discovery of DNA CAG-repeat expansions in the ATXN2 gene. ATXN2 repeat alleles cover the range from recessive and dominant mendelian alleles to risk alleles for amyotrophic lateral sclerosis. We review studies aimed at defining the normal function of ATXN2 and mutant ATXN2 using cellular and mouse models. Progress in testing small compounds and antisense oligonucleotides in preclinical studies is described as well including our recent focus on staufen-1 (STAU1) and mRNA metabolism and control of autophagy.}, }
@article {pmid39871559, year = {2025}, author = {Rani, S and Tuteja, M}, title = {Chaperones as Potential Pharmacological Targets for Treating Protein Aggregation Illness.}, journal = {Current protein &amp; peptide science}, volume = {26}, number = {6}, pages = {451-466}, pmid = {39871559}, issn = {1875-5550}, mesh = {Humans ; *Molecular Chaperones/metabolism ; Animals ; Protein Folding/drug effects ; *Neurodegenerative Diseases/metabolism/drug therapy ; Heat-Shock Proteins/metabolism ; *Protein Aggregation, Pathological/drug therapy/metabolism ; Protein Aggregates/drug effects ; Molecular Targeted Therapy ; *Proteostasis Deficiencies/drug therapy/metabolism ; }, abstract = {The three-dimensional structure of proteins, achieved through the folding of the nascent polypeptide chain in vivo, is largely facilitated by molecular chaperones, which are crucial for determining protein functionality. In addition to aiding in the folding process, chaperones target misfolded proteins for degradation, acting as a quality control system within the cell. Defective protein folding has been implicated in a wide range of clinical conditions, including neurodegenerative and metabolic disorders. It is now well understood that the pathogenesis of neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Huntington's disease, Amyotrophic Lateral Sclerosis, and Creutzfeldt-Jakob disease shares a common mechanism: the accumulation of misfolded proteins, which aggregate and become toxic to cells. Among the family of molecular chaperones, Heat Shock Proteins (HSPs) are highly expressed in response to cellular stress and play a pivotal role in preventing protein aggregation. Specific chaperones, particularly HSPs, are now recognized as critical in halting the accumulation and aggregation of misfolded proteins in these conditions. Consequently, these chaperones are increasingly considered promising pharmacological targets for the treatment of protein aggregation-related diseases. This review highlights research exploring the potential roles of specific molecular chaperones in disorders characterized by the accumulation of misfolded proteins.}, }
@article {pmid39870443, year = {2025}, author = {Zhang, Q and Walkley, CR}, title = {Mouse models for understanding physiological functions of ADARs.}, journal = {Methods in enzymology}, volume = {710}, number = {}, pages = {153-185}, doi = {10.1016/bs.mie.2024.11.024}, pmid = {39870443}, issn = {1557-7988}, mesh = {Animals ; *Adenosine Deaminase/genetics/metabolism ; Mice ; Humans ; *Disease Models, Animal ; RNA Editing ; Adenosine/metabolism/genetics ; Autoimmune Diseases of the Nervous System/genetics ; *RNA-Binding Proteins/genetics/metabolism ; Nervous System Malformations/genetics ; Amyotrophic Lateral Sclerosis/genetics ; Mutation ; }, abstract = {Adenosine-to-inosine (A-to-I) editing, is a highly prevalent posttranscriptional modification of RNA, mediated by the adenosine deaminases acting on RNA (ADAR) proteins. Mammalian transcriptomes contain tens of thousands to millions of A-to-I editing events. Mutations in ADAR can result in rare autoinflammatory disorders such as Aicardi-Goutières syndrome (AGS) through to irreversible conditions such as motor neuron disease, amyotrophic lateral sclerosis (ALS). Mouse models have played an important role in our current understanding of the physiology of ADAR proteins. With the advancement of genetic engineering technologies, a number of new mouse models have been recently generated, each providing additional insight into ADAR function. This review highlights both past and current mouse models, exploring the methodologies used in their generation, their respective discoveries, and the significance of these findings in relation to human ADAR physiology.}, }
@article {pmid39863029, year = {2025}, author = {Liu, X and Li, T and Tu, X and Xu, M and Wang, J}, title = {Mitochondrial fission and fusion in neurodegenerative diseases:Ca[2+] signalling.}, journal = {Molecular and cellular neurosciences}, volume = {132}, number = {}, pages = {103992}, doi = {10.1016/j.mcn.2025.103992}, pmid = {39863029}, issn = {1095-9327}, mesh = {Humans ; *Mitochondrial Dynamics/physiology ; *Neurodegenerative Diseases/metabolism/pathology ; *Calcium Signaling ; Animals ; *Mitochondria/metabolism ; Mitochondrial Proteins/metabolism ; }, abstract = {Neurodegenerative diseases (NDs) are a group of disorders characterized by the progressive loss of neuronal structure and function. The pathogenesis is intricate and involves a network of interactions among multiple causes and systems. Mitochondria and Ca[2+] signaling have long been considered to play important roles in the development of various NDs. Mitochondrial fission and fusion dynamics are important processes of mitochondrial quality control, ensuring the stability of mitochondrial structure and function. Mitochondrial fission and fusion imbalance and Ca[2+] signaling disorders can aggravate the disease progression of NDs. In this review, we explore the relationship between mitochondrial dynamics and Ca[2+] signaling in AD, PD, ALS, and HD, focusing on the roles of key regulatory proteins (Drp1, Fis1, Mfn1/2, and Opa1) and the association structures between mitochondria and the endoplasmic reticulum (MERCs/MAMs). We provide a detailed analysis of their involvement in the pathogenesis of these four NDs. By integrating these mechanisms, we aim to clarify their contributions to disease progression and offer insights into the development of therapeutic strategies that target mitochondrial dynamics and Ca[2+] signaling. We also examine the progress in drug research targeting these pathways, highlighting their potential as therapeutic targets in the treatment of NDs.}, }
@article {pmid39862884, year = {2025}, author = {Moens, TG and Da Cruz, S and Neumann, M and Shelkovnikova, TA and Shneider, NA and Van Den Bosch, L}, title = {Amyotrophic lateral sclerosis caused by FUS mutations: advances with broad implications.}, journal = {The Lancet. Neurology}, volume = {24}, number = {2}, pages = {166-178}, doi = {10.1016/S1474-4422(24)00517-9}, pmid = {39862884}, issn = {1474-4465}, support = {SHELKOVNIKOVA/OCT17/968-799/MNDA_/Motor Neurone Disease Association/United Kingdom ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/therapy/pathology ; *RNA-Binding Protein FUS/genetics ; *Mutation/genetics ; Animals ; }, abstract = {Autosomal dominant mutations in the gene encoding the DNA and RNA binding protein FUS are a cause of amyotrophic lateral sclerosis (ALS), and about 0·3-0·9% of patients with ALS are FUS mutation carriers. FUS-mutation-associated ALS (FUS-ALS) is characterised by early onset and rapid progression, compared with other forms of ALS. However, different pathogenic mutations in FUS can result in markedly different age at symptom onset and rate of disease progression. Most FUS mutations disrupt its nuclear localisation, leading to its cytoplasmic accumulation in the CNS. FUS also forms inclusions in around 5% of patients with the related neurodegenerative condition frontotemporal dementia. However, there are key differences between the two diseases at the genetic and neuropathological level, which suggest distinct pathogenic processes. Experimental models have uncovered potential pathogenic mechanisms in FUS-ALS and informed therapeutic strategies that are currently in development, including the silencing of FUS expression using an intrathecally administered antisense oligonucleotide.}, }
@article {pmid39860557, year = {2025}, author = {Chmiel, J and Stępień-Słodkowska, M}, title = {Resting-State EEG Oscillations in Amyotrophic Lateral Sclerosis (ALS): Toward Mechanistic Insights and Clinical Markers.}, journal = {Journal of clinical medicine}, volume = {14}, number = {2}, pages = {}, pmid = {39860557}, issn = {2077-0383}, abstract = {Introduction: Amyotrophic lateral sclerosis (ALS) is a complex, progressive neurodegenerative disorder characterized by the degeneration of motor neurons in the brain, brainstem, and spinal cord. Several neuroimaging techniques can help reveal the pathophysiology of ALS. One of these is the electroencephalogram (EEG), a noninvasive and relatively inexpensive tool for examining electrical activity of the brain with excellent temporal precision. Methods: This mechanistic review examines the pattern of resting-state EEG activity. With a focus on publications published between January 1995 and October 2024, we carried out a comprehensive search in October 2024 across a number of databases, including PubMed/Medline, Research Gate, Google Scholar, and Cochrane. Results: The literature search yielded 17 studies included in this review. The studies varied significantly in their methodology and patient characteristics. Despite this, a common biomarker typical of ALS was found-reduced alpha power. Regarding other oscillations, the findings are less consistent and sometimes contradictory. As this is a mechanistic review, three possible explanations for this biomarker are provided. The main and most important one is increased cortical excitability. In addition, due to the limitations of the studies, recommendations for future research on this topic are outlined to enable a further and better understanding of EEG patterns in ALS. Conclusions: Most studies included in this review showed alpha power deficits in ALS patients, reflecting pathological hyperexcitability of the cerebral cortex. Future studies should address the methodological limitations identified in this review, including small sample sizes, inconsistent frequency-band definitions, and insufficient functional outcome measures, to solidify and extend current findings.}, }
@article {pmid39859339, year = {2025}, author = {Yashooa, RK and Duranti, E and Conconi, D and Lavitrano, M and Mustafa, SA and Villa, C}, title = {Mitochondrial microRNAs: Key Drivers in Unraveling Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {26}, number = {2}, pages = {}, pmid = {39859339}, issn = {1422-0067}, mesh = {Humans ; *MicroRNAs/genetics/metabolism ; *Mitochondria/genetics/metabolism ; *Neurodegenerative Diseases/genetics/metabolism/pathology ; Animals ; Gene Expression Regulation ; Parkinson Disease/genetics/metabolism ; DNA, Mitochondrial/genetics ; }, abstract = {MicroRNAs (miRNAs) are a class of small non-coding RNAs (ncRNAs) crucial for regulating gene expression at the post-transcriptional level. Recent evidence has shown that miRNAs are also found in mitochondria, organelles that produce energy in the cell. These mitochondrial miRNAs, also known as mitomiRs, are essential for regulating mitochondrial function and metabolism. MitomiRs can originate from the nucleus, following traditional miRNA biogenesis pathways, or potentially from mitochondrial DNA, allowing them to directly affect gene expression and cellular energy dynamics within the mitochondrion. While miRNAs have been extensively investigated, the function and involvement of mitomiRs in the development of neurodegenerative disorders like Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis remain to be elucidated. This review aims to discuss findings on the role of mitomiRs in such diseases and their potential as therapeutic targets, as well as to highlight future research directions.}, }
@article {pmid39859258, year = {2025}, author = {Szablewski, L}, title = {Associations Between Diabetes Mellitus and Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {26}, number = {2}, pages = {}, pmid = {39859258}, issn = {1422-0067}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/etiology/complications/pathology ; *Diabetes Mellitus, Type 2/complications/metabolism ; Oxidative Stress ; Animals ; Parkinson Disease ; Huntington Disease ; *Diabetes Mellitus, Type 1/complications/metabolism ; Alzheimer Disease/metabolism ; Amyotrophic Lateral Sclerosis ; *Diabetes Mellitus/metabolism ; }, abstract = {Diabetes mellitus (DM) and neurodegenerative diseases/disturbances are worldwide health problems. The most common chronic conditions diagnosed in persons 60 years and older are type 2 diabetes mellitus (T2DM) and cognitive impairment. It was found that diabetes mellitus is a major risk for cognitive decline, dementia, Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS) and other neurodegenerative disorders. Different mechanisms of associations between these diseases and diabetes mellitus have been suggested. For example, it is postulated that an impaired intracellular insulin signaling pathway, together with hyperglycemia and hyperinsulinemia, may cause pathological changes, such as dysfunction of the mitochondria, oxidative stress inflammatory responses, etc. The association between diabetes mellitus and neurodegenerative diseases, as well as the mechanisms of these associations, needs further investigation. The aim of this review is to describe the associations between diabetes mellitus, especially type 1 (T1DM) and type 2 diabetes mellitus, and selected neurodegenerative diseases, i.e., Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis. Suggested mechanisms of these associations are also described.}, }
@article {pmid39858428, year = {2024}, author = {Argueti-Ostrovsky, S and Barel, S and Kahn, J and Israelson, A}, title = {VDAC1: A Key Player in the Mitochondrial Landscape of Neurodegeneration.}, journal = {Biomolecules}, volume = {15}, number = {1}, pages = {}, pmid = {39858428}, issn = {2218-273X}, support = {#284/19 and #485/24//Israel Science Foundation/ ; }, mesh = {Humans ; *Voltage-Dependent Anion Channel 1/metabolism/genetics ; *Mitochondria/metabolism/pathology ; *Neurodegenerative Diseases/metabolism/pathology ; Animals ; alpha-Synuclein/metabolism/genetics ; Amyloid beta-Peptides/metabolism ; Superoxide Dismutase-1/metabolism/genetics ; Oxidative Stress ; }, abstract = {Voltage-Dependent Anion Channel 1 (VDAC1) is a mitochondrial outer membrane protein that plays a crucial role in regulating cellular energy metabolism and apoptosis by mediating the exchange of ions and metabolites between mitochondria and the cytosol. Mitochondrial dysfunction and oxidative stress are central features of neurodegenerative diseases. The pivotal functions of VDAC1 in controlling mitochondrial membrane permeability, regulating calcium balance, and facilitating programmed cell death pathways, position it as a key determinant in the delicate balance between neuronal viability and degeneration. Accordingly, increasing evidence suggests that VDAC1 is implicated in the pathophysiology of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and others. This review summarizes the current findings on the contribution of VDAC1 to neurodegeneration, focusing on its interactions with disease-specific proteins, such as amyloid-β, α-synuclein, and mutant SOD1. By unraveling the complex involvement of VDAC1 in neurodegenerative processes, this review highlights potential avenues for future research and drug development aimed at alleviating mitochondrial-related neurodegeneration.}, }
@article {pmid39857620, year = {2024}, author = {Frawley, L and Taylor, NT and Sivills, O and McPhillamy, E and To, TD and Wu, Y and Chin, BY and Wong, CY}, title = {Stem Cell Therapy for the Treatment of Amyotrophic Lateral Sclerosis: Comparison of the Efficacy of Mesenchymal Stem Cells, Neural Stem Cells, and Induced Pluripotent Stem Cells.}, journal = {Biomedicines}, volume = {13}, number = {1}, pages = {}, pmid = {39857620}, issn = {2227-9059}, support = {Australian Government New Colombo Plan (NCP) scheme//Australian Government New Colombo Plan (NCP) scheme/ ; }, abstract = {BACKGROUND/OBJECTIVES: Amyotrophic lateral sclerosis (ALS), or Lou Gehrig's disease, is a debilitating, incurable neurodegenerative disorder characterised by motor neuron death in the spinal cord, brainstem, and motor cortex. With an incidence rate of about 4.42 cases per 100,000 people annually, ALS severely impacts motor function and quality of life, causing progressive muscle atrophy, spasticity, paralysis, and eventually death. The cause of ALS is largely unknown, with 90% of cases being sporadic and 10% familial. Current research targets molecular mechanisms of inflammation, excitotoxicity, aggregation-prone proteins, and proteinopathy.<br><br>METHODS: This review evaluates the efficacy of three stem cell types in ALS treatment: mesenchymal stem cells (MSCs), neural stem cells (NSCs), and induced pluripotent stem cells (iPSCs).<br><br>RESULTS: MSCs, derived from various tissues, show neuroprotective and regenerative qualities, with clinical trials suggesting potential benefits but limited by small sample sizes and non-randomised designs. NSCs, isolated from the fetal spinal cord or brain, demonstrate promise in animal models but face functional integration and ethical challenges. iPSCs, created by reprogramming patient-specific somatic cells, offer a novel approach by potentially replacing or supporting neurons. iPSC therapy addresses ethical issues related to embryonic stem cells but encounters challenges regarding genotoxicity and epigenetic irregularities, somatic cell sources, privacy concerns, the need for extensive clinical trials, and high reprogramming costs.<br><br>CONCLUSIONS: This research is significant for advancing ALS treatment beyond symptomatic relief and modest survival extensions to actively modifying disease progression and improving patient outcomes. Successful stem cell therapies could lead to new ALS treatments, slowing motor function loss and reducing symptom severity.}, }
@article {pmid39857328, year = {2025}, author = {Stoccoro, A}, title = {Epigenetic Mechanisms Underlying Sex Differences in Neurodegenerative Diseases.}, journal = {Biology}, volume = {14}, number = {1}, pages = {}, pmid = {39857328}, issn = {2079-7737}, support = {GR-2021-12374436//Italian Ministry of Health, Ricerca Finalizzata/ ; }, abstract = {Neurodegenerative diseases are characterized by profound differences between females and males in terms of incidence, clinical presentation, and disease progression. Furthermore, there is evidence suggesting that differences in sensitivity to medical treatments may exist between the two sexes. Although the role of sex hormones and sex chromosomes in driving differential susceptibility to these diseases is well-established, the molecular alterations underlying these differences remain poorly understood. Epigenetic mechanisms, including DNA methylation, histone tail modifications, and the activity of non-coding RNAs, are strongly implicated in the pathogenesis of neurodegenerative diseases. While it is known that epigenetic mechanisms play a crucial role in sexual differentiation and that distinct epigenetic patterns characterize females and males, sex-specific epigenetic patterns have been largely overlooked in studies aiming to identify epigenetic alterations associated with neurodegenerative diseases. This review aims to provide an overview of sex differences in epigenetic mechanisms, the role of sex-specific epigenetic processes in the central nervous system, and the main evidence of sex-specific epigenetic alterations in three neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Understanding the sex-related differences of these diseases is essential for developing personalized treatments and interventions that account for the unique epigenetic landscapes of each sex.}, }
@article {pmid39855275, year = {2025}, author = {Zhang, W and Zhang, L and Fu, S and Yan, R and Zhang, X and Song, J and Lu, Y}, title = {Roles of NLRC4 inflammasome in neurological disorders: Mechanisms, implications, and therapeutic potential.}, journal = {Pharmacology &amp; therapeutics}, volume = {267}, number = {}, pages = {108803}, doi = {10.1016/j.pharmthera.2025.108803}, pmid = {39855275}, issn = {1879-016X}, mesh = {Humans ; *Inflammasomes/metabolism/immunology ; Animals ; *Calcium-Binding Proteins/metabolism ; *Nervous System Diseases/drug therapy/immunology/metabolism ; *CARD Signaling Adaptor Proteins/metabolism ; *Apoptosis Regulatory Proteins/metabolism ; Neurodegenerative Diseases/drug therapy/immunology ; }, abstract = {The nucleotide-binding oligomerization domain-like receptor family caspase recruitment domain containing 4 (NLRC4) inflammasome, a vital component of the innate immune system, is known for defending against bacterial infections. However, recent insights have revealed its significant impact on neurological disorders. This comprehensive review discussed the mechanisms underlying the activation and regulation of the NLRC4 inflammasome, highlighting the complexity of its response to cellular stress and damage signals. The biological functions of NLRC4 were explored, particularly its influence on cytokine production and the induction of pyroptosis, a form of inflammatory cell death. This review further emphasized the role of the NLRC4 inflammasome in brain injuries and neurodegenerative disorders. In the realm of brain injuries such as stroke and traumatic brain injury, as well as in neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis, the NLRC4 inflammasome played a pivotal role in modulating neuroinflammatory responses, which was crucial for understanding the progression and potential therapeutic targeting of these conditions. The emerging role of NLRC4 in psychiatric disorders and its potential impact on glioma progression were also examined. Additionally, this review presented a thorough summary of the latest research on inhibitors that impeded the assembly and activation of the NLRC4 inflammasome, pointing to new therapeutic possibilities in neurological disorders. In conclusion, by integrating current knowledge on the activation and regulation of NLRC4 with its biological functions and clinical implications, this article underscored the importance of NLRC4 inflammasome in neurological pathologies, which opened new possibilities for the treatment of challenging neurological conditions.}, }
@article {pmid39849126, year = {2025}, author = {Gupta, S and Kishore, A and Rishi, V and Aggarwal, A}, title = {Mitochondria and its epigenetic dynamics: Insight into synaptic regulation and synaptopathies.}, journal = {Functional &amp; integrative genomics}, volume = {25}, number = {1}, pages = {26}, pmid = {39849126}, issn = {1438-7948}, mesh = {Humans ; *Mitochondria/metabolism/genetics ; *Epigenesis, Genetic ; *Synapses/metabolism/genetics/pathology ; *Mitochondrial Dynamics/genetics ; Animals ; Synaptic Transmission ; Calcium/metabolism ; }, abstract = {Mitochondria, the cellular powerhouses, are pivotal to neuronal function and health, particularly through their role in regulating synaptic structure and function. Spine reprogramming, which underlies synapse development, depends heavily on mitochondrial dynamics-such as biogenesis, fission, fusion, and mitophagy as well as functions including ATP production, calcium (Ca[2+]) regulation, and retrograde signaling. Mitochondria supply the energy necessary for assisting synapse development and plasticity, while also regulating intracellular Ca[2+] homeostasis to prevent excitotoxicity and support synaptic neurotransmission. Additionally, the dynamic processes of mitochondria ensure mitochondrial quality and adaptability, which are essential for maintaining effective synaptic activity. Emerging evidence highlights the significant role of epigenetic modifications in regulating mitochondrial dynamics and function. Epigenetic changes influence gene expression, which in turn affects mitochondrial activity, ensuring coordinated responses necessary for synapse development. Furthermore, metabolic changes within mitochondria can impact the epigenetic machinery, thereby modulating gene expression patterns that support synaptic integrity. Altered epigenetic regulation affecting mitochondrial dynamics and functions is linked to several neurological disorders, including Amyotrophic Lateral Sclerosis, Huntington's, Alzheimer's, and Parkinson's diseases, emphasizing its crucial function. The review delves into the molecular machinery involved in mitochondrial dynamics, ATP and Ca[2+] regulation, highlighting the role of key proteins that facilitate the processes. Additionally, it also shed light on the emerging epigenetic factors influencing these regulations. It provides a thorough summary on the current understanding of the role of mitochondria in synapse development and emphasizes the importance of both molecular and epigenetic mechanisms in maintaining synaptic integrity.}, }
@article {pmid39845577, year = {2025}, author = {Ludolph, A and Wiesenfarth, M}, title = {Tofersen and other antisense oligonucleotides in ALS.}, journal = {Therapeutic advances in neurological disorders}, volume = {18}, number = {}, pages = {17562864251313915}, pmid = {39845577}, issn = {1756-2856}, abstract = {The advent of antisense oligonucleotide (ASO) therapies in neurodegenerative disorders is associated with enormous hope. Nusinersen treatment was a breakthrough intervention in the recessive disease spinal muscular atrophy, and superoxide dismutase 1 (SOD1) amyotrophic lateral sclerosis (ALS) seems to be the paradigm disease in dominant degenerative diseases. The results of treatment with the ASO tofersen in SOD1-ALS show that the drug has a convincing beneficial effect on ALS caused by SOD1 mutations, that preclinical studies in rodents predicted the therapeutic effect in the human disease, and that clinical efficacy is associated with a specific sequence of effects of the drug on mechanistic and degenerative biomarkers and, subsequently, functional outcomes such as weight stabilization and ALSFRS-R. Therefore, the enthusiasm seems to be justified; but this should be followed by an attempt to obtain further insights with the goal to improve this therapy. In particular, the following issues are only partially resolved: Which mechanisms are responsible for the clinical effect following the downregulation of SOD1 protein by ASOs? Is long-term downregulation of SOD1 function associated with side effects? Is there an autoimmune response caused by this and other ASO? Is prevention of SOD1-associated ALS possible?}, }
@article {pmid39844762, year = {2025}, author = {Theuriet, J and Bernard, E and Guy, N and Taithe, F and Even, C and Maisonobe, T and Sangaré, A and Lardeux, P and Tilikete, CF and Couratier, P and Lenglet, T and Pegat, A}, title = {Electrophysiological Abnormalities in Finger Extension Weakness and DOwnbeat Nystagmus Motor Neuron Disease: Three New Patients and Review of the Literature.}, journal = {Muscle &amp; nerve}, volume = {71}, number = {4}, pages = {644-650}, pmid = {39844762}, issn = {1097-4598}, mesh = {Humans ; *Motor Neuron Disease/physiopathology/complications/diagnosis ; Male ; Electromyography ; *Nystagmus, Pathologic/physiopathology/complications/diagnosis ; Female ; Middle Aged ; *Fingers/physiopathology ; *Muscle Weakness/physiopathology/etiology/diagnosis ; Adult ; Neural Conduction/physiology ; Action Potentials/physiology ; Muscle, Skeletal/physiopathology ; }, abstract = {INTRODUCTION/AIMS: Finger Extension Weakness and DOwnbeat Nystagmus Motor Neuron Disease (FEWDON-MND) is characterized by motor weakness predominantly affecting finger extension, accompanied by downbeat nystagmus. To date, only 11 patients have been reported. The present study adds a further three and aims to provide a more detailed description of the electrodiagnostic features of these patients.<br><br>METHODS: We present the clinical and electrophysiological features of three French patients from specialized motor neuron centers and review the electrophysiological findings of previously reported patients.<br><br>RESULTS: These three patients presented with pure motor weakness affecting finger extension and downbeat nystagmus. They exhibited a slowly progressive disease course without respiratory involvement. Nerve conduction studies showed decreased compound muscle action potential amplitudes in the extensor indicis muscles. Abnormal spontaneous activity on needle electromyography (EMG) was rare in two patients, absent in one, and otherwise limited to weak muscles. Additionally, chronic motor axon loss features suggestive of motor neuronopathy were seen in our patients. Importantly, they were also detected in distant asymptomatic muscles.<br><br>DISCUSSION: The three patients reported here confirm the typical phenotype of FEWDON-MND, characterized by slowly progressive distal motor weakness initially affecting finger extension, associated with downbeat nystagmus. Although chronic motor axon loss features have been found in all reported patients, our three patients show that active denervation can be absent or rare. Thus, finger drop and diffuse chronic neurogenic changes on EMG should lead clinicians to look for downbeat nystagmus and to consider FEWDON-MND.}, }
@article {pmid39842248, year = {2025}, author = {Micallef, C and Somanadhan, S and O'Donnell, D and Thompson, W and Stokes, D and Koe, S and Davies, C}, title = {Distraction-based interventions for children in the emergency care setting: A realist synthesis based on primary research.}, journal = {Journal of pediatric nursing}, volume = {81}, number = {}, pages = {43-54}, doi = {10.1016/j.pedn.2025.01.017}, pmid = {39842248}, issn = {1532-8449}, mesh = {Humans ; Child ; *Pain Management/methods ; *Emergency Service, Hospital ; *Anxiety/prevention &amp; control/therapy ; Male ; Female ; *Stress, Psychological/prevention &amp; control ; Child, Preschool ; }, abstract = {BACKGROUND: The literature underscores the prevalence of pain as the most common presenting symptom in the Emergency Care Setting (ECS) and is associated with anxiety and stress for children. On top of that painful procedures are often required as part of their treatment, making procedural pain a common experience. The substantial evidence supporting the effectiveness of distraction-based interventions (DBI) in relieving pain and anxiety and reducing stress underscores the urgency of addressing this issue. However, the fragmented adoption of standardised DBI highlights the need for further research and implementation.<br><br>PURPOSE: To conduct a realist synthesis based on primary research exploring "what works for whom under what circumstances, how and why?" when implementing DBI in the ECS.<br><br>REVIEW METHODS: Empirical research evidence was retrieved systematically from eight databases covering health and social sciences. The studies were synthesised based on the principles of realist science, drawing on Pawson and Tilley's (1997) and Dalkin et al.'s (2015) programme theory development, which explains the contexts and mechanisms that generate positive outcomes about DBI for children in the ECS.<br><br>RESULTS: Of the 2099 studies screened, 64 were included. Screening was conducted 2023 to December 2024. A synthesis of the findings generated five Programme Theories (PT). PT1 focuses on the personalisation of DBI for children in the ECS, PT2 explains the importance of parental participation, PT3 highlights the importance of healthcare workers (HCWs) commitment to adopting DBI in practice, PT4 draws attention to policy-level efforts necessary for implementation support, and PT5 focuses on engaging all stakeholders in the implementation process.<br><br>CONCLUSION: To the authors' knowledge, this is the first study to apply a realist lens to understand the use of DBI in children attending the ECS and present the mechanisms that enable and/or inhibit its implementation and utilisation in everyday clinical practice.<br><br>IMPLICATIONS TO PRACTICE: This realist synthesis provides methodological guidance in the form of PT that can be utilised by clinical practitioners to adopt and implement DBI within the healthcare setting.}, }
@article {pmid39840019, year = {2024}, author = {De Cleene, N and Schwarzová, K and Labrecque, S and Cerejo, C and Djamshidian, A and Seppi, K and Heim, B}, title = {Olfactory dysfunction as potential biomarker in neurodegenerative diseases: a narrative review.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1505029}, pmid = {39840019}, issn = {1662-4548}, abstract = {Neurodegenerative diseases represent a group of disorders characterized by progressive degeneration of neurons in the central nervous system, leading to a range of cognitive, motor, and sensory impairments. In recent years, there has been growing interest in the association between neurodegenerative diseases and olfactory dysfunction (OD). Characterized by a decline in the ability to detect or identify odors, OD has been observed in various conditions, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic Lateral Sclerosis (ALS). This phenomenon often precedes the onset of other clinical symptoms, suggesting its potential utility as an early marker or prodromal symptom of neurodegenerative diseases. This review provides a vast literature overview on the current knowledge of OD in PD, AD, ALS, and HD in order to evaluate its potential as a biomarker, particularly in the early and prodromal stages of these diseases. We summarize the most common methods used to measure olfactory function and delve into neuropathological correlations and the alterations in neurotransmitter systems associated with OD in those neurodegenerative diseases, including differences in genetic variants if applicable, and cater to current pitfalls and shortcomings in the research.}, }
@article {pmid39838446, year = {2025}, author = {Ou, K and Jia, Q and Li, D and Li, S and Li, XJ and Yin, P}, title = {Application of antisense oligonucleotide drugs in amyotrophic lateral sclerosis and Huntington's disease.}, journal = {Translational neurodegeneration}, volume = {14}, number = {1}, pages = {4}, pmid = {39838446}, issn = {2047-9158}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/genetics/therapy ; Humans ; *Huntington Disease/drug therapy/genetics/therapy ; *Oligonucleotides, Antisense/therapeutic use ; Animals ; *Genetic Therapy/methods ; *Neuroprotective Agents/therapeutic use ; }, abstract = {Amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD) are diverse in clinical presentation and are caused by complex and multiple factors, including genetic mutations and environmental factors. Numerous therapeutic approaches have been developed based on the genetic causes and potential mechanisms of ALS and HD. Currently, available treatments for various neurodegenerative diseases can alleviate symptoms but do not provide a definitive cure. Gene therapy, which aims to modify or express specific proteins for neuroprotection or correction, is considered a powerful tool in managing neurodegenerative conditions. To date, antisense oligonucleotide (ASO) drugs targeting the pathological genes associated with ALS and HD have shown promising results in numerous animal studies and several clinical trials. This review provides a comprehensive overview of the development, mechanisms of action, limitations, and clinical applications of ASO drugs in neurodegenerative diseases, with a specific focus on ALS and HD therapeutic strategies.}, }
@article {pmid39838017, year = {2025}, author = {McCaig, CD}, title = {Neurological Diseases can be Regulated by Phase Separation.}, journal = {Reviews of physiology, biochemistry and pharmacology}, volume = {187}, number = {}, pages = {273-338}, pmid = {39838017}, issn = {0303-4240}, mesh = {Humans ; Animals ; *Nervous System Diseases/physiopathology/metabolism ; Superoxide Dismutase/metabolism ; Motor Neuron Disease/physiopathology/metabolism ; Protein Aggregation, Pathological ; Phase Separation ; }, abstract = {Several neurological diseases arise from abnormal protein aggregation within neurones and this is closely regulated by phase separation. One such is motor neurone disease and aberrant aggregation of superoxide dismutase. Again these events are regulated by electrical forces that are examined.}, }
@article {pmid39835561, year = {2025}, author = {Rai, A and Shukla, S and Gupta, RK and Mishra, A}, title = {ALS: A Silent Slayer of Motor Neurons. Traditional Chinese Herbal Medicine as an Effective Therapy.}, journal = {Current pharmaceutical design}, volume = {31}, number = {17}, pages = {1328-1346}, pmid = {39835561}, issn = {1873-4286}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Drugs, Chinese Herbal/therapeutic use/pharmacology ; *Neuroprotective Agents/therapeutic use/pharmacology ; *Motor Neurons/drug effects/pathology ; *Medicine, Chinese Traditional ; Animals ; }, abstract = {Amyotrophic lateral sclerosis (ALS), is a progressive neurodegenerative disease characterized by motor symptoms, and cognitive impairment. The complexity in treating ALS arises from genetic and environmental factors, contributing to the gradual decline of lower and upper motor neurons. The anticipated pharmaceutical market valuation for ALS is projected to reach $1,038.94 million by 2032. This projection underscores the escalating impact of ALS on global healthcare systems. ALS prevalence is expected to surge to 376,674 cases by 2040. In 2022, India ranked among the top 3 Asian-Pacific nations, while North America dominated the global ALS market. Ongoing investigations explore the potential of neuroprotective drugs like riluzole and edaravone in ALS treatment. Recently approved drugs, Relyvrio (sodium phenylbutyrate and taurursodiol) and Tofersen (Qalsody) have completed the trials, and others are currently undergoing extensive clinical trials. Continuous research and exploration of therapeutic avenues, including gene therapy and neuroprotective treatments, are imperative to address the challenges posed by ALS and other neurodegenerative diseases. Traditional Chinese medicine (TCM) approaches and clinical trials are being explored for treating ALS symptoms, targeting neuroinflammation, oxidative damage, and muscle weakness, showcasing the potential benefits of integrating traditional and modern approaches in ALS management.}, }
@article {pmid39834554, year = {2025}, author = {Sarallah, R and Jahani, S and Soltani Khaboushan, A and Moaveni, AK and Amiri, M and Majidi Zolbin, M}, title = {The role of CXCL12/CXCR4/CXCR7 axis in cognitive impairment associated with neurodegenerative diseases.}, journal = {Brain, behavior, &amp; immunity - health}, volume = {43}, number = {}, pages = {100932}, pmid = {39834554}, issn = {2666-3546}, abstract = {Neurodegenerative diseases, including Alzheimer's Disease (AD), Parkinson's Disease (PD), Multiple Sclerosis (MS), and Amyotrophic Lateral Sclerosis (ALS), are characterized by progressive neuronal loss and cognitive impairment (CI). The: Cysteine-X-cysteine chemokine ligand 12(CXCL12)/CXC chemokine receptor type 4 (CXCR4)/CXC chemokine receptor type 7 (CXCR7) axis has emerged as a critical molecular pathway in the development of CI in these disorders. This review explores the role of this axis in the pathogenesis of CI across these neurodegenerative diseases, synthesizing current evidence and its implications for targeted therapies. In AD, dysregulation of this axis contributes to amyloid-β accumulation and tau hyperphosphorylation, leading to synaptic dysfunction and cognitive decline. PD studies reveal that CXCL12/CXCR4 signaling influences dopaminergic neuron survival and microglial activation, affecting cognitive function. In MS, the axis modulates neuroinflammation and demyelination processes, impacting cognitive performance. ALS research indicates that the CXCL12/CXCR4/CXCR7 pathway is involved in motor neuron degeneration and associated cognitive deficits. Across these diseases, the axis influences neuroinflammation, synaptic plasticity, and neuronal survival through various signaling cascades, including PI3K/AKT, MAPK, and JAK/STAT pathways. Emerging evidence suggests that modulating this axis could provide neuroprotective effects and potentially alleviate cognitive symptoms. This review highlights the potential of the CXCL12/CXCR4/CXCR7 axis as a therapeutic target for addressing CI in neurodegenerative diseases. It also underscores the need for further research to fully elucidate its role and develop effective interventions, potentially leading to improved clinical management strategies for these devastating disorders.}, }
@article {pmid39834320, year = {2025}, author = {Lero, CM and Park, S and Mroz, EL}, title = {Mapping the evidence of self-compassion in caregiver wellbeing for caregivers of persons with neurodegenerative disease: A scoping review.}, journal = {Palliative &amp; supportive care}, volume = {23}, number = {}, pages = {e38}, doi = {10.1017/S1478951524001639}, pmid = {39834320}, issn = {1478-9523}, mesh = {Humans ; *Caregivers/psychology ; *Empathy ; *Neurodegenerative Diseases/psychology/complications ; }, abstract = {OBJECTIVES: Caregivers of those with neurodegenerative disease (ND) manage complex symptoms which impact their wellbeing. Self-compassion can promote maintenance of wellbeing during challenging experiences, including caregiving. Little guidance exists for observationally studying self-compassion or targeted interventions for this population. Our objective was to complete a scoping review of research describing self-compassion in the context of caregiver wellbeing of caregivers of those living with ND.<br><br>METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-analysis extension for Scoping Reviews (PRISMA-ScR) guidelines, 3 online databases identified 350 peer-reviewed articles, 18 of which were included in this study. Eligibility included being written in English, targeting caregivers of those living with ND, and examination of self-compassion. Articles were organized by the incorporation or characterization of self-compassion in the study design.<br><br>RESULTS: Alzheimer's disease predominated study samples of care recipients. Across study types self-compassion appeared as a theoretical concept, emerging theme, variable associated with other outcomes, and main outcome variable. Self-compassion is frequently measured using the Self-Compassion Scale, full or short form .<br><br>SIGNIFICANCE OF RESULTS: The study of self-compassion with caregivers of individuals living with ND is growing. Current literature is somewhat unfocussed, leading to gaps in understanding conceptualization to achieve maximum intervention benefits. Clarifying the role of self-compassion in caregiver wellbeing will provide a lens through which non-pharmacologic, psychotherapeutic, and behavioral intervention development may be framed to reduce negative psychological outcomes. The most frequently represented ND is Alzheimer's disease or other dementia, obscuring other NDs like amyotrophic lateral sclerosis, Parkinson's disease, and others.}, }
@article {pmid39833536, year = {2025}, author = {Curtis, TJ and Chant, C and Quek, S and Giarenis, I and Gray, TG}, title = {Fistulae Secondary to Vaginal Pessary Use for Pelvic Organ Prolapse: A Systematic Review.}, journal = {International urogynecology journal}, volume = {36}, number = {3}, pages = {491-521}, pmid = {39833536}, issn = {1433-3023}, mesh = {Humans ; *Pessaries/adverse effects ; Female ; *Pelvic Organ Prolapse/therapy ; Risk Factors ; *Rectovaginal Fistula/etiology/epidemiology ; Retrospective Studies ; Prevalence ; }, abstract = {INTRODUCTION AND HYPOTHESIS: Urogenital and rectovaginal fistulae are rare complications of pessary use for pelvic organ prolapse (POP). This systematic review investigates the prevalence of these complications in patients using pessary for POP, potential risk factors and approaches to their investigation and management.<br><br>METHODS: All studies in English reporting urogenital or rectovaginal fistulae secondary to pessaries for POP were eligible for inclusion. AMED, CINAHL, MedLine, Scopus and Web of Science databases were searched from inception to March 2024. Risk of bias was assessed using validated tools: Murad et al.'s tool for case series/reports and ROBINS-I for non-randomised studies. Quantitative synthesis of descriptive statistics and narrative summary were performed.<br><br>RESULTS: Two retrospective studies and 60 case series/reports were included, describing 76 fistulae (34 urogenital, 42 rectovaginal). The retrospective studies estimated the prevalence of fistulae to be 3%. Of reported fistulae, 45% occurred with Gellhorn, 16% with ring, 11% with shelf and 9% with cube pessaries. Fifty percent were associated with neglected pessary care. Conservative management resulted in size reduction or resolution in 69% of fistulae: this approach should be considered. Vaginal (88%) and abdominal (100%) vesicovaginal fistula repairs were successful. Diverting ostomies were popular for rectovaginal fistulae but often resulted in permanent stoma without reducing mortality, recurrence or repair failure. Colpocleisis represents an effective procedure for managing co-existing POP.<br><br>CONCLUSIONS: The prevalence of fistulae from pessary use is likely&#x2009;<&#x2009;1% but may rise to 3% with risk factors present, including Gellhorn pessaries and neglected care. Both conservative and surgical management are viable treatment options.}, }
@article {pmid39832811, year = {2025}, author = {Ghaderi, S and Mohammadi, S and Ahmadzadeh, AM and Darmiani, K and Arab Bafrani, M and Jashirenezhad, N and Helfi, M and Alibabaei, S and Azadi, S and Heidary, S and Fatehi, F}, title = {Thalamic Magnetic Susceptibility (χ) Alterations in Neurodegenerative Diseases: A Systematic Review and Meta-Analysis of Quantitative Susceptibility Mapping Studies.}, journal = {Journal of magnetic resonance imaging : JMRI}, volume = {62}, number = {1}, pages = {271-294}, doi = {10.1002/jmri.29698}, pmid = {39832811}, issn = {1522-2586}, mesh = {Humans ; *Brain Mapping/methods ; Iron/metabolism ; *Magnetic Resonance Imaging/methods ; *Neurodegenerative Diseases/diagnostic imaging ; *Thalamus/diagnostic imaging ; }, abstract = {BACKGROUND: Quantitative Susceptibility Mapping (QSM) provides a non-invasive post-processing method to investigate alterations in magnetic susceptibility (χ), reflecting iron content within brain regions implicated in neurodegenerative diseases (NDDs).<br><br>PURPOSE: To investigate alterations in thalamic &#x3c7; in patients with NDDs using QSM.<br><br>STUDY TYPE: Systematic review and meta-analysis.<br><br>POPULATION: A total of 696 patients with NDDs and 760 healthy controls (HCs) were included in 27 studies.<br><br>FIELD STRENGTH/SEQUENCE: Three-dimensional multi-echo gradient echo sequence for QSM at mostly 3 Tesla.<br><br>ASSESSMENT: Studies reporting QSM values in the thalamus of patients with NDDs were included. Following PRISMA 2020, we searched the four major databases including PubMed, Scopus, Web of Science, and Embase for peer-reviewed studies published until October 2024.<br><br>STATISTICAL TESTS: Meta-analysis was conducted using a random-effects model to calculate the standardized mean difference (SMD) between patients and HCs.<br><br>RESULTS: The pooled SMD indicated a significant increase in thalamic &#x3c7; in NDDs compared to HCs (SMD&#x2009;=&#x2009;0.42, 95% CI: 0.05-0.79; k&#x2009;=&#x2009;27). Notably, amyotrophic lateral sclerosis patients showed a significant increase in thalamic &#x3c7; (1.09, 95% CI: 0.65-1.53, k&#x2009;=&#x2009;2) compared to HCs. Subgroup analyses revealed significant &#x3c7; alterations in younger patients (mean age&#x2009;&#x2264;&#x2009;62&#x2009;years; 0.56, 95% CI: 0.10-1.02, k&#x2009;=&#x2009;11) and studies using greater coil channels (coil channels&#x2009;>&#x2009;16; 0.64, 95% CI: 0.28-1.00, k&#x2009;=&#x2009;9). Publication bias was not detected and quality assessment indicated that studies with a lower risk of bias presented more reliable findings (0.75, 95% CI: 0.32-1.18, k&#x2009;=&#x2009;9). Disease type was the primary driver of heterogeneity, while other factors, such as coil type and geographic location, also contributed to variability.<br><br>DATA CONCLUSION: Our findings support the potential of QSM for investigating thalamic involvement in NDDs. Future research should focus on disease-specific patterns, thalamic-specific nucleus analysis, and temporal evolution.<br><br>PLAIN LANGUAGE SUMMARY: Our research investigated changes in iron levels within the thalamus, a brain region crucial for motor and cognitive functions, in patients with various neurodegenerative diseases (NDDs). The study utilized a specific magnetic resonance imaging technique called Quantitative Susceptibility Mapping (QSM) to measure iron content. It identified a significant increase in thalamic iron levels in NDD patients compared to healthy individuals. This increase was particularly prominent in patients with Amyotrophic Lateral Sclerosis, younger individuals, and studies employing advanced imaging equipment.<br><br>LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.}, }
@article {pmid39831374, year = {2025}, author = {Risi, B and Imarisio, A and Cuconato, G and Padovani, A and Valente, EM and Filosto, M}, title = {Mitochondrial DNA (mtDNA) as fluid biomarker in neurodegenerative disorders: A systematic review.}, journal = {European journal of neurology}, volume = {32}, number = {1}, pages = {e70014}, pmid = {39831374}, issn = {1468-1331}, mesh = {Humans ; Alzheimer Disease/cerebrospinal fluid/blood ; Amyotrophic Lateral Sclerosis/cerebrospinal fluid/blood ; Biomarkers/cerebrospinal fluid/blood ; *DNA, Mitochondrial/cerebrospinal fluid/blood ; *Neurodegenerative Diseases/cerebrospinal fluid/blood/genetics/diagnosis ; Parkinson Disease/cerebrospinal fluid/blood ; }, abstract = {BACKGROUND: Several studies evaluated peripheral and cerebrospinal fluid (CSF) mtDNA as a putative biomarker in neurodegenerative diseases, often yielding inconsistent findings. We systematically reviewed the current evidence assessing blood and CSF mtDNA levels and variant burden in Parkinson's disease (PD), Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS). Multiple sclerosis (MS) was also included as a paradigm of chronic neuroinflammation-driven neurodegeneration.<br><br>METHODS: Medline, Embase, Scopus and Web of Science were searched for articles published from inception until October 2023. Studies focused on mtDNA haplogroups or hereditary pathogenic variants were excluded. Critical appraisal was performed using the Quality Assessment for Diagnostic Accuracy Studies criteria.<br><br>RESULTS: Fifty-nine original studies met our a priori-defined inclusion criteria. The majority of CSF-focused studies showed (i) decreased mtDNA levels in PD and AD; (ii) increased levels in MS compared to controls. No studies evaluated CSF mtDNA in ALS. Results focused on blood cell-free and intracellular mtDNA were contradictory, even within studies evaluating the same disease. This poor reproducibility is likely due to the lack of consideration of the many factors known to affect mtDNA levels. mtDNA damage and methylation levels were increased and reduced in patients compared to controls, respectively. A few studies investigated the correlation between mtDNA and disease severity, with conflicting results.<br><br>CONCLUSIONS: Additional well-designed studies are needed to evaluate CSF and blood mtDNA profiles as putative biomarkers in neurodegenerative diseases. The identification of "mitochondrial subtypes" of disease may enable novel precision medicine strategies to counteract neurodegeneration.}, }
@article {pmid39828029, year = {2025}, author = {Fantini, J and Azzaz, F and Di Scala, C and Aulas, A and Chahinian, H and Yahi, N}, title = {Conformationally adaptive therapeutic peptides for diseases caused by intrinsically disordered proteins (IDPs). New paradigm for drug discovery: Target the target, not the arrow.}, journal = {Pharmacology &amp; therapeutics}, volume = {267}, number = {}, pages = {108797}, doi = {10.1016/j.pharmthera.2025.108797}, pmid = {39828029}, issn = {1879-016X}, mesh = {*Intrinsically Disordered Proteins/chemistry/metabolism/antagonists &amp; inhibitors ; Humans ; *Drug Discovery/methods ; *Peptides/therapeutic use/chemistry/pharmacology ; Protein Conformation ; Animals ; Drug Design ; }, abstract = {The traditional model of protein structure determined by the amino acid sequence is today seriously challenged by the fact that approximately half of the human proteome is made up of proteins that do not have a stable 3D structure, either partially or in totality. These proteins, called intrinsically disordered proteins (IDPs), are involved in numerous physiological functions and are associated with severe pathologies, e.g. Alzheimer, Parkinson, Creutzfeldt-Jakob, amyotrophic lateral sclerosis (ALS), and type 2 diabetes. Targeting these proteins is challenging for two reasons: i) we need to preserve their physiological functions, and ii) drug design by molecular docking is not possible due to the lack of reliable starting conditions. Faced with this challenge, the solutions proposed by artificial intelligence (AI) such as AlphaFold are clearly unsuitable. Instead, we suggest an innovative approach consisting of mimicking, in short synthetic peptides, the conformational flexibility of IDPs. These peptides, which we call adaptive peptides, are derived from the domains of IDPs that become structured after interacting with a ligand. Adaptive peptides are designed with the aim of selectively antagonizing the harmful effects of IDPs, without targeting them directly but through selected ligands, without affecting their physiological properties. This "target the target, not the arrow" strategy is promised to open a new route to drug discovery for currently undruggable proteins.}, }
@article {pmid39828018, year = {2025}, author = {Sharma, D and Singh, V and Kumar, A and Singh, TG}, title = {Genistein: A promising ally in combating neurodegenerative disorders.}, journal = {European journal of pharmacology}, volume = {991}, number = {}, pages = {177273}, doi = {10.1016/j.ejphar.2025.177273}, pmid = {39828018}, issn = {1879-0712}, mesh = {*Genistein/therapeutic use/pharmacology ; Humans ; Animals ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Neuroprotective Agents/therapeutic use/pharmacology ; }, abstract = {Neurodegenerative disorders arise when nerve cells in the brain or peripheral nervous system gradually lose functions and eventually die. Although certain therapies may alleviate some of the physical and mental symptoms associated with neurodegenerative disorders, hence slowing their progression, but no sure-shot treatment is currently available. It was shown that the rise in life expectancy and the number of elderly people in the community led to an increasing trend in the incidence and prevalence of neurodegenerative disease. Phytomolecules are demonstrating their effectiveness in combating, regression, and delaying various diseases. Genistein is one of soy isoflavone with antioxidant, anti-inflammatory, and estrogenic effects. Researchers demonstrated that Genistein treatment significantly reduced hyperglycemia, improved cognitive performance by modulating acetylcholinesterase activity and oxidative stress, and alleviated neuroinflammatory conditions in mice. This paper evaluates (in vivo and in vitro) various molecular targets of isoflavones and their ability to effectively counter several neurodegenerative disorders such as Parkinson's, Alzheimer's, and Huntington's diseases and amyotrophic lateral sclerosis. In this review, we aim to provide an overview of the role that genistein plays in delaying the development of neurodegenerative disorders.}, }
@article {pmid39827337, year = {2025}, author = {Mwale, PF and Hsieh, CT and Yen, TL and Jan, JS and Taliyan, R and Yang, CH and Yang, WB}, title = {Chitinase-3-like-1: a multifaceted player in neuroinflammation and degenerative pathologies with therapeutic implications.}, journal = {Molecular neurodegeneration}, volume = {20}, number = {1}, pages = {7}, pmid = {39827337}, issn = {1750-1326}, support = {NSTC 112-2320-B-038 -018 -MY3//National Science and Technology Council/ ; CGH-MR-A11315//Cathay General Hospital/ ; CGH-MR-A11314//Cathay General Hospital/ ; }, mesh = {Humans ; *Chitinase-3-Like Protein 1/metabolism ; *Neuroinflammatory Diseases/metabolism/pathology ; *Neurodegenerative Diseases/metabolism/pathology ; Animals ; Biomarkers/metabolism ; Inflammation/metabolism ; }, abstract = {Chitinase-3-like-1 (CHI3L1) is an evolutionarily conserved protein involved in key biological processes, including tissue remodeling, angiogenesis, and neuroinflammation. It has emerged as a significant player in various neurodegenerative diseases and brain disorders. Elevated CHI3L1 levels have been observed in neurological conditions such as traumatic brain injury (TBI), Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), Creutzfeldt-Jakob disease (CJD), multiple sclerosis (MS), Neuromyelitis optica (NMO), HIV-associated dementia (HAD), Cerebral ischemic stroke (CIS), and brain tumors. This review explores the role of CHI3L1 in the pathogenesis of these disorders, with a focus on its contributions to neuroinflammation, immune cell infiltration, and neuronal degeneration. As a key regulator of neuroinflammation, CHI3L1 modulates microglia and astrocyte activity, driving the release of proinflammatory cytokines that exacerbate disease progression. In addition to its role in disease pathology, CHI3L1 has emerged as a promising biomarker for the diagnosis and monitoring of brain disorders. Elevated cerebrospinal fluid (CSF) levels of CHI3L1 have been linked to disease severity and cognitive decline, particularly in AD and MS, highlighting its potential for clinical diagnostics. Furthermore, therapeutic strategies targeting CHI3L1, such as small-molecule inhibitors and neutralizing antibodies, have shown promise in preclinical studies, demonstrating reduced neuroinflammation, amyloid plaque accumulation, and improved neuronal survival. Despite its therapeutic potential, challenges remain in developing selective and safe CHI3L1-targeted therapies, particularly in ensuring effective delivery across the blood-brain barrier and mitigating off-target effects. This review addresses the complexities of targeting CHI3L1, highlights its potential in precision medicine, and outlines future research directions aimed at unlocking its full therapeutic potential in treating neurodegenerative diseases and brain pathologies.}, }
@article {pmid39822898, year = {2024}, author = {Malamule, MM and Gundo, R and Mulaudzi, M}, title = {The effect of coronavirus disease 2019 vaccination on pregnant women: A scoping review.}, journal = {Health SA = SA Gesondheid}, volume = {29}, number = {}, pages = {2577}, pmid = {39822898}, issn = {2071-9736}, abstract = {BACKGROUND: Globally, reports have shown that pregnant women refuse to receive the coronavirus disease 2019 (COVID-19) vaccine. This has posed a significant concern given the global impact of the COVID-19 pandemic.<br><br>AIM: This study aims to explore the current evidence on the effect of COVID-19 vaccination on pregnant women.<br><br>METHOD: A scoping review was conducted using Levac et al.'s five-stage framework. Relevant articles were searched in the Web of Science, PubMed, Scopus and EBSCOhost (CINAHL) databases. The identified articles were screened based on predetermined inclusion and exclusion criteria. Data from the selected articles were charted and summarised into meaningful units.<br><br>RESULTS: Twelve articles from developed countries were included in the review. Studies have reported that COVID-19 vaccination during pregnancy is generally safe and does not increase the risk of pregnancy complications. There was no significant difference in delivery outcomes between vaccinated and unvaccinated women. Neonatal outcomes were not affected by the vaccination. However, one study identified a potential risk of spontaneous abortion between 6 and 9 weeks of gestation among vaccinated women.<br><br>CONCLUSION: Coronavirus disease 2019 vaccination is considered safe during pregnancy. While some studies have identified potential associations with certain conditions, the overall benefits of vaccination outweigh the risks. Continued monitoring of the safety and effectiveness of COVID-19 vaccines during pregnancy is recommended. Pregnant women should consult healthcare providers to make informed decisions regarding vaccination.<br><br>CONTRIBUTION: The findings of this review may assist in alleviating anxiety and reducing vaccine hesitancy among pregnant women.}, }
@article {pmid39822067, year = {2025}, author = {Zhu, Y and Verkhratsky, A and Chen, H and Yi, C}, title = {Understanding glucose metabolism and insulin action at the blood-brain barrier: Implications for brain health and neurodegenerative diseases.}, journal = {Acta physiologica (Oxford, England)}, volume = {241}, number = {2}, pages = {e14283}, pmid = {39822067}, issn = {1748-1716}, support = {RCJC20231211090018040//Shenzhen Fundamental Research Program/ ; ZDSYS20220606100801003//Shenzhen Fundamental Research Program/ ; 2022B1515020012//Basic and Applied Basic Research Foundation of Guangdong Province/ ; 32170980//National Natural Science Foundation of China/ ; }, mesh = {*Blood-Brain Barrier/metabolism ; Humans ; *Neurodegenerative Diseases/metabolism ; Animals ; *Insulin/metabolism ; *Glucose/metabolism ; *Brain/metabolism ; }, abstract = {The blood-brain barrier (BBB) is a highly selective, semipermeable barrier critical for maintaining brain homeostasis. The BBB regulates the transport of essential nutrients, hormones, and signaling molecules between the bloodstream and the central nervous system (CNS), while simultaneously protecting the brain from potentially harmful substances and pathogens. This selective permeability ensures that the brain is nourished and shielded from toxins. An exception to this are brain regions, such as the hypothalamus and circumventricular organs, which are irrigated by fenestrated capillaries, allowing rapid and direct response to various blood components. We overview the metabolic functions of the BBB, with an emphasis on the impact of altered glucose metabolism and insulin signaling on BBB in the pathogenesis of neurodegenerative diseases. Notably, endothelial cells constituting the BBB exhibit distinct metabolic characteristics, primarily generating ATP through aerobic glycolysis. This occurs despite their direct exposure to the abundant oxygen in the bloodstream, which typically supports oxidative phosphorylation. The effects of insulin on astrocytes, which form the glial limitans component of the BBB, show a marked sexual dimorphism. BBB nutrient sensing in the hypothalamus, along with insulin signaling, regulates systemic metabolism. Insulin modifies BBB permeability by regulating the expression of tight junction proteins, angiogenesis, and vascular remodeling, as well as modulating blood flow in the brain. The disruptions in glucose and insulin signaling are particularly evident in neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, where BBB breakdown accelerates cognitive decline. This review highlights the critical role of normal glucose metabolism and insulin signaling in maintaining BBB functionality and investigates how disruptions in these pathways contribute to the onset and progression of neurodegenerative diseases.}, }
@article {pmid39821843, year = {2025}, author = {Zhang, J and Guo, R and Zhou, Z and Fu, Z and Akogo, HY and Li, Y and Zhang, X and Wang, N and Liu, Y and Li, H and Feng, B and Cui, H and Ma, J}, title = {Neural Stem/Progenitor Cell Therapy in Patients and Animals with Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-analysis.}, journal = {Molecular neurobiology}, volume = {62}, number = {5}, pages = {6521-6536}, pmid = {39821843}, issn = {1559-1182}, support = {81801278//National Natural Science Foundation of China/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/therapy/physiopathology ; Animals ; Humans ; *Neural Stem Cells/transplantation/cytology ; *Stem Cell Transplantation/methods ; Disease Models, Animal ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative malady that causes progressive degeneration and loss of motor neuron function in the brain and spinal cord, eventually resulting in muscular atrophy, paralysis, and death. Neural stem/progenitor cell (NSPC) transplantation can improve bodily function in animals and delay disease progression in patients with ALS. This paper summarizes and analyzes the efficacy and safety of neural stem/progenitor cell (NSPC) transplantation as a treatment for ALS, aiming to improve function and delay disease progression in patients. We present a summary of the pathogenic mechanism and causative genes associated with ALS and describe the mechanism and efficacy of NSPC treatment for ALS. We comprehensively searched for relevant English-language articles published between January 1, 2000 and October 1, 2023, across the following five medical databases: PubMed, EMBASE, OVID, Web of Science, and the Cochrane Library. We examined experimental indices of physical function in animals and patients who underwent stem cell transplantation. All statistical analyses were performed via Review Manager 5.4. The study comprised a total of 16 investigations, including 5 clinical studies and 11 animal studies and involving 66 patients and 203 animals. The meta-analysis revealed that the administration of NSPCs appeared to yield positive outcomes in clinical patients, as assessed by the ALS functional rating scale and forced vital capacity. Furthermore, improvements following cell injection were observed in the rotarod test results, the Basso-Beattie-Bresnahan Locomotor Rating Scale score, weight, and survival time. Our meta-analysis, which was grounded in randomized controlled trials, revealed that the transplantation of neural stem/progenitor cells (NSPCs), has potential effects on ALS patients, enhancing the physical function of animals and mitigating degenerative effects in individuals. These underscored the promise of NSPC therapy as a viable treatment option. We report that the transplantation of neural stem/progenitor cells (NSPCs) is promising for enhancing bodily function and slowing the progression of ALS in affected patients. In this review, we summarize the treatment of ALS with NSPCs, evaluating both its efficacy and safety. Through database searches, we identified 16 studies involving 66 patients and 203 animals and analyzed the experimental indices of physical function following stem cell transplantation. The meta-analysis results indicated a positive impact of NSPCs on the clinical conditions of patients and the behavior of animals. A meta-analysis of randomized controlled trials further supported the conclusion that NSPC transplantation has a beneficial effect on improving physical function and mitigating degeneration in ALS patients.}, }
@article {pmid39820998, year = {2025}, author = {Hamad, AA and Alkhawaldeh, IM and Nashwan, AJ and Meshref, M and Imam, Y}, title = {Tofersen for SOD1 amyotrophic lateral sclerosis: a systematic review and meta-analysis.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {46}, number = {5}, pages = {1977-1985}, pmid = {39820998}, issn = {1590-3478}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics ; *Superoxide Dismutase-1/genetics ; *Oligonucleotides/therapeutic use/pharmacology ; *Oligonucleotides, Antisense/therapeutic use/pharmacology ; }, abstract = {OBJECTIVE: Tofersen, an antisense oligonucleotide, has recently received FDA and EMA approval for treating amyotrophic lateral sclerosis (ALS) in adults with SOD1 gene mutations. This systematic review and meta-analysis synthesized evidence on tofersen's safety and efficacy in patients with SOD1-related ALS.<br><br>METHODS: A comprehensive search of three databases was conducted from inception through October 2024. Eligible studies included clinical trials, observational studies, and case studies. Meta-analyses were conducted using a random-effects model in RevMan.<br><br>RESULTS: Twelve studies involving 195 patients treated with tofersen met the inclusion criteria, comprising two randomized controlled trials (RCTs), five cohort studies, one case series, and four case reports. Tofersen demonstrated promising effects, notably reducing SOD1 levels in cerebrospinal fluid and neurofilament light chain (NfL) in plasma, a biomarker strongly correlated with ALS progression and survival. Meta-analysis of RCTs showed a significantly lower rate of decline in ALS Functional Rating Scale-Revised (ALSFRS-R) scores from baseline in the tofersen group compared to placebo (SMD&#x2009;=&#x2009;0.44, 95% CI [0.05 to 0.83], P&#x2009;=&#x2009;0.03) and a significant reduction in the decline of predicted Slow Vital Capacity (P&#x2009;=&#x2009;0.005). In a pre-post meta-analysis of five studies, a significant decrease in ALS progression rate (ALSFRS-R decline rate) was observed (MD = -0.28, 95% CI [-0.40 to -0.15], P&#x2009;<&#x2009;0.0001). Reported adverse events were consistent with ALS progression or procedural effects.<br><br>CONCLUSION: Current evidence suggests that tofersen effectively reduces SOD1 and NfL levels and slow disease progression in SOD1 ALS, showing promise as a targeted therapeutic option.}, }
@article {pmid39820861, year = {2025}, author = {van Zundert, B and Montecino, M}, title = {Epigenetics in Neurodegenerative Diseases.}, journal = {Sub-cellular biochemistry}, volume = {108}, number = {}, pages = {73-109}, pmid = {39820861}, issn = {0306-0225}, mesh = {Humans ; *Epigenesis, Genetic ; Animals ; *Neurodegenerative Diseases/genetics/metabolism/pathology ; *DNA Methylation ; *Alzheimer Disease/genetics/pathology/metabolism ; *Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism ; Frontotemporal Dementia/genetics/pathology/metabolism ; }, abstract = {Healthy brain functioning requires a continuous fine-tuning of gene expression, involving changes in the epigenetic landscape and 3D chromatin organization. Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD) are three multifactorial neurodegenerative diseases (NDDs) that are partially explained by genetics (gene mutations and genetic risk factors) and influenced by non-genetic factors (i.e., aging, lifestyle, and environmental conditions). Examining comprehensive studies of global and locus-specific (epi)genomic and transcriptomic alterations in human and mouse brain samples at the cell-type resolution has uncovered important phenomena associated with AD. First, DNA methylation and histone marks at promoters contribute to transcriptional dysregulation of genes that are directly implicated in AD pathogenesis (i.e., APP), neuroplasticity and cognition (i.e., PSD95), and microglial activation (i.e., TREM2). Second, the presence of AD genetic risk variants in cell-type-specific distal enhancers (i.e., BIN1 in microglia) alters transcription, presumably by disrupting associated enhancer-promoter interactions and chromatin looping. Third, epigenomic erosion is associated with widespread transcriptional disruption and cell identity loss. And fourth, aging, high cholesterol, air pollution, and pesticides have emerged as potential drivers of AD by inducing locus-specific and global epigenetic modifications that impact key AD-related pathways. Epigenetic studies in ALS/FTD also provide evidence that genetic and non-genetic factors alter gene expression profiles in neurons and astrocytes through aberrant epigenetic mechanisms. We additionally overview the recent development of potential new therapeutic strategies involving (epi)genetic editing and the use of small chromatin-modifying molecules (epidrugs).}, }
@article {pmid39819742, year = {2025}, author = {Xu, B and Lei, X and Yang, Y and Yu, J and Chen, J and Xu, Z and Ye, K and Zhang, J}, title = {Peripheral proteinopathy in neurodegenerative diseases.}, journal = {Translational neurodegeneration}, volume = {14}, number = {1}, pages = {2}, pmid = {39819742}, issn = {2047-9158}, support = {82020108012//National Natural Science Foundation of China/ ; 82371250//National Natural Science Foundation of China/ ; LY24H090006//Natural Science Foundation of Zhejiang Province/ ; LZ23H090002//Natural Science Foundation of Zhejiang Province/ ; 2024C03098//Key Research and Development Program of Zhejiang Province/ ; 2024SSYS0018//Key Research and Development Program of Zhejiang Province/ ; ZR2022QH177//Natural Science Foundation of Shandong Province/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/pathology ; Animals ; alpha-Synuclein/metabolism ; Amyloid beta-Peptides/metabolism ; tau Proteins/metabolism ; }, abstract = {Proteinopathies in neurology typically refer to pathological changes in proteins associated with neurological diseases, such as the aggregation of amyloid β and Tau in Alzheimer's disease, α-synuclein in Parkinson's disease and multiple system atrophy, and TAR DNA-binding protein 43 in amyotrophic lateral sclerosis and frontotemporal dementia. Interestingly, these proteins are also commonly found in peripheral tissues, raising important questions about their roles in neurological disorders. Multiple studies have shown that peripherally derived pathological proteins not only travel to the brain through various routes, aggravating brain pathology, but also contribute significantly to peripheral dysfunction, highlighting their crucial impact on neurological diseases. Investigating how these peripherally derived proteins influence the progression of neurological disorders could open new horizons for achieving early diagnosis and treatment. This review summarizes the distribution, transportation pathways, and pathogenic mechanisms of several neurodegenerative disease-related pathological proteins in the periphery, proposing that targeting these peripheral pathological proteins could be a promising strategy for preventing and managing neurological diseases.}, }
@article {pmid39816800, year = {2025}, author = {Shokr, MM and Badawi, GA and Elshazly, SM and Zaki, HF and Mohamed, AF}, title = {Sigma 1 Receptor and Its Pivotal Role in Neurological Disorders.}, journal = {ACS pharmacology &amp; translational science}, volume = {8}, number = {1}, pages = {47-65}, pmid = {39816800}, issn = {2575-9108}, abstract = {Sigma 1 receptor (S1R) is a multifunctional, ligand-activated protein located in the membranes of the endoplasmic reticulum (ER). It mediates a variety of neurological disorders, including epilepsy, amyotrophic lateral sclerosis, Alzheimer's disease, Huntington's disease. The wide neuroprotective effects of S1R agonists are achieved by a variety of pro-survival and antiapoptotic S1R-mediated signaling functions. Nonetheless, relatively little is known about the specific molecular mechanisms underlying S1R activity. Many studies on S1R protein have highlighted the importance of maintaining normal cellular homeostasis through its control of calcium and lipid exchange between the ER and mitochondria, ER-stress response, and many other mechanisms. In this review, we will discuss S1R different cellular localization and explain S1R-associated biological activity, such as its localization in the ER-plasma membrane and Mitochondrion-Associated ER Membrane interfaces. While outlining the cellular mechanisms and important binding partners involved in these processes, we also explained how the dysregulation of these pathways contributes to neurodegenerative disorders.}, }
@article {pmid39809929, year = {2025}, author = {Antico, O and Thompson, PW and Hertz, NT and Muqit, MMK and Parton, LE}, title = {Targeting mitophagy in neurodegenerative diseases.}, journal = {Nature reviews. Drug discovery}, volume = {24}, number = {4}, pages = {276-299}, pmid = {39809929}, issn = {1474-1784}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; *Mitophagy/drug effects/physiology ; *Neurodegenerative Diseases/drug therapy/metabolism/genetics ; Animals ; Mitochondria/drug effects/metabolism ; Protein Kinases ; }, abstract = {Mitochondrial dysfunction is a hallmark of idiopathic neurodegenerative diseases, including Parkinson disease, amyotrophic lateral sclerosis, Alzheimer disease and Huntington disease. Familial forms of Parkinson disease and amyotrophic lateral sclerosis are often characterized by mutations in genes associated with mitophagy deficits. Therefore, enhancing the mitophagy pathway may represent a novel therapeutic approach to targeting an underlying pathogenic cause of neurodegenerative diseases, with the potential to deliver neuroprotection and disease modification, which is an important unmet need. Accumulating genetic, molecular and preclinical model-based evidence now supports targeting mitophagy in neurodegenerative diseases. Despite clinical development challenges, small-molecule-based approaches for selective mitophagy enhancement - namely, USP30 inhibitors and PINK1 activators - are entering phase I clinical trials for the first time.}, }
@article {pmid39801792, year = {2024}, author = {Ansari, U and Wen, J and Syed, B and Nadora, D and Sedighi, R and Nadora, D and Chen, V and Lui, F}, title = {Analyzing the potential of neuronal pentraxin 2 as a biomarker in neurological disorders: A literature review.}, journal = {AIMS neuroscience}, volume = {11}, number = {4}, pages = {505-519}, pmid = {39801792}, issn = {2373-7972}, abstract = {Neuronal pentraxin 2 (NP2) plays a significant role in synaptic plasticity, neuronal survival, and excitatory synapse regulation. Emerging research suggests that NP2 is implicated in the pathogenesis of various neurological disorders, including neurodegenerative diseases, neuropsychiatric disorders, and neuropathies. This literature review extensively analyzes NP2's role in these conditions, thereby highlighting its contributions to synaptic dysfunction, neuroinflammation, and neurotoxic protein aggregation. In Alzheimer's and Parkinson's diseases, NP2 is linked to amyloid-beta aggregation and dopaminergic neuron degeneration, respectively. Additionally, altered NP2 expression is observed in schizophrenia and bipolar disorder, thus suggesting its involvement in synaptic dysfunction and neurotransmitter imbalance. In neuropathic pain and epilepsy, NP2 modulates the synaptic plasticity and inflammatory responses, with altered levels correlating with disease severity. Furthermore, NP2's involvement in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) emphasizes its broad impact on neuronal health. Understanding NP2's multifaceted roles may reveal novel therapeutic targets and improve the clinical outcomes for these neurological disorders. Though the precise role of NP2 remains uncertain, its clinical potential and initial findings justify further investigations into neuronal pentraxins and other related neuroproteins.}, }
@article {pmid39799559, year = {2025}, author = {Üremiş, N and Üremiş, MM}, title = {Oxidative/Nitrosative Stress, Apoptosis, and Redox Signaling: Key Players in Neurodegenerative Diseases.}, journal = {Journal of biochemical and molecular toxicology}, volume = {39}, number = {1}, pages = {e70133}, pmid = {39799559}, issn = {1099-0461}, support = {//This research was supported by the T&#xfc;rkiye Bilimsel ve Teknolojik Ara&#x15f;t&#x131;rma Kurumu (grant number: TUB1)./ ; }, mesh = {Humans ; *Apoptosis ; *Oxidative Stress ; *Neurodegenerative Diseases/metabolism/pathology ; *Nitrosative Stress ; Animals ; *Signal Transduction ; Oxidation-Reduction ; Reactive Nitrogen Species/metabolism ; Reactive Oxygen Species/metabolism ; }, abstract = {Neurodegenerative diseases are significant health concerns that have a profound impact on the quality and duration of life for millions of individuals. These diseases are characterized by pathological changes in various brain regions, specific genetic mutations associated with the disease, deposits of abnormal proteins, and the degeneration of neurological cells. As neurodegenerative disorders vary in their epidemiological characteristics and vulnerability of neurons, treatment of these diseases is usually aimed at slowing disease progression. The heterogeneity of genetic and environmental factors involved in the process of neurodegeneration makes current treatment methods inadequate. However, the existence of common molecular mechanisms in the pathogenesis of these diseases may allow the development of new targeted therapeutic strategies. Oxidative and nitrosative stress damages membrane components by accumulating ROS and RNS and disrupting redox balance. This process results in the induction of apoptosis, which is important in the pathogenesis of neurodegenerative diseases through oxidative stress. Studies conducted using postmortem human samples, animal models, and cell cultures have demonstrated that oxidative stress, nitrosative stress, and apoptosis are crucial factors in the development of diseases such as Alzheimer's, Parkinson's, Multiple Sclerosis, amyotrophic lateral sclerosis, and Huntington's disease. The excessive production of reactive oxygen and nitrogen species, elevated levels of free radicals, heightened mitochondrial stress, disturbances in energy metabolism, and the oxidation and nitrosylation of cellular macromolecules are recognized as triggers for neuronal cell death. Challenges in managing and treating neurodegenerative diseases require a better understanding of this field at the molecular level. Therefore, this review elaborates on the molecular mechanisms by which oxidative and nitrosative stress are involved in neuronal apoptosis.}, }
@article {pmid39798853, year = {2025}, author = {Guan, D and Liang, C and Zheng, D and Liu, S and Luo, J and Cai, Z and Zhang, H and Chen, J}, title = {The role of mitochondrial remodeling in neurodegenerative diseases.}, journal = {Neurochemistry international}, volume = {183}, number = {}, pages = {105927}, doi = {10.1016/j.neuint.2024.105927}, pmid = {39798853}, issn = {1872-9754}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/pathology ; *Mitochondria/metabolism/pathology ; Animals ; Energy Metabolism/physiology ; *Mitochondrial Dynamics/physiology ; }, abstract = {Neurodegenerative diseases are a group of diseases that pose a serious threat to human health, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and Amyotrophic Lateral Sclerosis (ALS). In recent years, it has been found that mitochondrial remodeling plays an important role in the onset and progression of neurodegenerative diseases. Mitochondrial remodeling refers to the dynamic regulatory process of mitochondrial morphology, number and function, which can affect neuronal cell function and survival by regulating mechanisms such as mitochondrial fusion, division, clearance and biosynthesis. Mitochondrial dysfunction is an important intrinsic cause of the pathogenesis of neurodegenerative diseases. Mitochondrial remodeling abnormalities are involved in energy metabolism in neurodegenerative diseases. Pathological changes in mitochondrial function and morphology, as well as interactions with other organelles, can affect the energy metabolism of dopaminergic neurons and participate in the development of neurodegenerative diseases. Since the number of patients with PD and AD has been increasing year by year in recent years, it is extremely important to take effective interventions to significantly reduce the number of morbidities and to improve people's quality of life. More and more researchers have suggested that mitochondrial remodeling and related dynamics may positively affect neurodegenerative diseases in terms of neuronal and self-adaptation to the surrounding environment. Mitochondrial remodeling mainly involves its own fission and fusion, energy metabolism, changes in channels, mitophagy, and interactions with other cellular organelles. This review will provide a systematic summary of the role of mitochondrial remodeling in neurodegenerative diseases, with the aim of providing new ideas and strategies for further research on the treatment of neurodegenerative diseases.}, }
@article {pmid39796536, year = {2024}, author = {Cuffaro, F and Lamminpää, I and Niccolai, E and Amedei, A}, title = {Nutritional and Microbiota-Based Approaches in Amyotrophic Lateral Sclerosis: From Prevention to Treatment.}, journal = {Nutrients}, volume = {17}, number = {1}, pages = {}, pmid = {39796536}, issn = {2072-6643}, support = {PNRR-MAD-2022-12375798//Ministero della Salute/ ; PE0000006//Ministry of University and Research (MUR)/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/prevention &amp; control/therapy/microbiology/diet therapy ; Humans ; *Gastrointestinal Microbiome/physiology ; Probiotics ; Dysbiosis ; Prebiotics/administration &amp; dosage ; Fecal Microbiota Transplantation ; Oxidative Stress ; Fatty Acids, Omega-3/administration &amp; dosage ; }, abstract = {Metabolic alterations, including hypermetabolism, lipid imbalances, and glucose dysregulation, are pivotal contributors to the onset and progression of Amyotrophic Lateral Sclerosis (ALS). These changes exacerbate systemic energy deficits, heighten oxidative stress, and fuel neuroinflammation. Simultaneously, gastrointestinal dysfunction and gut microbiota (GM) dysbiosis intensify disease pathology by driving immune dysregulation, compromising the intestinal barrier, and altering gut-brain axis (GBA) signaling, and lastly advancing neurodegeneration. Therapeutic and preventive strategies focused on nutrition offer promising opportunities to address these interconnected pathophysiological mechanisms. Diets enriched with antioxidants, omega-3 fatty acids, and anti-inflammatory compounds-such as the Mediterranean diet-have shown potential in reducing oxidative stress and systemic inflammation. Additionally, microbiota-targeted approaches, including probiotics, prebiotics, postbiotics, and fecal microbiota transplantation, are emerging as innovative tools to restore microbial balance, strengthen gut integrity, and optimize GBA function. This review highlights the critical need for personalized strategies integrating immunonutrition and microbiota modulation to slow ALS progression, improve quality of life, and develop preventive measures for neurodegenerative and neuroinflammatory diseases. Future research should prioritize comprehensive dietary and microbiota-based interventions to uncover their therapeutic potential and establish evidence-based guidelines for managing ALS and related disorders.}, }
@article {pmid39795468, year = {2024}, author = {Yao, X and Yang, X and Lu, Y and Qiu, Y and Zeng, Q}, title = {Review of the Synthesis and Degradation Mechanisms of Some Biodegradable Polymers in Natural Environments.}, journal = {Polymers}, volume = {17}, number = {1}, pages = {}, pmid = {39795468}, issn = {2073-4360}, support = {E0600591//Fujian University of Technology/ ; GY-Z23074//Fujian University of Technology/ ; JAT210285//Education Department of Fujian Province/ ; }, abstract = {The escalating demand for sustainable materials has been fueling the rapid proliferation of the biopolymer market. Biodegradable polymers within natural habitats predominantly undergo degradation mediated by microorganisms. These microorganisms secrete enzymes that cleave long-chain polymers into smaller fragments for metabolic assimilation. This review is centered around dissecting the degradation mechanisms of specific biodegradable polymers, namely PLA, starch-based polymers, and plant fiber-based polymers. Recent investigations have unveiled that PLA exhibits augmented biocompatibility when combined with HA, and its degradation is subject to the influence of enzymatic and abiotic determinants. In the case of starch-based polymers, chemical or physical modifications can modulate their degradation kinetics, as evidenced by Wang et al.'s superhydrophobic starch-based nanocomposite cryogel. For plant fiber-based polymers, the effects of temperature, humidity, and cellulose degradation on their properties, along with the implications of various treatments and additives, are probed, as exemplified by Liu et al.'s study on jute/SiO2/PP composites. Specifically, with respect to PLA, the polymerization process and the role of catalysts such as SnCl2 in governing the structure and biodegradability are expounded in detail. The degradation of PLA in SBF and its interaction with β-TCP particles constitute crucial aspects. For starch-based polymers, the enzymatic degradation catalyzed by amylase and glucosidase and the environmental impacts of temperature and humidity, in addition to the structural ramifications of amylose and amylopectin, are further elucidated. In plant fiber-based polymers, the biodegradation of cellulose and the effects of plasma treatment, electron beam irradiation, nanoparticles, and crosslinking agents on water resistance and stability are explicated with experimental substantiation. This manuscript also delineates technological accomplishments. PLA incorporated with HA demonstrates enhanced biocompatibility and finds utility in drug delivery systems. Starch-based polymers can be engineered for tailored degradation. Plant fiber-based polymers acquire water resistance and durability through specific treatments or the addition of nanoparticles, thereby widening their application spectrum. Synthetic and surface modification methodologies can be harnessed to optimize these materials. This paper also consolidates reaction conditions, research techniques, their merits, and demerits and delves into the biodegradation reaction mechanisms of these polymers. A comprehensive understanding of these degradation mechanisms is conducive to their application and progression in the context of sustainable development and environmental conservation.}, }
@article {pmid39793505, year = {2025}, author = {Ansorge, L and Stejskalová, L}, title = {Water footprint which is not the water footprint: Critical review of the article by Müller et al. (2024).}, journal = {Journal of environmental management}, volume = {374}, number = {}, pages = {124038}, doi = {10.1016/j.jenvman.2025.124038}, pmid = {39793505}, issn = {1095-8630}, mesh = {Water ; *Water Supply ; }, abstract = {This paper presents a critical analysis of the article "Comparison of cooling tower blowdown and enhanced make up water treatment to minimize cooling water footprint" by Müller et al. (2024), which claims to reduce the water footprint (WF) of cooling circuits. The WF concept, introduced in 2002, has evolved with two main approaches: the "volumetric" approach, quantifying water consumption, and the "impact-oriented" approach, assessing impacts associated with water usage. Müller et al.'s method is examined against these established methodologies. The analysis reveals that Müller et al. do not specify their WF approach, but their calculation suggests a "volumetric" WF focus. They claim WF reduction by minimizing cooling tower make-up water and blowdown discharge. However, this does not necessarily reduce the blue WF, as blowdown is typically a return flow that is not included in WF calculations unless it is discharged to another watershed or during a different period. Additionally, the grey WF impact is unclear due to insufficient data on pollutant concentrations in discharged water. The article also does not mention any characterization models or impact categories, making it unlikely that an "impact-oriented" WF approach was used. In conclusion, Müller et al.'s study does not align with established "volumetric" or "impact-oriented" WF methodologies. Instead of reducing water consumption (WF), it focuses on reducing water withdrawals. The use of the term "water footprint" appears to be a misapplication, taking advantage of its popularity. This misuse may mislead readers and underscores the need for rigorous review and critical assessment of published papers.}, }
@article {pmid39792201, year = {2025}, author = {Fu, Z and Feng, B and Akogo, HY and Ma, J and Liu, Y and Quan, H and Zhang, X and Hou, Y and Zhang, X and Ma, J and Cui, H}, title = {Amyotrophic Lateral Sclerosis and Parkinson's Disease: Brain Tissue Transcriptome Analysis Reveals Interactions.}, journal = {Molecular neurobiology}, volume = {62}, number = {5}, pages = {6383-6396}, pmid = {39792201}, issn = {1559-1182}, support = {81801278//National Natural Science Foundation of China/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics ; Humans ; *Parkinson Disease/genetics/metabolism ; *Brain/metabolism/pathology ; *Gene Expression Profiling/methods ; *Transcriptome/genetics ; Gene Regulatory Networks ; Protein Interaction Maps/genetics ; MicroRNAs/genetics/metabolism ; }, abstract = {This study utilises amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD) human brain samples from the GEO database and employs differential expression gene (DEG) analysis to identify genes that are pivotal in both neurodegenerative diseases. Through in depth GO and KEGG enrichment analyses, we elucidated the biological functions and potential pathways associated with these DEGs. Furthermore, by constructing protein‒protein interaction networks, we highlight the significance of shared DEGs in both cellular physiology and disease contexts. Analysis of drug‒gene associations revealed potential therapeutic compounds linked to ALS and PD treatment. Additionally, we explored the interactions between transcription factors, miRNAs, and common DEGs, revealing aspects of gene regulatory networks. This study provides insights into the molecular mechanisms of ALS and PD, offering valuable contributions to ongoing research and potential therapeutic avenues.}, }
@article {pmid39791748, year = {2025}, author = {Moss, KR and Saxena, S}, title = {Schwann Cells in Neuromuscular Disorders: A Spotlight on Amyotrophic Lateral Sclerosis.}, journal = {Cells}, volume = {14}, number = {1}, pages = {}, pmid = {39791748}, issn = {2073-4409}, support = {K22 NS125057/NS/NINDS NIH HHS/United States ; }, mesh = {*Schwann Cells/pathology/metabolism ; *Amyotrophic Lateral Sclerosis/pathology ; Humans ; Animals ; Neuromuscular Diseases/pathology ; Motor Neurons/pathology/metabolism ; Charcot-Marie-Tooth Disease/pathology ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a complex neurodegenerative disease primarily affecting motor neurons, leading to progressive muscle atrophy and paralysis. This review explores the role of Schwann cells in ALS pathogenesis, highlighting their influence on disease progression through mechanisms involving demyelination, neuroinflammation, and impaired synaptic function. While Schwann cells have been traditionally viewed as peripheral supportive cells, especially in motor neuron disease, recent evidence indicates that they play a significant role in ALS by impacting motor neuron survival and plasticity, influencing inflammatory responses, and altering myelination processes. Furthermore, advancements in understanding Schwann cell pathology in ALS combined with lessons learned from studying Charcot-Marie-Tooth disease Type 1 (CMT1) suggest potential therapeutic strategies targeting these cells may support nerve repair and slow disease progression. Overall, this review aims to provide comprehensive insights into Schwann cell classification, physiology, and function, underscoring the critical pathological contributions of Schwann cells in ALS and suggests new avenues for targeted therapeutic interventions aimed at modulating Schwann cell function in ALS.}, }
@article {pmid39791705, year = {2024}, author = {Sun, D and Amiri, M and Meng, Q and Unnithan, RR and French, C}, title = {Calcium Signalling in Neurological Disorders, with Insights from Miniature Fluorescence Microscopy.}, journal = {Cells}, volume = {14}, number = {1}, pages = {}, pmid = {39791705}, issn = {2073-4409}, support = {DP170100363//Australian Research Council under Discovery Project/ ; }, mesh = {*Calcium Signaling ; Humans ; *Nervous System Diseases/metabolism/pathology ; Animals ; *Microscopy, Fluorescence/methods ; Calcium/metabolism ; Neurons/metabolism ; }, abstract = {Neurological disorders (NDs), such as amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and schizophrenia, represent a complex and multifaceted health challenge that affects millions of people around the world. Growing evidence suggests that disrupted neuronal calcium signalling contributes to the pathophysiology of NDs. Additionally, calcium functions as a ubiquitous second messenger involved in diverse cellular processes, from synaptic activity to intercellular communication, making it a potential therapeutic target. Recently, the development of the miniature fluorescence microscope (miniscope) enabled simultaneous recording of the spatiotemporal calcium activity from large neuronal ensembles in unrestrained animals, providing a novel method for studying NDs. In this review, we discuss the abnormalities observed in calcium signalling and its potential as a therapeutic target for NDs. Additionally, we highlight recent studies that utilise miniscope technology to investigate the alterations in calcium dynamics associated with NDs.}, }
@article {pmid39788313, year = {2025}, author = {Cassina, P and Miquel, E and Martínez-Palma, L and Cassina, A}, title = {Mitochondria and astrocyte reactivity: Key mechanism behind neuronal injury.}, journal = {Neuroscience}, volume = {567}, number = {}, pages = {227-234}, doi = {10.1016/j.neuroscience.2024.12.058}, pmid = {39788313}, issn = {1873-7544}, mesh = {Animals ; Humans ; *Astrocytes/metabolism/pathology ; *Mitochondria/metabolism ; *Neurons/metabolism/pathology ; }, abstract = {In this special issue to celebrate the 30th anniversary of the Uruguayan Society for Neuroscience (SNU), we find it pertinent to highlight that research on glial cells in Uruguay began almost alongside the history of SNU and contributed to the understanding of neuron-glia interactions within the international scientific community. Glial cells, particularly astrocytes, traditionally regarded as supportive components in the central nervous system (CNS), undergo notable morphological and functional alterations in response to neuronal damage, a phenomenon referred to as glial reactivity. Among the myriad functions of astrocytes, metabolic support holds significant relevance for neuronal function, given the high energy demand of the nervous system. Although astrocytes are typically considered to exhibit low mitochondrial respiratory chain activity, they possess a noteworthy mitochondrial network. Interestingly, both the morphology and activity of these organelles change following glial reactivity. Despite receiving less attention compared to studies on neuronal mitochondria, recent studies indicate that mitochondria play a crucial role in driving the transition of astrocytes from a quiescent to a reactive state in various neurological disorders. Notably, stimulating mitochondria in astrocytes has been shown to reduce damage associated with the neurodegenerative disease amyotrophic lateral sclerosis. Here, we focus on studies supporting the emerging paradigm that metabolic reprogramming occurs in astrocytes following damage, which is associated with their phenotypic shift to a new functional state that significantly influences the progression of pathology. Thus, exploring mitochondrial activity and metabolic reprogramming within glial cells may provide valuable insights for developing innovative therapeutic approaches to mitigate neuronal damage. In this review, we focus on studies supporting the emerging paradigm that metabolic reprogramming occurs in astrocytes following damage, which is associated with their phenotypic shift to a new functional state that significantly influences the progression of pathology. Thus, exploring mitochondrial activity and metabolic reprogramming within glial cells may provide valuable insights for developing innovative therapeutic approaches to mitigate neuronal damage.}, }
@article {pmid39787049, year = {2025}, author = {Gurung, S and Chaudhury, H}, title = {Relationship-Centered Care for Older Adults in Long-Term Care Homes: A Scoping Review.}, journal = {Journal of applied gerontology : the official journal of the Southern Gerontological Society}, volume = {44}, number = {9}, pages = {1513-1532}, pmid = {39787049}, issn = {1552-4523}, mesh = {Humans ; *Long-Term Care/organization &amp; administration ; Aged ; *Patient-Centered Care/organization &amp; administration ; *Nursing Homes/organization &amp; administration ; *Homes for the Aged/organization &amp; administration ; Quality of Health Care ; New Zealand ; }, abstract = {This scoping review, following Levac et al.'s methodology, examines the implementation and impact of relationship-centered care (RCC) in long-term care (LTC) settings for older adults. Peer-reviewed articles from AgeLine, CINAHL Complete, MEDLINE, PsycINFO, and Web of Science were included if published after 2000, involved older adults in LTC homes, focused on RCC, and conducted in Australia, Europe, New Zealand, or North America. Key findings were organized using inductive content analysis, and 41 empirical studies with qualitative, quantitative, and mixed-methods designs were included. Three categories emerged: (1) Core Practices of RCC-relationship building and reciprocal exchange; (2) Transformative Impacts of RCC-improved care quality and collaboration; and (3) Pathways and Roadblocks to RCC-individual and organizational factors. By understanding the key elements, facilitators, and barriers of RCC, policymakers and practitioners can develop targeted strategies to improve care experiences and outcomes for residents, families, staff, and all others involved in LTC.}, }
@article {pmid39779313, year = {2025}, author = {Xiao, Y and Tan, Y and Li, C and Wei, Q and Jiang, Q and Wang, S and Yang, T and Lin, J and Zhang, L and Shang, H}, title = {Genetic and clinical analysis of OPTN in amyotrophic lateral sclerosis.}, journal = {Journal of medical genetics}, volume = {62}, number = {4}, pages = {242-248}, doi = {10.1136/jmg-2024-109978}, pmid = {39779313}, issn = {1468-6244}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; Asian People/genetics ; *Cell Cycle Proteins/genetics ; Genetic Association Studies ; *Genetic Predisposition to Disease ; Genotype ; *Membrane Transport Proteins/genetics ; Mutation ; Phenotype ; *Transcription Factor TFIIIA/genetics ; White People/genetics ; Cohort Studies ; }, abstract = {BACKGROUND: Considerable heterogeneity in genotypes and phenotypes has been observed among patients with amyotrophic lateral sclerosis (ALS) harbouring optineurin gene (OPTN) mutations, as reported in prior studies. The study aimed to elucidate the correlation between OPTN genotypes and phenotypes.<br><br>METHODS: OPTN gene variants were screened within a substantial Chinese cohort of patients with ALS, encompassing LoF and rare missense variants. Additionally, a systematic literature review was conducted to compile the spectrum of OPTN mutations and explore the relationship between the genotype and phenotype of patients with ALS with OPTN.<br><br>RESULTS: A total of 33 unrelated patients with ALS with 24 rare OPTN variants, including 17 novel variants, were identified in 2279 patients with ALS. Among 24 variants in our cohort and 106 variants in previous studies, only 33.3% and 35.8% were pathogenic/likely pathogenic variants. Moreover, the frequency of OPTN variants in the Asian ALS population was higher (1.08%) than that of the Caucasian population (0.55%). For the phenotype of patients with ALS carrying OPTN variants, we found that patients with pathogenic/likely pathogenic variants had the highest baseline progression rate and the shortest survival time among groups in our cohort.<br><br>CONCLUSION: Our study contributed to a broader understanding of the genotype and phenotype spectrum of patients with ALS carrying OPTN variants. Further investigations are warranted to definitively establish the genotype-phenotype associations.}, }
@article {pmid39778593, year = {2025}, author = {Chen, Q and Chen, G and Wang, Q}, title = {Application of Network Pharmacology in the Treatment of Neurodegenerative Diseases with Traditional Chinese Medicine.}, journal = {Planta medica}, volume = {91}, number = {5}, pages = {226-237}, pmid = {39778593}, issn = {1439-0221}, support = {2023AFB677//the Natural Science Foundation of Hubei Province/ ; 2024AFB578//the Natural Science Foundation of Hubei Province/ ; 2023LYYYGZRP0003//the Intramural Research Program of Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology/ ; 2023LYYYSZRP0001//the Intramural Research Program of Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology/ ; }, mesh = {Humans ; *Medicine, Chinese Traditional/methods ; *Neurodegenerative Diseases/drug therapy ; *Network Pharmacology/methods ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; }, abstract = {In recent years, the incidence of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, has exhibited a steadily rising trend, which has posed a major challenge to the global public health. Traditional Chinese medicine, with its multicomponent and multitarget characteristics, offers a promising approach to treating neurodegenerative diseases. However, comprehensively elucidating the complex mechanisms underlying traditional Chinese medicine formulations remains challenging. As an emerging systems biology method, network pharmacology has provided a vital tool for revealing the multitarget mechanisms of traditional Chinese medicine through high-throughput technologies, molecular docking, and network analysis. This paper reviews the advancements in the application of network pharmacology in treating neurodegenerative diseases using traditional Chinese medicine, analyzes the current status of relevant databases and technological methods, discusses the limitations, and proposes future directions to promote the modernization of traditional Chinese medicine and the development of precision medicine.}, }
@article {pmid39777244, year = {2025}, author = {Moura, FA and Siqueira, AIAN}, title = {Gut-liver axis in sepsis-associated liver injury: Epidemiology, challenges and clinical practice.}, journal = {World journal of gastroenterology}, volume = {31}, number = {1}, pages = {99987}, pmid = {39777244}, issn = {2219-2840}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Sepsis/complications/epidemiology ; *Dysbiosis ; *Liver/metabolism/pathology ; Animals ; *Oxidative Stress ; Bacterial Translocation ; Liver Diseases/epidemiology/microbiology ; Critical Illness ; Intensive Care Units/statistics &amp; numerical data ; Anti-Bacterial Agents/therapeutic use ; }, abstract = {Although the liver has a remarkable regenerative capacity, sepsis-associated liver injury (SLI) is a complication often seen in intensive care units. Due to its role in immune and inflammatory regulation, the liver is particularly vulnerable during severe infections. Understanding the global prevalence, causes, and management of SLI is essential to improve outcomes and reduce healthcare costs. This paper aims to explore these factors, with an emphasis on identifying effective strategies for clinical management. Zhang et al's bibliometric analysis of 787 publications (745 original articles and 42 reviews, mostly in animal models) from 2000 to 2023 highlights the growing interest in SLI, focusing on oxidative stress, gut microbiota, and inflammatory processes. Key components such as nuclear factor-kappa B and the NOD-like receptor thermal protein domain associated protein 3 inflammasome pathway, along with their links to gut microbiota imbalance and oxidative stress, are crucial for understanding SLI pathogenesis. The gut-liver axis, particularly the role of intestinal permeability and bacterial translocation in liver inflammation, is emphasized. In this context, bacterial translocation is especially relevant for critically ill patients, as it can exacerbate liver inflammation. The findings underscore the need for integrated care in intensive care units, prioritizing gut health and careful antibiotic use to prevent dysbiosis. Despite extensive research, there remains a lack of clinical trials to validate therapeutic approaches. The abundance of experimental studies highlights potential therapeutic targets, stressing the need for high-quality randomized clinical trials to translate these findings into clinical practice.}, }
@article {pmid39775908, year = {2025}, author = {de Vries, E and Hagbohm, C and Ouellette, R and Granberg, T}, title = {Clinical 7 Tesla magnetic resonance imaging: Impact and patient value in neurological disorders.}, journal = {Journal of internal medicine}, volume = {297}, number = {3}, pages = {244-261}, pmid = {39775908}, issn = {1365-2796}, mesh = {Humans ; *Magnetic Resonance Imaging/methods ; *Nervous System Diseases/diagnostic imaging ; Amyotrophic Lateral Sclerosis/diagnostic imaging ; }, abstract = {Magnetic resonance imaging (MRI) is a cornerstone of non-invasive diagnostics and treatment monitoring, particularly for diseases of the central nervous system. Although 1.5- and 3 Tesla (T) field strengths remain the clinical standard, the advent of 7 T MRI represents a transformative step forward, offering superior spatial resolution, contrast, and sensitivity for visualizing neuroanatomy, metabolism, and function. Recent innovations, including parallel transmission and deep learning-based reconstruction, have resolved many prior technical challenges of 7 T MRI, enabling its routine clinical use. This review examines the diagnostic impact, patient value, and practical considerations of 7 T MRI, emphasizing its role in facilitating earlier diagnoses and improving care in conditions, such as amyotrophic lateral sclerosis (ALS), epilepsy, multiple sclerosis (MS), dementia, parkinsonism, tumors, and vascular diseases. Based on insights from over 1200 clinical scans with a second-generation 7 T system, the review highlights disease-specific biomarkers such as the motor band sign in ALS and the new diagnostic markers in MS, the central vein sign, and paramagnetic rim lesions. The unparalleled ability of 7 T MRI to study neurological diseases ex vivo at ultra-high resolution is also explored, offering new opportunities to understand pathophysiology and identify novel treatment targets. Additionally, the review provides a clinical perspective on patient handling and safety considerations, addressing challenges and practicalities associated with clinical 7 T MRI. By bridging research and clinical practice, 7 T MRI has the potential to redefine neuroimaging and advance the understanding and management of complex neurological disorders.}, }
@article {pmid39770989, year = {2024}, author = {Pekdemir, B and Raposo, A and Saraiva, A and Lima, MJ and Alsharari, ZD and BinMowyna, MN and Karav, S}, title = {Mechanisms and Potential Benefits of Neuroprotective Agents in Neurological Health.}, journal = {Nutrients}, volume = {16}, number = {24}, pages = {}, pmid = {39770989}, issn = {2072-6643}, mesh = {Humans ; *Neuroprotective Agents/pharmacology/therapeutic use ; *Neurodegenerative Diseases/drug therapy ; Brain/drug effects/metabolism ; Animals ; Flavonoids/pharmacology/therapeutic use ; Apoptosis/drug effects ; Antioxidants/pharmacology/therapeutic use ; Oxidative Stress/drug effects ; }, abstract = {The brain contains many interconnected and complex cellular and molecular mechanisms. Injury to the brain causes permanent dysfunctions in these mechanisms. So, it continues to be an area where surgical intervention cannot be performed except for the removal of tumors and the repair of some aneurysms. Some agents that can cross the blood-brain barrier and reach neurons show neuroprotective effects in the brain due to their anti-apoptotic, anti-inflammatory and antioxidant properties. In particular, some agents act by reducing or modulating the accumulation of protein aggregates in neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, Huntington's disease, Amyotrophic lateral sclerosis, and prion disease) caused by protein accumulation. Substrate accumulation causes increased oxidative stress and stimulates the brain's immune cells, microglia, and astrocytes, to secrete proinflammatory cytokines. Long-term or chronic neuroinflammatory response triggers apoptosis. Brain damage is observed with neuronal apoptosis and brain functions are impaired. This situation negatively affects processes such as motor movements, memory, perception, and learning. Neuroprotective agents prevent apoptosis by modulating molecules that play a role in apoptosis. In addition, they can improve impaired brain functions by supporting neuroplasticity and neurogenesis. Due to the important roles that these agents play in central nervous system damage or neurodegenerative diseases, it is important to elucidate many mechanisms. This review provides an overview of the mechanisms of flavonoids, which constitute a large part of the agents with neuroprotective effects, as well as vitamins, neurotransmitters, hormones, amino acids, and their derivatives. It is thought that understanding these mechanisms will enable the development of new therapeutic agents and different treatment strategies.}, }
@article {pmid39769209, year = {2024}, author = {Xing, C and Chen, H and Bi, W and Lei, T and Hang, Z and Du, H}, title = {Targeting 5-HT Is a Potential Therapeutic Strategy for Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {25}, number = {24}, pages = {}, pmid = {39769209}, issn = {1422-0067}, support = {32300682//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Serotonin/metabolism ; *Neurodegenerative Diseases/metabolism/drug therapy ; Animals ; Alzheimer Disease/metabolism/drug therapy ; Amyotrophic Lateral Sclerosis/metabolism/drug therapy ; Parkinson Disease/metabolism/drug therapy ; Receptors, Serotonin/metabolism ; }, abstract = {There is increasing interest in the potential therapeutic role of 5-HT (serotonin) in the treatment of neurodegenerative diseases, which are characterized by the progressive degeneration and death of nerve cells. 5-HT is a vital neurotransmitter that plays a central role in regulating mood, cognition, and various physiological processes in the body. Disruptions in the 5-HT system have been linked to several neurological and psychiatric disorders, making it an attractive target for therapeutic intervention. Although the exact causes of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) are not fully understood, researchers believe that regulating the 5-HT system could help alleviate symptoms and potentially slow the progression of these diseases. Here, we delve into the potential of harnessing 5-HT as a therapeutic target for the treatment of neurodegenerative diseases. It is important to note that the current clinical drugs targeting 5-HT are still limited in the treatment of these complex diseases. Therefore, further research and clinical trials are needed to evaluate the feasibility and effectiveness of its clinical application.}, }
@article {pmid39769187, year = {2024}, author = {O'Day, DH}, title = {The Search for a Universal Treatment for Defined and Mixed Pathology Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {25}, number = {24}, pages = {}, pmid = {39769187}, issn = {1422-0067}, mesh = {Animals ; Humans ; alpha-Synuclein/metabolism ; Alzheimer Disease/metabolism/pathology/drug therapy/therapy ; Amyloid beta-Peptides/metabolism ; Biomarkers/metabolism ; Calmodulin/metabolism ; *Neurodegenerative Diseases/metabolism/pathology/therapy ; Parkinson Disease/metabolism/pathology/therapy ; Protein Glutamine gamma Glutamyltransferase 2 ; RNA-Binding Protein FUS/metabolism/genetics ; tau Proteins/metabolism ; Transglutaminases/metabolism ; }, abstract = {The predominant neurodegenerative diseases, Alzheimer's disease, Parkinson's disease, dementia with Lewy Bodies, Huntington's disease, amyotrophic lateral sclerosis, and frontotemporal dementia, are rarely pure diseases but, instead, show a diversity of mixed pathologies. At some level, all of them share a combination of one or more different toxic biomarker proteins: amyloid beta (Aβ), phosphorylated Tau (pTau), alpha-synuclein (αSyn), mutant huntingtin (mHtt), fused in sarcoma, superoxide dismutase 1, and TAR DNA-binding protein 43. These toxic proteins share some common attributes, making them potentially universal and simultaneous targets for therapeutic intervention. First, they all form toxic aggregates prior to taking on their final forms as contributors to plaques, neurofibrillary tangles, Lewy bodies, and other protein deposits. Second, the primary enzyme that directs their aggregation is transglutaminase 2 (TGM2), a brain-localized enzyme involved in neurodegeneration. Third, TGM2 binds to calmodulin, a regulatory event that can increase the activity of this enzyme threefold. Fourth, the most common mixed pathology toxic biomarkers (Aβ, pTau, αSyn, nHtt) also bind calmodulin, which can affect their ability to aggregate. This review examines the potential therapeutic routes opened up by this knowledge. The end goal reveals multiple opportunities that are immediately available for universal therapeutic treatment of the most devastating neurodegenerative diseases facing humankind.}, }
@article {pmid39768371, year = {2024}, author = {Orlova, A and Malygin, Y and Gofman, A and Sotulenko, S and Gandalian, V and Kartashov, I and Brylev, L and Bolevich, S and Nikolic Turnic, T and Jakovljevic, V}, title = {Survival Prognostic Factors of Non-Invasive Ventilation in Amyotrophic Lateral Sclerosis: A Systematic Review.}, journal = {Life (Basel, Switzerland)}, volume = {14}, number = {12}, pages = {}, pmid = {39768371}, issn = {2075-1729}, abstract = {OBJECTIVE: Amyotrophic lateral sclerosis is a neurodegenerative disease with high rates of disability and mortality. Non-invasive ventilation (NIV) is an effective method of treating patients, increasing life expectancy, but currently, predictors available to determine the best outcome of therapy in this category of patients are unknown. This systematic review aimed to determine the impact of prognostic factors on benefits from NIV application compared with non-NIV tools of treatment (invasive ventilation and standard care) in case of survival of ALS patients.<br><br>METHOD: We systematically sought relevant longitudinal cohort and case-control studies published in PubMed, CINAHL/EMBASE, Cochrane library, and Scopus.<br><br>RESULTS: We included seven prospective studies, published in 2010-2020, in the analysis. According to the evidence base available to date, NIV favors survival compared to non-NIV in patients with bulbar onset ALS. We obtained conflicting data on the significance of spinal onset and bulbar function. Survival depending on patient age, and also for spinal, cervical, and flail limb phenotypes during NIV therapy has not been sufficiently studied and needs further investigation.<br><br>CONCLUSIONS: The studies analyzed in this review allow us to state with confidence that NIV is effective in bulbar onset ALS, taking into account recommendations for duration of ventilation and the use of the full range of symptomatic therapy, including mechanically assisted coughing. The effectiveness of NIV on severe bulbar symptoms requires further research.}, }
@article {pmid39768167, year = {2024}, author = {Chen, X and Lv, S and Liu, J and Guan, Y and Xu, C and Ma, X and Li, M and Bai, X and Liu, K and Zhang, H and Yan, Q and Zhou, F and Chen, Y}, title = {Exploring the Role of Axons in ALS from Multiple Perspectives.}, journal = {Cells}, volume = {13}, number = {24}, pages = {}, pmid = {39768167}, issn = {2073-4409}, support = {82271483//The National Natural Science Foundation of China/ ; ZR2024MH112; ZR2024QH628//Shandong Province Natural Science Foundation of China/ ; 2023YX036; 2022YX043//Weifang Science and Technology Development Plan Project/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology ; *Axons/pathology/metabolism ; Animals ; Axonal Transport ; Motor Neurons/pathology ; Disease Progression ; }, abstract = {Amyotrophic lateral sclerosis (ALS), commonly known as motor neuron disease, is a neurodegenerative disorder characterized by the progressive degeneration of both upper and lower motor neurons. This pathological process results in muscle weakness and can culminate in paralysis. To date, the precise etiology of ALS remains unclear. However, a burgeoning body of research indicates that axonal dysfunction is a pivotal element in the pathogenesis of ALS and significantly influences the progression of disease. Dysfunction of axons in ALS can result in impediments to nerve impulse transmission, leading to motor impairment, muscle atrophy, and other associated complications that severely compromise patients' quality of life and survival prognosis. In this review, we concentrate on several key areas: the ultrastructure of axons, the mechanisms of axonal degeneration in ALS, the impact of impaired axonal transport on disease progression in ALS, and the potential for axonal regeneration within the central nervous system (CNS). Our objective is to achieve a more holistic and profound understanding of the multifaceted role that axons play in ALS, thereby offering a more intricate and refined perspective on targeted axonal therapeutic interventions.}, }
@article {pmid39766450, year = {2024}, author = {Donaghy, R and Pioro, EP}, title = {Neurophysiologic Innovations in ALS: Enhancing Diagnosis, Monitoring, and Treatment Evaluation.}, journal = {Brain sciences}, volume = {14}, number = {12}, pages = {}, pmid = {39766450}, issn = {2076-3425}, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive disease of both upper motor neurons (UMNs) and lower motor neurons (LMNs) leading invariably to decline in motor function. The clinical exam is foundational to the diagnosis of the disease, and ordinal severity scales are used to track its progression. However, the lack of objective biomarkers of disease classification and progression delay clinical trial enrollment, muddle inclusion criteria, and limit accurate assessment of drug efficacy. Ultimately, biomarker evidence of therapeutic target engagement will support, and perhaps supplant, more traditional clinical trial outcome measures. Electrophysiology tools including nerve conduction study and electromyography (EMG) have already been established as diagnostic biomarkers of LMN degeneration in ALS. Additional understanding of the motor manifestations of disease is provided by motor unit number estimation, electrical impedance myography, and single-fiber EMG techniques. Dysfunction of UMN and non-motor brain areas is being increasingly assessed with transcranial magnetic stimulation, high-density electroencephalography, and magnetoencephalography; less common autonomic and sensory nervous system dysfunction in ALS can also be characterized. Although most of these techniques are used to explore the underlying disease mechanisms of ALS in research settings, they have the potential on a broader scale to noninvasively identify disease subtypes, predict progression rates, and assess physiologic engagement of experimental therapies.}, }
@article {pmid39766276, year = {2024}, author = {Wysoczański, B and Świątek, M and Wójcik-Gładysz, A}, title = {Organ-on-a-Chip Models-New Possibilities in Experimental Science and Disease Modeling.}, journal = {Biomolecules}, volume = {14}, number = {12}, pages = {}, pmid = {39766276}, issn = {2218-273X}, mesh = {*Lab-On-A-Chip Devices ; Humans ; Animals ; Models, Biological ; Liver/metabolism/cytology ; Cell Culture Techniques/methods ; Microphysiological Systems ; }, abstract = {'Organ-on-a-chip' technology is a promising and rapidly evolving model in biological research. This innovative microfluidic cell culture device was created using a microchip with continuously perfused chambers, populated by living cells arranged to replicate physiological processes at the tissue and organ levels. By consolidating multicellular structures, tissue-tissue interfaces, and physicochemical microenvironments, these microchips can replicate key organ functions. They also enable the high-resolution, real-time imaging and analysis of the biochemical, genetic, and metabolic activities of living cells in the functional tissue and organ contexts. This technology can accelerate research into tissue development, organ physiology and disease etiology, therapeutic approaches, and drug testing. It enables the replication of entire organ functions (e.g., liver-on-a-chip, hypothalamus-pituitary-on-a-chip) or the creation of disease models (e.g., amyotrophic lateral sclerosis-on-a-chip, Parkinson's disease-on-a-chip) using specialized microchips and combining them into an integrated functional system. This technology allows for a significant reduction in the number of animals used in experiments, high reproducibility of results, and the possibility of simultaneous use of multiple cell types in a single model. However, its application requires specialized equipment, advanced expertise, and currently incurs high costs. Additionally, achieving the level of standardization needed for commercialization remains a challenge at this stage of development.}, }
@article {pmid39759457, year = {2024}, author = {Ahmad, SR and Zeyaullah, M and Khan, MS and AlShahrani, AM and Altijani, AAG and Ali, H and Dawria, A and Mohieldin, A and Alam, MS and Mohamed, AOA}, title = {Pharmacogenomics for neurodegenerative disorders - a focused review.}, journal = {Frontiers in pharmacology}, volume = {15}, number = {}, pages = {1478964}, pmid = {39759457}, issn = {1663-9812}, abstract = {Neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) are characterized by the progressive degeneration of neuronal structure and function, leading to severe cognitive and motor impairments. These conditions present significant challenges to healthcare systems, and traditional treatments often fail to account for genetic variability among patients, resulting in inconsistent therapeutic outcomes. Pharmacogenomics aims to tailor medical treatments based on an individual's genetic profile, thereby improving therapeutic efficacy and reducing adverse effects. This focused review explores the genetic factors influencing drug responses in neurodegenerative diseases and the potential of pharmacogenomics to revolutionize their treatment. Key genetic markers, such as the APOE ε4 allele in AD and the CYP2D6 polymorphisms in PD, are highlighted for their roles in modulating drug efficacy. Additionally, advancements in pharmacogenomic tools, including genome-wide association studies (GWAS), next-generation sequencing (NGS), and CRISPR-Cas9, are discussed for their contributions to personalized medicine. The application of pharmacogenomics in clinical practice and its prospects, including ethical and data integration challenges, are also examined.}, }
@article {pmid39756021, year = {2025}, author = {Akaree, N and Secco, V and Levy-Adam, F and Younis, A and Carra, S and Shalgi, R}, title = {Regulation of physiological and pathological condensates by molecular chaperones.}, journal = {The FEBS journal}, volume = {292}, number = {13}, pages = {3271-3297}, pmid = {39756021}, issn = {1742-4658}, support = {//AriSLA/ ; //Giovanni Armenise Harvard Foundation/ ; HT94252310319//Congressionally Directed Medical Research Programs/ ; AHA-MCA 2022//AriAlzh/ ; //Rappaport Family Institute for Research in Medical Sciences/ ; //Prince Center for Neurodegenerative Disorders of the Brain/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *Stress Granules/metabolism/pathology/genetics ; *Molecular Chaperones/metabolism/genetics ; *Frontotemporal Dementia/genetics/metabolism/pathology ; RNA-Binding Protein FUS/genetics/metabolism ; Animals ; *Biomolecular Condensates/metabolism/genetics ; DNA-Binding Proteins/genetics/metabolism ; *Protein Aggregation, Pathological/genetics/metabolism/pathology ; Heterogeneous Nuclear Ribonucleoprotein A1/genetics/metabolism ; }, abstract = {Biomolecular condensates are dynamic membraneless compartments that regulate a myriad of cellular functions. A particular type of physiological condensate called stress granules (SGs) has gained increasing interest due to its role in the cellular stress response and various diseases. SGs, composed of several hundred RNA-binding proteins, form transiently in response to stress to protect mRNAs from translation and disassemble when the stress subsides. Interestingly, SGs contain several aggregation-prone proteins, such as TDP-43, FUS, hnRNPA1, and others, which are typically found in pathological inclusions seen in autopsy tissues from amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) patients. Moreover, mutations in these genes lead to the familial form of ALS and FTD. This has led researchers to propose that pathological aggregation is seeded by aberrant SGs: SGs that fail to properly disassemble, lose their dynamic properties, and become pathological condensates which finally 'mature' into aggregates. Here, we discuss the evidence supporting this model for various ALS/FTD-associated proteins. We further continue to focus on molecular chaperone-mediated regulation of ALS/FTD-associated physiological condensates on one hand, and pathological condensates on the other. In addition to SGs, we review ALS/FTD-relevant nuclear condensates, namely paraspeckles, anisosomes, and nucleolar amyloid bodies, and discuss their emerging regulation by chaperones. As the majority of chaperoning mechanisms regulate physiological condensate disassembly, we highlight parallel themes of physiological and pathological condensation regulation across different chaperone families, underscoring the potential for early disease intervention.}, }
@article {pmid39753993, year = {2025}, author = {Cheng, L and Liu, Z and Shen, C and Xiong, Y and Shin, SY and Hwang, Y and Yang, SB and Chen, Z and Zhang, X}, title = {A Wonderful Journey: The Diverse Roles of Adenosine Deaminase Action on RNA 1 (ADAR1) in Central Nervous System Diseases.}, journal = {CNS neuroscience &amp; therapeutics}, volume = {31}, number = {1}, pages = {e70208}, pmid = {39753993}, issn = {1755-5949}, support = {20224BAB216045//Youth Foundation of Natural Science Foundation of Jiangxi Province/ ; GJJ211812//Science and Technology Project Funded by the Education Department of Jiangxi Province/ ; GJJ211813//Science and Technology Project Funded by the Education Department of Jiangxi Province/ ; 202131084//Jiangxi Provincial Health Commission Science and Technology Plan Project/ ; 202211982//Jiangxi Provincial Health Commission Science and Technology Plan Project/ ; RZYB202201//Research project of Cognitive Science and Transdisciplinary Studies Center of Jiangxi Province/ ; 20224BAB206040//Provincial Natural Science Foundation of Jiangxi Province/ ; 202411843024//Foundation of Students' Platform for Innovation and Entrepreneurship Training Program/ ; S202411843050//Foundation of Students' Platform for Innovation and Entrepreneurship Training Program/ ; 2022B1010//Administration of Traditional Chinese Medicine of Jiangxi Province/ ; }, mesh = {*Adenosine Deaminase/genetics/metabolism ; Humans ; Animals ; *RNA-Binding Proteins/metabolism/genetics ; *Central Nervous System Diseases/genetics/metabolism/therapy ; RNA Editing ; }, abstract = {BACKGROUND: Adenosine deaminase action on RNA 1 (ADAR1) can convert the adenosine in double-stranded RNA (dsRNA) molecules into inosine in a process known as A-to-I RNA editing. ADAR1 regulates gene expression output by interacting with RNA and other proteins; plays important roles in development, including growth; and is linked to innate immunity, tumors, and central nervous system (CNS) diseases.<br><br>RESULTS: In recent years, the role of ADAR1 in tumors has been widely discussed, but its role in CNS diseases has not been reviewed. It is worth noting that recent studies have shown ADAR1 has great potential in the treatment of neurodegenerative diseases, but the mechanisms are still unclear. Therefore, it is necessary to elaborate on the role of ADAR1 in CNS diseases.<br><br>CONCLUSIONS: Here, we focus on the effects and mechanisms of ADAR1 on CNS diseases such as Aicardi-AicardiGouti&#xe8;res syndrome, Alzheimer's disease, Parkinson's disease, glioblastoma, epilepsy, amyotrophic lateral sclerosis, and autism. We also evaluate the impact of ADAR1-based treatment strategies on these diseases, with a particular focus on the development and treatment strategies of new technologies such as microRNAs, nanotechnology, gene editing, and stem cell therapy. We hope to provide new directions and insights for the future development of ADAR1 gene editing technology in brain science and the treatment of CNS diseases.}, }
@article {pmid39753182, year = {2025}, author = {Swarup, G and Medchalmi, S and Ramachandran, G and Sayyad, Z}, title = {Molecular aspects of cytoprotection by Optineurin during stress and disease.}, journal = {Biochimica et biophysica acta. Molecular cell research}, volume = {1872}, number = {3}, pages = {119895}, doi = {10.1016/j.bbamcr.2024.119895}, pmid = {39753182}, issn = {1879-2596}, mesh = {Humans ; Membrane Transport Proteins ; Cell Cycle Proteins ; Animals ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *Transcription Factor TFIIIA/genetics/metabolism ; *Cytoprotection ; Endoplasmic Reticulum Stress ; Signal Transduction ; Oxidative Stress ; Autophagy ; *Glaucoma/genetics/metabolism/pathology ; *Neurodegenerative Diseases/genetics/metabolism/pathology ; }, abstract = {Optineurin/OPTN is an adapter protein that plays a crucial role in mediating many cellular functions, including autophagy, vesicle trafficking, and various signalling pathways. Mutations of OPTN are linked with neurodegenerative disorders, glaucoma, and amyotrophic lateral sclerosis (ALS). Recent work has shown that OPTN provides cytoprotection from many types of stress, including oxidative stress, endoplasmic reticulum stress, protein homeostasis stress, tumour necrosis factor α, and microbial infection. Here, we discuss the mechanisms involved in cytoprotective functions of OPTN, which possibly depend on its ability to modulate various stress-induced signalling pathways. ALS- and glaucoma-causing mutants of OPTN are altered in this regulation, which may affect cell survival, particularly under various stress conditions. We suggest that OPTN deficiency created by mutations may cooperate with stress-induced signalling to enhance or cause neurodegeneration. Other functions of OPTN, such as neurotrophin secretion and vesicle trafficking, may also contribute to cytoprotection.}, }
@article {pmid39749367, year = {2025}, author = {Bhardwaj, G and Smitha, MV and Jelly, P and Stephen, S and Cook, JE and Panda, S}, title = {Breastfeeding Challenges Experienced by Mothers Following Multiple Births-a Systematic Review and Meta-Synthesis of Quantitative, Qualitative, and Mixed-Methods Studies.}, journal = {Breastfeeding medicine : the official journal of the Academy of Breastfeeding Medicine}, volume = {20}, number = {4}, pages = {219-230}, doi = {10.1089/bfm.2024.0207}, pmid = {39749367}, issn = {1556-8342}, mesh = {Female ; Humans ; Infant, Newborn ; Pregnancy ; *Breast Feeding/psychology ; *Mothers/psychology ; *Multiple Birth Offspring/psychology ; Qualitative Research ; Twins ; }, abstract = {Background: Breastfeeding is vital for infant nutrition, especially for multiple babies (twins) born prematurely, yet breastfeeding rates among mothers of twins are lower compared with mothers of singleton babies. This review presents a synthesis of research findings on breastfeeding challenges experienced by mothers following twins' births. Methods: The electronic databases of CINAHL, MEDLINE, PsycINFO, EMBASE, and Web of Science were systematically searched in August 2023. All eligible quantitative, qualitative, and mixed-methods studies reported on breastfeeding challenges experienced by mothers of twins were included. The review adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and followed Lucas et al.'s framework for thematic synthesis. Two reviewers independently screened all studies by title, abstract, and full text. The methodological quality of studies was independently assessed by two reviewers using the Joanna Briggs Institute critical appraisal tool and mixed-methods appraisal tool based on study design. Results: The review included 16 studies: quantitative (n = 5), qualitative (n = 8), and mixed methods (n = 3), published between 1980 and 2022, involving 3,351 mothers from 16 countries. Three main themes were generated as follows: (1) transitioning to a new role, finding the balance between self and the newborns' needs; (2) the inevitability of emotional challenges; and (3) navigating support and information. Conclusion: The integrated findings of quantitative, qualitative, and mixed-methods studies on challenges experienced by mothers of twins will have scope for researchers to address the challenges through tailored intervention, education, and support and can help health care professionals revisit policy and practices to extend support services for mothers of twins beyond the initial postpartum and to the community for improving breastfeeding practices among mothers following multiple births.}, }
@article {pmid39743546, year = {2025}, author = {Faller, KME and Chaytow, H and Gillingwater, TH}, title = {Targeting common disease pathomechanisms to treat amyotrophic lateral sclerosis.}, journal = {Nature reviews. Neurology}, volume = {21}, number = {2}, pages = {86-102}, pmid = {39743546}, issn = {1759-4766}, mesh = {Animals ; Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology/therapy ; }, abstract = {The motor neuron disease amyotrophic lateral sclerosis (ALS) is a devastating condition with limited treatment options. The past few years have witnessed a ramping up of translational ALS research, offering the prospect of disease-modifying therapies. Although breakthroughs using gene-targeted approaches have shown potential to treat patients with specific disease-causing mutations, the applicability of such therapies remains restricted to a minority of individuals. Therapies targeting more general mechanisms that underlie motor neuron pathology in ALS are therefore of considerable interest. ALS pathology is associated with disruption to a complex array of key cellular pathways, including RNA processing, proteostasis, metabolism and inflammation. This Review details attempts to restore cellular homeostasis by targeting these pathways in order to develop effective, broadly-applicable ALS therapeutics.}, }
@article {pmid39743215, year = {2024}, author = {Chiu, Y and Xia, S and Qiao, H and Zhao, Z}, title = {Genetically Engineered Mouse Models for Alzheimer Disease and Frontotemporal Dementia: New Insights from Single-Cell and Spatial Transcriptomics.}, journal = {The American journal of pathology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajpath.2024.11.006}, pmid = {39743215}, issn = {1525-2191}, support = {R21 AG066090/AG/NIA NIH HHS/United States ; R56 AG082361/AG/NIA NIH HHS/United States ; R61 NS137365/NS/NINDS NIH HHS/United States ; R01 AG089640/AG/NIA NIH HHS/United States ; R03 AG063287/AG/NIA NIH HHS/United States ; R01 AG089756/AG/NIA NIH HHS/United States ; R01 AG061288/AG/NIA NIH HHS/United States ; }, abstract = {Neurodegenerative diseases, including Alzheimer disease, frontotemporal dementia, Parkinson disease, Huntington disease, and amyotrophic lateral sclerosis, are often casually linked to protein aggregation and inclusion. As the origins of those proteinopathies have been biochemically traced and genetically mapped, genetically engineered animal models carrying the specific mutations or variants are widely used for investigating the etiology of these diseases, as well as for testing potential therapeutics. This article focuses on the mouse models of Alzheimer disease and closely related frontotemporal dementia, particularly the ones that have provided most valuable knowledge, or are in a trajectory of doing so. More importantly, some of the major findings from these models are summarized, based on the recent single-cell transcriptomics, multiomics, and spatial transcriptomics studies. While no model is perfect, it is hoped that the new insights from these models and the practical use of these models will continue to help to establish a path forward.}, }
@article {pmid39743032, year = {2025}, author = {Li, Y and Zhang, W and Zhang, Q and Li, Y and Xin, C and Tu, R and Yan, H}, title = {Oxidative stress of mitophagy in neurodegenerative diseases: Mechanism and potential therapeutic targets.}, journal = {Archives of biochemistry and biophysics}, volume = {764}, number = {}, pages = {110283}, doi = {10.1016/j.abb.2024.110283}, pmid = {39743032}, issn = {1096-0384}, mesh = {Humans ; *Mitophagy/drug effects ; *Oxidative Stress/drug effects ; *Neurodegenerative Diseases/metabolism/drug therapy/pathology ; Animals ; Antioxidants/therapeutic use/pharmacology ; Mitochondria/metabolism/pathology ; }, abstract = {Neurodegenerative diseases are now significant chronic progressive neurological conditions that affect individuals' physical health. Oxidative stress is crucial in the development of these diseases. Among the various neurodegenerative diseases, mitochondrial damage has become a major factor in oxidative stress and disease advancement. During this process, oxidative stress and mitophagy plays an important role. In this paper, we introduced the role of mitophagy and oxidative stress in detail, and expounded the relationship between them. In addition, we summarized the pathogenesis of some neurodegenerative diseases and the mechanism of three antioxidants. The former includes AD, PD, HD and ALS, while the latter includes carnosine, adiponectin and resveratrol. Provide goals and directions for further research and treatment of neurodegenerative diseases. This review summarizes the impact of oxidative stress on neurodegenerative diseases by regulating mitophagy, provides a deeper understanding of their pathological mechanisms, and suggests potential new therapeutic targets.}, }
@article {pmid39740575, year = {2025}, author = {Fortuna, A and Sorarù, G}, title = {Cervical lower motor neuron syndromes: A diagnostic challenge.}, journal = {Journal of the neurological sciences}, volume = {468}, number = {}, pages = {123357}, doi = {10.1016/j.jns.2024.123357}, pmid = {39740575}, issn = {1878-5883}, mesh = {Humans ; *Motor Neuron Disease/diagnosis/physiopathology/diagnostic imaging ; Magnetic Resonance Imaging/methods ; }, abstract = {Cervical lower motor neuron (LMN) syndromes, also known as brachial paresis, are characterized by muscle atrophy, weakness, and decreased reflexes in the upper limbs, devoid of sensory symptoms. These syndromes can stem from various factors, including degenerative conditions, immune-mediated diseases, infections, toxic exposures, metabolic disorders, and vascular anomalies.[1] Clinical presentations vary, with motor neuron involvement potentially limited to the cervical area or extending to other regions, affecting prognosis. Misdiagnosis is a significant issue, particularly in lower motor neuron presentations, with an error rate nearing 20 %.[2] This review proposes a classification system based on magnetic resonance imaging (MRI) findings, the onset timing of symptoms (acute, subacute, or chronic), the symmetry and distribution of atrophy, and the etiology (sporadic or hereditary). Acute conditions may include spinal ischemia,[3] whereas subacute or chronic forms can manifest as symmetric (e.g., cervical spondylogenic myelopathy)[4] or asymmetric (e.g., Hirayama disease)[5] presentations. Neurophysiological assessments and cervical MRI are crucial for accurate diagnosis, as they reveal patterns that provide lesion localization and additional clues to the underlying cause. A systematic diagnostic approach is essential for navigating the complexities of these syndromes.}, }
@article {pmid39737769, year = {2025}, author = {Akyuz, E and Aslan, FS and Hekimoglu, A and Yilmaz, BN}, title = {Insights Into Retinal Pathologies in Neurological Disorders: A Focus on Parkinson's Disease, Multiple Sclerosis, Amyotrophic Lateral Sclerosis, and Alzheimer's Disease.}, journal = {Journal of neuroscience research}, volume = {103}, number = {1}, pages = {e70006}, doi = {10.1002/jnr.70006}, pmid = {39737769}, issn = {1097-4547}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/pathology ; *Parkinson Disease/diagnosis/diagnostic imaging/pathology ; *Multiple Sclerosis/pathology/diagnosis/diagnostic imaging ; *Alzheimer Disease/pathology/diagnosis ; *Retina/pathology/diagnostic imaging ; Tomography, Optical Coherence/methods ; Retinal Diseases/diagnosis/pathology/etiology ; Animals ; }, abstract = {Neurological diseases are central nervous system (CNS) disorders affecting the whole body. Early diagnosis of the diseases is difficult due to the lack of disease-specific tests. Adding new biomarkers external to the CNS facilitates the diagnosis of neurological diseases. In this respect, the retina has a common embryologic origin with the CNS. Retinal imaging technologies including optical coherence tomography (OCT) can be used in the understanding and processual monitoring of neurological diseases. Retinal imaging has been recently recognized as a potential source of biomarkers for neurological diseases, increasing the number of studies in this direction. In this review, the association of retinal abnormalities with Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and Alzheimer's disease (AD) is explained. Structural and functional abnormalities in retina as a predictive marker may facilitate early diagnosis of diseases. Although not all retinal abnormalities are predictive of neurologic diseases, changes in the retinal layers including retinal pigment epithelium and plexiform layers should suggest the risk of PD, MS, ALS, and AD.}, }
@article {pmid39736981, year = {2024}, author = {Zhang, Y and Li, N and Ge, Z and Li, F}, title = {Blood component therapy for dry eye disease: a systematic review and network meta-analysis.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1500160}, pmid = {39736981}, issn = {2296-858X}, abstract = {OBJECTIVE: Blood component therapy has shown promising potential as an emerging treatment for dry eye disease; however, it remains unclear which specific blood component is the most effective. This study aims to compare the efficacy of different blood components in the treatment of dry eye disease through a network meta-analysis, with the goal of providing the latest and most reliable evidence for clinical practice.<br><br>METHODS: We conducted a systematic search of the PubMed, Web of Science, Cochrane, Embase, and Scopus databases, with the search concluding on June 1, 2024. Two independent researchers performed literature screening, data extraction, and quality assessment.<br><br>RESULTS: A total of 16 randomized controlled trials (RCTs) involving 898 patients with dry eye disease were included. Six different blood components were utilized in treating dry eye disease, with platelet-rich plasma (PRP) being the most widely used. The results of the network meta-analysis indicated that platelet-rich plasma eye drops (PRPD) significantly outperformed artificial tears (AT) in improving the corneal fluorescein staining score (CFSS), while autologous serum (ALS) and umbilical cord serum (UCS) also demonstrated significantly better effects than AT in enhancing tear break-up time (TBUT). Additionally, ALS, PRP injection (PRPI), and PRPD showed significantly superior outcomes compared to AT in improving the ocular surface disease index (OSDI). However, no statistically significant differences were found among the various treatment modalities regarding their effects on Schirmer's I value, CFSS, TBUT, and OSDI. SUCRA analysis predicted that UCS was the most effective in improving Schirmer's I value and TBUT, while PRP excelled in enhancing CFSS and OSDI. Limitations such as publication bias and issues related to randomization, allocation concealment, and blinding may affect the reliability of the current findings.<br><br>CONCLUSION: Blood component therapy can significantly improve the pathological damage and ocular surface health in patients with dry eye disease. For those with aqueous-deficient dry eye, UCS may represent the optimal treatment option. In contrast, for patients with more severe corneal epithelial damage, PRP may offer a more effective therapeutic approach.<br><br>https://www.crd.york.ac.uk/PROSPERO/, CRD42024534091.}, }
@article {pmid39736783, year = {2024}, author = {Zeng, J and Luo, C and Jiang, Y and Hu, T and Lin, B and Xie, Y and Lan, J and Miao, J}, title = {Decoding TDP-43: the molecular chameleon of neurodegenerative diseases.}, journal = {Acta neuropathologica communications}, volume = {12}, number = {1}, pages = {205}, pmid = {39736783}, issn = {2051-5960}, support = {YNXM2024062//High-quality development project of public hospitals in Baoan District, Shenzhen/ ; YNXM2024015//High-quality development project of public hospitals in Baoan District, Shenzhen/ ; }, mesh = {Humans ; *DNA-Binding Proteins/metabolism/genetics ; *Neurodegenerative Diseases/metabolism/genetics/pathology ; Animals ; }, abstract = {TAR DNA-binding protein 43 (TDP-43) has emerged as a critical player in neurodegenerative disorders, with its dysfunction implicated in a wide spectrum of diseases including amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), and Alzheimer's disease (AD). This comprehensive review explores the multifaceted roles of TDP-43 in both physiological and pathological contexts. We delve into TDP-43's crucial functions in RNA metabolism, including splicing regulation, mRNA stability, and miRNA biogenesis. Particular emphasis is placed on recent discoveries regarding TDP-43's involvement in DNA interactions and chromatin dynamics, highlighting its broader impact on gene expression and genome stability. The review also examines the complex pathogenesis of TDP-43-related disorders, discussing the protein's propensity for aggregation, its effects on mitochondrial function, and its non-cell autonomous impacts on glial cells. We provide an in-depth analysis of TDP-43 pathology across various neurodegenerative conditions, from well-established associations in ALS and FTLD to emerging roles in diseases such as Huntington's disease and Niemann-Pick C disease. The potential of TDP-43 as a therapeutic target is explored, with a focus on recent developments in targeting cryptic exon inclusion and other TDP-43-mediated processes. This review synthesizes current knowledge on TDP-43 biology and pathology, offering insights into the protein's central role in neurodegeneration and highlighting promising avenues for future research and therapeutic interventions.}, }
@article {pmid39735081, year = {2024}, author = {Dost, W and Rasully, MQ and Zaman, MN and Dost, W and Ali, W and Ayobi, SA and Dost, R and Niazi, J and Bakht, K and Iqbal, A and Bokhari, SFH}, title = {Predictive Biomarkers for the Early Detection of Anastomotic Leaks in Colorectal Surgeries: A Systematic Review.}, journal = {Cureus}, volume = {16}, number = {11}, pages = {e74616}, pmid = {39735081}, issn = {2168-8184}, abstract = {Anastomotic leaks (ALs) remain a serious postoperative complication in colorectal surgery, often resulting in significant morbidity, prolonged hospitalization, and increased mortality risk. This systematic review aims to evaluate the role of predictive biomarkers in the early detection of ALs, focusing on their diagnostic accuracy and clinical utility. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a comprehensive literature search was conducted across MEDLINE, Scopus, CENTRAL, and Web of Science, identifying studies that examined biomarkers such as C-reactive protein (CRP), procalcitonin (PCT), and white blood cell (WBC) count in the context of AL. A total of 20 studies met the inclusion criteria, with sample sizes ranging from 59 to 2,655 patients undergoing colorectal surgeries with primary anastomosis. CRP emerged as the most widely studied and reliable biomarker, with studies suggesting that elevated CRP levels, particularly on postoperative days 3-4, can effectively indicate AL risk, showing high negative predictive value. PCT has also shown promise as a complementary biomarker, offering enhanced specificity for infectious complications. Although WBC count alone was a limited predictor, it may add diagnostic value when used with other markers. In addition, innovative biomarkers, such as inflammatory indices in peritoneal fluid, demonstrated potential for further improving AL detection accuracy.}, }
@article {pmid39728809, year = {2024}, author = {Al Haffar, M and Fajloun, Z and Azar, S and Sabatier, JM and Abi Khattar, Z}, title = {Lesser-Known Cyanotoxins: A Comprehensive Review of Their Health and Environmental Impacts.}, journal = {Toxins}, volume = {16}, number = {12}, pages = {}, pmid = {39728809}, issn = {2072-6651}, mesh = {Humans ; *Cyanobacteria/metabolism ; *Bacterial Toxins/toxicity ; Animals ; Harmful Algal Bloom ; Cyanobacteria Toxins ; Microcystins/toxicity ; }, abstract = {Cyanobacteria, also known as blue-green algae, are a diverse phylum of photosynthetic, Gram-negative bacteria and one of the largest microbial taxa. These organisms produce cyanotoxins, which are secondary metabolites that can have significant impacts on both human health and the environment. While toxins like Microcystins and Cylindrospermopsins are well-documented and have been extensively studied, other cyanotoxins, including those produced by Lyngbya and Nostoc, remain underexplored. These lesser-known toxins can cause various health issues in humans, including neurotoxicity, hepatotoxicity, and dermatotoxicity, each through distinct mechanisms. Moreover, recent studies have shown that cyanobacteria can be aerosolized and transmitted through the air over long distances, providing an additional route for human exposure to their harmful effects. However, it remains an area that requires much more investigation to accurately assess the health risks and develop appropriate public health guidelines. In addition to direct exposure to toxins, cyanobacteria can lead to harmful algal blooms, which pose further risks to human and wildlife health, and are a global concern. There is limited knowledge about these lesser-known cyanotoxins, highlighting the need for further research to understand their clinical manifestations and improve society's preparedness for the associated health risks. This work aims to review the existing literature on these underexplored cyanotoxins, which are associated with human intoxication, elucidate their clinical relevance, address significant challenges in cyanobacterial research, and provide guidance on mitigating their adverse effects.}, }
@article {pmid39728753, year = {2024}, author = {Boziki, M and Theotokis, P and Kesidou, E and Nella, M and Bakirtzis, C and Karafoulidou, E and Tzitiridou-Chatzopoulou, M and Doulberis, M and Kazakos, E and Deretzi, G and Grigoriadis, N and Kountouras, J}, title = {Impact of Mast Cell Activation on Neurodegeneration: A Potential Role for Gut-Brain Axis and Helicobacter pylori Infection.}, journal = {Neurology international}, volume = {16}, number = {6}, pages = {1750-1778}, pmid = {39728753}, issn = {2035-8385}, abstract = {BACKGROUND: The innate immune response aims to prevent pathogens from entering the organism and/or to facilitate pathogen clearance. Innate immune cells, such as macrophages, mast cells (MCs), natural killer cells and neutrophils, bear pattern recognition receptors and are thus able to recognize common molecular patterns, such as pathogen-associated molecular patterns (PAMPs), and damage-associated molecular patterns (DAMPs), the later occurring in the context of neuroinflammation. An inflammatory component in the pathology of otherwise "primary cerebrovascular and neurodegenerative" disease has recently been recognized and targeted as a means of therapeutic intervention. Activated MCs are multifunctional effector cells generated from hematopoietic stem cells that, together with dendritic cells, represent first-line immune defense mechanisms against pathogens and/or tissue destruction.<br><br>METHODS: This review aims to summarize evidence of MC implication in the pathogenesis of neurodegenerative diseases, namely, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and multiple sclerosis.<br><br>RESULTS: In view of recent evidence that the gut-brain axis may be implicated in the pathogenesis of neurodegenerative diseases and the characterization of the neuroinflammatory component in the pathology of these diseases, this review also focuses on MCs as potential mediators in the gut-brain axis bi-directional communication and the possible role of Helicobacter pylori, a gastric pathogen known to alter the gut-brain axis homeostasis towards local and systemic pro-inflammatory responses.<br><br>CONCLUSION: As MCs and Helicobacter pylori infection may offer targets of intervention with potential therapeutic implications for neurodegenerative disease, more clinical and translational evidence is needed to elucidate this field.}, }
@article {pmid39727293, year = {2025}, author = {Gefen, N and Mazer, B and Krasovsky, T and Weiss, PL}, title = {Novel rehabilitation technologies in pediatric rehabilitation: knowledge towards translation.}, journal = {Disability and rehabilitation. Assistive technology}, volume = {20}, number = {5}, pages = {1209-1218}, doi = {10.1080/17483107.2024.2445017}, pmid = {39727293}, issn = {1748-3115}, mesh = {Humans ; Child ; *Self-Help Devices ; *Children with Disabilities/rehabilitation ; *Translational Research, Biomedical ; Telerehabilitation ; Brain-Computer Interfaces ; Robotics ; }, abstract = {PURPOSE: Knowledge translation (KT) refers to the process of applying the most promising research outcomes into practice to ensure that new discoveries and innovations improve healthcare accessibility, effectiveness, and accountability. The objective of this perspective paper is to discuss and illustrate via examples how the KT process can be implemented in an era of rapid advancement in rehabilitation technologies that have the potential to significantly impact pediatric healthcare.<br><br>METHODS: Using Graham et&#xa0;al.'s (2006) Knowledge-to-Action cycle, which includes the knowledge creation funnel and the action cycle, we illustrate its application in implementing novel technologies into clinical practice and informing healthcare policy changes. We explore three successful applications of technology research: powered mobility, head support systems, and telerehabilitation. Additionally, we examine less clinically mature technologies such as brain-computer interfaces and robotic assistive devices, which are hindered by cost, robustness, and ease-of-use issues.<br><br>CONCLUSIONS: The paper concludes by discussing how technology acceptance and usage in clinical settings are influenced by various barriers and facilitators at different stakeholder levels, including clients, families, clinicians, management, researchers, developers, and society. Recommendations include focusing on early and ongoing design partnerships, transitioning from research to real-life implementation, and identifying optimal timing for clinical adoption of new technologies.}, }
@article {pmid39717968, year = {2024}, author = {Vergini, DE and Hadjipavlou-Litina, D}, title = {"A patent review on arachidonic acid lipoxygenase (LOX) inhibitors for the treatment of neurodegenerative diseases (2018-present)".}, journal = {Expert opinion on therapeutic patents}, volume = {}, number = {}, pages = {1-14}, doi = {10.1080/13543776.2024.2447067}, pmid = {39717968}, issn = {1744-7674}, abstract = {INTRODUCTION: Neuroinflammation is correlated to neurodegenerative diseases like Alzheimer's disease (AD), Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (MS), Huntington Disease (HD), and Parkinson's disease (PD). A lot of recent research and patents are focused on the design and synthesis of arachidonic acid lipoxygenase (ALOX) inhibitors for the treatment of neurodegenerative diseases.<br><br>AREAS COVERED: The survey covers natural products, synthesis, hybrids, and assessments of biological effects in biological studies as ALOX inhibitors. A survey of patent publications from 2018 to present, taken from Google Scholar, Espanet, Web of Science, Drugbank, Scopus, or PubMed is analyzed.<br><br>EXPERT OPINION: The authors suggest that (i) numerous areas of biology-pharmacology need to be considered: selectivity, in vivo studies, toxicity, bioavailability, and drug-likeness, the mechanism of action in different animals and humans, evaluation of more efficient and selective biological tests; (ii) synthetic method outbalance in the discovery and production of ALOX inhibitors with greater selectivity. Several ALOX inhibitors show promising results for the treatment of neurological disorders. Their clinical evaluation will be critical to assess therapeutic utility. The compounds for which the mechanism of action and their bioavailability are well defined can be used as lead compounds for the treatment of neurodegenerative diseases.}, }
@article {pmid39715366, year = {2024}, author = {Eisenberg, N and Spinrad, TL and Hernández, MM and Zuffianò, A}, title = {Top-down self-regulation as a core construct in children's and adolescents' optimal development.}, journal = {The American psychologist}, volume = {79}, number = {9}, pages = {1255-1268}, doi = {10.1037/amp0001408}, pmid = {39715366}, issn = {1935-990X}, support = {//American Institutes for Research's Equity Initiative/ ; //Bill and Melinda Gates Foundation/ ; //Progetto di Ricerca di Rilevante Interesse Nazionale/ ; }, mesh = {Humans ; *Self-Control ; Child ; Adolescent ; *Child Development ; Adolescent Development ; Social Skills ; }, abstract = {Research and theory on the role of top-down self-regulation (TDSR) in children's developmental outcomes has received considerable attention in the last few decades. In this review, we distinguish TDSR (and overlapping self-regulatory processes) from bottom-up regulation. With a particular focus on Eisenberg et al.'s body of work, we review evidence for the role of individual differences in children's TDSR to a variety of developmental outcomes. Children's TDSR processes are consistently inversely related to externalizing problems and internalizing problems, although less consistently for the latter. Moreover, TDSR processes are positively associated with social competence, empathy-related responding and prosocial outcomes, and school-related outcomes. We briefly review complexities in these associations, such as bidirectional relations, mediators, and moderators. Key areas for future work are also discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).}, }
@article {pmid39714593, year = {2025}, author = {Eldeeb, MA and Hohman, G and Shahid, M}, title = {Novel Approaches in Targeting Cell Surface and Secreted Proteins for Lysosomal Degradation.}, journal = {Chembiochem : a European journal of chemical biology}, volume = {26}, number = {7}, pages = {e202400887}, doi = {10.1002/cbic.202400887}, pmid = {39714593}, issn = {1439-7633}, mesh = {*Lysosomes/metabolism ; Humans ; Proteolysis ; *Membrane Proteins/metabolism ; Animals ; Proteasome Endopeptidase Complex/metabolism ; Autophagy ; *Proteins/metabolism ; }, abstract = {Protein degradation is pivotal for all biochemical aspects of cellular function. In mammalian cells, protein degradation is mediated mainly by the ubiquitin proteasome system (UPS) and the autophagic-lysosomal system (ALS). Over the last two decades, different types of targeted protein degradation approaches have been developed including proteolysis targeting chimeras (PROTACs) and lysosome targeting chimeras (LYTACs), which employ the UPS to degrade intracellular proteins and the ALS to degrade extracellular and membrane proteins respectively. Nevertheless, Current targeted membrane protein degradation approaches face some inherent challenges including limited target protein degradation efficacy and cell type specific applicability. Herein, we highlight some recent developments of novel targeted membrane protein degradation modalities that exhibit wide-applicability and high protein degradation efficiency. These novel membrane protein degraders hold tremendous promise as new pharmacological and biochemical tools in targeting membrane and secretory proteins for lysosomal degradation.}, }
@article {pmid39709547, year = {2025}, author = {Bakshi, B and Yerraguntla, S and Armon, C and Barkhaus, P and Bertorini, T and Bowser, R and Breevoort, S and Bromberg, M and Brown, A and Carter, GT and Chang, V and Crayle, J and Fullam, T and Greene, M and Heiman-Patterson, T and Jackson, C and Jhooty, S and Mallon, E and Cadavid, JM and Mcdermott, CJ and Pattee, G and Pierce, K and Ratner, D and Sun, Y and Wang, O and Wicks, P and Wiedau, M and Bedlack, R}, title = {ALSUntangled #77: Psilocybin.}, journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration}, volume = {26}, number = {3-4}, pages = {385-388}, doi = {10.1080/21678421.2024.2441274}, pmid = {39709547}, issn = {2167-9223}, mesh = {*Psilocybin/therapeutic use/pharmacology ; Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Hallucinogens/therapeutic use/pharmacology ; Animals ; }, abstract = {ALSUntangled reviews alternate and off-label treatments prompted by patient interest. Here, we review psilocybin, a chemical derived from mushrooms and belonging in the category of drugs known as psychedelics. Psilocybin has plausible mechanisms for slowing ALS progression because of its ability to cross the blood brain barrier and effect neurogenesis and inflammation. Currently, there are no pre-clinical ALS models, case reports, or trials for psilocybin and ALS in the context of disease modifying therapy. Depending on dosing, there can be a high risk of psychological side effects including hallucinations and physical harm. Based on the above information, we do not currently support the use of psilocybin as a means to slow ALS progression.}, }
@article {pmid39705668, year = {2024}, author = {Khandia, R and Gurjar, P and Priyanka,  and Romashchenko, V and Al-Hussain, SA and Zaki, MEA}, title = {Recent advances in stem cell therapy: efficacy, ethics, safety concerns, and future directions focusing on neurodegenerative disorders - a review.}, journal = {International journal of surgery (London, England)}, volume = {110}, number = {10}, pages = {6367-6381}, pmid = {39705668}, issn = {1743-9159}, mesh = {Humans ; *Neurodegenerative Diseases/therapy ; *Stem Cell Transplantation/methods ; }, abstract = {Neurodegeneration refers to the gradual loss of neurons and extensive changes in glial cells like tau inclusions in astrocytes and oligodendrocytes, α-synuclein inclusions in oligodendrocytes and SOD1 aggregates in astrocytes along with deterioration in the motor, cognition, learning, and behavior. Common neurodegenerative disorders are Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), spinocerebellar ataxia (SCA), and supranuclear palsy. There is a lack of effective treatment for neurodegenerative diseases, and scientists are putting their efforts into developing therapies against them. Stem cell therapy has emerged as a hope for neurodegenerative disorders since it is not only the damaged neurons that might be replaced, but other neuromodulators and neuroprotectors are secreted. Stem cell terminal differentiation before implantation ensures the implantation of correct cells and molecular markers like carbonic anhydrase II, CNPase (2',3'-cyclic nucleotide 3'-phosphohydrolase), myelin basic protein (MBP), and myelin oligodendrocyte glycoprotein (MOG) elucidate the differentiation. Secretion of various growth factors like epidermal growth factor (EGF), keratinocyte growth factor (KGF), vascular endothelial growth factor-α (VEGF-α), transforming growth factor (TGF), and macrophage inflammatory protein (MIP) supports cell survival, cell proliferation, blood vessel formation, axon regeneration, and neuroglial functional connection formation at the site of degeneration. Adverse effects of stem cell therapy, like teratogenicity and differentiation in different cells other than the desired one under the influence of microenvironment, are a few key concerns. Post-transplantation improved synaptic plasticity, apoptosis inhibition, and reduction in tau-phosphorylation and amyloid beta (Aβ) production has been observed in Alzheimer's patients. A large number of experimental, preclinical, and clinical studies have been conducted, and encouraging results have been obtained. The present review exhaustively discusses various kinds of stem cells, their usage in treating neurodegenerative disorders, limitations and challenges, and ethical issues related to stem cell therapy.}, }
@article {pmid39700696, year = {2025}, author = {Ghaderi, S and Mohammadi, S and Fatehi, F}, title = {Current evidence of arterial spin labeling in amyotrophic lateral sclerosis: A systematic review.}, journal = {Clinical neurology and neurosurgery}, volume = {249}, number = {}, pages = {108691}, doi = {10.1016/j.clineuro.2024.108691}, pmid = {39700696}, issn = {1872-6968}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/physiopathology ; *Spin Labels ; *Cerebrovascular Circulation/physiology ; *Brain/diagnostic imaging/blood supply ; Magnetic Resonance Imaging/methods ; }, abstract = {OBJECTIVE: This study aimed to evaluate the utility of arterial spin labeling (ASL) in assessing cerebral blood flow (CBF) changes in amyotrophic lateral sclerosis (ALS), and its potential as a biomarker for early diagnosis.<br><br>METHODS: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies that employed ASL to compare CBF between ALS patients and healthy controls were included.<br><br>RESULTS: Seven studies were included. A consistent finding across these studies was hypoperfusion in both the motor and non-motor regions, particularly in the frontotemporal cortex. Hypoperfusion in motor regions was correlated with functional impairment and was observed prior to structural changes, suggesting its potential as an early biomarker. There is limited evidence to suggest that monitoring changes in CBF patterns in the brain. Besides, limited findings showed initial hyperperfusion in regions not yet involved in the pathological process, and progressing hypoperfusion in regions with increasing pathological burden.<br><br>CONCLUSIONS: This review highlights the potential of ASL as a valuable tool for understanding the neurovascular dysfunction in ALS. Further research is required to validate its clinical utility for diagnosing ALS and monitoring disease progression.}, }
@article {pmid39698283, year = {2024}, author = {Kos, JA and Langiu, M and Hellyer, SD and Gregory, KJ}, title = {Pharmacology, Signaling and Therapeutic Potential of Metabotropic Glutamate Receptor 5 Negative Allosteric Modulators.}, journal = {ACS pharmacology &amp; translational science}, volume = {7}, number = {12}, pages = {3671-3690}, pmid = {39698283}, issn = {2575-9108}, abstract = {Metabotropic glutamate receptors are a family of eight class C G protein-coupled receptors regulating higher order brain functions including cognition and motion. Metabotropic glutamate receptors have thus been heavily investigated as potential drug targets for treating neurological disorders. Drug discovery efforts directed toward metabotropic glutamate receptor subtype 5 (mGlu5) have been particularly fruitful, with a wealth of drug candidates and pharmacological tools identified. mGlu5 negative allosteric modulators (NAMs) are promising novel therapeutics for developmental, neuropsychiatric and neurodegenerative disorders (e.g., Alzheimer's Disease, Huntington's Disease, Parkinson's Disease, amyotrophic lateral sclerosis, autism spectrum disorders, substance use disorders, stroke, anxiety and depression) and show promise in ameliorating adverse effects induced by other medications (e.g., L-dopa induced dyskinesia in Parkinson's Disease). However, despite preclinical success, mGlu5 NAMs are yet to reach the market due to poor safety and efficacy profiles in clinical trials. Herein, we review the physiology and signal transduction of mGlu5. We provide a comprehensive critique of therapeutic options with respect to mGlu5 inhibitors, spanning from orthosteric antagonists to NAMs. Finally, we address the challenges associated with drug development and highlight future directions to guide rational drug discovery of safe and effective novel therapeutics.}, }
@article {pmid39691422, year = {2024}, author = {Fang, K}, title = {Modulation of the central nervous system immune response and neuroinflammation via Wnt signaling in health and neurodegenerative diseases.}, journal = {Ibrain}, volume = {10}, number = {4}, pages = {462-476}, pmid = {39691422}, issn = {2769-2795}, abstract = {The immune response in the central nervous system (CNS) is a highly specialized and tightly regulated process essential for maintaining neural health and protecting against pathogens and injuries. The primary immune cells within the CNS include microglia, astrocytes, T cells, and B cells. They work together, continuously monitor the CNS environment for signs of infection, injury, or disease, and respond by phagocytosing debris, releasing cytokines, and recruiting other immune cells. In addition to providing neuroprotection, these immune responses must be carefully balanced to prevent excessive inflammation that can lead to neuronal damage and contribute to neurodegenerative diseases. Dysregulated immune responses in the CNS are implicated in various neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Wnt signaling is a crucial pathway in the CNS that regulates various cellular processes critical for brain development, function, and maintenance. Despite enhancing immune responses in the health CNS, dysregulated Wnt signaling exacerbates neuroinflammation in the neurodegenerative brains. This review summarized the role of Wnt signaling in regulating immune response under different conditions. We then examined the role of immune response in healthy brains and during the development of neurodegenerative diseases. We also discussed therapeutic intervention in various neurodegenerative diseases through the modulation of the Wnt signaling pathway and neuroinflammation and highlighted challenges and limitations in current clinical trials.}, }
@article {pmid39690343, year = {2025}, author = {Lamichhane, S and Seo, JE and Jeong, JH and Lee, S and Lee, S}, title = {Ideal animal models according to multifaceted mechanisms and peculiarities in neurological disorders: present and challenges.}, journal = {Archives of pharmacal research}, volume = {48}, number = {1}, pages = {62-88}, pmid = {39690343}, issn = {1976-3786}, support = {Research grant 2024//Chung-Ang University/ ; NRF-2016R1A6A1A03011325//Ministry of Education/ ; }, mesh = {Animals ; *Disease Models, Animal ; Humans ; *Nervous System Diseases/physiopathology/pathology/drug therapy ; Translational Research, Biomedical/methods ; }, abstract = {Neurological disorders, encompassing conditions such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), pose a significant global health challenge, affecting millions worldwide. With an aging population and increased life expectancy, the prevalence of these disorders is escalating rapidly, leading to substantial economic burdens exceeding trillions of dollars annually. Animal models play a crucial role in understanding the underlying mechanisms of these disorders and developing effective treatments. Various species, including rodents, non-human primates, and fruit flies, are utilized to replicate specific aspects of human neurological conditions. However, selecting the ideal animal model requires careful consideration of its proximity to human disease conditions and its ability to mimic disease pathobiology and pharmacological responses. An Animal Model Quality Assessment (AMQA) tool has been developed to facilitate this selection process, focusing on assessing models based on their similarity to human conditions and disease pathobiology. Therefore, integrating intrinsic and extrinsic factors linked to the disease into the study's objectives aids in constructing a biological information matrix for comparing disease progression between the animal model and human disease. Ultimately, selecting an ideal animal disease model depends on its predictive, face, and construct validity, ensuring relevance and reliability in translational research efforts.}, }
@article {pmid39690247, year = {2025}, author = {Jiao, XF and Zhang, Z and Gong, L and Lan, S and Zhang, S and Wang, J and Chen, X and Wei, Q and Li, H and Zeng, L and Han, L and Zhang, L}, title = {The quantity, reliability, transparency, reporting, and interpretation of pharmacovigilance signal detection studies in pregnancy: a meta-epidemiological study.}, journal = {European journal of clinical pharmacology}, volume = {81}, number = {2}, pages = {309-319}, pmid = {39690247}, issn = {1432-1041}, support = {2022NSFSC0644//Natural Science Foundation of Sichuan Province/ ; }, mesh = {*Pharmacovigilance ; Humans ; Pregnancy ; Female ; *Adverse Drug Reaction Reporting Systems/standards ; *Drug-Related Side Effects and Adverse Reactions/epidemiology ; Reproducibility of Results ; Pregnancy Complications ; Epidemiologic Studies ; Databases, Factual ; }, abstract = {PURPOSE: To systematically review the characteristics of the available pharmacovigilance signal detection studies in pregnancy, and comprehensively assess the reliability, transparency, reporting, and interpretation of these studies.<br><br>METHODS: We searched five databases from inception to February 2024 to identify the available pharmacovigilance signal detection studies in pregnancy. We extracted three aspects of information (basic information, data processing modes, signal detection analyses) to assess the reliability, transparency, and reporting of each study. Moreover, we adopted the criteria of Mouffak et al.'s study to assess the misinterpretation of signal detection results in these studies.<br><br>RESULTS: A total of 33 pharmacovigilance signal detection studies in pregnancy were identified. Among them, there were great methodological heterogeneities in the data processing modes (restriction to the population, comparator, standardization of drug names and adverse event names, the assigned roles of drugs, counting unit, etc.) and signal detection analyses (signal detection method, sensitivity analysis, subgroup analysis, adjustment for confounding factors, etc.). Moreover, 13 (39%) studies had at least one type of inappropriate interpretation and/or extrapolation of signal detection results.<br><br>CONCLUSION: Our results reveals that the quantity of pharmacovigilance signal detection studies in pregnancy is relatively limited. Furthermore, the reliability, transparency, reporting, and interpretation of the existing studies are less optimistic. The main issues existing in the available pharmacovigilance signal detection studies in pregnancy consist of two aspects: (1) great methodological heterogeneities exist in the data processing modes and signal detection analyses among different studies and (2) inappropriate interpretation and extrapolation of signal detection results are frequent.}, }
@article {pmid39688317, year = {2025}, author = {Tseriotis, VS and Eleftheriadou, K and Mavridis, T and Konstantis, G and Falkenburger, B and Arnaoutoglou, M}, title = {Is the Swallow Tail Sign a Useful Imaging Biomarker in Clinical Neurology? A Systematic Review.}, journal = {Movement disorders clinical practice}, volume = {12}, number = {2}, pages = {134-147}, pmid = {39688317}, issn = {2330-1619}, support = {//Hellenic Academic Libraries Link/ ; }, mesh = {Humans ; *Magnetic Resonance Imaging/methods ; *Parkinson Disease/diagnostic imaging ; *Substantia Nigra/diagnostic imaging/pathology ; Biomarkers ; *Parkinsonian Disorders/diagnostic imaging ; }, abstract = {BACKGROUND: Loss of dorsolateral nigral hyperintensity (DNH) in iron-sensitive sequences of Magnetic Resonance Imaging (MRI), also described as "swallow tail sign" (STS) loss, has shown promising diagnostic value in Parkinson's Disease (PD) and Atypical Parkinsonian Syndromes (APS).<br><br>OBJECTIVE: To conduct a bibliometric analysis on substantia nigra MRI and a systematic review on the clinical utility of STS visual assessment on Susceptibility-Weighted Imaging in various clinical entities.<br><br>METHODS: VOSviewer's keyword co-occurrence network was employed using Web of Science (WOS). Complying with the PRISMA statement, we searched MEDLINE, WOS, SCOPUS, ProQuest and Google Scholar for peer-reviewed studies conducted in vivo, excluding quantitative imaging techniques.<br><br>RESULTS: DNH is a relatively novel parameter in substantia nigra MRI literature. Our SWI-focused review included 42 studies (3281 patients). Diagnostic accuracy of STS loss for PD/APS differentiation from controls and for Lewy Body Dementia differentiation from other dementias was 47.8-98.5% and 76-90%, respectively, with poorer capacity, however, in delineating PD from APS. STS evaluation in idiopathic REM sleep behavior disorder, a sign of prodromal PD, was typically concordant with nuclear scans, identifying subjects with high conversion risk. Iron deposition can affect STS in Multiple Sclerosis and STS loss in Amyotrophic Lateral Sclerosis is linked with multisystem degeneration, with poorer prognosis. In healthy individuals iron-induced microvessel changes are suspected for false positive results.<br><br>CONCLUSION: STS assessment exhibits potential in different settings, with a possibly intermediate role in the diagnostic work-up of various conditions. Its clinical utility should be explored further, through standardized MRI protocols on larger cohorts.}, }
@article {pmid39684324, year = {2024}, author = {Toader, C and Tataru, CP and Munteanu, O and Serban, M and Covache-Busuioc, RA and Ciurea, AV and Enyedi, M}, title = {Decoding Neurodegeneration: A Review of Molecular Mechanisms and Therapeutic Advances in Alzheimer's, Parkinson's, and ALS.}, journal = {International journal of molecular sciences}, volume = {25}, number = {23}, pages = {}, pmid = {39684324}, issn = {1422-0067}, mesh = {Humans ; *Alzheimer Disease/therapy/metabolism/genetics ; *Parkinson Disease/therapy/genetics/metabolism ; *Amyotrophic Lateral Sclerosis/therapy/genetics/metabolism ; Animals ; Neurodegenerative Diseases/therapy/metabolism/genetics ; Drug Delivery Systems ; Gene Editing ; }, abstract = {Neurodegenerative diseases, such as Alzheimer's, Parkinson's, ALS, and Huntington's, remain formidable challenges in medicine, with their relentless progression and limited therapeutic options. These diseases arise from a web of molecular disturbances-misfolded proteins, chronic neuroinflammation, mitochondrial dysfunction, and genetic mutations-that slowly dismantle neuronal integrity. Yet, recent scientific breakthroughs are opening new paths to intervene in these once-intractable conditions. This review synthesizes the latest insights into the underlying molecular dynamics of neurodegeneration, revealing how intertwined pathways drive the course of these diseases. With an eye on the most promising advances, we explore innovative therapies emerging from cutting-edge research: nanotechnology-based drug delivery systems capable of navigating the blood-brain barrier, gene-editing tools like CRISPR designed to correct harmful genetic variants, and stem cell strategies that not only replace lost neurons but foster neuroprotective environments. Pharmacogenomics is reshaping treatment personalization, enabling tailored therapies that align with individual genetic profiles, while molecular diagnostics and biomarkers are ushering in an era of early, precise disease detection. Furthermore, novel perspectives on the gut-brain axis are sparking interest as mounting evidence suggests that microbiome modulation may play a role in reducing neuroinflammatory responses linked to neurodegenerative progression. Taken together, these advances signal a shift toward a comprehensive, personalized approach that could transform neurodegenerative care. By integrating molecular insights and innovative therapeutic techniques, this review offers a forward-looking perspective on a future where treatments aim not just to manage symptoms but to fundamentally alter disease progression, presenting renewed hope for improved patient outcomes.}, }
@article {pmid39684308, year = {2024}, author = {Ścibior, A and Llopis, J and Dobrakowski, PP and Męcik-Kronenberg, T}, title = {Magnesium (Mg) and Neurodegeneration: A Comprehensive Overview of Studies on Mg Levels in Biological Specimens in Humans Affected Some Neurodegenerative Disorders with an Update on Therapy and Clinical Trials Supplemented with Selected Animal Studies.}, journal = {International journal of molecular sciences}, volume = {25}, number = {23}, pages = {}, pmid = {39684308}, issn = {1422-0067}, mesh = {Humans ; *Magnesium/therapeutic use ; Animals ; *Neurodegenerative Diseases/drug therapy ; Amyotrophic Lateral Sclerosis/drug therapy/metabolism ; Clinical Trials as Topic ; Disease Models, Animal ; Neuroprotective Agents/therapeutic use/pharmacology ; Parkinson Disease/drug therapy/metabolism ; Alzheimer Disease/drug therapy/metabolism ; }, abstract = {Neurodegenerative diseases, characterized by neuron loss, are a group of neurological disorders that adversely affect the lives of millions of people worldwide. Although several medicines have been approved for managing neurodegenerative diseases, new therapies allowing for a significant slowdown in the progression of neurodegenerative syndromes are constantly being sought. Magnesium (Mg), a crucial mineral necessary for the functioning of organisms, is important to normal central nervous system (CNS) activity. Although the effects of this bioelement on the CNS are relatively well recognized, its role in the pathophysiology of neurological disorders in humans is not yet well characterized. Therefore, the main goal of this review is to collect data about a possible association between Mg and neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's Disease (PD), and Amyotrophic lateral sclerosis (ALS) in humans. Hence, the levels of Mg in blood, cerebrospinal fluid (CSF), urine, and hair from subjects with AD, PD, and ALS are compiled to detect possible variations in the levels of this mineral in the biological specimens of people with neurodegenerative illnesses. Additionally, the findings from an animal model are summarized to offer the reader a deeper insight into studies on Mg in the context of neuroprotection and neurodegeneration. Data provided in the present review indicate that Mg, due to its neuroprotective, antioxidant, anti-inflammatory, and mitochondrial-supportive properties, could be a potential therapeutic agent for AD, PD, and ALS. However, more epidemiological studies with standardized methods of dietary assessment and Mg measurement are necessary to recognize its exact role in neurodegenerative disorders. Moreover, extensive well-designed clinical trials are also needed to establish definitive therapeutic protocols and optimal dosages, and to ensure long-term safety of this mineral supplementation in AD, PD, and ALS patients.}, }
@article {pmid39684197, year = {2024}, author = {García-González, N and Gonçalves-Sánchez, J and Gómez-Nieto, R and Gonçalves-Estella, JM and López, DE}, title = {Advances and Challenges in Gene Therapy for Neurodegenerative Diseases: A Systematic Review.}, journal = {International journal of molecular sciences}, volume = {25}, number = {23}, pages = {}, pmid = {39684197}, issn = {1422-0067}, mesh = {Humans ; *Genetic Therapy/methods ; *Neurodegenerative Diseases/therapy/genetics ; Animals ; Amyotrophic Lateral Sclerosis/therapy/genetics ; }, abstract = {This review explores recent advancements in gene therapy as a potential treatment for neurodegenerative diseases, focusing on intervention mechanisms, administration routes, and associated limitations. Following the PRISMA procedure guidelines, we systematically analyzed studies published since 2020 using the PICO framework to derive reliable conclusions. The efficacy of various gene therapies was evaluated for Parkinson's disease (n = 12), spinal muscular atrophy (n = 8), Huntington's disease (n = 3), Alzheimer's disease (n = 3), and amyotrophic lateral sclerosis (n = 6). For each condition, we assessed the therapeutic approach, curative or disease-modifying potential, delivery methods, advantages, drawbacks, and side effects. Results indicate that gene therapies targeting specific genes are particularly effective in monogenic disorders, with promising clinical outcomes expected in the near future. In contrast, in polygenic diseases, therapies primarily aim to promote cell survival. A major challenge remains: the translation of animal model success to human clinical application. Additionally, while intracerebral delivery methods enhance therapeutic efficacy, they are highly invasive. Despite these hurdles, gene therapy represents a promising frontier in the treatment of neurodegenerative diseases, underscoring the need for continued research to refine and personalize treatments for each condition.}, }
@article {pmid39681722, year = {2025}, author = {Weiner, HL}, title = {Immune mechanisms and shared immune targets in neurodegenerative diseases.}, journal = {Nature reviews. Neurology}, volume = {21}, number = {2}, pages = {67-85}, pmid = {39681722}, issn = {1759-4766}, mesh = {Humans ; *Neurodegenerative Diseases/immunology/therapy ; Animals ; Microglia/immunology ; *Immunotherapy/methods ; Multiple Sclerosis/immunology ; Amyotrophic Lateral Sclerosis/immunology ; }, abstract = {The immune system plays a major part in neurodegenerative diseases. In some, such as multiple sclerosis, it is the primary driver of the disease. In others, such as Alzheimer disease, amyotrophic lateral sclerosis and Parkinson disease, it has an amplifying role. Immunotherapeutic approaches that target the adaptive and innate immune systems are being explored for the treatment of almost all neurological diseases, and the targets and approaches are often common across diseases. Microglia are the primary immune cells in the brain that contribute to disease pathogenesis, and are consequently a common immune target for therapy. Other therapeutic approaches target components of the peripheral immune system, such as regulatory T cells and monocytes, which in turn act within the CNS. This Review considers in detail how microglia, monocytes and T cells contribute to the pathogenesis of multiple sclerosis, Alzheimer disease, amyotrophic lateral sclerosis and Parkinson disease, and their potential as shared therapeutic targets across these diseases. The microbiome is also highlighted as an emerging therapeutic target that indirectly modulates the immune system. Therapeutic approaches being developed to target immune function in neurodegenerative diseases are discussed, highlighting how immune-based approaches developed to treat one disease could be applicable to multiple other neurological diseases.}, }
@article {pmid39678458, year = {2024}, author = {Sulek, A}, title = {Secretome - the role of extracellular vesicles in the pathogenesis and therapy of neurodegenerative diseases.}, journal = {Postepy psychiatrii neurologii}, volume = {33}, number = {3}, pages = {147-162}, pmid = {39678458}, issn = {2720-5371}, abstract = {PURPOSE: Extracellular vesicles are the subject of many studies in various medical specialties. Their role in neurodegenerative diseases is increasing and they worth introducing in more detail.<br><br>METHODS: This review was performed following an electronic search of the database PubMed/Medline and Web of Science for English-language articles between 2010 and 2024 in the fields of medicine, molecular biology, and biochemistry. Keywords searches included combinations of the following terms: "extracellular vesicles" OR "exosomes" AND "neurodeg*" AND "microRNA" OR "miRNA" AND "AD" OR "PD" OR "ALS" OR "HD". Articles had to be original work or reviews.<br><br>RESULTS: The classification of extracellular vesicles is based on their size or origin. Their content is of key importance in communication between cells and can be treated as a physiological determinant of the normal or pathological condition of a body. The cargo transported in the extracellular space and over longer distances in various body fluids is diversified and may be nucleic acids (DNA, RNA, miRNA) as well as proteins and lipids, and, in the case of apoptotic bodies also a cell's organelles. Exosomes are the most thoroughly studied extracellular vesicles and the most often considered for therapeutic applications. Vesicles carrying biological substances in the body perform three basic functions: participation in a pathological mechanism, a biomarker role that also has diagnostic and prognostic functions, and a role in therapeutic activities. In the case of neurodegenerative diseases, it appears that extracellular vesicles can transport misfolded proteins, initiating pathological processes in previously normal cells.<br><br>CONCLUSIONS: The transport of various substances enclosed in vesicles seems to be very promising in therapeutic prospects in various diseases, and the possibility of their crossing the blood-brain barrier particularly indicates diseases of the central nervous system. Despite many years of research on extracellular vesicles in the context of neurodegenerative diseases, their practical use is currently limited to studies on animal and cellular models, and their practical application in clinical trials in neurodegenerative diseases is to date extremely rare.}, }
@article {pmid39672208, year = {2025}, author = {Liu, Y and Wu, L and Peng, W and Mao, X}, title = {Glial polarization in neurological diseases: Molecular mechanisms and therapeutic opportunities.}, journal = {Ageing research reviews}, volume = {104}, number = {}, pages = {102638}, doi = {10.1016/j.arr.2024.102638}, pmid = {39672208}, issn = {1872-9649}, mesh = {Humans ; *Neuroglia/pathology/metabolism/physiology ; *Nervous System Diseases/therapy/pathology/metabolism ; Animals ; *Cell Polarity/physiology ; Microglia/metabolism/pathology ; }, abstract = {Glial cell polarization plays a pivotal role in various neurological disorders. In response to distinct stimuli, glial cells undergo polarization to either mitigate neurotoxicity or facilitate neural repair following injury, underscoring the importance of glial phenotypic polarization in modulating central nervous system function. This review presents an overview of glial cell polarization, focusing on astrocytes and microglia. It explores the involvement of glial polarization in neurological diseases such as Alzheimer's disease, Parkinson's disease, stroke, epilepsy, traumatic brain injury, amyotrophic lateral sclerosis, multiple sclerosis and meningoencephalitis. Specifically, it emphasizes the role of glial cell polarization in disease pathogenesis through mechanisms including neuroinflammation, neurodegeneration, calcium signaling dysregulation, synaptic dysfunction and immune response. Additionally, it summarizes various therapeutic strategies including pharmacological treatments, dietary supplements and cell-based therapies, aimed at modulating glial cell polarization to ameliorate brain dysfunction. Future research focused on the spatio-temporal manipulation of glial polarization holds promise for advancing precision diagnosis and treatment of neurological diseases.}, }
@article {pmid39667295, year = {2025}, author = {Spencer, PS and Berntsson, SG and Buguet, A and Butterfield, P and Calne, DB and Calne, SM and Giménez-Roldán, S and Hugon, J and Kahlon, S and Kisby, GE and Lagrange, E and Landtblom, AE and Ludolph, AC and Nunn, PB and Palmer, VS and Reis, J and Román, GC and Sipilä, JOT and Spencer, SS and Angues, RV and Vernoux, JP and Yabushita, M}, title = {Brain health: Pathway to primary prevention of neurodegenerative disorders of environmental origin.}, journal = {Journal of the neurological sciences}, volume = {468}, number = {}, pages = {123340}, doi = {10.1016/j.jns.2024.123340}, pmid = {39667295}, issn = {1878-5883}, mesh = {Humans ; *Neurodegenerative Diseases/prevention &amp; control/etiology/epidemiology ; *Primary Prevention/methods ; *Brain ; *Environmental Exposure/adverse effects ; }, abstract = {While rising global rates of neurodegenerative disease encourage early diagnosis and therapeutic intervention to block clinical expression (secondary prevention), a more powerful approach is to identify and remove environmental factors that trigger long-latencybrain disease (primary prevention) by acting on a susceptible genotype or acting alone. The latter is illustrated by the post-World War II decline and disappearance of Amyotrophic Lateral Sclerosis and Parkinsonism-Dementia Complex (ALS/PDC), a prototypical often-familial neurodegenerative disease formerly present in very high incidence on the island of Guam. Lessons learned from 75 years of investigation on the etiology of ALS/PDC include: the importance of focusing field research on the disease epicenter and patients with early-onset disease; soliciting exposure history from patients, family, and community to guide multidisciplinary biomedical investigation; recognition that disease phenotype may vary with exposure history, and that familial brain disease may have a primarily environmental origin. Furthermore, removal from exposure to the environmental trigger effects primary disease prevention.}, }
@article {pmid39666202, year = {2024}, author = {van Eijk, RPA and van Loon, FT and van Unnik, JWJ and Weemering, DN and Seitidis, G and Mavridis, D and van den Berg, LH and Nikolakopoulos, S}, title = {Attrition and discontinuation in amyotrophic lateral sclerosis clinical trials: a meta-analysis.}, journal = {Journal of neurology}, volume = {272}, number = {1}, pages = {40}, pmid = {39666202}, issn = {1432-1459}, support = {EVIDENCE//Stichting ALS Nederland/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/therapy ; Humans ; *Randomized Controlled Trials as Topic ; Patient Dropouts/statistics &amp; numerical data ; }, abstract = {OBJECTIVES: Attrition due to adverse events and disease progression impacts the integrity and generalizability of clinical trials. The aim of this study is to provide evidence-based estimates of attrition for clinical trials in amyotrophic lateral sclerosis (ALS), and identify study-related predictors, through a comprehensive systematic review and meta-analysis.<br><br>METHODS: We systematically reviewed the literature to identify all randomized, placebo-controlled clinical trials in ALS and determined the number of patients who discontinued the study per randomized arm. Subsequently, we meta-analyzed attrition rates across studies, evaluated the difference between study arms, and explored the impact of study-level characteristics. Finally, a meta-regression model predicting study discontinuation for future clinical trials was translated into a web application.<br><br>RESULTS: In total, 60 randomized placebo-controlled clinical trials were included in the meta-analysis, randomizing 14,493 patients with ALS. Attrition varied significantly between studies, ranging from 3.1% to 75.7% of all randomized patients, with a pooled effect of 32.0% (90% prediction interval 6.1% to 66.3%). Attrition was similar between the intervention and placebo arm (odds ratio 1.08, 95% CI 0.89 to 1.31, p&#x2009;=&#x2009;0.43). The follow-up duration was identified as the sole study-level predictor (0.032, 95% CI 0.026 to 0.039, p&#x2009;<&#x2009;0.001), resulting in predicted attrition of 19.3% for 6-month, 36.4% for 12-month, and 55.6% for 18-month clinical trials.<br><br>CONCLUSIONS: ALS clinical trials encounter high attrition, which increases with the follow-up duration. These findings underscore the need to refine our strategies to manage attrition, preserving the integrity and generalizability of ALS clinical trials.}, }
@article {pmid39662855, year = {2025}, author = {Yang, ZF and Jiang, XC and Gao, JQ}, title = {Present insights into the progress in gene therapy delivery systems for central nervous system diseases.}, journal = {International journal of pharmaceutics}, volume = {669}, number = {}, pages = {125069}, doi = {10.1016/j.ijpharm.2024.125069}, pmid = {39662855}, issn = {1873-3476}, mesh = {Humans ; *Genetic Therapy/methods ; *Central Nervous System Diseases/therapy ; Animals ; *Gene Transfer Techniques ; *Genetic Vectors/administration &amp; dosage ; Dependovirus/genetics ; }, abstract = {Central nervous system (CNS) diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), spinal cord injury (SCI), and ischemic strokes and certain rare diseases, such as amyotrophic lateral sclerosis (ALS) and ataxia, present significant obstacles to treatment using conventional molecular pharmaceuticals. Gene therapy, with its ability to target previously "undruggable" proteins with high specificity and safety, is increasingly utilized in both preclinical and clinical research for CNS ailments. As our comprehension of the pathophysiology of these conditions deepens, gene therapy stands out as a versatile and promising strategy with the potential to both prevent and treat these diseases. Despite the remarkable progress in refining and enhancing the structural design of gene therapy agents, substantial obstacles persist in their effective and safe delivery within living systems. To surmount these obstacles, a diverse array of gene delivery systems has been devised and continuously improved. Notably, Adeno-Associated Virus (AAVs)-based viral gene vectors and lipid-based nanocarriers have each advanced the in vivo delivery of gene therapies to various extents. This review aims to concisely summarize the pathophysiological foundations of CNS diseases and to shed light on the latest advancements in gene delivery vector technologies. It discusses the primary categories of these vectors, their respective advantages and limitations, and their specialized uses in the context of gene therapy delivery.}, }
@article {pmid39662651, year = {2025}, author = {Keethedeth, N and Anantha Shenoi, R}, title = {Mitochondria-targeted nanotherapeutics: A new frontier in neurodegenerative disease treatment.}, journal = {Mitochondrion}, volume = {81}, number = {}, pages = {102000}, doi = {10.1016/j.mito.2024.102000}, pmid = {39662651}, issn = {1872-8278}, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy ; *Mitochondria/drug effects/metabolism ; Animals ; *Drug Delivery Systems/methods ; Nanoparticles ; }, abstract = {Mitochondria are the seat of cellular energy and play key roles in regulating several cellular processes such as oxidative phosphorylation, respiration, calcium homeostasis and apoptotic pathways. Mitochondrial dysfunction results in error in oxidative phosphorylation, redox imbalance, mitochondrial DNA mutations, and disturbances in mitochondrial dynamics, all of which can lead to several metabolic and degenerative diseases. A plethora of studies have provided evidence for the involvement of mitochondrial dysfunction in the pathogenesis of neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis. Hence mitochondria have been used as possible therapeutic targets in the regulation of neurodegenerative diseases. However, the double membranous structure of mitochondria poses an additional barrier to most drugs even if they are able to cross the plasma membrane. Most of the drugs acting on mitochondria also required very high doses to exhibit the desired mitochondrial accumulation and therapeutic effect which in-turn result in toxic effects. Mitochondrial targeting has been improved by direct conjugation of drugs to mitochondriotropic molecules like dequalinium (DQA) and triphenyl phosphonium (TPP) cations. But being cationic in nature, these molecules also exhibit toxicity at higher doses. In order to further improve the mitochondrial localization with minimal toxicity, TPP was conjugated with various nanomaterials like liposomes. inorganic nanoparticles, polymeric nanoparticles, micelles and dendrimers. This review provides an overview of the role of mitochondrial dysfunction in neurodegenerative diseases and various nanotherapeutic strategies for efficient targeting of mitochondria-acting drugs in these diseases.}, }
@article {pmid39645221, year = {2025}, author = {Bajpai, A and Bharathi, V and Patel, BK}, title = {Therapeutic targeting of the oxidative stress generated by pathological molecular pathways in the neurodegenerative diseases, ALS and Huntington's.}, journal = {European journal of pharmacology}, volume = {987}, number = {}, pages = {177187}, doi = {10.1016/j.ejphar.2024.177187}, pmid = {39645221}, issn = {1879-0712}, mesh = {Animals ; Humans ; *Amyotrophic Lateral Sclerosis/metabolism/drug therapy/pathology/genetics ; *Antioxidants/pharmacology/therapeutic use ; *Huntington Disease/metabolism/drug therapy/pathology/genetics ; Molecular Targeted Therapy/methods ; Neurodegenerative Diseases/metabolism/drug therapy/pathology ; *Oxidative Stress/drug effects ; }, abstract = {Neurodegenerative disorders are characterized by a progressive decline of specific neuronal populations in the brain and spinal cord, typically containing aggregates of one or more proteins. They can result in behavioral alterations, memory loss and a decline in cognitive and motor abilities. Various pathways and mechanisms have been outlined for the potential treatment of these diseases, where redox regulation is considered as one of the most common druggable targets. For example, in amyotrophic lateral sclerosis (ALS) with superoxide dismutase-1 (SOD1) pathology, there is a downregulation of the antioxidant response nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. TDP-43 proteinopathy in ALS is associated with elevated levels of reactive oxygen species and mitochondrial dyshomeostasis. In ALS with mutant FUS, poly ADP ribose polymerase-dependent X ray repair cross complementing 1/DNA-ligase recruitment to the sites of oxidative DNA damage is affected, thereby causing defects in DNA damage repair. Oxidative stress in Huntington's disease (HD) with mutant huntingtin accumulation manifests as protein oxidation, metabolic energetics dysfunction, metal ion dyshomeostasis, DNA damage and mitochondrial dysfunction. The impact of oxidative stress in the progression of these diseases further warrants studies into the role of antioxidants in their treatment. While an antioxidant, edaravone, has been approved for therapeutics of ALS, numerous antioxidant molecules failed to pass the clinical trials despite promising initial studies. In this review, we summarize the oxidative stress pathways and redox modulators that are investigated in ALS and HD using various models.}, }
@article {pmid39639468, year = {2024}, author = {Arango-Cortes, ML and Giraldo-Cadavid, LF and Latorre Quintana, M and Forero-Cubides, JD and Gonzalez-Bermejo, J}, title = {Diaphragm pacing compared with mechanical ventilation in patients with chronic respiratory failure caused by diaphragmatic dysfunction: a systematic review and meta-analysis.}, journal = {Expert review of respiratory medicine}, volume = {18}, number = {12}, pages = {1101-1111}, doi = {10.1080/17476348.2024.2421846}, pmid = {39639468}, issn = {1747-6356}, mesh = {Humans ; Chronic Disease/therapy ; *Diaphragm/physiopathology ; *Electric Stimulation Therapy/methods/statistics &amp; numerical data ; Length of Stay/statistics &amp; numerical data ; Quality of Life ; *Respiration, Artificial/adverse effects/methods/statistics &amp; numerical data ; *Respiratory Paralysis/etiology/mortality/physiopathology/therapy ; Spinal Cord Injuries/complications/mortality/physiopathology/therapy ; Treatment Outcome ; }, abstract = {BACKGROUND: The effectiveness of diaphragmatic electrical stimulation (DES) compared to mechanical ventilation (MV) in improving clinical outcomes such as quality-of-life (QOL) and hospital stay remains inconsistent.<br><br>METHODS: We conducted a systematic review and meta-analysis by searching PubMed, Scopus, Google Scholar, LILACS, and IEEE Xplore. We included comparative studies (randomized controlled trials and observational studies) of DES administered via the phrenic nerve or intramuscular electrodes, compared with MV in adults with diaphragmatic paralysis or paresis. Two authors independently extracted data and assessed bias, with discrepancies resolved by a senior author. Results were pooled using the inverse variance method.<br><br>RESULTS: Out of 1,290 articles, nine were included in the systematic review, totaling 852 subjects. In spinal cord injury (SCI), one study reported lower mortality with DES, while three found no difference compared to MV. In these patients, DES was associated with shorter hospital stay, similar QOL, and heterogeneous results on respiratory infections. In amyotrophic lateral sclerosis (ALS), DES was associated with higher mortality and similar QOL compared to MV. Most SCI studies had a serious risk of bias.<br><br>CONCLUSION: DES shows potential in reducing hospital stay and respiratory infections in SCI but is associated with higher mortality in ALS.}, }
@article {pmid39636751, year = {2025}, author = {Desai, AB and Agarwal, A and Mohamed, AS and Mohamed, KH and Middlebrooks, EH and Bhatt, AA and Gupta, V and Kumar, N and Sechi, E and Flanagan, EP and López Chiriboga, S}, title = {Motor Neuron Diseases and Central Nervous System Tractopathies: Clinical-Radiologic Correlation and Diagnostic Approach.}, journal = {Radiographics : a review publication of the Radiological Society of North America, Inc}, volume = {45}, number = {1}, pages = {e240067}, doi = {10.1148/rg.240067}, pmid = {39636751}, issn = {1527-1323}, mesh = {Humans ; *Motor Neuron Disease/diagnostic imaging ; Diagnosis, Differential ; Magnetic Resonance Imaging/methods ; Pyramidal Tracts/diagnostic imaging ; }, abstract = {White matter tracts within the central nervous system are organized into ascending and descending pathways that transmit sensory input and motor output, respectively. Tractopathy, or damage to these tracts, can impair sensory or motor functions. Motor neuron diseases are pathologic processes affecting the upper or lower motor neurons. Amyotrophic lateral sclerosis (ALS) is the most common form of acquired motor neuron disease. Traditionally, ALS has affected upper and lower motor neurons of the extremities, torso, and head and neck. There are several ALS variants, some of which affect only the upper motor neurons (eg, primary lateral sclerosis), lower motor neurons (eg, progressive muscular atrophy), or motor neurons of the head and neck (eg, progressive bulbar palsy). Characteristic imaging features of ALS include abnormal T2 hyperintensity within the brain along the corticospinal tract, as well as cortical susceptibility signal intensity along the precentral gyrus, termed the "motor band" sign. Spinal muscular atrophy is a less common primary motor neuron disease and appears on images as atrophy of the anterior horn of the spinal cord, as well as proximal muscle atrophy. In addition to pure motor neuron diseases, there are numerous toxic and metabolic conditions, genetic disorders, infectious diseases, and immune-mediated disorders that can secondarily affect the corticospinal tracts (corticospinal tractopathies), producing symptoms of upper motor neuron injury. These tractopathies are visible at MRI as T2-hyperintense lesions along varying segments of the corticospinal tract. A comprehensive diagnostic approach that integrates clinical symptoms with radiologic and laboratory findings is crucial to distinguish among these varied conditions. [©]RSNA, 2024 Supplemental material is available for this article.}, }
@article {pmid39636698, year = {2025}, author = {Nona, RJ and Henderson, RD and Mccombe, PA}, title = {Routine blood biochemical biomarkers in amyotrophic lateral sclerosis: Systematic review and cohort analysis.}, journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration}, volume = {26}, number = {3-4}, pages = {303-321}, doi = {10.1080/21678421.2024.2435976}, pmid = {39636698}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/blood/mortality/diagnosis ; *Biomarkers/blood ; Cohort Studies ; Creatine Kinase/blood ; Creatinine/blood ; Uric Acid/blood ; }, abstract = {Introduction: Blood biochemical biomarkers, including urate, creatinine, albumin, and creatine kinase, have been shown to be useful in ALS. To provide further information about the roles of these four biomarkers roles we performed a systematic review. In addition, we also performed a new study of the role of these biomarkers in predicting survival, using data from our local ALS cohort. Methods: (1) Using established databases and other sources, we searched for papers about the use of urate, creatinine, albumin, and creatine kinase as biomarkers in ALS. Included articles were reviewed for information about biomarker levels in ALS and controls, association with markers of functional decline, and survival. (2) For our local ALS cohort, we performed survival analysis, Cox-proportionate-hazard ratio and ROC curves to investigate the use of these biomarkers in predicting survival. Results: (1) For systematic review, 104 papers were included. There was some variability in the findings. For urate, there was evidence of decreased levels in ALS, with higher levels associated ith longer survival. For creatinine, there was evidence of decreased levels in ALS, and higher levels correlated with longer survival. For albumin, some reports of reduced levels in ALS, but no consistent association with survival. For creatine kinase, some reports of increased levels in ALS, with inconsistent association with survival. (2) For the local ALS cohort there was evidence that urate and creatinine were associated with survival, but no significant association with survival. There was less evidence for albumin and CK. Discussion: This study provides support for further studies of these readily available biochemical measurement as bioamerkers in ALS.}, }
@article {pmid39628659, year = {2024}, author = {Ye, Q and Li, X and Gao, W and Gao, J and Zheng, L and Zhang, M and Yang, F and Li, H}, title = {Role of Rho-associated kinases and their inhibitor fasudil in neurodegenerative diseases.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1481983}, pmid = {39628659}, issn = {1662-4548}, abstract = {Neurodegenerative diseases (NDDs) are prevalent in the elderly. The pathogenesis of NDDs is complex, and currently, there is no cure available. With the increase in aging population, over 20 million people are affected by common NDDs alone (Alzheimer's disease and Parkinson's disease). Therefore, NDDs have profound negative impacts on patients, their families, and society, making them a major global health concern. Rho-associated kinases (ROCKs) belong to the serine/threonine protein kinases family, which modulate diverse cellular processes (e.g., apoptosis). ROCKs may elevate the risk of various NDDs (including Huntington's disease, Parkinson's disease, and Alzheimer's disease) by disrupting synaptic plasticity and promoting inflammatory responses. Therefore, ROCK inhibitors have been regarded as ideal therapies for NDDs in recent years. Fasudil, one of the classic ROCK inhibitor, is a potential drug for treating NDDs, as it repairs nerve damage and promotes axonal regeneration. Thus, the current review summarizes the relationship between ROCKs and NDDs and the mechanism by which fasudil inhibits ROCKs to provide new ideas for the treatment of NDDs.}, }
@article {pmid39627617, year = {2024}, author = {Wiersema, AF and Rennenberg, A and Smith, G and Varderidou-Minasian, S and Pasterkamp, RJ}, title = {Shared and distinct changes in the molecular cargo of extracellular vesicles in different neurodegenerative diseases.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {81}, number = {1}, pages = {479}, pmid = {39627617}, issn = {1420-9071}, support = {XS grant//Nederlandse Organisatie voor Wetenschappelijk Onderzoek/ ; GoALS//Stichting ALS Nederland/ ; TOTALS//Stichting ALS Nederland/ ; MUSALS//Stichting ALS Nederland/ ; ATAXALS//Stichting ALS Nederland/ ; MAXOMOD//E-rare3/ ; INTEGRALS//Rare-3/ ; TRIAGE//JPND/ ; }, mesh = {Animals ; Humans ; Alzheimer Disease/metabolism/pathology ; Amyloid beta-Peptides/metabolism ; Amyotrophic Lateral Sclerosis/metabolism/pathology ; Biomarkers/analysis/metabolism ; *Cell Communication ; *Extracellular Vesicles/metabolism ; MicroRNAs/metabolism/genetics ; *Neurodegenerative Diseases/diagnosis/metabolism/pathology ; Parkinson Disease/metabolism/pathology ; tau Proteins/metabolism ; }, abstract = {Neurodegenerative disorders such as Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD) affect millions of people worldwide. Curative treatment for these neurodegenerative disorders is still lacking and therefore a further understanding of their cause and progression is urgently needed. Extracellular vesicles (EVs) are nanosized vesicles loaded with cargo, such as proteins and miRNAs, that are released by cells and play an important role in intercellular communication. Intercellular communication through EVs can contribute to the spread of pathological proteins, such as amyloid-beta and tau, or cause pathogenesis through other mechanisms. In addition, EVs may serve as potential biomarkers for diagnosis and for monitoring disease progression. In this review, we summarize and discuss recent advances in our understanding of the role of EVs in AD, ALS an PD with an emphasis on dysregulated cargo in each disease. We highlight shared dysregulated cargo between these diseases, discuss underlying pathways, and outline future implications for therapeutic strategies.}, }
@article {pmid39624969, year = {2024}, author = {Yuan, D and Jiang, S and Xu, R}, title = {Clinical features and progress in diagnosis and treatment of amyotrophic lateral sclerosis.}, journal = {Annals of medicine}, volume = {56}, number = {1}, pages = {2399962}, pmid = {39624969}, issn = {1365-2060}, mesh = {*Amyotrophic Lateral Sclerosis/diagnosis/therapy/epidemiology/genetics ; Humans ; Prognosis ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of the central nervous system. Despite a large number of studies, the current prognosis of ALS is still not ideal. This article briefly describes the clinical features including epidemiology, genetic structure and clinical manifestations, as well as the progress of new diagnostic criteria and treatment of ALS. Meanwhile, we also discussed further both developments and improvements to enhance understanding and accelerating the introduction of the effective treatments of ALS.}, }
@article {pmid39623427, year = {2024}, author = {Chamut, S and Alhassan, M and Hameedaldeen, A and Kaplish, S and Yang, AH and Wade, CG and Alghamdi, S and Chamut, D and Novy, BB and Chandel, T}, title = {Every bite counts to achieve oral health: a scoping review on diet and oral health preventive practices.}, journal = {International journal for equity in health}, volume = {23}, number = {1}, pages = {261}, pmid = {39623427}, issn = {1475-9276}, mesh = {Humans ; *Oral Health/standards ; *Dental Caries/prevention &amp; control ; *Diet/standards ; Oral Hygiene/methods ; Health Behavior ; Social Determinants of Health ; }, abstract = {OBJECTIVE: To examine the landscape of preventive strategies and interventions directed to achieve oral health equity, with particular emphasis on the interplay between dental caries prevention, individual behaviors, and population-level strategies across various demographic and geographic regions.<br><br>METHODS: This scoping review was guided by Peters et al.'s framework, which incorporates four key concepts aimed at reducing caries: education for individuals and healthcare providers, behavioral modifications, addressing broader social determinants of health, and extending oral health education programs beyond traditional dental settings. A systematic search was conducted across five databases, from 2011 to 2022.<br><br>RESULTS: This review identified 107 studies highlighting three main themes: behavioral practices (N&#x2009;=&#x2009;33), which focused on reducing the prevalence of caries, improving oral hygiene practices, and enhancing overall oral health knowledge; educational interventions (N&#x2009;=&#x2009;39), which explored strategies to integrate oral health with broader public health initiatives; and dietary interventions (N&#x2009;=&#x2009;35), which emphasized the critical relationship between diet and oral health.<br><br>CONCLUSION: This SR highlights the critical need for comprehensive multilevel approaches that address the complex interplay between nutrition, oral health, and sociodemographic factors, while emphasizing the critical relationship between societal factors and individual health behaviors. Multifaceted interventions that include behavioral change, education, and dietary modifications are crucial for improving oral and overall health outcomes across diverse populations. Comprehensive strategies should prioritize medical-dental integration and data-driven approaches to effectively reduce oral health disparities for vulnerable populations, promoting long-term health equity.}, }
@article {pmid39622292, year = {2025}, author = {Ojo, O and Boateng, J and Pacella, R and Hanrahan, A and Essex, R and Dibley, L}, title = {Factors Influencing the Care and Management of Diabetic Foot Ulcers: A Scoping Review.}, journal = {Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists}, volume = {31}, number = {3}, pages = {380-389}, doi = {10.1016/j.eprac.2024.11.010}, pmid = {39622292}, issn = {1530-891X}, mesh = {Humans ; *Diabetic Foot/therapy ; *Health Knowledge, Attitudes, Practice ; Patient Education as Topic ; Disease Management ; }, abstract = {OBJECTIVE: The objective of this scoping review is to explore the experiences of patients' and healthcare practitioners on the factors that influence the care and management of diabetes-related foot ulcers (DFUs).<br><br>METHODS: Levac et&#xa0;al's 6-stage framework and the Preferred Reporting Items for Systematic Review and Meta-analysis extension for scoping reviews, guided the review. The SPIDER tool was used to define key elements of the review question. Searches for relevant articles were conducted in electronic databases (PUBMED, CINAHL, AMED, Embase, Cochrane Database of Systematic Reviews, and PsycINFO), Google Scholar, and hand searches of reference lists.<br><br>RESULTS: Eight articles met the inclusion criteria and were included in the review. Three themes were identified: Communication and Education about DFUs; Challenges of managing DFUs; and Barriers to treatment and management. The themes are presented as a narrative synthesis.<br><br>CONCLUSION: Inadequate knowledge of diabetic foot care by patients and inconsistent communication by healthcare professionals were primary factors affecting the effective management of diabetes-related foot ulcers. Consistent, patient-focused education that is supported by knowledgeable health care professionals should form the foundation of effective diabetic foot ulcer care.}, }
@article {pmid39615954, year = {2024}, author = {Murphy, BA and Hall, JA}, title = {How a strong measurement validity review can go astray: A look at and recommendations for future measurement-focused reviews.}, journal = {Clinical psychology review}, volume = {114}, number = {}, pages = {102506}, doi = {10.1016/j.cpr.2024.102506}, pmid = {39615954}, issn = {1873-7811}, mesh = {Humans ; *Psychometrics/standards ; Reproducibility of Results ; }, abstract = {Critical reviews of a test's measurement validity are valuable scientific contributions, yet even strong reviews can be undermined by subtle problems in how evidence is compiled and presented to readers. First, if discussions of poor reporting practices by a test's users are interwoven with discussions about validity support for the test itself, readers can be inadvertently misled into impressions of the latter which are improperly conflated with the former. Second, test reviewers should give at least as much careful attention to a test's external validity as to its structural validity; test reviewers who prioritize factor analysis and internal consistency at the expense of discriminant and convergent validity can inadvertently mislead readers into perceptions of a test which are more negative or more positive than is warranted by the evidence overall. In this commentary, we aim to help test evaluators in crafting critical investigations of measurement validity. We use Higgins et al.'s (2024) review of the Reading the Mind in the Eyes Test (RMET; Baron-Cohen et al., 2001) as a basis for discussion. We argue that their otherwise impressive review went astray in the two ways described above. After considering both the psychometric evidence that Higgins et al. (2024) provided and the external validity evidence that they did not provide, we conclude that their recommendations that the RMET should be abandoned, and that most prior research findings based on it should be reassessed or disregarded, are unwarranted.}, }
@article {pmid39614020, year = {2025}, author = {Shi, DL and Grifone, R and Zhang, X and Li, H}, title = {Rbm24-mediated post-transcriptional regulation of skeletal and cardiac muscle development, function and regeneration.}, journal = {Journal of muscle research and cell motility}, volume = {46}, number = {1}, pages = {53-65}, pmid = {39614020}, issn = {1573-2657}, support = {23545//the French Muscular Dystrophy Association/ ; }, mesh = {*RNA-Binding Proteins/metabolism/genetics ; Humans ; Animals ; *Muscle, Skeletal/metabolism/physiology ; *Regeneration/physiology ; *Muscle Development/physiology/genetics ; *Myocardium/metabolism ; *RNA Processing, Post-Transcriptional ; Cell Differentiation ; }, abstract = {RNA-binding proteins are critically involved in the post-transcriptional control of gene expression during embryonic development and in adult life, contributing to regulating cell differentiation and maintaining tissue homeostasis. Compared to the relatively well documented functions of transcription factors, the regulatory roles of RNA-binding proteins in muscle development and function remain largely elusive. However, deficiency of many RNA-binding proteins has been associated with muscular defects, neuromuscular disorders and heart diseases, such as myotonic dystrophy, amyotrophic lateral sclerosis, and cardiomyopathy. Rbm24 is highly conserved among vertebrates and is one of the best characterized RNA-binding proteins with crucial implication in the myogenic and cardiomyogenic programs. It presents the distinctive particularity of displaying highly restricted expression in both skeletal and cardiac muscles, with changes in subcellular localization during the process of differentiation. Functional analyses using different vertebrate models have clearly demonstrated its requirement for skeletal muscle differentiation and regeneration as well as for myocardium organization and cardiac function, by regulating the expression of both common and distinct target genes in these tissues. The challenge remains to decipher the dynamic feature of post-transcriptional circuits regulated by Rbm24 during skeletal myogenesis, cardiomyogenesis, and muscle repair. This review discusses current understanding of its function in striated muscles and its possible implication in human disease, with the aim of identifying research gaps for future investigation.}, }
@article {pmid39608699, year = {2025}, author = {Kale, MB and Wankhede, NL and Bishoyi, AK and Ballal, S and Kalia, R and Arya, R and Kumar, S and Khalid, M and Gulati, M and Umare, M and Taksande, BG and Upaganlawar, AB and Umekar, MJ and Kopalli, SR and Fareed, M and Koppula, S}, title = {Emerging biophysical techniques for probing synaptic transmission in neurodegenerative disorders.}, journal = {Neuroscience}, volume = {565}, number = {}, pages = {63-79}, doi = {10.1016/j.neuroscience.2024.11.055}, pmid = {39608699}, issn = {1873-7544}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/pathology/physiopathology ; *Synaptic Transmission/physiology ; Animals ; Synapses/metabolism/pathology/physiology ; }, abstract = {Plethora of research has shed light on the critical role of synaptic dysfunction in various neurodegenerative disorders (NDDs), including Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD). Synapses, the fundamental units for neural communication in the brain, are highly vulnerable to pathological conditions and are central to the progression of neurological diseases. The presynaptic terminal, a key component of synapses responsible for neurotransmitter release and synaptic communication, undergoes structural and functional alterations in these disorders. Understanding synaptic transmission abnormalities is crucial for unravelling the pathophysiological mechanisms underlying neurodegeneration. In the quest to probe synaptic transmission in NDDs, emerging biophysical techniques play a pivotal role. These advanced methods offer insights into the structural and functional changes occurring at nerve terminals in conditions like AD, PD, HD &amp; ALS. By investigating synaptic plasticity and alterations in neurotransmitter release dynamics, researchers can uncover valuable information about disease progression and potential therapeutic targets. The review articles highlighted provide a comprehensive overview of how synaptic vulnerability and pathology are shared mechanisms across a spectrum of neurological disorders. In major neurodegenerative diseases, synaptic dysfunction is a common thread linking these conditions. The intricate molecular machinery involved in neurotransmitter release, synaptic vesicle dynamics, and presynaptic protein regulation are key areas of focus for understanding synaptic alterations in neurodegenerative diseases.}, }
@article {pmid39598374, year = {2024}, author = {Li, Y and Fu, J and Wang, H}, title = {Advancements in Targeting Ion Channels for the Treatment of Neurodegenerative Diseases.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {17}, number = {11}, pages = {}, pmid = {39598374}, issn = {1424-8247}, support = {2023YFF1205500//National Key Research and Development Program of China/ ; 82471465//NSFC/ ; C2024202005//Distinguished Young Scholars Science Fund of the Natural Science Foundation of Hebei Province/ ; JZX2023002//Technology Project of Hebei Education Department/ ; 22JCQNJC01110//Tianjin Applied Basic Research Project/ ; 236Z2602G, 246Z2605G, 236Z2401G//the central government guides local funds for science and technology development for Hebei Province/ ; NV20230015//The Key Laboratory of Neural and Vascular Biology, Ministry of Education/ ; }, abstract = {Ion channels are integral membrane proteins embedded in biological membranes, and they comprise specific proteins that control the flow of ion transporters in and out of cells, playing crucial roles in the biological functions of different cells. They maintain the homeostasis of water and ion metabolism by facilitating ion transport and participate in the physiological processes of neurons and glial cells by regulating signaling pathways. Neurodegenerative diseases are a group of disorders characterized by the progressive loss of neurons in the central nervous system (CNS) or peripheral nervous system (PNS). Despite significant progress in understanding the pathophysiological processes of various neurological diseases in recent years, effective treatments for mitigating the damage caused by these diseases remain inadequate. Increasing evidence suggests that ion channels are closely associated with neuroinflammation; oxidative stress; and the characteristic proteins in neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). Therefore, studying the pathogenic mechanisms closely related to ion channels in neurodegenerative diseases can help identify more effective therapeutic targets for treating neurodegenerative diseases. Here, we discuss the progress of research on ion channels in different neurodegenerative diseases and emphasize the feasibility and potential of treating such diseases from the perspective of ion channels.}, }
@article {pmid39596864, year = {2024}, author = {McKenna, MC and Kleinerova, J and Power, A and Garcia-Gallardo, A and Tan, EL and Bede, P}, title = {Quantitative and Computational Spinal Imaging in Neurodegenerative Conditions and Acquired Spinal Disorders: Academic Advances and Clinical Prospects.}, journal = {Biology}, volume = {13}, number = {11}, pages = {}, pmid = {39596864}, issn = {2079-7737}, support = {2023//Spastic Paraplegia Foundation/ ; }, abstract = {Introduction: Quantitative spinal cord imaging has facilitated the objective appraisal of spinal cord pathology in a range of neurological conditions both in the academic and clinical setting. Diverse methodological approaches have been implemented, encompassing a range of morphometric, diffusivity, susceptibility, magnetization transfer, and spectroscopy techniques. Advances have been fueled both by new MRI platforms and acquisition protocols as well as novel analysis pipelines. The quantitative evaluation of specific spinal tracts and grey matter indices has the potential to be used in diagnostic and monitoring applications. The comprehensive characterization of spinal disease burden in pre-symptomatic cohorts, in carriers of specific genetic mutations, and in conditions primarily associated with cerebral disease, has contributed important academic insights. Methods: A narrative review was conducted to examine the clinical and academic role of quantitative spinal cord imaging in a range of neurodegenerative and acquired spinal cord disorders, including hereditary spastic paraparesis, hereditary ataxias, motor neuron diseases, Huntington's disease, and post-infectious or vascular disorders. Results: The clinical utility of specific methods, sample size considerations, academic role of spinal imaging, key radiological findings, and relevant clinical correlates are presented in each disease group. Conclusions: Quantitative spinal cord imaging studies have demonstrated the feasibility to reliably appraise structural, microstructural, diffusivity, and metabolic spinal cord alterations. Despite the notable academic advances, novel acquisition protocols and analysis pipelines are yet to be implemented in the clinical setting.}, }
@article {pmid39596609, year = {2024}, author = {Luglio, A and Maggi, E and Riviello, FN and Conforti, A and Sorrentino, U and Zuccarello, D}, title = {Hereditary Neuromuscular Disorders in Reproductive Medicine.}, journal = {Genes}, volume = {15}, number = {11}, pages = {}, pmid = {39596609}, issn = {2073-4425}, support = {PNRR-MR1-2022-12376108//European Union/ ; }, mesh = {Humans ; *Neuromuscular Diseases/genetics/diagnosis ; Female ; Pregnancy ; Reproductive Medicine/methods ; Genetic Testing/methods ; Prenatal Diagnosis ; Preimplantation Diagnosis ; Muscular Atrophy, Spinal/genetics ; Charcot-Marie-Tooth Disease/genetics/diagnosis ; }, abstract = {Neuromuscular disorders (NMDs) encompass a broad range of hereditary and acquired conditions that affect motor units, significantly impacting patients' quality of life and reproductive health. This narrative review aims to explore in detail the reproductive challenges associated with major hereditary NMDs, including Charcot-Marie-Tooth disease (CMT), dystrophinopathies, Myotonic Dystrophy (DM), Facioscapulohumeral Muscular Dystrophy (FSHD), Spinal Muscular Atrophy (SMA), Limb-Girdle Muscular Dystrophy (LGMD), and Amyotrophic Lateral Sclerosis (ALS). Specifically, it discusses the stages of diagnosis and genetic testing, recurrence risk estimation, options for preimplantation genetic testing (PGT) and prenatal diagnosis (PND), the reciprocal influence between pregnancy and disease, potential obstetric complications, and risks to the newborn.}, }
@article {pmid39596445, year = {2024}, author = {Jiang, LL and Zhang, XL and Hu, HY}, title = {Co-Aggregation of TDP-43 with Other Pathogenic Proteins and Their Co-Pathologies in Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {25}, number = {22}, pages = {}, pmid = {39596445}, issn = {1422-0067}, support = {31670782, 31700669//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/pathology ; *DNA-Binding Proteins/metabolism ; *Protein Aggregation, Pathological/metabolism ; Animals ; Amyotrophic Lateral Sclerosis/metabolism/pathology ; Protein Aggregates ; }, abstract = {Pathological aggregation of a specific protein into insoluble aggregates is a common hallmark of various neurodegenerative diseases (NDDs). In the earlier literature, each NDD is characterized by the aggregation of one or two pathogenic proteins, which can serve as disease-specific biomarkers. The aggregation of these specific proteins is thought to be a major cause of or deleterious result in most NDDs. However, accumulating evidence shows that a pathogenic protein can interact and co-aggregate with other pathogenic proteins in different NDDs, thereby contributing to disease onset and progression synergistically. During the past years, more than one type of NDD has been found to co-exist in some individuals, which may increase the complexity and pathogenicity of these diseases. This article reviews and discusses the biochemical characteristics and molecular mechanisms underlying the co-aggregation and co-pathologies associated with TDP-43 pathology. The TDP-43 aggregates, as a hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), can often be detected in other NDDs, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and spinocerebellar ataxia type 2 (SCA2). In many cases, TDP-43 is shown to interact and co-aggregate with multiple pathogenic proteins in vitro and in vivo. Furthermore, the co-occurrence and co-aggregation of TDP-43 with other pathogenic proteins have important consequences that may aggravate the diseases. Thus, the current viewpoint that the co-aggregation of TDP-43 with other pathogenic proteins in NDDs and their relevance to disease progression may gain insights into the patho-mechanisms and therapeutic potential of various NDDs.}, }
@article {pmid39595895, year = {2024}, author = {Pongrácová, E and Buratti, E and Romano, M}, title = {Prion-like Spreading of Disease in TDP-43 Proteinopathies.}, journal = {Brain sciences}, volume = {14}, number = {11}, pages = {}, pmid = {39595895}, issn = {2076-3425}, abstract = {TDP-43 is a ubiquitous nuclear protein that plays a central role in neurodegenerative disorders collectively known as TDP-43 proteinopathies. Under physiological conditions, TDP-43 is primarily localized to the nucleus, but in its pathological form it aggregates in the cytoplasm, contributing to neuronal death. Given its association with numerous diseases, particularly ALS and FTLD, the mechanisms underlying TDP-43 aggregation and its impact on neuronal function have been extensively investigated. However, little is still known about the spreading of this pathology from cell to cell. Recent research has unveiled the possibility that TDP-43 may possess prion-like properties. Specifically, misfolded TDP-43 aggregates can act as templates inducing conformational changes in native TDP-43 molecules and propagating the misfolded state across neural networks. This review summarizes the mounting and most recent evidence from in vitro and in vivo studies supporting the prion-like hypothesis and its underlying mechanisms. The prion-like behavior of TDP-43 has significant implications for diagnostics and therapeutics. Importantly, emerging strategies such as small molecule inhibitors, immunotherapies, and gene therapies targeting TDP-43 propagation offer promising avenues for developing effective treatments. By elucidating the mechanisms of TDP-43 spreading, we therefore aim to pave the way for novel therapies for TDP-43-related neurodegenerative diseases.}, }
@article {pmid39595812, year = {2024}, author = {Zhang, S and Yang, Y and Lv, X and Zhou, X and Zhao, W and Meng, L and Zhu, S and Zhang, Z and Wang, Y}, title = {Exosome Cargo in Neurodegenerative Diseases: Leveraging Their Intercellular Communication Capabilities for Biomarker Discovery and Therapeutic Delivery.}, journal = {Brain sciences}, volume = {14}, number = {11}, pages = {}, pmid = {39595812}, issn = {2076-3425}, support = {82171871//National Natural Science Foundation of China/ ; BK20230488//Youth Fund Project of the Jiangsu Province Basic Research Program (Natural Science Foundation)/ ; None//Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)/ ; }, abstract = {The inexorable progression of neurodegenerative diseases (NDs), including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis, is closely related to irreversible brain decline. Accurately characterizing pathophysiological features and identifying reliable biomarkers for early diagnosis and optimized treatment are critical. Hindered by the blood-brain barrier (BBB), obtaining sensitive monitoring indicators for disease progression and achieving efficient drug delivery remain significant challenges. Exosomes, endogenous nanoscale vesicles that carry key bioactive substances, reflect the intracellular environment and play an important role in cell signaling. They have shown promise in traversing the BBB, serving dual roles as potential biomarkers for NDs and vehicles for targeted drug delivery. However, the specific mechanisms by which exosome influence NDs are not fully understood, necessitating further investigation into their attributes and functionalities in the context of NDs. This review explores how exosomes mediate multifaceted interactions, particularly in exacerbating pathogenic processes such as oxidative stress, neuronal dysfunction, and apoptosis integral to NDs. It provides a comprehensive analysis of the profound impact of exosomes under stress and disease states, assessing their prospective utility as biomarkers and drug delivery vectors, offering new perspectives for tackling these challenging diseases.}, }
@article {pmid39595543, year = {2024}, author = {Stoccoro, A and Coppedè, F}, title = {Exposure to Metals, Pesticides, and Air Pollutants: Focus on Resulting DNA Methylation Changes in Neurodegenerative Diseases.}, journal = {Biomolecules}, volume = {14}, number = {11}, pages = {}, pmid = {39595543}, issn = {2218-273X}, mesh = {*DNA Methylation/drug effects ; Humans ; *Pesticides/toxicity/adverse effects ; *Neurodegenerative Diseases/genetics/metabolism/chemically induced ; *Epigenesis, Genetic/drug effects ; *Air Pollutants/toxicity/adverse effects ; Environmental Exposure/adverse effects ; Animals ; Metals, Heavy/toxicity/adverse effects ; Metals/toxicity/metabolism/adverse effects ; }, abstract = {Individuals affected by neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), are dramatically increasing worldwide. Thus, several efforts are being made to develop strategies for stopping or slowing the spread of these illnesses. Although causative genetic variants linked to the onset of these diseases are known, they can explain only a small portion of cases. The etiopathology underlying the neurodegenerative process in most of the patients is likely due to the interplay between predisposing genetic variants and environmental factors. Epigenetic mechanisms, including DNA methylation, are central candidates in translating the effects of environmental factors in genome modulation, and they play a critical role in the etiology of AD, PD, and ALS. Among the main environmental exposures that have been linked to an increased risk for these diseases, accumulating evidence points to the role of heavy metals, pesticides, and air pollutants. These compounds could trigger neurodegeneration through different mechanisms, mainly neuroinflammation and the induction of oxidative stress. However, increasing evidence suggests that they are also capable of inducing epigenetic alterations in neurons. In this article, we review the available literature linking exposure to metals, pesticides, and air pollutants to DNA methylation changes relevant to neurodegeneration.}, }
@article {pmid39593881, year = {2024}, author = {Favier, G and Rocha, DS}, title = {Overview of Tensor-Based Cooperative MIMO Communication Systems-Part 2: Semi-Blind Receivers.}, journal = {Entropy (Basel, Switzerland)}, volume = {26}, number = {11}, pages = {}, pmid = {39593881}, issn = {1099-4300}, abstract = {Cooperative MIMO communication systems play an important role in the development of future sixth-generation (6G) wireless systems incorporating new technologies such as massive MIMO relay systems, dual-polarized antenna arrays, millimeter-wave communications, and, more recently, communications assisted using intelligent reflecting surfaces (IRSs), and unmanned aerial vehicles (UAVs). In a companion paper, we provided an overview of cooperative communication systems from a tensor modeling perspective. The objective of the present paper is to provide a comprehensive tutorial on semi-blind receivers for MIMO one-way two-hop relay systems, allowing the joint estimation of transmitted symbols and individual communication channels with only a few pilot symbols. After a reminder of some tensor prerequisites, we present an overview of tensor models, with a detailed, unified, and original description of two classes of tensor decomposition frequently used in the design of relay systems, namely nested CPD/PARAFAC and nested Tucker decomposition (TD). Some new variants of nested models are introduced. Uniqueness and identifiability conditions, depending on the algorithm used to estimate the parameters of these models, are established. Two families of algorithms are presented: iterative algorithms based on alternating least squares (ALS) and closed-form solutions using Khatri-Rao and Kronecker factorization methods, which consist of SVD-based rank-one matrix or tensor approximations. In a second part of the paper, the overview of cooperative communication systems is completed before presenting several two-hop relay systems using different codings and configurations in terms of relaying protocol (AF/DF) and channel modeling. The aim of this presentation is firstly to show how these choices lead to different nested tensor models for the signals received at destination. Then, by capitalizing on these models and their correspondence with the generic models studied in the first part, we derive semi-blind receivers to jointly estimate the transmitted symbols and the individual communication channels for each relay system considered. In a third part, extensive Monte Carlo simulation results are presented to compare the performance of relay systems and associated semi-blind receivers in terms of the symbol error rate (SER) and channel estimate normalized mean-square error (NMSE). Their computation time is also compared. Finally, some perspectives are drawn for future research work.}, }
@article {pmid39592088, year = {2025}, author = {Mahakalakar, N and Mohariya, G and Taksande, B and Kotagale, N and Umekar, M and Vinchurney, M}, title = {"Nattokinase as a potential therapeutic agent for preventing blood-brain barrier dysfunction in neurodegenerative disorders".}, journal = {Brain research}, volume = {1849}, number = {}, pages = {149352}, doi = {10.1016/j.brainres.2024.149352}, pmid = {39592088}, issn = {1872-6240}, mesh = {*Blood-Brain Barrier/drug effects/metabolism ; Humans ; Animals ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Subtilisins/therapeutic use/pharmacology ; *Neuroprotective Agents/pharmacology/therapeutic use ; }, abstract = {Neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis are characterized by progressive destruction of neurons and cognitive impairment, and thorough studies have provided evidence that these pathologies have a close relationship to the failure of the blood-brain barrier (BBB). Nattokinase (NK), a protease found in fermented soybeans, has been extensively studied because it displays powerful neuroprotective abilities, which is why current research was reviewed in the present article. It was concluded that there is enough evidence in preclinical studies using experimental animals that NK supplementation can alleviate the condition related to BBB dysfunction, reduce brain inflammation, and improve cognitive ability. Furthermore, the study of NK on the cardiovascular system leads to certain assumptions, which include the impact on vasculature function and the ability to manage blood flow, which is the key feature of BBB integrity. Such assumed mechanisms are fibrinolytic action, anti-inflammatory and antioxidant action, and endothelium function modulation. There are many positive research findings, and it seems that NK may serve as an effective opponent for BBB breakdown; however, a new research level should be taken to disclose the application and therapeutic use of NK in brain neurodegenerative disease.}, }
@article {pmid39592063, year = {2024}, author = {Lorenc, F and Dupuis, L and Cassel, R}, title = {Impairments of inhibitory neurons in amyotrophic lateral sclerosis and frontotemporal dementia.}, journal = {Neurobiology of disease}, volume = {203}, number = {}, pages = {106748}, doi = {10.1016/j.nbd.2024.106748}, pmid = {39592063}, issn = {1095-953X}, mesh = {*Amyotrophic Lateral Sclerosis/pathology/physiopathology ; *Frontotemporal Dementia/pathology/physiopathology ; Humans ; Animals ; *Neurons/pathology ; *Neural Inhibition/physiology ; }, abstract = {Amyotrophic lateral sclerosis and frontotemporal dementia are two fatal neurodegenerative disorders. They are part of a pathophysiological continuum, displaying clinical, neuropathological, and genetic overlaps. There is compelling evidence that neuronal circuit dysfunction is an early feature of both diseases. Impaired neuronal excitability, imbalanced excitatory and inhibitory influences, and altered functional connectivity have been reported. These phenomena are likely due to combined alterations in the various cellular components involved in the functioning of neuronal networks. This review focuses on one of these cellular components: inhibitory neurons. We assess the evidence for inhibitory neuron impairments in amyotrophic lateral sclerosis and frontotemporal dementia, as well as the mechanisms leading to the loss of inhibition. We also discuss the contributions of these alterations to symptoms, and the potential therapeutic strategies for targeting inhibitory neuron deficits.}, }
@article {pmid39585162, year = {2024}, author = {Savvidis, C and Kouroglou, E and Kallistrou, E and Ragia, D and Dionysopoulou, S and Gavriiloglou, G and Tsiama, V and Proikaki, S and Belis, K and Ilias, I}, title = {IGFBP-2 in Critical Illness: A Prognostic Marker in the Growth Hormone/Insulin-like Growth Factor Axis.}, journal = {Pathophysiology : the official journal of the International Society for Pathophysiology}, volume = {31}, number = {4}, pages = {621-630}, pmid = {39585162}, issn = {1873-149X}, abstract = {Critical illness (CI) triggers complex disruptions in the growth hormone (GH)/insulin-like growth factor (IGF) axis, significantly affecting the dynamics of insulin-like growth-factor-binding proteins (IGFBPs). Among these, IGFBP-2 shows a sustained elevation during CI, which inversely correlates with serum levels of IGF-1, IGFBP-3, and the acid-labile subunit (ALS). Although IGFBP-2 does not directly interact with ALS, it may influence the availability of IGFs by competing with other IGFBPs for binding to IGF-1 and IGF-2. Research suggests that this persistent elevation of IGFBP-2 is largely driven by cytokine activity during CI, reflecting an adaptive response rather than a direct result of GH/IGF axis dysregulation. The clinical importance of IGFBP-2 is emphasized by its correlation with disease severity in conditions like sepsis and coronavirus disease 2019 (COVID-19), where its levels are markedly elevated compared to healthy controls and are similar to those observed in sepsis from various causes. Beyond its role in endocrine regulation, IGFBP-2 appears to play a part in metabolic and inflammatory pathways. Elevated IGFBP-2 levels have been linked to increased mortality and longer hospital stays, indicating its potential utility as a prognostic marker. Furthermore, measuring plasma IGFBP-2 may have other diagnostic applications, aiding in the assessment of CI when traditional biomarkers are inconclusive.}, }
@article {pmid39584466, year = {2025}, author = {Daneshpour, A and Rezvanimehr, A and Niktalab, P and Sharif, H and Yazdanpanah, N and Saleki, K and Rezaei, N}, title = {Exploring the role of vault complex in the nervous system: a literature review.}, journal = {Reviews in the neurosciences}, volume = {36}, number = {3}, pages = {327-338}, pmid = {39584466}, issn = {2191-0200}, mesh = {Humans ; Animals ; *Vault Ribonucleoprotein Particles/metabolism/genetics ; *Nervous System/metabolism ; }, abstract = {Vault RNAs (vtRNAs) are a novel group of non-coding RNAs that are involved in various signaling mechanisms. vtRNAs are joined by three proteins major vault protein (MVP), vault poly (ADP-ribose) polymerase (VPARP), and telomerase-associated protein 1 (TEP1) to form the vault complex. In humans, only four vtRNA including vtRNA 1-1, vtRNA 1-2, vtRNA 1-3, vtRNA 2-1) have been discovered. In nerve cells, vtRNA is involved in synapse formation through MAPK signaling. vtRNA travels to the distal area of neurites as a key unit in the vault complex. Moreover, tRNA is detached from the vault complex in the neurite via a mitotic kinase Aurora-A-reliant MVP phosphorylation. Several molecules contribute to the formation of vtRNAs. For instance, SRSF2 and NSUN2 and their attachment to vtRNA1-1 determines the production of small-vtRNAs. Through the same factors, vtRNAs could play a role in neurodevelopmental deficits. Addition the role of vtRNA expression and vault proteins has been recently studied in neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) as well as brain cancers. While the mechanisms of vtRNA involvement in neurological disorders is not well-demonstrated, we believe this could be related to the impact of vtRNA regulation in autophagy, immunoregulation, RNA stability, cellular stress, apoptosis, and regulation of other epigenetic pathways. The present review captures the state-of-the-art regarding the role of vtRNAs in neurodevelopment, normal nervous system function, and neurological disorders.}, }
@article {pmid39579963, year = {2024}, author = {Carracedo, S and Launay, A and Dechelle-Marquet, PA and Faivre, E and Blum, D and Delarasse, C and Boué-Grabot, E}, title = {Purinergic-associated immune responses in neurodegenerative diseases.}, journal = {Progress in neurobiology}, volume = {243}, number = {}, pages = {102693}, doi = {10.1016/j.pneurobio.2024.102693}, pmid = {39579963}, issn = {1873-5118}, mesh = {Humans ; *Neurodegenerative Diseases/immunology/metabolism ; Animals ; *Receptors, Purinergic/metabolism ; }, abstract = {The chronic activation of immune cells can participate in the development of pathological conditions such as neurodegenerative diseases including Alzheimer's disease (AD), Multiple Sclerosis (MS), Parkinson's disease (PD), Huntington's disease (HD) and Amyotrophic Lateral Sclerosis (ALS). In recent years, compelling evidence indicates that purinergic signaling plays a key role in neuro-immune cell functions. The extracellular release of adenosine 5'-triphosphate (ATP), and its breakdown products (ADP and adenosine) provide the versatile basis for complex purinergic signaling through the activation of several families of receptors. G-protein coupled adenosine A2A receptors, ionotropic P2X and G-protein coupled P2Y receptors for ATP and other nucleotides are abundant and widely distributed in neurons, microglia, and astrocytes of the central nervous system as well as in peripheral immune cells. These receptors are strongly linked to inflammation, with a functional interplay that may influence the intricate purinergic signaling involved in inflammatory responses. In the present review, we examine the roles of the purinergic receptors in neuro-immune cell functions with particular emphasis on A2AR, P2X4 and P2X7 and their possible relevance to specific neurodegenerative disorders. Understanding the molecular mechanisms governing purinergic receptor interaction will be crucial for advancing the development of effective immunotherapies targeting neurodegenerative diseases.}, }
@article {pmid39578404, year = {2025}, author = {Phrathep, DD and Abdo, Z and Tadros, M and Lewandowski, E and Evans, J}, title = {The role of osteopathic manipulative treatment for dystonia: a literature review.}, journal = {Journal of osteopathic medicine}, volume = {125}, number = {4}, pages = {203-211}, pmid = {39578404}, issn = {2702-3648}, mesh = {Humans ; *Manipulation, Osteopathic/methods ; *Dystonia/therapy ; }, abstract = {CONTEXT: Dystonia is a movement disorder that causes involuntary muscle contractions leading to abnormal movements and postures, such as twisting. Dystonia is the third most common movement disorder in the United States, with as many as 250,000 people affected. Because of its complexity, dystonia presents a significant challenge in terms of management and treatment. Despite limited research, osteopathic manipulative treatment (OMT) has been considered as an adjunctive treatment due to its inexpensive and noninvasive nature, as opposed to other modalities such as botulinum toxin injections, deep brain stimulation (DBS), and transcranial magnetic stimulation, which are often expensive and inaccessible. OMT treatments performed in case studies and series such as balanced ligamentous tension/articular ligamentous strain (BLT/ALS), muscle energy (ME), high-velocity low-amplitude (HVLA), and myofascial release (MFR) have shown reduction of pain and muscle hypertonicity, including in patients with dystonia.<br><br>OBJECTIVES: The studies reviewed in this paper provide a snapshot of the literature regarding the current evidence of OMT's role for dystonia.<br><br>METHODS: A medical reference librarian conducted a thorough literature search across multiple databases including PubMed and Google Scholar to find articles relevant to the use of OMT for dystonia. The search employed a combination of Medical Subject Headings (MeSH) terms and keywords related to osteopathic medicine and dystonia to ensure precise retrieval of relevant articles within the last 20 years. Despite limited research on the topic, all four relevant reports found in the literature were selected for review.<br><br>RESULTS: Of the four relevant reports, case series and studies highlighted the potential benefits of OMT in managing dystonia, particularly cervical dystonia and foot dystonia. OMT has shown promising results addressing pain, stiffness, and impaired motor function. In cases of foot dystonia in Parkinson's disease, OMT has helped improve gait and reduce pain by targeting somatic dysfunctions (SDs) associated with dystonia, such as abnormalities in foot progression angle (FPA) and musculoskeletal imbalances. Also, OMT has been found to alleviate symptoms of cervical dystonia, including tremors, muscle spasms, and neck stiffness. These interventions performed in case studies and series led to improvements in gait biomechanics in foot dystonia and overall symptom severity in patients with cervical dystonia.<br><br>CONCLUSIONS: Currently, botulinum toxin, oral medications, physical therapy, and rehabilitation are commonly utilized in managing dystonia. The studies reviewed in this paper suggest that these treatments may lead to improvements in pain and muscle hypertonicity in patients with dystonia. It is important to investigate whether factors such as the type of dystonia (eg, focal vs. segmental) and its underlying cause (eg, idiopathic, trauma, infection, autoimmune, medication side effects) influence treatment outcomes. Further research is recommended to explore the role of OMT in managing dystonia.}, }
@article {pmid39578133, year = {2025}, author = {Travaglia, A and Lal, S and Pullagura, SR}, title = {Advancing ALS research: public-private partnerships to accelerate drug and biomarker development.}, journal = {Trends in neurosciences}, volume = {48}, number = {1}, pages = {1-2}, doi = {10.1016/j.tins.2024.10.008}, pmid = {39578133}, issn = {1878-108X}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy ; Humans ; *Public-Private Sector Partnerships ; Biomarkers ; *Drug Development ; *Drug Discovery ; *Biomedical Research ; }, abstract = {Developing effective treatments for amyotrophic lateral sclerosis (ALS) has been hindered by both the complexity of the disease and decentralized research efforts. By fostering collaboration, standardization, and inclusivity, the Accelerating Medicines Partnership® (AMP®) ALS initiative aims to lay the foundation for future discoveries in ALS biomarkers and treatments.}, }
@article {pmid39577774, year = {2025}, author = {Olesen, MA and Villavicencio-Tejo, F and Cuevas-Espinoza, V and Quintanilla, RA}, title = {Unknown roles of tau pathology in neurological disorders. Challenges and new perspectives.}, journal = {Ageing research reviews}, volume = {103}, number = {}, pages = {102594}, doi = {10.1016/j.arr.2024.102594}, pmid = {39577774}, issn = {1872-9649}, mesh = {Humans ; *tau Proteins/metabolism ; Animals ; *Nervous System Diseases/metabolism/pathology ; Tauopathies/metabolism/pathology ; Aging/metabolism/pathology ; }, abstract = {Aging presents progressive changes that increase the susceptibility of the central nervous system (CNS) to suffer neurological disorders (NDs). Several studies have reported that an aged brain suffering from NDs shows the presence of pathological forms of tau protein, a microtubule accessory protein (MAP) critical for neuronal function. In this context, accumulative evidence has shown a pivotal contribution of pathological forms of tau to Alzheimer's disease (AD) and tauopathies. However, current investigations have implicated tau toxicity in other NDs that affect the central nervous system (CNS), including Parkinson's disease (PD), Huntington's disease (HD), Traumatic brain injury (TBI), Multiple sclerosis (MS), and Amyotrophic lateral sclerosis (ALS). These diseases are long-term acquired, affecting essential functions such as motor movement, cognition, hearing, and vision. Previous evidence indicated that toxic forms of tau do not have a critical contribution to the genesis or progression of these diseases. However, recent studies have shown that these tau forms contribute to neuronal dysfunction, inflammation, oxidative damage, and mitochondrial impairment events that contribute to the pathogenesis of these NDs. Recent studies have suggested that these neuropathologies could be associated with a prion-like behavior of tau, which induces a pathological dissemination of these toxic protein forms to different brain areas. Moreover, it has been suggested that this toxic propagation of tau from neurons into neighboring cells impairs the function of glial cells, oligodendrocytes, and endothelial cells by affecting metabolic function and mitochondrial health and inducing oxidative damage by tau pathology. Therefore, in this review, we will discuss current evidence demonstrating the critical role of toxic tau forms on NDs not related to AD and how its propagation and induced-bioenergetics failure may contribute to the pathogenic mechanism present in these NDs.}, }
@article {pmid39577228, year = {2025}, author = {Sojdeh, S and Safarkhani, M and Daneshgar, H and Aldhaher, A and Heidari, G and Nazarzadeh Zare, E and Iravani, S and Zarrabi, A and Rabiee, N}, title = {Promising breakthroughs in amyotrophic lateral sclerosis treatment through nanotechnology's unexplored frontier.}, journal = {European journal of medicinal chemistry}, volume = {282}, number = {}, pages = {117080}, doi = {10.1016/j.ejmech.2024.117080}, pmid = {39577228}, issn = {1768-3254}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/therapy ; Humans ; *Nanotechnology ; Genetic Therapy ; Animals ; Drug Delivery Systems ; Neuroprotective Agents/chemistry/therapeutic use/pharmacology ; }, abstract = {This review explores the transformative potential of nanotechnology in the treatment and diagnosis of amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disorder characterized by motor neuron degeneration, muscle weakness, and eventual paralysis. Nanotechnology offers innovative solutions across various domains, including targeted drug delivery, neuroprotection, gene therapy and editing, biomarker detection, advanced imaging techniques, and tissue engineering. By enhancing the precision and efficacy of therapeutic interventions, nanotechnology facilitates key advancements such as crossing the blood-brain barrier, targeting specific cell types, achieving sustained therapeutic release, and enabling combination therapies tailored to the complex pathophysiology of ALS. Despite its immense promise, the clinical translation of these approaches faces challenges, including potential cytotoxicity, biocompatibility, and regulatory compliance, which must be addressed through rigorous research and testing. This review emphasizes the application of nanotechnology in targeted drug delivery and gene therapy/editing for ALS, drawing on the author's prior work with various nanotechnological platforms to illustrate strategies for overcoming similar obstacles in drug and gene delivery. By bridging the gap between cutting-edge technology and clinical application, this article aims to highlight the vital role of nanotechnology in shaping the future of ALS treatment.}, }
@article {pmid39577115, year = {2024}, author = {Abdian, S and Fakhri, S and Moradi, SZ and Khirehgesh, MR and Echeverría, J}, title = {Saffron and its major constituents against neurodegenerative diseases: A mechanistic review.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {135}, number = {}, pages = {156097}, doi = {10.1016/j.phymed.2024.156097}, pmid = {39577115}, issn = {1618-095X}, mesh = {Animals ; Humans ; *Carotenoids/pharmacology/therapeutic use ; *Crocus/chemistry ; Cyclohexenes/pharmacology ; Glucosides/pharmacology ; *Neurodegenerative Diseases/drug therapy ; Neuroprotective Agents/chemistry/pharmacology ; Phytochemicals/pharmacology ; *Plant Extracts/chemistry/pharmacology/therapeutic use ; Signal Transduction/drug effects ; Terpenes/pharmacology ; Vitamin A/analogs &amp; derivatives ; }, abstract = {BACKGROUND: Neurodegeneration has been recognized as the main pathophysiological alteration in the majority of brain-related diseases. Despite contemporary attempts to provide acceptable medicinal therapies, the conclusion has not been much beneficial. Besides, the complex pathophysiological mechanisms behind neurodegenerative diseases (NDDs) urge the needs for finding novel multi-target agents. Accordingly, saffron with major active constituents and as multi-targeting agents have shown beneficial effects in modulating NDDs with higher efficacy and lower side effects.<br><br>PURPOSE: The present study provides a systematic and comprehensive review of the existing in vitro, in vivo, and clinical data on the effectiveness, and signaling pathways of saffron and its key phytochemical components in the management of NDDs. The need to develop novel saffron delivery systems is also considered.<br><br>METHODS: Studies were identified through a systematic and comprehensive search in Science Direct, PubMed, and Scopus databases through April 30, 2024. The whole saffron major constituents (e.g., saffron, crocin, crocetin, picrocrocin, and safranal) and NDDs (e.g., neuro*, spinal cord injury, multiple sclerosis, amyotrophic lateral sclerosis, Huntington*, Parkinson*, Alzheimer*, and brain) were selected as keywords to find related studies. In the systematic analysis, 64 articles were directly included in the current study. Additional reports were added within the comprehensive studies in the review.<br><br>RESULTS: Saffron and its active metabolites crocin, crocetin, safranal, and picrocrocin have shown acceptable efficacy in managing NDDs like Alzheimer's disease, Parkinson's disease, Attention deficit hyperactivity disorder, depression, and other NDDs via modulating apoptotic (e.g., caspases, Bax/Bcl-2, cytochrome c, and death receptors), inflammatory (e.g., NF-&#x3ba;B, IL-1&#x3b2;, IL-6, TNF-&#x3b1;, and COX-2), and oxidative strass (e.g., Nrf2, GSH, GPx, CAT, SOD, MDA, ROS, and nitrite) signaling pathways. The presented in vitro, in vivo, and clinical evidences showed us a better future of controlling NDDs with higher efficacy, while decreasing associated side effects with no significant toxicity. Additionally, employing novel delivery systems could increase the efficacy of saffron phytoconstituents to resolve the issues pharmacokinetic limitations.<br><br>CONCLUSION: Saffron and its major constituents employ anti-inflammatory, anti-apoptotic and antioxidant mechanisms in modulating several dysregulated-signaling pathways in NDDs. However, further research is necessary to elucidate the precise underlying mechanisms in exploring the feasibility of using saffron active compounds against NDDs. More studies should focus on dose-response relationships, long-term effects, highlighting key mechanisms, and designing more well-controlled clinical trials. Additionally, developing stable and cost-benefit novel delivery systems in future works helps to remove the pharmacokinetic limitations of saffron major constituents.}, }
@article {pmid39575748, year = {2024}, author = {Xu, Z and He, S and Begum, MM and Han, X}, title = {Myelin Lipid Alterations in Neurodegenerative Diseases: Landscape and Pathogenic Implications.}, journal = {Antioxidants &amp; redox signaling}, volume = {41}, number = {16-18}, pages = {1073-1099}, pmid = {39575748}, issn = {1557-7716}, support = {P30 AG013319/AG/NIA NIH HHS/United States ; P30 AG044271/AG/NIA NIH HHS/United States ; R01 AG061729/AG/NIA NIH HHS/United States ; R01 AG085545/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Neurodegenerative Diseases/metabolism ; *Myelin Sheath/metabolism ; *Lipid Metabolism ; Animals ; Lipids ; }, abstract = {Significance: Lipids, which constitute the highest portion (over 50%) of brain dry mass, are crucial for brain integrity, energy homeostasis, and signaling regulation. Emerging evidence revealed that lipid profile alterations and abnormal lipid metabolism occur during normal aging and in different forms of neurodegenerative diseases. Moreover, increasing genome-wide association studies have validated new targets on lipid-associated pathways involved in disease development. Myelin, the protective sheath surrounding axons, is crucial for efficient neural signaling transduction. As the primary site enriched with lipids, impairments of myelin are increasingly recognized as playing significant and complex roles in various neurodegenerative diseases, beyond simply being secondary effects of neuronal loss. Recent Advances: With advances in the lipidomics field, myelin lipid alterations and their roles in contributing to or reflecting the progression of diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, and others, have recently caught great attention. Critical Issues: This review summarizes recent findings of myelin lipid alterations in the five most common neurodegenerative diseases and discusses their implications in disease pathogenesis. Future Directions: By highlighting myelin lipid abnormalities in neurodegenerative diseases, this review aims to encourage further research focused on lipids and the development of new lipid-oriented therapeutic approaches in this area. Antioxid. Redox Signal. 00, 000-000.}, }
@article {pmid39574800, year = {2024}, author = {Bouajila, N and Domenighetti, C and Aubin, HJ and Naassila, M}, title = {Alcohol consumption and its association with cancer, cardiovascular, liver and brain diseases: a systematic review of Mendelian randomization studies.}, journal = {Frontiers in epidemiology}, volume = {4}, number = {}, pages = {1385064}, pmid = {39574800}, issn = {2674-1199}, abstract = {BACKGROUND: The health effects of alcohol consumption, particularly regarding potential protective benefits of light to moderate intake compared to abstinence, remain a subject of ongoing debate. However, epidemiological studies face limitations due to imprecise exposure measurements and the potential for bias through residual confounding and reverse causation. To address these limitations, we conducted a systematic review of Mendelian Randomization (MR) studies examining the causal relationship between alcohol consumption and cancers, cardiovascular, liver, and neurological diseases.<br><br>METHODOLOGY: We searched PubMed, ScienceDirect and Embase and Europe PMC up to 05/2024 for MR studies investigating the association of genetically predicted alcohol consumption with cancers, cardiovascular, liver and neurological diseases. We assessed methodological quality based on key elements of the MR design a genetic association studies tool.<br><br>RESULTS: We included 70 MR studies that matched our inclusion criteria. Our review showed a significant association of alcohol consumption with multiple cancers such as oral and oropharyngeal, esophageal, colorectal cancers, hepatocellular carcinoma and cutaneous melanoma. While the available studies did not consistently confirm the adverse or protective effects of alcohol on other cancers, such as lung cancer, as suggested by observational studies. Additionally, MR studies confirmed a likely causal effect of alcohol on the risk of hypertension, atrial fibrillation, myocardial infraction and vessels disease. However, there was no evidence to support the protective effects of light to moderate alcohol consumption on cognitive function, Alzheimer's disease, and amyotrophic lateral sclerosis, as reported in observational studies while our review revealed an increased risk of epilepsy and multiple sclerosis. The available studies provided limited results on the link between alcohol consumption and liver disease.<br><br>CONCLUSIONS: Despite the valuable insights into the causal relationship between alcohol consumption and various health outcomes that MR studies provided, it is worth noting that the inconsistent ability of genetic instrumental variables to distinguish between abstainers, light and moderate drinkers makes it difficult to differentiate between U or J-shaped vs. linear relationships between exposure and outcome. Additional research is necessary to establish formal quality assessment tools for MR studies and to conduct more studies in diverse populations, including non-European ancestries.<br><br>www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021246154, Identifier: PROSPERO (CRD42021246154).}, }
@article {pmid39572918, year = {2025}, author = {Changkakoti, L and Rajabalaya, R and David, SR and Balaraman, AK and Sivasubramanian, H and Mukherjee, AK and Bala, A}, title = {Exploration of the Role of Vitamins in Preventing Neurodegenerative Diseases: Comprehensive Review on Preclinical and Clinical Findings.}, journal = {Current neuropharmacology}, volume = {23}, number = {5}, pages = {547-563}, pmid = {39572918}, issn = {1875-6190}, mesh = {Humans ; *Neurodegenerative Diseases/prevention &amp; control ; Animals ; *Vitamins/therapeutic use ; }, abstract = {Neurodegenerative diseases (NDDs) are a multifaceted and heterogeneous group of complex diseases. Unfortunately, a cure for these conditions has yet to be found, but there are ways to reduce the risk of developing them. Studies have shown that specific vitamins regulate the brain molecules and signaling pathways, which may help prevent degeneration. This review focuses on examining the role of vitamins in preventing five significant types of neurodegenerative diseases, including Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD), Multiple Sclerosis (MS), and Amyotrophic Lateral Sclerosis (ALS). This review also highlights promising and controversial findings about the potential impact of vitamins on this group of diseases. Several developed countries standardize daily dietary vitamin intake to meet nutrient requirements, improve health, and prevent chronic diseases like NDDs. However, more research is necessary to gain a more comprehensive understanding of their therapeutic benefits, including studies exploring different drug-dose paradigms, diverse humanized animal models, and clinical trials conducted in various locations.}, }
@article {pmid39572211, year = {2025}, author = {Benatar, M and Heiman-Patterson, TD and Cooper-Knock, J and Brickman, D and Casaletto, KB and Goutman, SA and Vinceti, M and Dratch, L and Arias, JJ and Swidler, J and Turner, MR and Shefner, J and Westeneng, HJ and van den Berg, LH and Al-Chalabi, A and , }, title = {Guidance for clinical management of pathogenic variant carriers at elevated genetic risk for ALS/FTD.}, journal = {Journal of neurology, neurosurgery, and psychiatry}, volume = {96}, number = {3}, pages = {209-218}, pmid = {39572211}, issn = {1468-330X}, support = {/WT_/Wellcome Trust/United Kingdom ; R01 NS105479/NS/NINDS NIH HHS/United States ; U01 NS107027/NS/NINDS NIH HHS/United States ; U54 NS092091/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/therapy ; *Frontotemporal Dementia/genetics/therapy ; *Genetic Predisposition to Disease ; Genetic Testing ; Heterozygote ; }, abstract = {There is a growing understanding of the presymptomatic stages of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) and nascent efforts aiming to prevent these devastating neurodegenerative diseases have emerged. This progress is attributable, in no small part, to the altruism of people living with pathogenic variants at elevated genetic risk for ALS/FTD via their willingness to participate in natural history studies and disease prevention trials. Increasingly, this community has also highlighted the urgent need to develop paradigms for providing appropriate clinical care for those at elevated risk for ALS and FTD. This manuscript summarises recommendations emanating from a multi-stakeholder Workshop (Malvern, Pennsylvania, 2023) that aimed to develop guidance for at-risk carriers and their treating physicians. Clinical care recommendations span genetic testing (including counselling and sociolegal implications); monitoring for the emergence of early motor, cognitive and behavioural signs of disease; and the use of Food and Drug Administration-approved small molecule drugs and gene-targeting therapies. Lifestyle recommendations focus on exercise, smoking, statin use, supplement use, caffeine intake and head trauma, as well as occupational and environmental exposures. While the evidence base to inform clinical and lifestyle recommendations is limited, this guidance document aims to appraise carriers and clinicians of the issues and best available evidence, and also to define the research agenda that could yield more evidence-informed guidelines.}, }
@article {pmid39570437, year = {2025}, author = {Maity, D and Kaundal, RK}, title = {Exploring dysregulated miRNAs in ALS: implications for disease pathogenesis and early diagnosis.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {46}, number = {4}, pages = {1661-1686}, pmid = {39570437}, issn = {1590-3478}, mesh = {*Amyotrophic Lateral Sclerosis/diagnosis/genetics/metabolism ; Humans ; *MicroRNAs/metabolism/genetics ; Early Diagnosis ; Biomarkers/metabolism ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease marked by motor neuron degeneration, leading to muscle weakness and paralysis, with no effective treatments available. Early diagnosis could slow disease progression and optimize treatment. MicroRNAs (miRNAs) are being investigated as potential biomarkers due to their regulatory roles in cellular processes and stability in biofluids. However, variability across studies complicates their diagnostic utility in ALS. This study aims to identify significantly dysregulated miRNAs in ALS through meta-analysis to elucidate disease mechanisms and improve diagnostic strategies.<br><br>METHODS: We systematically searched PubMed, Google Scholar, and the Cochrane Library, following predefined inclusion and exclusion criteria. The primary effect measure was the standardized mean difference (SMD) with a 95% confidence interval, analyzed using a random-effects model. Additionally, we used network pharmacology to examine the targets of dysregulated miRNAs and their roles in ALS pathology.<br><br>RESULTS: Analysing 34 studies, we found significant upregulation of hsa-miR-206, hsa-miR-133b, hsa-miR-23a, and hsa-miR-338-3p, and significant downregulation of hsa-miR-218, hsa-miR-21-5p, and hsa-let-7b-5p in ALS patients. These miRNAs are involved in ALS pathophysiology, including stress granule formation, nuclear pore complex, SMCR8 and Sig1R dysfunction, histone methyltransferase complex alterations, and MAPK signaling perturbation, highlighting their critical role in ALS progression.<br><br>CONCLUSION: This study identifies several dysregulated miRNAs in ALS patients, offering insights into their role in the disease and potential as diagnostic biomarkers. These findings enhance our understanding of ALS mechanisms and may inform future diagnostic strategies. Validating these results and exploring miRNA-based interventions are crucial for improving ALS diagnosis and treatment outcomes.}, }
@article {pmid39569894, year = {2024}, author = {Brannigan, JFM and Liyanage, K and Horsfall, HL and Bashford, L and Muirhead, W and Fry, A}, title = {Brain-computer interfaces patient preferences: a systematic review.}, journal = {Journal of neural engineering}, volume = {21}, number = {6}, pages = {}, doi = {10.1088/1741-2552/ad94a6}, pmid = {39569894}, issn = {1741-2552}, mesh = {*Brain-Computer Interfaces ; Humans ; *Patient Preference ; Adult ; Middle Aged ; Spinal Cord Injuries/rehabilitation/psychology/physiopathology ; Amyotrophic Lateral Sclerosis/psychology/rehabilitation/physiopathology ; }, abstract = {Objective. Brain-computer interfaces (BCIs) have the potential to restore motor capabilities and functional independence in individuals with motor impairments. Despite accelerating advances in the performance of implanted devices, few studies have identified patient preferences underlying device design, and each study typically captures a single aetiology of motor impairment. We aimed to characterise BCI patient preferences in a large cohort across multiple aetiologies.Approach. We performed a systematic review of all published studies reporting patient preferences for BCI devices, including both qualitative and quantitative data. We searched MEDLINE, Embase, and CINAHL from inception to 18 April 2023. Two reviewers independently screened articles and extracted data on demographic information, device use, invasiveness preference, device design, and functional preferences.Main results. From 1316 articles identified, 28 studies met inclusion criteria, capturing preferences from 1701 patients (mean age 42.1-64.3 years). The most represented conditions were amyotrophic lateral sclerosis (n= 15 studies, 53.6%) and spinal cord injury (n= 13 studies 46.4%). Individuals with motor impairments prioritised device accuracy over other design characteristics. In four studies where patients ranked performance characteristics, accuracy was ranked first each time. We found that the speed and accuracy of BCI systems in recent publications exceeds reported patient preferences, however this performance has been achieved with a level of training and setup burden that would not be tolerated by most patients. Preferences varied by disease aetiology and severity; amyotrophic lateral sclerosis patients typically prioritised communication functions, whereas spinal cord injury patients emphasised limb control and sphincteric functions.Significance.Our findings highlight that despite advances in BCI performance exceeding patient expectations, there remains a need to reduce training and setup burdens to enhance usability. Moreover, patient preferences differ across conditions and impairment severities, underscoring the importance of personalised BCI configurations and tailored training regimens to meet individual needs.}, }
@article {pmid39567497, year = {2024}, author = {Zhu, Z and Song, M and Ren, J and Liang, L and Mao, G and Chen, M}, title = {Copper homeostasis and cuproptosis in central nervous system diseases.}, journal = {Cell death &amp; disease}, volume = {15}, number = {11}, pages = {850}, pmid = {39567497}, issn = {2041-4889}, mesh = {Humans ; *Copper/metabolism ; *Homeostasis ; *Central Nervous System Diseases/metabolism/pathology ; Animals ; }, abstract = {Copper (Cu), an indispensable micronutrient for the sustenance of living organisms, contributes significantly to a vast array of fundamental metabolic processes. The human body maintains a relatively low concentration of copper, which is mostly found in the bones, liver, and brain. Despite its low concentration, Cu plays a crucial role as an indispensable element in the progression and pathogenesis of central nervous system (CNS) diseases. Extensive studies have been conducted in recent years on copper homeostasis and copper-induced cell death in CNS disorders, including glioma, Alzheimer's disease, Amyotrophic lateral sclerosis, Huntington's disease, and stroke. Cuproptosis, a novel copper-induced cell death pathway distinct from apoptosis, necrosis, pyroptosis, and ferroptosis, has been identified as potentially intricately linked to the pathogenic mechanisms underlying various CNS diseases. Therefore, a systematic review of copper homeostasis and cuproptosis and their relationship with CNS disorders could deepen our understanding of the pathogenesis of these diseases. In addition, it may provide new insights and strategies for the treatment of CNS disorders.}, }
@article {pmid39567371, year = {2024}, author = {Nuzum, ND and Deady, C and Kittel-Schneider, S and Cryan, JF and O'Mahony, SM and Clarke, G}, title = {More than just a number: the gut microbiota and brain function across the extremes of life.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2418988}, pmid = {39567371}, issn = {1949-0984}, mesh = {*Gastrointestinal Microbiome/physiology ; Humans ; *Brain/microbiology ; Animals ; Brain-Gut Axis/physiology ; Alzheimer Disease/microbiology/physiopathology ; Neurodegenerative Diseases/microbiology ; }, abstract = {Understanding the interrelationship between the gut microbiota and host physiology, although still in its relative infancy, has taken important steps forward over the past decade. In the context of brain disorders including those characterized by neurodevelopmental and neurodegenerative changes there have been important advances. However, initially research involved correlational analyses, had limited translational scope, and lacked functional assessments. Thus, largescale longitudinal clinical investigations that assess causation and underlying mechanisms via in depth analysis methods are needed. In neurodegeneration research, strong causal evidence now links the gut microbiome to Alzheimer's (AD), and Parkinson's Disease (PD), as supported by human-to-animal transplantation studies. Longitudinal interventions are being conducted in AD, PD, amyotrophic lateral sclerosis, Huntington's disease, and multiple sclerosis. Neurodevelopmental research has also seen a boon in microbiome-related clinical research including in autism, Attention-deficit/hyperactivity disorder, and schizophrenia, which is confirming prior animal model work regarding the key time-windows in the gut microbiome important for infant cognition. While recent research advances represent important progress, fundamental knowledge gaps and obstacles remain. Knowing how and why the gut microbiome changes at the extremes of life will develop our mechanistic understanding and help build the evidence base as we strive toward counteracting microbial missteps with precision therapeutic interventions.}, }
@article {pmid39557152, year = {2025}, author = {Yu, H and Ren, K and Jin, Y and Zhang, L and Liu, H and Huang, Z and Zhang, Z and Chen, X and Yang, Y and Wei, Z}, title = {Mitochondrial DAMPs: Key mediators in neuroinflammation and neurodegenerative disease pathogenesis.}, journal = {Neuropharmacology}, volume = {264}, number = {}, pages = {110217}, doi = {10.1016/j.neuropharm.2024.110217}, pmid = {39557152}, issn = {1873-7064}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/pathology/immunology ; *Neuroinflammatory Diseases/metabolism/immunology/pathology ; Animals ; *Mitochondria/metabolism ; *Alarmins/metabolism ; Inflammasomes/metabolism ; DNA, Mitochondrial/metabolism ; Reactive Oxygen Species/metabolism ; }, abstract = {Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) are increasingly linked to mitochondrial dysfunction and neuroinflammation. Central to this link are mitochondrial damage-associated molecular patterns (mtDAMPs), including mitochondrial DNA, ATP, and reactive oxygen species, released during mitochondrial stress or damage. These mtDAMPs activate inflammatory pathways, such as the NLRP3 inflammasome and cGAS-STING, contributing to the progression of neurodegenerative diseases. This review delves into the mechanisms by which mtDAMPs drive neuroinflammation and discusses potential therapeutic strategies targeting these pathways to mitigate neurodegeneration. Additionally, it explores the cross-talk between mitochondria and the immune system, highlighting the complex interplay that exacerbates neuronal damage. Understanding the role of mtDAMPs could pave the way for novel treatments aimed at modulating neuroinflammation and slowing disease progression, ultimately improving patient outcome.}, }
@article {pmid39556113, year = {2025}, author = {Yeganeh Markid, T and Pourahmadiyan, A and Hamzeh, S and Sharifi-Bonab, M and Asadi, MR and Jalaiei, A and Rezazadeh, M and Ghafouri-Fard, S}, title = {A special focus on polyadenylation and alternative polyadenylation in neurodegenerative diseases: A systematic review.}, journal = {Journal of neurochemistry}, volume = {169}, number = {2}, pages = {e16255}, doi = {10.1111/jnc.16255}, pmid = {39556113}, issn = {1471-4159}, mesh = {Humans ; *Neurodegenerative Diseases/genetics/metabolism ; *Polyadenylation/physiology ; Animals ; }, abstract = {Neurodegenerative diseases (NDDs) are one of the prevailing conditions characterized by progressive neuronal loss. Polyadenylation (PA) and alternative polyadenylation (APA) are the two main post-transcriptional events that regulate neuronal gene expression and protein production. This systematic review analyzed the available literature on the role of PA and APA in NDDs, with an emphasis on their contributions to disease development. A comprehensive literature search was performed using the PubMed, Scopus, Cochrane, Google Scholar, Embase, Web of Science, and ProQuest databases. The search strategy was developed based on the framework introduced by Arksey and O'Malley and supplemented by the inclusion and exclusion criteria. The study selection was performed by two independent reviewers. Extraction and data organization were performed in accordance with the predefined variables. Subsequently, quantitative and qualitative analyses were performed. Forty-seven studies were included, related to a variety of NDDs, namely Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. Disease induction was performed using different models, including human tissues, animal models, and cultured cells. Most investigations were related to PA, although some were related to APA or both. Amyloid precursor protein (APP), Tau, SNCA, and STMN2 were the major genes identified; most of the altered PA patterns were related to mRNA stability and translation efficiency. This review particularly underscores the key roles of PA and APA in the pathogenesis of NDDs through their mechanisms that contribute to gene expression dysregulation, protein aggregation, and neuronal dysfunction. Insights into these mechanisms may lead to new therapeutic strategies focused on the modulation of PA and APA activities. Further research is required to investigate the translational potential of targeting these pathways for NDD treatment.}, }
@article {pmid39551788, year = {2024}, author = {Sadeghdoust, M and Das, A and Kaushik, DK}, title = {Fueling neurodegeneration: metabolic insights into microglia functions.}, journal = {Journal of neuroinflammation}, volume = {21}, number = {1}, pages = {300}, pmid = {39551788}, issn = {1742-2094}, support = {MS220110//U.S. Department of Defense/ ; 916184//Multiple Sclerosis Society of Canada/ ; }, mesh = {*Microglia/metabolism/pathology ; Humans ; *Neurodegenerative Diseases/metabolism/pathology ; Animals ; }, abstract = {Microglia, the resident immune cells of the central nervous system, emerge in the brain during early embryonic development and persist throughout life. They play essential roles in brain homeostasis, and their dysfunction contributes to neuroinflammation and the progression of neurodegenerative diseases. Recent studies have uncovered an intricate relationship between microglia functions and metabolic processes, offering fresh perspectives on disease mechanisms and possible treatments. Despite these advancements, there are still significant gaps in our understanding of how metabolic dysregulation affects microglial phenotypes in these disorders. This review aims to address these gaps, laying the groundwork for future research on the topic. We specifically examine how metabolic shifts in microglia, such as the transition from oxidative phosphorylation and mitochondrial metabolism to heightened glycolysis during proinflammatory states, impact the disease progression in Alzheimer's disease, multiple sclerosis, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease. Additionally, we explore the role of iron, fatty and amino acid metabolism in microglial homeostasis and repair. Identifying both distinct and shared metabolic adaptations in microglia across neurodegenerative diseases could reveal common therapeutic targets and provide a deeper understanding of disease-specific mechanisms underlying multiple CNS disorders.}, }
@article {pmid39547910, year = {2025}, author = {Khamaysa, M and El Mendili, M and Marchand, V and Querin, G and Pradat, PF}, title = {Quantitative spinal cord imaging: Early ALS diagnosis and monitoring of disease progression.}, journal = {Revue neurologique}, volume = {181}, number = {3}, pages = {172-183}, doi = {10.1016/j.neurol.2024.10.005}, pmid = {39547910}, issn = {0035-3787}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/diagnostic imaging/pathology ; Disease Progression ; *Spinal Cord/diagnostic imaging/pathology ; Early Diagnosis ; *Neuroimaging/methods ; Magnetic Resonance Imaging/methods ; Prognosis ; Biomarkers ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive degeneration of motor neurons in the cortex, brainstem, and spinal cord. This degeneration leads to muscular weakness, progressively impairing motor functions and ultimately resulting in respiratory failure. The clinical, genetic, and pathological heterogeneity of ALS, combined with the absence of reliable biomarkers, significantly challenge the efficacy of therapeutic trials. Despite these hurdles, neuroimaging, and particularly spinal cord imaging, has emerged as a promising tool. It provides insights into the involvement of both upper and lower motor neurons. Quantitative spinal imaging has the potential to facilitate early diagnosis, enable accurate monitoring of disease progression, and refine the design of clinical trials. In this review, we explore the utility of spinal cord imaging within the broader context of developing spinal imaging biomarkers in ALS. We focus on a both diagnostic and prognostic biomarker in ALS, highlighting its pivotal role in elucidating the disease's underlying pathology. We also discuss the existing limitations and future avenues for research, aiming to bridge the translational gap between academic research and its application in clinical practice and therapeutic trials.}, }
@article {pmid39546178, year = {2025}, author = {Li, N and Zhang, Z and Shen, L and Song, G and Tian, J and Liu, Q and Ni, J}, title = {Selenium metabolism and selenoproteins function in brain and encephalopathy.}, journal = {Science China. Life sciences}, volume = {68}, number = {3}, pages = {628-656}, pmid = {39546178}, issn = {1869-1889}, mesh = {*Selenoproteins/metabolism ; Humans ; *Selenium/metabolism/deficiency ; *Brain/metabolism ; Animals ; *Brain Diseases/metabolism ; Neurodegenerative Diseases/metabolism ; }, abstract = {Selenium (Se) is an essential trace element of the utmost importance to human health. Its deficiency induces various disorders. Se species can be absorbed by organisms and metabolized to hydrogen selenide for the biosynthesis of selenoproteins, selenonucleic acids, or selenosugars. Se in mammals mainly acts as selenoproteins to exert their biological functions. The brain ranks highest in the specific hierarchy of organs to maintain the level of Se and the expression of selenoproteins under the circumstances of Se deficiency. Dyshomeostasis of Se and dysregulation of selenoproteins result in encephalopathy such as Alzheimer's disease, Parkinson's disease, depression, amyotrophic lateral sclerosis, and multiple sclerosis. This review provides a summary and discussion of Se metabolism, selenoprotein function, and their roles in modulating brain diseases based on the most currently published literature. It focuses on how Se is utilized and transported to the brain, how selenoproteins are biosynthesized and function physiologically in the brain, and how selenoproteins are involved in neurodegenerative diseases. At the end of this review, the perspectives and problems are outlined regarding Se and selenoproteins in the regulation of encephalopathy.}, }
@article {pmid39545606, year = {2024}, author = {A Virata, MC and Catahay, JA and Lippi, G and Henry, BM}, title = {Neurofilament light chain: a biomarker at the crossroads of clarity and confusion for gene-directed therapies.}, journal = {Neurodegenerative disease management}, volume = {14}, number = {6}, pages = {227-239}, pmid = {39545606}, issn = {1758-2032}, mesh = {Humans ; *Biomarkers/blood ; *Genetic Therapy/methods ; *Neurodegenerative Diseases/diagnosis/drug therapy/genetics ; *Neurofilament Proteins/blood ; }, abstract = {Neurofilament light chain (NfL) is a promising biomarker for neurodegenerative diseases, measurable in both CSF and blood upon neuroaxonal damage. While CSF analysis was traditionally used, blood-based assays now offer a less invasive alternative. NfL levels correlate with disease severity and progression in conditions like Alzheimer's disease, amyotrophic lateral sclerosis, multiple sclerosis and Huntington's disease. Clinical trials demonstrate its utility as a pharmacodynamic biomarker in MS and ALS. The FDA's approval of Tofersen for SOD1-ALS based on NfL reduction underscores its growing acceptance as surrogate marker. However, challenges remain in standardizing assays, interpreting clinical correlations, low specificity and understanding the dynamics between CSF and blood NfL levels. Addressing these issues is crucial for maximizing NfL's potential in neurodegenerative disease management.}, }
@article {pmid39542176, year = {2024}, author = {Tian, Z and Zhang, Q and Wang, L and Li, M and Li, T and Wang, Y and Cao, Z and Jiang, X and Luo, P}, title = {Progress in the mechanisms of pain associated with neurodegenerative diseases.}, journal = {Ageing research reviews}, volume = {102}, number = {}, pages = {102579}, doi = {10.1016/j.arr.2024.102579}, pmid = {39542176}, issn = {1872-9649}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/physiopathology ; *Pain/physiopathology/metabolism/etiology ; Animals ; Neuroinflammatory Diseases ; }, abstract = {Neurodegenerative diseases (NDDs) represent a class of neurological disorders characterized by the progressive degeneration or loss of neurons, impacting millions of individuals globally. In addition to the typical manifestations, pain is a prevalent symptom associated with NDDs, seriously impacting the quality of life for patients. The pathogenesis of pain associated with NDDs is intricate and multifaceted. Currently, the clinical management of NDDs-related pain symptoms predominantly relies on conventional pharmacological agents or physical therapy. However, these approaches often fail to produce satisfactory outcomes. This article summarizes the underlying mechanisms of major NDDs-associated pain: Neuroinflammation, Brain and spinal cord dysfunctions, Mitochondrial dysfunction, Risk gene and pathological protein, as well as Receptor, channel, and neurotransmitter. While numerous studies have investigated the downstream pathological processes associated with these mechanisms, there remains a significant gap in identifying the key initiating factors. Specifically, there is insufficient evidence for the upstream elements that activate microglia and astrocytes in neuroinflammation leading to pain in NDDs. Likewise, there is an absence of upstream factors elucidating how dysfunctions in the brain and spinal cord, as well as mitochondrial impairments, contribute to the development of pain. Furthermore, the specific mechanisms through which hallmark pathological proteins related to NDDs contribute to these pathological processes remain inadequately understood. The objective of this article is to synthesize the existing mechanisms underlying pain associated with NDDs, including Alzheimer's disease, Parkinson's disease, Huntington's disease, Schizophrenia, Amyotrophic lateral sclerosis, and Multiple sclerosis, while also identifying gaps and deficiencies in these mechanisms. This paper offers insights for future research trajectories. Given the intricate pathogenesis of NDDs-related pain, it emphasizes that a promising short-term strategy is combination therapy-intervening concurrently in multiple pathological processes-akin to the cocktail approach utilized in treating acquired immunodeficiency syndrome (AIDS). For long-term advancements, achieving breakthroughs in the treatment of the NDDs themselves will remain essential for alleviating accompanying pain symptoms.}, }
@article {pmid39524179, year = {2024}, author = {Trinh, QD and Mai, HN and Pham, DT}, title = {Application of mesenchymal stem cells for neurodegenerative diseases therapy discovery.}, journal = {Regenerative therapy}, volume = {26}, number = {}, pages = {981-989}, pmid = {39524179}, issn = {2352-3204}, abstract = {Neurodegenerative diseases are central or peripheral nervous system disorders associated with progressive brain cell degeneration. Common neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis have been widely studied. However, current therapeutics only reduce the symptoms and do not ameliorate the pathogenesis of these diseases. Recent studies suggested the roles of neuroinflammation, apoptosis, and oxidative stress in neurodegenerative diseases. Mesenchymal stem cells (MSCs) exert anti-apoptotic, anti-inflammatory, and antioxidative effects. Therefore, investigating the effects of MSCs and their applications may lead to the discovery of more effective therapies for neurodegenerative diseases. In this study, we review different approaches used to identify therapies for neurodegenerative diseases using MSCs.}, }
@article {pmid39534483, year = {2024}, author = {Sbarigia, C and Rome, S and Dini, L and Tacconi, S}, title = {New perspectives of the role of skeletal muscle derived extracellular vesicles in the pathogenesis of amyotrophic lateral sclerosis: the 'dying back' hypothesis.}, journal = {Journal of extracellular biology}, volume = {3}, number = {11}, pages = {e70019}, pmid = {39534483}, issn = {2768-2811}, abstract = {Amyotrophic lateral sclerosis (ALS), is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord, and is characterized by muscle weakness, paralysis and ultimately, respiratory failure. The exact causes of ALS are not understood, though it is believed to combine genetic and environmental factors. Until now, it was admitted that motor neurons (MN) in the brain and spinal cord degenerate, leading to muscle weakness and paralysis. However, as ALS symptoms typically begin with muscle weakness or stiffness, a new hypothesis has recently emerged to explain the development of the pathology, that is, the 'dying back hypothesis', suggesting that this degeneration starts at the connections between MN and muscles, resulting in the loss of muscle function. Over time, this damage extends along the length of the MN, ultimately affecting their cell bodies in the spinal cord and brain. While the dying back hypothesis provides a potential framework for understanding the progression of ALS, the exact mechanisms underlying the disease remain complex and not fully understood. In this review, we are positioning the role of extracellular vesicles as new actors in ALS development.}, }
@article {pmid39523617, year = {2024}, author = {Iguchi, Y and Katsuno, M}, title = {[Current Status of Drug Development for Amyotrophic Lateral Sclerosis].}, journal = {Brain and nerve = Shinkei kenkyu no shinpo}, volume = {76}, number = {11}, pages = {1241-1249}, doi = {10.11477/mf.1416202766}, pmid = {39523617}, issn = {1881-6096}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy ; Humans ; *Drug Development ; Clinical Trials as Topic ; Animals ; Riluzole/therapeutic use ; Neuroprotective Agents/therapeutic use ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive and fatal disease of motor neuron. Although riluzole and edaravone have been approved for the treatment of ALS, it remains a lethal disease that causes rapid motor impairment, and there is an urgent need to develop more effective treatments. Advances in understanding the pathomechanisms of ALS, efficient clinical trial design, and research support programs have led to many clinical trials for ALS both domestically and internationally.}, }
@article {pmid39523614, year = {2024}, author = {Yamakawa, I and Urushitani, M}, title = {[Gold Coast Criteria: A New Diagnostic Paradigm in the Era of Disease-Modifying Therapy for Amyotrophic Lateral Sclerosis].}, journal = {Brain and nerve = Shinkei kenkyu no shinpo}, volume = {76}, number = {11}, pages = {1217-1223}, doi = {10.11477/mf.1416202763}, pmid = {39523614}, issn = {1881-6096}, mesh = {*Amyotrophic Lateral Sclerosis/diagnosis/drug therapy ; Humans ; }, abstract = {Significant progress has been made in the development of disease-modifying drugs for amyotrophic lateral sclerosis (ALS), with the introduction of tofersen, an antisense oligonucleotide drug for familial ALS, marking a turning point in the treatment. These drugs are most effective when administered early in the disease course, highlighting the need for improved diagnostic sensitivity. The 2020 Gold Coast Diagnostic Criteria allow ALS diagnosis in cases without upper motor neuron symptoms, potentially increasing early detection rates. However, careful differential diagnoses are necessary when applying these criteria to maintain diagnostic specificity. This review outlines the key points to consider when using the Gold Coast Criteria, balancing the need for an early diagnosis with caution to avoid overdiagnosis.}, }
@article {pmid39522697, year = {2024}, author = {Gao, L and Yang, XN and Dong, YX and Han, YJ and Zhang, XY and Zhou, XL and Liu, Y and Liu, F and Fang, JS and Ji, JL and Gao, ZR and Qin, XM}, title = {The potential therapeutic strategy in combating neurodegenerative diseases: Focusing on natural products.}, journal = {Pharmacology &amp; therapeutics}, volume = {264}, number = {}, pages = {108751}, doi = {10.1016/j.pharmthera.2024.108751}, pmid = {39522697}, issn = {1879-016X}, mesh = {Humans ; *Biological Products/therapeutic use/pharmacology ; *Neurodegenerative Diseases/drug therapy ; Animals ; *Neuroprotective Agents/therapeutic use/pharmacology ; }, abstract = {Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), Huntington disease (HD), and Multiple sclerosis (MS), pose a significant global health challenge due to their intricate pathology and limited therapeutic interventions. Natural products represent invaluable reservoirs for combating these neurodegenerative diseases by targeting key pathological hallmarks such as protein aggregation, synaptic dysfunction, aberrant proteostasis, cytoskeletal abnormalities, altered energy homeostasis, inflammation, and neuronal cell death. This review provides an in-depth analysis of the mechanisms and therapeutic targets of natural products for their neuroprotective effects. Furthermore, it elucidates the current progress of clinical trials investigating the potential of natural products in delaying neurodegeneration. The objective of this review is to enhance the comprehension of natural products in the prevention and treatment of neurodegenerative diseases, offering new insights and potential avenues for future pharmaceutical research.}, }
@article {pmid39520508, year = {2024}, author = {Larose, A and Miller, CCJ and Mórotz, GM}, title = {The lemur tail kinase family in neuronal function and disfunction in neurodegenerative diseases.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {81}, number = {1}, pages = {447}, pmid = {39520508}, issn = {1420-9071}, mesh = {Humans ; *Neurodegenerative Diseases/pathology/metabolism/enzymology ; Animals ; *Neurons/metabolism/pathology ; Cyclin-Dependent Kinase 5/metabolism/genetics ; Signal Transduction ; Synapses/metabolism/pathology ; Protein-Tyrosine Kinases/metabolism/genetics ; Phosphorylation ; Axonal Transport ; Glycogen Synthase Kinase 3 beta/metabolism ; }, abstract = {The complex neuronal architecture and the long distance of synapses from the cell body require precisely orchestrated axonal and dendritic transport processes to support key neuronal functions including synaptic signalling, learning and memory formation. Protein phosphorylation is a major regulator of both intracellular transport and synaptic functions. Some kinases and phosphatases such as cyclin dependent kinase-5 (cdk5)/p35, glycogen synthase kinase-3β (GSK3β) and protein phosphatase-1 (PP1) are strongly involved in these processes. A primary pathological hallmark of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis/frontotemporal dementia, is synaptic degeneration together with disrupted intracellular transport. One attractive possibility is that alterations to key kinases and phosphatases may underlie both synaptic and axonal transport damages. The brain enriched lemur tail kinases (LMTKs, formerly known as lemur tyrosine kinases) are involved in intracellular transport and synaptic functions, and are also centrally placed in cdk5/p35, GSK3β and PP1 signalling pathways. Loss of LMTKs is documented in major neurodegenerative diseases and thus can contribute to pathological defects in these disorders. However, whilst function of their signalling partners became clearer in modulating both synaptic signalling and axonal transport progress has only recently been made around LMTKs. In this review, we describe this progress with a special focus on intracellular transport, synaptic functions and neurodegenerative diseases.}, }
@article {pmid39520111, year = {2025}, author = {Walls, M and Claffey, A and Mockler, D and Galvin, M}, title = {Working with people living with motor neurone disease and the impact on professionals' emotional and psychological well-being: A scoping review.}, journal = {Palliative medicine}, volume = {39}, number = {2}, pages = {221-244}, pmid = {39520111}, issn = {1477-030X}, mesh = {Humans ; *Motor Neuron Disease/psychology/therapy ; *Health Personnel/psychology ; Male ; Emotions ; Job Satisfaction ; Female ; *Attitude of Health Personnel ; Middle Aged ; Adult ; Psychological Well-Being ; }, abstract = {BACKGROUND: Integrated multidisciplinary care is required to manage the progressive and debilitating symptoms associated with motor neurone disease. Professionals can find providing the level of care required by this population clinically and emotionally challenging. To support those working with these patients it is important to understand the experience of the entire multidisciplinary team involved and the impact of working with motor neurone disease on their emotional and psychological well-being.<br><br>AIM: To identify what is known about (1) healthcare professionals' experience of working with motor neurone disease and (2) the impact of this work on their emotional and psychological well-being.<br><br>DESIGN: Scoping review. Review protocol registered on Open Science Framework.<br><br>SOURCES: Five electronic databases were searched in January 2023 and 2024. Grey literature and hand searches were completed.<br><br>RESULTS: Fifty-one sources published between 1990 and 2023 were included. A total of 1692 healthcare professionals are represented. Three main categories were identified: (1) The demands of providing motor neurone disease care. (2) Factors influencing professionals' ability to provide desired levels of care. (3) The emotional impact of working with motor neurone disease. Subcategories are depicted within these.<br><br>CONCLUSION: Positive experiences included job satisfaction, enhanced perspective and receiving gratitude, while negative implications such as stress, emotional exhaustion and burnout also featured. The demands of motor neurone disease patient care, the organisation of services and resources required to meet patient and family needs and the emotional burden for professionals involved, warrant greater recognition in clinical practice, guidelines and future research.}, }
@article {pmid39519213, year = {2024}, author = {Bova, V and Mannino, D and Capra, AP and Lanza, M and Palermo, N and Filippone, A and Esposito, E}, title = {CK and LRRK2 Involvement in Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {25}, number = {21}, pages = {}, pmid = {39519213}, issn = {1422-0067}, mesh = {Humans ; *Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/metabolism/genetics ; *Neurodegenerative Diseases/metabolism/genetics ; Animals ; Mutation ; Phosphorylation ; Autophagy/genetics ; }, abstract = {Neurodegenerative diseases (NDDs) are currently the most widespread neuronal pathologies in the world. Among these, the most widespread are Alzheimer's disease (AD), dementia, Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD)-all characterized by a progressive loss of neurons in specific regions of the brain leading to varied clinical symptoms. At the basis of neurodegenerative diseases, an emerging role is played by genetic mutations in the leucine-rich repeat kinase 2 (LRRK2) gene that cause increased LRRK2 activity with consequent alteration of neuronal autophagy pathways. LRRK2 kinase activity requires GTPase activity which functions independently of kinase activity and is required for neurotoxicity and to potentiate neuronal death. Important in the neurodegeneration process is the upregulation of casein kinase (CK), which causes the alteration of the AMPK pathway by enhancing the phosphorylation of α-synuclein and huntingtin proteins, known to be involved in PD and HD, and increasing the accumulation of the amyloid-β protein (Aβ) for AD. Recent research has identified CK of the kinases upstream of LRRK2 as a regulator of the stability of the LRRK2 protein. Based on this evidence, this review aims to understand the direct involvement of individual kinases in NDDs and how their crosstalk may impact the pathogenesis and early onset of neurodegenerative diseases.}, }
@article {pmid39519209, year = {2024}, author = {Firdaus, Z and Li, X}, title = {Epigenetic Explorations of Neurological Disorders, the Identification Methods, and Therapeutic Avenues.}, journal = {International journal of molecular sciences}, volume = {25}, number = {21}, pages = {}, pmid = {39519209}, issn = {1422-0067}, support = {R01 DK126662/DK/NIDDK NIH HHS/United States ; R01 DK129241/DK/NIDDK NIH HHS/United States ; DK129241 DK126662/GF/NIH HHS/United States ; }, mesh = {Humans ; *Epigenesis, Genetic ; *DNA Methylation ; Neurodegenerative Diseases/genetics/therapy ; Animals ; Nervous System Diseases/genetics/therapy ; Histones/metabolism/genetics ; Epigenomics/methods ; Histone Code/genetics ; }, abstract = {Neurodegenerative disorders are major health concerns globally, especially in aging societies. The exploration of brain epigenomes, which consist of multiple forms of DNA methylation and covalent histone modifications, offers new and unanticipated perspective into the mechanisms of aging and neurodegenerative diseases. Initially, chromatin defects in the brain were thought to be static abnormalities from early development associated with rare genetic syndromes. However, it is now evident that mutations and the dysregulation of the epigenetic machinery extend across a broader spectrum, encompassing adult-onset neurodegenerative diseases. Hence, it is crucial to develop methodologies that can enhance epigenetic research. Several approaches have been created to investigate alterations in epigenetics on a spectrum of scales-ranging from low to high-with a particular focus on detecting DNA methylation and histone modifications. This article explores the burgeoning realm of neuroepigenetics, emphasizing its role in enhancing our mechanistic comprehension of neurodegenerative disorders and elucidating the predominant techniques employed for detecting modifications in the epigenome. Additionally, we ponder the potential influence of these advancements on shaping future therapeutic approaches.}, }
@article {pmid39511939, year = {2025}, author = {Eisen, A and Vucic, S and Kiernan, MC}, title = {Amyotrophic lateral sclerosis represents corticomotoneuronal system failure.}, journal = {Muscle &amp; nerve}, volume = {71}, number = {4}, pages = {499-511}, pmid = {39511939}, issn = {1097-4598}, mesh = {*Amyotrophic Lateral Sclerosis/pathology/physiopathology ; Humans ; Animals ; *Motor Neurons/pathology/physiology ; *Motor Cortex/pathology/physiopathology ; }, abstract = {Several decades have passed since the anterograde corticomotoneuronal hypothesis for amyotrophic lateral sclerosis (ALS) was proposed. The intervening years have witnessed its emergent support based on anatomical, pathological, physiological, neuroimaging, and molecular biological studies. The evolution of an extensive corticomotoneuronal system appears restricted to the human species, with ALS representing a uniquely human disease. While some, very select non-human primates have limited corticomotoneuronal projections, these tend to be absent in all other animals. From a general perspective, the early clinical features of ALS may be considered to reflect failure of the corticomotoneuronal system. The characteristic loss of skilled motor dexterity involving the limbs, and speech impairment through progressive bulbar dysfunction specifically involve those motor units having the strongest corticomotoneuronal projections. A similar explanation likely underlies the unique "split phenotypes" that have now been well characterized in ALS. Large Betz cells and other pyramidal corticomotoneuronal projecting neurons, with their extensive dendritic arborization, are particularly vulnerable to the elements of the ALS exposome such as aging, environmental stress and lifestyle changes. Progressive failure of the proteosome impairs nucleocytoplasmic shuffling and induces toxic but soluble TDP-43 to aggregate in corticomotoneurons. Betz cell failure is further accentuated through dysfunction of its profuse dendritic arborizations. Clarification of system specific genomes and neural networks will likely promote the initiation of precision medicine approaches directed to support the key structure that underlies the neurological manifestations of ALS, the corticomotoneuronal system.}, }
@article {pmid39511821, year = {2025}, author = {Grady, A and Lorch, R and Giles, L and Lamont, H and Anderson, A and Pearson, N and Romiti, M and Lum, M and Stuart, A and Leigh, L and Yoong, SL}, title = {The impact of early childhood education and care-based interventions on child physical activity, anthropometrics, fundamental movement skills, cognitive functioning, and social-emotional wellbeing: A systematic review and meta-analysis.}, journal = {Obesity reviews : an official journal of the International Association for the Study of Obesity}, volume = {26}, number = {2}, pages = {e13852}, pmid = {39511821}, issn = {1467-789X}, support = {APP1170042//National Health and Medical Research Council/ ; Heart Foundation Postdoctoral Fellowship 102518//National Heart Foundation of Australia/ ; Heart Foundation Future Leader Fellowship 106654//National Heart Foundation of Australia/ ; }, mesh = {Humans ; *Cognition ; Child, Preschool ; *Exercise/psychology ; Child ; Infant ; Motor Skills/physiology ; Pediatric Obesity/psychology/prevention &amp; control ; Anthropometry ; Early Intervention, Educational ; }, abstract = {This review assessed the effectiveness of ECEC-based interventions to improve child physical activity, and intervention impact on child weight-based anthropometrics, fundamental movement skills (FMS), cognitive functioning, and social-emotional wellbeing. Adverse effects and costs were assessed. Finch et al's 2014 systematic review was updated. Electronic databases were searched 10 September 2014 to 27 October 2022. Included studies were randomized controlled trials of ECEC interventions targeting physical activity among children aged 0-6 years. The methodological quality of studies was assessed using Cochrane's Risk of Bias tool v2. Standardized mean differences (SMD) were calculated for each outcome with meta-analysis undertaken; otherwise, findings were described narratively. Fifty-three studies were included. ECEC-based interventions were found to significantly improve child physical activity (SMD 0.193, 95% confidence interval [CI] 0.09 to 0.3; p < 0.001) and FMS (SMD 0.544, 95% CI 0.1 to 0.98; p = 0.015), compared to control. Small positive, but non-significant, effects were found for weight-based anthropometrics, cognitive functioning, and social-emotional wellbeing. Few studies reported adverse effects (n = 10), and no studies reported formal economic analyses. While ECEC-based interventions can significantly improve child physical activity and FMS, further evidence of their impact on cognitive functioning, social-emotional wellbeing, and the cost-effectiveness of such interventions is required to inform policy and practice.}, }
@article {pmid39510899, year = {2024}, author = {Kaul, M and Mukherjee, D and Weiner, HL and Cox, LM}, title = {Gut microbiota immune cross-talk in amyotrophic lateral sclerosis.}, journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics}, volume = {21}, number = {6}, pages = {e00469}, pmid = {39510899}, issn = {1878-7479}, support = {P51 OD011133/OD/NIH HHS/United States ; R01 NS115951/NS/NINDS NIH HHS/United States ; R21 NS126866/NS/NINDS NIH HHS/United States ; }, mesh = {*Amyotrophic Lateral Sclerosis/immunology/microbiology ; *Gastrointestinal Microbiome/immunology/physiology ; Humans ; Animals ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the loss of motor neurons. While there has been significant progress in defining the genetic contributions to ALS, greater than 90 % of cases are sporadic, which suggests an environmental component. The gut microbiota is altered in ALS and is an ecological factor that contributes to disease by modulating immunologic, metabolic, and neuronal signaling. Depleting the microbiome worsens disease in the SOD1 ALS animal model, while it ameliorates disease in the C9orf72 model of ALS, indicating critical subtype-specific interactions. Furthermore, administering beneficial microbiota or microbial metabolites can slow disease progression in animal models. This review discusses the current state of microbiome research in ALS, including interactions with different ALS subtypes, evidence in animal models and human studies, key immunologic and metabolomic mediators, and a path toward microbiome-based therapies for ALS.}, }
@article {pmid39505137, year = {2024}, author = {Abbasi, H and Jourabchi-Ghadim, N and Asgarzade, A and Mirshekari, M and Ebrahimi-Mameghani, M}, title = {Unveiling the veil of adipokines: A meta-analysis and systematic review in amyotrophic lateral sclerosis.}, journal = {Neuroscience}, volume = {563}, number = {}, pages = {1-9}, doi = {10.1016/j.neuroscience.2024.11.003}, pmid = {39505137}, issn = {1873-7544}, mesh = {*Amyotrophic Lateral Sclerosis/blood/metabolism ; Humans ; *Adipokines/blood ; Ghrelin/blood ; Leptin/blood ; Adiponectin/blood ; Disease Progression ; }, abstract = {BACKGROUND: Adipokines are proposed to be associated with ALS progression through assorted pathways. Therefore, The present meta-analysis explored the link between various adipokines and ALS progression.<br><br>METHOD: International database like PubMed, Scopus, and Web of Science databases were searched to achieve eligible papers published before December 2023. The following PICO structure was utilized: Population (patients with ALS); Intervention (serum concentrations of ghrelin, leptin, and adiponectin), Comparison (with or without controls), and Outcome (ALS progression). the risk of bias of selected papers was assessed through the Newcastle-Ottawa Scale (NOS) tool.<br><br>RESULTS: 11 out of 240 papers were selected for this study which were published between 2010 and 2024. Lower serum leptin concentrations were detected in the ALS compared to control groups (WMD: -0.91, 95% CI:-1.77, -0.05). Serum concentrations of adiponectin were higher in ALS compared to control groups (WMD: 0.41, 95% CI:-0.7, 0.89). Ultimately, The serum concentrations of ghrelin in the ALS groups were lower than control groups (WMD: -1.21, 95% CI: -2.95, 0.53).<br><br>CONCLUSION: Our findings revealed that serum concentrations of ghrelin and leptin were higher in ALS patients compared to control, unlike adiponectin.}, }
@article {pmid39503319, year = {2024}, author = {Bedlack, R and Li, X and Evangelista, BA and Panzetta, ME and Kwan, J and Gittings, LM and Sattler, R}, title = {The Scientific and Therapeutic Rationale for Off-Label Treatments in Amyotrophic Lateral Sclerosis.}, journal = {Annals of neurology}, volume = {97}, number = {1}, pages = {15-27}, pmid = {39503319}, issn = {1531-8249}, support = {//ALS Association/ ; }, abstract = {There are no dramatically effective pharmacological treatments for most patients with amyotrophic lateral sclerosis, a complex disease with multiple underlying mechanisms, such as neuroinflammation, oxidative stress, mitochondrial dysfunction, microbiome alteration, and antiretroviral activity. We sifted through 15 years of reviews by a group called ALSUntangled to identify 8 alternative and off-label treatments that target ≥1 of these mechanisms, and have ≥1 human trial suggesting meaningful benefits. Given the overlapping pathological mechanisms of the highlighted products, we suggest that combinations of these treatments targeting diverse mechanisms might be worthwhile for future amyotrophic lateral sclerosis therapy development. ANN NEUROL 2024.}, }
@article {pmid39503018, year = {2024}, author = {Rennie, O and Sharma, M and Helwa, N}, title = {Hepatobiliary anastomotic leakage: a narrative review of definitions, grading systems, and consequences of leaks.}, journal = {Translational gastroenterology and hepatology}, volume = {9}, number = {}, pages = {70}, pmid = {39503018}, issn = {2415-1289}, abstract = {BACKGROUND AND OBJECTIVE: Hepatobiliary diseases are a longstanding and significant medical challenge which, despite advances in surgical techniques, still carry risks for postoperative complications such as anastomotic leaks (ALs), which can include both postoperative pancreatic fistula (POPF) and bile leaks (BL). These complications incur significant human and economic costs on all those involved, including the patient, healthcare providers, and hospital systems. The aim of this study was to construct a narrative review of literature surrounding definitions and grading systems for ALs in the context of hepato-pancreato-biliary (HPB) procedures, and consequences of POPF and BL.<br><br>METHODS: A literature review was conducted by examining databases including PubMed, Web of Science, OVID Embase, Google Scholar, and Cochrane library databases. Searches were performed with the following search criteria: (((((((anastomosis) OR (anastomotic leak*)) OR (postoperative pancreatic fistula)) OR (bile leak*)) OR (pancreaticoduodenectomy)) OR (whipple)) AND ((hepatobiliary) OR (hepato-pancreato-biliary)) AND ((definition) OR (grading system*) OR (consequences) OR (outcomes) OR (risk factor*) OR (morbidity) OR (mortality))). Publications that were retrieved underwent further assessment to ensure other relevant publications were identified and included.<br><br>KEY CONTENT AND FINDINGS: A universally accepted definition and grading system for POPF and BL continues to be lacking, leading to variability in reported incidence in the literature. Various groups have worked to publish guidelines for defining and grading POPF and BL, with the International Study Group in Pancreatic Surgery (ISGPS) and International Study Group for Liver Surgery (ISGLS) definitions the current most recommended definitions for POPF and BL, respectively. The burden of AL on patients, healthcare providers, and hospitals is well documented in evidence from leak consequences, such as increased morbidity and mortality, higher reoperation rates, and increased readmission rates, among others.<br><br>CONCLUSIONS: AL remains a significant challenge in HPB surgery, despite medical advancements. Understanding the progress made in defining and grading leaks, as well as the range of negative outcomes that arise from AL, is crucial in improving patient care, reduce surgical mortality, and drive further advancements in earlier detection and treatment of AL.}, }
@article {pmid39501538, year = {2024}, author = {Bampton, A and McHutchison, C and Talbot, K and Benatar, M and Thompson, AG and Turner, MR}, title = {The Basis of Cognitive and Behavioral Dysfunction in Amyotrophic Lateral Sclerosis.}, journal = {Brain and behavior}, volume = {14}, number = {11}, pages = {e70115}, pmid = {39501538}, issn = {2162-3279}, support = {MR/T006927/1/MRC_/Medical Research Council/United Kingdom ; Thompson/Jan20/952-795//Motor Neurone Disease Association Lady Edith Wolfson Clinician Scientist Fellowship/ ; //Foulkes Foundation/ ; //National Institutes of Health (NIH)/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/physiopathology ; Humans ; Cognitive Dysfunction/etiology/physiopathology ; }, abstract = {OBJECTIVE: To summarize and evaluate evidence pertaining to the clinical, genetic, histopathological, and neuroimaging correlates of cognitive and behavioral dysfunction in amyotrophic lateral sclerosis (ALS).<br><br>METHODOLOGY: We comprehensively reviewed the literature on cognitive and behavioral manifestations of ALS, narrating findings from both cross-sectional and longitudinal studies. We discussed knowledge gaps in the evidence base and key limitations affecting studies to date, before formulating a framework for future research paradigms aimed at investigating clinicopathological correlates of neuropsychological dysfunction in ALS.<br><br>RESULTS: Studies have demonstrated clinical associations with cognitive dysfunction in ALS e.g., bulbar-onset of symptoms, pathological associations (extramotor TDP-43 deposition), and imaging associations (frontotemporal involvement). The most common behavioral deficit, apathy, is highly associated with verbal fluency, but longitudinal studies assessing behavioral dysfunction in ALS are comparatively lacking.<br><br>CONCLUSION: Longitudinal studies have been helpful in identifying several potential correlates of cognitive and behavioral dysfunction but have frequently been confounded by selection bias and inappropriate testing platforms. This review provides a framework for more robust assessment of clinicopathological associations of neuropsychological abnormalities in ALS in the future, advocating for greater utilization of pre-symptomatic C9orf72 repeat expansion-carrying cohorts.}, }
@article {pmid39501147, year = {2024}, author = {Perron, ME and Hudon, C and Roux-Levy, PH and Poitras, ME}, title = {Shared decision-making with patients with complex care needs: a scoping review.}, journal = {BMC primary care}, volume = {25}, number = {1}, pages = {390}, pmid = {39501147}, issn = {2731-4553}, mesh = {Humans ; *Decision Making, Shared ; *Patient Participation/methods/psychology ; Multimorbidity ; }, abstract = {BACKGROUND: A number of patients have complex care needs that arise from interactions among multiple factors, such as multimorbidity, mental health issues, and social vulnerability. These factors influence decisions about healthcare and health services. Shared decision-making (SDM), a collaborative process between patients and professionals, is known to improve the quality of the decision-making process. However, follow-up challenges of patients with complex care needs (PCCNs) can lead to SDM specificities.<br><br>OBJECTIVE: To identify specificities of SDM with PCCNs.<br><br>METHODS: We conducted a scoping review using the Joanna Briggs Institute (JBI) methodology. We conducted a systematic search across MEDLINE, CINAHL, PsycINFO, and Academic Search Complete databases. Empirical studies about SDM with PCCNs published between 1997 and 2023 were eligible for inclusion. We conducted a mixed thematic analysis using deductive (Ottawa Decision Support Framework and Interprofessional Shared Decision-Making Model) and inductive approaches. Following Arksey &amp; O'Malley's and Levac et al.'s methodological recommendations, we consulted experts (researchers, healthcare professionals, and patient partners) to enhance the findings.<br><br>RESULTS: Twelve studies were included in the review. Overall, our results demonstrated the importance of recognizing some specificities of SDM with PCCNs, such as the simultaneous presence of multiple decisions and the multidisciplinary and intersectoral nature of the healthcare and health services they receive.<br><br>CONCLUSION: This scoping review highlights some specificities that must be considered in SDM with PCCNs to maintain its already-known benefits and ensure positive health and decision-making outcomes.}, }
@article {pmid39501102, year = {2025}, author = {Howard, J and Chaouch, A and Douglas, AGL and MacLeod, R and Roggenbuck, J and McNeill, A}, title = {Genetic testing for monogenic forms of motor neuron disease/amyotrophic lateral sclerosis in unaffected family members.}, journal = {European journal of human genetics : EJHG}, volume = {33}, number = {1}, pages = {7-13}, pmid = {39501102}, issn = {1476-5438}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/diagnosis ; *Family ; Genetic Counseling ; *Genetic Testing/methods/standards ; *Motor Neuron Disease/genetics/diagnosis ; }, abstract = {Motor neuron disease (MND), also referred to as amyotrophic lateral sclerosis (ALS), is a monogenic disease in a minority of cases, with autosomal dominant inheritance. Increasing numbers of people with MND are requesting genetic testing, and indeed receiving a genetic diagnosis. Consequently, requests for genetic counselling and predictive testing (i.e. of unaffected family members) are similarly expected to rise, alongside pre-symptomatic clinical trials. Despite this, there is no evidence-based guideline for predictive genetic testing in MND. This paper provides an overview of the genomic basis of MND, focusing specifically on the most common monogenic causes of MND. It then lays out the complexities of MND predictive testing, including the genetic landscape characterised by incomplete penetrance, clinical and genetic heterogeneity, and an oligogenic mechanism of pathogenesis in some cases. Additionally, there is limited research on the psychosocial impact of predictive genetic testing for MND, with studies suggesting potential difficulty in adjusting to the news, in part due to a lack of support and follow-up. This underscores a case for evidence-based, disease-specific guidance for predictive testing in MND.}, }
@article {pmid39492438, year = {2023}, author = {Hamzeh, O and Rabiei, F and Shakeri, M and Parsian, H and Saadat, P and Rostami-Mansoor, S}, title = {Mitochondrial dysfunction and inflammasome activation in neurodegenerative diseases: Mechanisms and therapeutic implications.}, journal = {Mitochondrion}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.mito.2023.10.003}, pmid = {39492438}, issn = {1872-8278}, abstract = {Impaired mitochondrial function is crucial to the pathogenesis of several neurodegenerative diseases. It causes the release of mitochondrial DNA (mtDNA), mitochondrial reactive oxygen species (mtROS), ATP, and cardiolipin, which activate the nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome. NLRP3 inflammasome is an important innate immune system element contributing to neuroinflammation and neurodegeneration. Therefore, targeting the NLRP3 inflammasome has become an interesting therapeutic approach for treating neurodegenerative diseases. This review describes the role of mitochondrial abnormalities and over-activated inflammasomes in the progression of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Multiple sclerosis (MS), Amyotrophic lateral sclerosis (ALS), and Friedrich ataxia (FRDA). We also discuss the therapeutic strategies focusing on signaling pathways associated with inflammasome activation, which potentially alleviate neurodegenerative symptoms and impede disease progression.}, }
@article {pmid39492095, year = {2023}, author = {Mohammadi, S and Mohammadi, M and Ghaderi, S}, title = {Sleep-related regions in neurodegenerative diseases by central nervous system localization using magnetic resonance imaging.}, journal = {Psychiatry research. Neuroimaging}, volume = {336}, number = {}, pages = {111727}, doi = {10.1016/j.pscychresns.2023.111727}, pmid = {39492095}, issn = {1872-7506}, abstract = {Sleep disruptions associated with neurodegenerative diseases (NDDs) damage the brain's sleep-regulating regions. Advanced magnetic resonance imaging (MRI) techniques can characterize the signature of each neurodegenerative pathology. We performed an evaluation of sleep-related regions in NDDs using MRI to localize the central nervous system (CNS). In the initial search, 61 related papers were discovered using predetermined inclusion and exclusion criteria. Finally, 30 articles were included in this study. The study included patients with Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), rapid eye movement (REM) sleep behavior disorder (RBD), idiopathic RBD (iRBD), amyotrophic lateral sclerosis (ALS), and mild cognitive impairment (MCI). Sleep-related regions recognized by CNS localization in NDDs can be linked to important regions. MRI also revealed cortical thinning, GM atrophy, WM, and tract loss, changes in diffusion tensor imaging (DTI) biomarkers (fractional anisotropy (FA), axial diffusivity (Da), and radial diffusivity (Dr)), a decrease in DMN connectivity, a reduction in functional connectivity (FC), and amplitude of low-frequency fluctuation (ALFF) alterations. Sleep plays an important role in predicting future risks for the development of NDDs. Other neuroimaging, cognitive-behavioral, and clinical research can use the information found in this research about the brain regions, MRI biomarker changes, and their relationships.}, }
@article {pmid39491718, year = {2024}, author = {Sharma, R and Khan, Z and Mehan, S and Das Gupta, G and Narula, AS}, title = {Unraveling the multifaceted insights into amyotrophic lateral sclerosis: Genetic underpinnings, pathogenesis, and therapeutic horizons.}, journal = {Mutation research. Reviews in mutation research}, volume = {794}, number = {}, pages = {108518}, doi = {10.1016/j.mrrev.2024.108518}, pmid = {39491718}, issn = {1388-2139}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/therapy ; Mutation/genetics ; RNA-Binding Protein FUS/genetics ; C9orf72 Protein/genetics ; Animals ; Superoxide Dismutase-1/genetics ; DNA-Binding Proteins/genetics ; Genetic Predisposition to Disease ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS), a progressive neurodegenerative disease, primarily impairs upper and lower motor neurons, leading to debilitating motor dysfunction and eventually respiratory failure, widely known as Lou Gehrig's disease. ALS presents with diverse symptomatology, including dysarthria, dysphagia, muscle atrophy, and hyperreflexia. The prevalence of ALS varies globally, with incidence rates ranging from 1.5 to 3.8 per 100,000 individuals, significantly affecting populations aged 45-80. A complex interplay of genetic and environmental factors underpins ALS pathogenesis. Key genetic contributors include mutations in chromosome 9 open reading frame 72 (C9ORF72), superoxide dismutase type 1 (SOD1), Fusedin sarcoma (FUS), and TAR DNA-binding protein (TARDBP) genes, accounting for a considerable fraction of both familial (fALS) and sporadic (sALS) cases. The disease mechanism encompasses aberrant protein folding, mitochondrial dysfunction, oxidative stress, excitotoxicity, and neuroinflammation, contributing to neuronal death. This review consolidates current insights into ALS's multifaceted etiology, highlighting the roles of environmental exposures (e.g., toxins, heavy metals) and their interaction with genetic predispositions. We emphasize the polygenic nature of ALS, where multiple genetic variations cumulatively influence disease susceptibility and progression. This aspect underscores the challenges in ALS diagnosis, which currently lacks specific biomarkers and relies on symptomatology and familial history. Therapeutic strategies for ALS, still in nascent stages, involve symptomatic management and experimental approaches targeting molecular pathways implicated in ALS pathology. Gene therapy, focusing on specific ALS mutations, and stem cell therapy emerge as promising avenues. However, effective treatments remain elusive, necessitating a deeper understanding of ALS's genetic architecture and the development of targeted therapies based on personalized medicine principles. This review aims to provide a comprehensive understanding of ALS, encouraging further research into its complex genetic underpinnings and the development of innovative, effective treatment modalities.}, }
@article {pmid39491419, year = {2023}, author = {Talebi, M and Sadoughi, MM and Ayatollahi, SA and Ainy, E and Kiani, R and Zali, A and Miri, M}, title = {Therapeutic potentials of cannabidiol: Focus on the Nrf2 signaling pathway.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {168}, number = {}, pages = {115805}, doi = {10.1016/j.biopha.2023.115805}, pmid = {39491419}, issn = {1950-6007}, abstract = {Cannabidiol (CBD), a cannabinoid that does not create psychoactive activities, has been identified as having a multitude of therapeutic benefits. This study delves into the chemical properties, pharmacokinetics, safety and toxicity, pharmacological effects, and most importantly, the association between the therapeutic potential of CBD and the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. The relationship between Nrf2 and CBD is closely linked to certain proteins that are associated with cardiovascular dysfunctions, cancers, and neurodegenerative conditions. Specifically, Nrf2 is connected to the initiation and progression of diverse health issues, including nephrotoxicity, bladder-related diseases, oral mucositis, cancers, obesity, myocardial injury and angiogenesis, skin-related inflammations, psychotic disorders, neuropathic pain, Huntington's disease, Alzheimer's disease, Parkinson's disease, neuroinflammation, Amyotrophic Lateral Sclerosis, and Multiple Sclerosis. The association between CBD and Nrf2 is a zone of great interest in the medical field, as it has the potential to significantly impact the treatment and prevention of wide-ranging health conditions. Additional investigation is necessary to entirely apprehend the mechanisms underlying this crucial interplay and to develop effective therapeutic interventions.}, }
@article {pmid39490400, year = {2024}, author = {Zhang, Y and Zou, M and Wu, H and Zhu, J and Jin, T}, title = {The cGAS-STING pathway drives neuroinflammation and neurodegeneration via cellular and molecular mechanisms in neurodegenerative diseases.}, journal = {Neurobiology of disease}, volume = {202}, number = {}, pages = {106710}, doi = {10.1016/j.nbd.2024.106710}, pmid = {39490400}, issn = {1095-953X}, mesh = {Humans ; *Nucleotidyltransferases/metabolism ; *Membrane Proteins/metabolism ; *Neurodegenerative Diseases/metabolism ; *Signal Transduction/physiology ; Animals ; *Neuroinflammatory Diseases/metabolism ; }, abstract = {Neurodegenerative diseases (NDs) are a type of common chronic progressive disorders characterized by progressive damage to specific cell populations in the nervous system, ultimately leading to disability or death. Effective treatments for these diseases are still lacking, due to a limited understanding of their pathogeneses, which involve multiple cellular and molecular pathways. The triggering of an immune response is a common feature in neurodegenerative disorders. A critical challenge is the intricate interplay between neuroinflammation, neurodegeneration, and immune responses, which are not yet fully characterized. In recent years, the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon gene (STING) pathway, a crucial immune response for intracellular DNA sensing, has gradually gained attention. However, the specific roles of this pathway within cellular types such as immune cells, glial and neuronal cells, and its contribution to ND pathogenesis, remain not fully elucidated. In this review, we systematically explore how the cGAS-STING signaling links various cell types with related cellular effector pathways under the context of NDs for multifaceted therapeutic directions. We emphasize the discovery of condition-dependent cellular heterogeneity in the cGAS-STING pathway, which is integral for understanding the diverse cellular responses and potential therapeutic targets. Additionally, we review the pathogenic role of cGAS-STING activation in Parkinson's disease, ataxia-telangiectasia, and amyotrophic lateral sclerosis. We focus on the complex bidirectional roles of the cGAS-STING pathway in Alzheimer's disease, Huntington's disease, and multiple sclerosis, revealing their double-edged nature in disease progression. The objective of this review is to elucidate the pivotal role of the cGAS-STING pathway in ND pathogenesis and catalyze new insights for facilitating the development of novel therapeutic strategies.}, }
@article {pmid39489397, year = {2024}, author = {Desouky, MA and Michel, HE and Elsherbiny, DA and George, MY}, title = {Recent pharmacological insights on abating toxic protein species burden in neurological disorders: Emphasis on 26S proteasome activation.}, journal = {Life sciences}, volume = {359}, number = {}, pages = {123206}, doi = {10.1016/j.lfs.2024.123206}, pmid = {39489397}, issn = {1879-0631}, mesh = {*Proteasome Endopeptidase Complex/metabolism ; Humans ; Animals ; Neurodegenerative Diseases/metabolism/drug therapy ; Nervous System Diseases/drug therapy/metabolism ; Proteolysis/drug effects ; Signal Transduction/drug effects ; Proteostasis/drug effects ; Ubiquitin/metabolism ; }, abstract = {Protein homeostasis (proteostasis) refers to the plethora of mechanisms that safeguard the proper folding of the newly synthesized proteins. It entails various intricately regulated cues that demolish the toxic protein species to prevent their aggregation. The ubiquitin-proteasome system (UPS) is recognized as a salient protein degradation system, with a substantial role in maintaining proteostasis. However, under certain circumstances the protein degradation capacity of the UPS is overwhelmed, leading to the accumulation of misfolded proteins. Several neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, Huntington disease, and amyotrophic lateral sclerosis are characterized with the presence of protein aggregates and proteinopathy. Accordingly, enhancing the 26S proteasome degradation activity might delineate a pioneering approach in targeting various proteotoxic disorders. Regrettably, the exact molecular approaches that enhance the proteasomal activity are still not fully understood. Therefore, this review aimed to underscore several signaling cascades that might restore the degradation capacity of this molecular machine. In this review, we discuss the different molecular components of the UPS and how 26S proteasomes are deleteriously affected in many neurodegenerative diseases. Moreover, we summarize different signaling pathways that can be utilized to renovate the 26S proteasome functional capacity, alongside currently known druggable targets in this circuit and various classes of proteasome activators.}, }
@article {pmid39474168, year = {2024}, author = {Sandler, AB and Wells, ME and Tran, C and Arakawa, R and Klahs, KJ and Scanaliato, JP and Green, CK and Hettrich, CM and Dunn, JC and Adler, A and Parnes, N}, title = {High rates of return to sport after suprascapular nerve decompression: an updated systematic review.}, journal = {JSES reviews, reports, and techniques}, volume = {4}, number = {4}, pages = {654-661}, pmid = {39474168}, issn = {2666-6391}, abstract = {BACKGROUND: Suprascapular nerve decompression (SSND) remains a controversial procedure. In 2018, Momaya et al published the first systematic review of SSND noting satisfactory outcomes with low rates of complications; however, numerous studies published since have noted no benefit in routinely adding SSND to other arthroscopic surgeries, contributing to existing contention regarding the procedure. The purpose of this study is to provide an updated assessment of outcomes after SSND.<br><br>METHODS: To conduct this updated systematic review, a search of PubMed (MEDLINE) for relevant studies published prior to January 21, 2023 was conducted. Outcomes including patient-reported clinical outcomes, return to sport, preoperative and postoperative electrodiagnostic testing, and adverse events were collected and pooled for assessment. Studies were eligible for inclusion if they met Momaya et&#xa0;al's inclusion criteria and/or reported outcomes following SSND at either the suprascapular notch or spinoglenoid notch.<br><br>RESULTS: In total, 730 patients from 33 studies were eligible for inclusion. All patient-reported outcome measure scores including American Shoulder Elbow Surgeon Standardized Shoulder Assessment; Constant-Murley score; Disabilities of the Arm, Shoulder, and Hand; Subjective Shoulder Value; University of California-Los Angeles shoulder; and visual analog scale pain scores improved significantly postoperatively, with improvements ranging from 53.5% to 102.6% of preoperative values. Ultimately, 98% (n&#xa0;= 90/92) of patients returned to sport or military duty and 96% of these patients returned at their previous level of activity (n&#xa0;= 48/50) without heterogeneity among rates between studies (P&#xa0;= .176, P&#xa0;= .238, respectively). Preoperative electrodiagnostic testing was conducted in 93% of patients, and 90% had associated abnormal findings. Continued symptoms were noted among 12% of patients (n&#xa0;= 39/322) with significantly different rates observed between studies. Complications from operative management not limited to SSND occurred in 11% of patients (n&#xa0;= 64/576) and reoperations occurred in 3.3% of patients (n&#xa0;= 15/455).<br><br>CONCLUSION: Suprascapular neuropathy treated with SSND significantly improves patient-reported outcomes and is noninferior to similar procedures without SSND. Appropriate clinical diagnosis of suprascapular neuropathy is required as opposed to a routine adjunct procedure with other arthroscopic shoulder surgery. Ultimately, SSND is associated with high rates of return to sport and relatively low rates of adverse events; however, the risk of continued symptoms and electrodiagnostic test-related complications is an important point on preoperative counseling.}, }
@article {pmid39473490, year = {2024}, author = {Fei, Y and Ding, Y}, title = {The role of ferroptosis in neurodegenerative diseases.}, journal = {Frontiers in cellular neuroscience}, volume = {18}, number = {}, pages = {1475934}, pmid = {39473490}, issn = {1662-5102}, abstract = {Ferroptosis represents an iron[-] and lipid peroxidation (LPO)-mediated form of regulated cell death (RCD). Recent evidence strongly suggests the involvement of ferroptosis in various neurodegenerative diseases (NDs), particularly Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS), among others. The treatment of ferroptosis poses both opportunities and challenges in the context of ND. This review provides a comprehensive overview of characteristic features, induction and inhibition of ferroptosis, highlighting the ferroptosis inhibitor and the underlying mechanisms responsible for its occurrence. Moreover, the review explores how these mechanisms contribute to the pathogenesis and progression of major neurodegenerative disorders. Additionally, it presents novel insights into the role of ferroptosis in ND and summarizes recent advancements in the development of therapeutic approaches targeting ferroptosis. These insights and advancements hold potential to guide future strategies aimed at effectively managing these debilitating medical conditions.}, }
@article {pmid39473221, year = {2024}, author = {Ito, D and Okada, K}, title = {Rethinking antisense oligonucleotide therapeutics for amyotrophic lateral sclerosis.}, journal = {Annals of clinical and translational neurology}, volume = {11}, number = {12}, pages = {3054-3063}, pmid = {39473221}, issn = {2328-9503}, support = {21H02812//Ministry of Education, Culture, Sports, Science and Technology of Japan/ ; }, mesh = {Animals ; Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics/therapy ; *Oligonucleotides, Antisense/administration &amp; dosage/genetics ; Superoxide Dismutase-1/genetics ; }, abstract = {Antisense oligonucleotides, which are used to silence target genes, are gaining attention as a novel drug discovery modality for proteinopathies. However, while clinical trials for neurodegenerative diseases like amyotrophic lateral sclerosis have been conducted in recent years, the results have not always been favorable. The results from a Phase III trial of the antisense oligonucleotide, that is, tofersen, which targets SOD1 mRNA, showed decreased levels of cerebrospinal fluid SOD1 and plasma neurofilament light chain but no improvements in primary clinical endpoint. Moreover, case reports pertaining to patients with amyotrophic lateral sclerosis carrying FUS and C9orf72 mutations who received antisense oligonucleotide-based treatments have demonstrated a notable reduction in the targeted protein (thus providing the proof of mechanism) but with no discernible clinical benefits. There are several possible reasons why antisense oligonucleotides knockdown fails to achieve proof of concept, which need to be addressed: on-target adverse effects resulting from the loss of function of target gene and irreversible neuronal death cascade due to toxic protein accumulation, among other factors. This review provides an overview of the current status and discusses the prospects of antisense oligonucleotides treatment for amyotrophic lateral sclerosis.}, }
@article {pmid39472796, year = {2024}, author = {Zheng, K and Chen, M and Xu, X and Li, P and Yin, C and Wang, J and Liu, B}, title = {Chemokine CXCL13-CXCR5 signaling in neuroinflammation and pathogenesis of chronic pain and neurological diseases.}, journal = {Cellular &amp; molecular biology letters}, volume = {29}, number = {1}, pages = {134}, pmid = {39472796}, issn = {1689-1392}, support = {82474625//National Natural Science Foundation of China/ ; 82305368//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Chemokine CXCL13/metabolism/genetics ; *Chronic Pain/metabolism/immunology ; *Receptors, CXCR5/metabolism ; *Signal Transduction ; *Nervous System Diseases/metabolism ; Animals ; *Neuroinflammatory Diseases/metabolism ; }, abstract = {Chronic pain dramatically affects life qualities of the sufferers. It has posed a heavy burden to both patients and the health care system. However, the current treatments for chronic pain are usually insufficient and cause many unwanted side effects. Chemokine C-X-C motif ligand 13 (CXCL13), formerly recognized as a B cell chemokine, binds with the cognate receptor CXCR5, a G-protein-coupled receptor (GPCR), to participate in immune cell recruitments and immune modulations. Recent studies further demonstrated that CXCL13-CXCR5 signaling is implicated in chronic pain via promoting neuroimmune interaction and neuroinflammation in the sensory system. In addition, some latest work also pointed out the involvement of CXCL13-CXCR5 in the pathogenesis of certain neurological diseases, including ischemic stroke and amyotrophic lateral sclerosis. Therefore, we aim to outline the recent findings in regard to the involvement of CXCL13-CXCR5 signaling in chronic pain as well as certain neurological diseases, with the focus on how this chemokine signaling contributes to the pathogenesis of these neurological diseases via regulating neuroimmune interaction and neuroinflammation. Strategies that can specifically target CXCL13-CXCR5 signaling in distinct locations may provide new therapeutic options for these neurological diseases.}, }
@article {pmid39470866, year = {2025}, author = {Liu, Y and Fu, R and Jia, H and Yang, K and Ren, F and Zhou, MS}, title = {GHRH and its analogues in central nervous system diseases.}, journal = {Reviews in endocrine &amp; metabolic disorders}, volume = {26}, number = {3}, pages = {427-442}, pmid = {39470866}, issn = {1573-2606}, support = {82270434//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Growth Hormone-Releasing Hormone/analogs &amp; derivatives/metabolism/therapeutic use ; Animals ; *Central Nervous System Diseases/metabolism/drug therapy ; Insulin-Like Growth Factor I/metabolism ; }, abstract = {Growth hormone-releasing hormone (GHRH) is primarily produced by the hypothalamus and stimulates the release of growth hormone (GH) in the anterior pituitary gland, which subsequently regulates the production of hepatic insulin-like growth factor-1 (IGF-1). GH and IGF-1 have potent effects on promoting cell proliferation, inhibiting cell apoptosis, as well as regulating cell metabolism. In central nerve system (CNS), GHRH/GH/IGF-1 promote brain development and growth, stimulate neuronal proliferation, and regulate neurotransmitter release, thereby participating in the regulation of various CNS physiological activities. In addition to hypothalamus-pituitary gland, GHRH and GHRH receptor (GHRH-R) are also expressed in other brain cells or tissues, such as endogenous neural stem cells (NSCs) and tumor cells. Alternations in GHRH/GH/IGF-1 axis are associated with various CNS diseases, for example, Alzheimer's disease, amyotrophic lateral sclerosis and emotional disorders manifest GHRH, GH or IGF-1 deficiency, and GH or IGF-1 supplementation exerts beneficial therapeutic effects on these diseases. CNS tumors, such as glioma, can express GHRH and GHRH-R, and activating this signaling pathway promotes tumor cell growth. The synthesized GHRH antagonists have shown to inhibit glioma cell growth and may hold promising as an adjuvant therapy for treating glioma. In addition, we have shown that GHRH agonist MR-409 can improve neurological sequelae after ischemic stroke by activating extrapituitary GHRH-R signaling and promoting endogenous NSCs-derived neuronal regeneration. This article reviews the involvement of GHRH/GH/IGF-1 in CNS diseases, and potential roles of GHRH agonists and antagonists in treating CNS diseases.}, }
@article {pmid39470847, year = {2025}, author = {Jellinger, KA}, title = {Mild cognitive impairment in amyotrophic lateral sclerosis: current view.}, journal = {Journal of neural transmission (Vienna, Austria : 1996)}, volume = {132}, number = {3}, pages = {357-368}, pmid = {39470847}, issn = {1435-1463}, support = {Society for the Promotion of Research in Experimental Neurology, Vienna, Austria//Society for the Promotion of Research in Experimental Neurology, Vienna, Austria/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications ; *Cognitive Dysfunction/etiology/diagnosis ; *Brain/pathology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal multi-system neurodegenerative disorder with no effective treatment or cure. Although primarily characterized by motor degeneration, cognitive dysfunction is an important non-motor symptom that has a negative impact on patient and caregiver burden. Mild cognitive deficits are present in a subgroup of non-demented patients with ALS, often preceding motor symptoms. Detailed neuropsychological assessments reveal deficits in a variety of cognitive domains, including those of verbal fluency and retrieval, language, executive function, attention and verbal memory. Mild cognitive impairment (MCI), a risk factor for developing dementia, affects between 10% and over 50% of ALS patients. Neuroimaging revealed atrophy of frontal and temporal cortices, disordered white matter Integrity, volume reduction in amygdala and thalamus, hypometabolism in the frontal and superior temporal gyrus and anterior insula. Neuronal loss in non-motor brain areas, associated with TDP-43 deposition, one of the morphological hallmarks of ALS, is linked to functional disruption of frontostriatal and frontotemporo-limbic connectivities as markers for cognitive deficits in ALS, the pathogenesis of which is still poorly understood. Early diagnosis by increased cerebrospinal fluid or serum levels of neurofilament light/heavy chain or glial fibrillary acidic protein awaits confirmation for MCI in ALS. These fluid biomarkers and early detection of brain connectivity signatures before structural changes will be helpful not only in establishing early premature diagnosis but also in clarifying the pathophysiological mechanisms of MCI in ALS, which might serve as novel targets for prohibition/delay and future adequate treatment of this debilitating disorder.}, }
@article {pmid39470153, year = {2024}, author = {Xu, R}, title = {Overview of nomenclature and diagnosis of amyotrophic lateral sclerosis.}, journal = {Annals of medicine}, volume = {56}, number = {1}, pages = {2422572}, pmid = {39470153}, issn = {1365-2060}, mesh = {*Amyotrophic Lateral Sclerosis/diagnosis/classification/physiopathology ; Humans ; *Terminology as Topic ; Electromyography/methods ; Motor Neurons/pathology ; }, abstract = {The nomenclature of amyotrophic lateral sclerosis (ALS) currently is blurred, indistinct and no accurate and haven't been properly updated since the first description, which is far from being suitable for the current implementation of clinical practise and scientific research of ALS, and urgently need an solution. Furthermore, the current diagnostic criteria need also further been improved, because the current clinical diagnosis of ALS majorly depends on the clinical manifestations yet. Up to now, no any objective clinical auxiliary examination can be helpful to diagnose ALS besides the electromyogram identifying the lower motor neuron damage, which isn't conducive to early diagnosis and prolongs the time of ALS confirmed diagnosis. In this mini review, we discussed the current doubt about the nomenclature and diagnostic criteria of ALS, and prospected in order to further improve and normalize the nomenclature and diagnosis of ALS.}, }
@article {pmid39467007, year = {2025}, author = {Jane, K and Wood, D and Gallagher, K and Livermore, P and Shoemark, H and Robert, G}, title = {Parents' experiences of psychotherapeutic support on the neonatal unit: A mixed methods systematic review to inform intervention development for a multicultural population.}, journal = {Nursing in critical care}, volume = {30}, number = {3}, pages = {e13194}, pmid = {39467007}, issn = {1478-5153}, support = {//National Institute for Health and Care Research/ ; }, mesh = {Humans ; *Parents/psychology ; *Intensive Care Units, Neonatal ; Infant, Newborn ; *Cultural Diversity ; *Psychotherapy/methods ; Intensive Care, Neonatal/psychology ; *Social Support ; }, abstract = {BACKGROUND: Parents of infants admitted to neonatal intensive care require support to minimize the impact on their mental health and to encourage engagement with their infants to support infant neurodevelopment. Many interventions aim to address this need, but there is a lack of research considering the accessibility of these for a multicultural population.<br><br>AIM: To systematically identify sources of psychotherapeutic support available for parents with infants admitted to neonatal care (NNU, neonatal intensive care unit [NICU] and special care units), assess their accessibility and acceptability and identify challenges and facilitators.<br><br>STUDY DESIGN: Six electronic databases with no restrictions on language or date were used to identify relevant studies following Preferred Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Publications were included in the review if they reviewed parent experience of an intervention actively in place to support parent experience during the neonatal unit stay. Any studies where the intervention's primary aim was infant focused, such as developmental care, were excluded. All publications were quality-assessed using quality appraisal tools appropriate for their design type. Data were extracted line by line using Sekhon et al.'s theoretical acceptability framework and questionnaire.<br><br>RESULTS: A total of 3309 studies were found, of which 36 studies met the inclusion criteria. Included studies were published worldwide between 2000 and 2023 and explored 15 different interventions. Challenges for parental engagement were due to preconceived ideas about intervention requirements and parents' ability to participate in them. Timely information and providers' experience in delivering the intervention were reported to support engagement and as being valuable for enhancing participant knowledge. The emotional content of interventions was found to be challenging by parents across most studies. This was prominent in interventions designed to be carried out in a group format and where keepsakes were created. However, the value of these interventions was in reducing parents' feelings of isolation through increased social support and providing a starting point for conversations with wider family and friends about the family's neonatal experience. Participant demographics were poorly reported, with only two studies taking into consideration the ethicality of the intervention.<br><br>CONCLUSION: Poor reporting of participant demographics, and a focus on mothers as participants, means findings are not transferrable to the wider population of parents in neonatal units. Future studies should consider how to ensure that research and interventions are accessible to multicultural populations to improve the understanding of the acceptability of interventions. Better knowledge of neonates and the NNU setting amongst intervention providers could increase the accessibility of psychotherapeutic support for parents. Training for providers on how to manage sensitive conversations may also be beneficial to support parents during interventions.<br><br>The impact of neonatal admission on parental mental health is increasingly recognized and reported. Interventions have been developed to reduce the negative impact on the mental health of parents. There continue to be significant health inequalities as a result of many services not taking into account the acceptability and accessibility of interventions in this setting for their multicultural populations. This review highlights the need for better reporting of participant demographics in research and the inclusion of those seldom heard to ensure interventions are culturally, religiously and linguistically appropriate for multicultural populations.}, }
@article {pmid39459534, year = {2024}, author = {Nakhal, MM and Yassin, LK and Alyaqoubi, R and Saeed, S and Alderei, A and Alhammadi, A and Alshehhi, M and Almehairbi, A and Al Houqani, S and BaniYas, S and Qanadilo, H and Ali, BR and Shehab, S and Statsenko, Y and Meribout, S and Sadek, B and Akour, A and Hamad, MIK}, title = {The Microbiota-Gut-Brain Axis and Neurological Disorders: A Comprehensive Review.}, journal = {Life (Basel, Switzerland)}, volume = {14}, number = {10}, pages = {}, pmid = {39459534}, issn = {2075-1729}, support = {12M159//UAEU/ ; G00004325//UAEU/ ; 12M142//UAEU/ ; }, abstract = {Microbes have inhabited the earth for hundreds of millions of years longer than humans. The microbiota-gut-brain axis (MGBA) represents a bidirectional communication pathway. These communications occur between the central nervous system (CNS), the enteric nervous system (ENS), and the emotional and cognitive centres of the brain. The field of research on the gut-brain axis has grown significantly during the past two decades. Signalling occurs between the gut microbiota and the brain through the neural, endocrine, immune, and humoral pathways. A substantial body of evidence indicates that the MGBA plays a pivotal role in various neurological diseases. These include Alzheimer's disease (AD), autism spectrum disorder (ASD), Rett syndrome, attention deficit hyperactivity disorder (ADHD), non-Alzheimer's neurodegeneration and dementias, fronto-temporal lobe dementia (FTLD), Wilson-Konovalov disease (WD), multisystem atrophy (MSA), Huntington's chorea (HC), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), temporal lobe epilepsy (TLE), depression, and schizophrenia (SCZ). Furthermore, the bidirectional correlation between therapeutics and the gut-brain axis will be discussed. Conversely, the mood of delivery, exercise, psychotropic agents, stress, and neurologic drugs can influence the MGBA. By understanding the MGBA, it may be possible to facilitate research into microbial-based interventions and therapeutic strategies for neurological diseases.}, }
@article {pmid39459030, year = {2024}, author = {Al-Khayri, JM and Ravindran, M and Banadka, A and Vandana, CD and Priya, K and Nagella, P and Kukkemane, K}, title = {Amyotrophic Lateral Sclerosis: Insights and New Prospects in Disease Pathophysiology, Biomarkers and Therapies.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {17}, number = {10}, pages = {}, pmid = {39459030}, issn = {1424-8247}, support = {GRANT0000//Deanship of Scientific Research, King Faisal University/ ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a severe neurodegenerative disorder marked by the gradual loss of motor neurons, leading to significant disability and eventual death. Despite ongoing research, there are still limited treatment options, underscoring the need for a deeper understanding of the disease's complex mechanisms and the identification of new therapeutic targets. This review provides a thorough examination of ALS, covering its epidemiology, pathology, and clinical features. It investigates the key molecular mechanisms, such as protein aggregation, neuroinflammation, oxidative stress, and excitotoxicity that contribute to motor neuron degeneration. The role of biomarkers is highlighted for their importance in early diagnosis and disease monitoring. Additionally, the review explores emerging therapeutic approaches, including inhibitors of protein aggregation, neuroinflammation modulators, antioxidant therapies, gene therapy, and stem cell-based treatments. The advantages and challenges of these strategies are discussed, with an emphasis on the potential for precision medicine to tailor treatments to individual patient needs. Overall, this review aims to provide a comprehensive overview of the current state of ALS research and suggest future directions for developing effective therapies.}, }
@article {pmid39457513, year = {2024}, author = {Montiel-Troya, M and Mohamed-Mohamed, H and Pardo-Moreno, T and González-Díaz, A and Ruger-Navarrete, A and de la Mata Fernández, M and Tovar-Gálvez, MI and Ramos-Rodríguez, JJ and García-Morales, V}, title = {Advancements in Pharmacological Interventions and Novel Therapeutic Approaches for Amyotrophic Lateral Sclerosis.}, journal = {Biomedicines}, volume = {12}, number = {10}, pages = {}, pmid = {39457513}, issn = {2227-9059}, support = {PID2019-110960GB-I00//Ministry of Science and Innovation, Spain./ ; }, abstract = {(1) Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease in which the patient suffers from an affection of both upper and lower motor neurons at the spinal and brainstem level, causing a progressive paralysis that leads to the patient's demise. Gender is also considered a predisposing risk factor for developing the disease. A brief review of the pathophysiological mechanisms of the disease is also described in this work. Despite the fact that a cure for ALS is currently unknown, there exists a variety of pharmacological and non-pharmacological therapies that can help reduce the progression of the disease over a certain period of time and alleviate symptoms. (2) We aim to analyze these pharmacological and non-pharmacological therapies through a systematic review. A comprehensive, multidisciplinary approach to treatment is necessary. (3) Drugs such as riluzole, edaravone, and sodium phenylbutyrate, among others, have been investigated. Additionally, it is important to stay updated on research on new drugs, such as masitinib, from which very good results have been obtained. (4) Therapies aimed at psychological support, speech and language, and physical therapy for the patient are also available, which increase the quality of life of the patients.}, }
@article {pmid39457470, year = {2024}, author = {Trabacca, A and Ferrante, C and Oliva, MC and Fanizza, I and Gallo, I and De Rinaldis, M}, title = {Update on Inherited Pediatric Motor Neuron Diseases: Clinical Features and Outcome.}, journal = {Genes}, volume = {15}, number = {10}, pages = {}, pmid = {39457470}, issn = {2073-4425}, support = {2024//The Italian Health Ministry - Ricerca Corrente/ ; }, mesh = {Humans ; *Motor Neuron Disease/genetics/pathology ; Child ; Mutation ; Muscular Atrophy, Spinal/genetics/pathology/diagnosis ; Exome Sequencing ; }, abstract = {BACKGROUND: Inherited pediatric motor neuron diseases (MNDs) are a group of neurodegenerative disorders characterized by the degeneration of motor neurons in the brain and the spinal cord. These diseases can manifest as early as infancy and originate from inherited pathogenic mutations in known genes. Key clinical features of MNDs include muscle weakness, hypotonia, and atrophy due to the degeneration of lower motor neurons or spasticity, hypertonia, and hyperreflexia caused by upper motor neuron dysfunction. The course of the disease varies among individuals and is influenced by the specific subtype.<br><br>METHODS: We performed a non-systematic, narrative clinical review, employing a systematic methodology for the literature search and article selection to delineate the features of hereditary pediatric motor neuron diseases.<br><br>RESULTS: The growing availability of advanced molecular testing, such as whole-exome sequencing (WES) and whole-genome sequencing (WGS), has expanded the range of identified genetic factors. These advancements provide insights into the genetic complexity and underlying mechanisms of these disorders. As more MND-related genes are discovered, the accumulating genetic data will help prioritize promising candidate genes for future research. In some cases, targeted treatments based on specific genetic mechanisms have already emerged, underscoring the critical role of early and timely diagnosis in improving patient outcomes. Common MNDs include amyotrophic lateral sclerosis, spinal muscular atrophy, and bulbar spinal muscular atrophy.<br><br>CONCLUSION: This narrative clinical review covers the clinical presentation, genetics, molecular features, and pathophysiology of inherited pediatric MNDs.}, }
@article {pmid39457468, year = {2024}, author = {Boura, I and Giannopoulou, IA and Pavlaki, V and Xiromerisiou, G and Mitsias, P and Spanaki, C}, title = {FIG4-Related Parkinsonism and the Particularities of the I41T Mutation: A Review of the Literature.}, journal = {Genes}, volume = {15}, number = {10}, pages = {}, pmid = {39457468}, issn = {2073-4425}, mesh = {Humans ; *Parkinsonian Disorders/genetics/pathology/diagnostic imaging ; *Charcot-Marie-Tooth Disease/genetics/pathology ; *Flavoproteins/genetics ; Female ; Male ; Mutation, Missense ; Middle Aged ; Mutation ; Adult ; Phosphoric Monoester Hydrolases ; }, abstract = {Background/Objectives: The genetic underpinnings of Parkinson's disease (PD) and parkinsonism have drawn increasing attention in recent years. Mutations in the Factor-Induced Gene 4 (FIG4) have been implicated in various neurological disorders, including Charcot-Marie-Tooth disease type 4J (CMT4J), amyotrophic lateral sclerosis (ALS), and Yunis-Varón syndrome. This review aims to explore the association between FIG4 mutations and parkinsonism, with a specific focus on the rare missense mutation p.Ile41Thr (I41T). Methods: We identified 12 cases from 10 different families in which parkinsonism was reported in conjunction with CMT4J polyneuropathy. All cases involved the I41T mutation in a compound heterozygous state, combined with a FIG4 loss-of-function mutation. Data from clinical observations, neuroimaging studies, and genetic analyses were evaluated to understand the characteristics of parkinsonism in these patients. Results: In all 12 cases, parkinsonism developed either concurrently or following the onset of CMT4J neuropathy, but was never observed in isolation. Cases of both early- and late-onset parkinsonism were identified, reflecting similarities to genetic forms of parkinsonism with autosomal recessive inheritance. Imaging studies, including Dopamine transporter Single Photon Emission Computed Tomography (DaTscan) and brain magnetic resonance imaging (MRI), revealed abnormalities indicative of neurodegeneration, consistent with findings in other neurodegenerative disorders. Conclusions: The co-occurrence of parkinsonism with CMT4J in patients carrying the I41T mutation suggests an expanded spectrum of FIG4-related disorders, potentially implicating the same molecular mechanisms seen in other neurodegenerative disorders. Further research into FIG4-mediated pathways may offer valuable insights into potential therapeutic targets for disorders of both the central and peripheral nervous systems.}, }
@article {pmid39457466, year = {2024}, author = {Moriyama, H and Yokota, T}, title = {Recent Progress of Antisense Oligonucleotide Therapy for Superoxide-Dismutase-1-Mutated Amyotrophic Lateral Sclerosis: Focus on Tofersen.}, journal = {Genes}, volume = {15}, number = {10}, pages = {}, pmid = {39457466}, issn = {2073-4425}, mesh = {*Amyotrophic Lateral Sclerosis/genetics/drug therapy/therapy ; Humans ; *Superoxide Dismutase-1/genetics ; *Oligonucleotides, Antisense/therapeutic use/genetics ; *Mutation ; Animals ; Oligonucleotides/therapeutic use/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a refractory neurodegenerative disease characterized by the degeneration and loss of motor neurons, typically resulting in death within five years of onset. There have been few effective treatments, making the development of robust therapies an urgent challenge. Genetic mutations have been identified as contributors to ALS, with mutations in superoxide dismutase 1 (SOD1), which neutralizes the harmful reactive oxygen species superoxide, accounting for approximately 2% of all ALS cases. To counteract the toxic gain of function caused by SOD1 mutations, therapeutic strategies aimed at suppressing SOD1 gene expression have shown promise. Antisense oligonucleotide (ASO) is an artificially synthesized, short, single-stranded DNA/RNA molecule that binds to target RNA to alter gene expression, representing a next-generation therapeutic approach. In 2023, tofersen became the first ASO drug approved by the FDA for ALS. Administered intrathecally, tofersen specifically binds to SOD1 mRNA, inhibiting the production of toxic SOD1 protein, thereby improving biomarkers of ALS. The long-term efficacy and safety of tofersen require further validation, and the development of more optimized treatment protocols is essential. A series of studies and therapeutic developments related to SOD1 mutations have advanced the understanding of ALS pathophysiology and significantly contributed to treatment strategies for central nervous system disorders. This review focuses on an overview of SOD1 mutations and the development process of tofersen, aiming to deepen the understanding of advancements in ALS research and discuss future challenges and directions for ASO therapy.}, }
@article {pmid39456682, year = {2024}, author = {Alshehri, RS and Abuzinadah, AR and Alrawaili, MS and Alotaibi, MK and Alsufyani, HA and Alshanketi, RM and AlShareef, AA}, title = {A Review of Biomarkers of Amyotrophic Lateral Sclerosis: A Pathophysiologic Approach.}, journal = {International journal of molecular sciences}, volume = {25}, number = {20}, pages = {}, pmid = {39456682}, issn = {1422-0067}, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/physiopathology/diagnosis ; Humans ; *Biomarkers/metabolism ; Motor Neurons/metabolism/pathology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive degeneration of upper and lower motor neurons. The heterogeneous nature of ALS at the clinical, genetic, and pathological levels makes it challenging to develop diagnostic and prognostic tools that fit all disease phenotypes. Limitations associated with the functional scales and the qualitative nature of mainstay electrophysiological testing prompt the investigation of more objective quantitative assessment. Biofluid biomarkers have the potential to fill that gap by providing evidence of a disease process potentially early in the disease, its progression, and its response to therapy. In contrast to other neurodegenerative diseases, no biomarker has yet been validated in clinical use for ALS. Several fluid biomarkers have been investigated in clinical studies in ALS. Biofluid biomarkers reflect the different pathophysiological processes, from protein aggregation to muscle denervation. This review takes a pathophysiologic approach to summarizing the findings of clinical studies utilizing quantitative biofluid biomarkers in ALS, discusses the utility and shortcomings of each biomarker, and highlights the superiority of neurofilaments as biomarkers of neurodegeneration over other candidate biomarkers.}, }
@article {pmid39456257, year = {2024}, author = {Perni, M and Mannini, B}, title = {Targeting Protein Aggregation in ALS.}, journal = {Biomolecules}, volume = {14}, number = {10}, pages = {}, pmid = {39456257}, issn = {2218-273X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/drug therapy ; *Protein Aggregation, Pathological/metabolism ; Protein Aggregates ; Animals ; }, abstract = {Proteinopathies involve the abnormal accumulation of specific proteins. Maintaining the balance of the proteome is a finely regulated process managed by a complex network of cellular machinery responsible for protein synthesis, folding, and degradation. However, stress and ageing can disrupt this balance, leading to widespread protein aggregation. Currently, several therapies targeting protein aggregation are in clinical trials for ALS. These approaches mainly focus on two strategies: addressing proteins that are prone to aggregation due to mutations and targeting the cellular mechanisms that maintain protein homeostasis to prevent aggregation. This review will cover these emerging drugs. Advances in ALS research not only offer hope for better outcomes for ALS patients but also provide valuable insights and methodologies that can benefit the broader field of neurodegenerative disease drug discovery.}, }
@article {pmid39455963, year = {2024}, author = {Alexander, E and Leong, KW}, title = {Discovery of nanobodies: a comprehensive review of their applications and potential over the past five years.}, journal = {Journal of nanobiotechnology}, volume = {22}, number = {1}, pages = {661}, pmid = {39455963}, issn = {1477-3155}, mesh = {*Single-Domain Antibodies/chemistry ; Humans ; Animals ; *SARS-CoV-2/immunology ; COVID-19/virology/immunology ; Neurodegenerative Diseases/drug therapy ; }, abstract = {Nanobodies (Nbs) are antibody fragments derived from heavy-chain-only IgG antibodies found in the Camelidae family as well as cartilaginous fish. Their unique structural and functional properties, such as their small size, the ability to be engineered for high antigen-binding affinity, stability under extreme conditions, and ease of production, have made them promising tools for diagnostics and therapeutics. This potential was realized in 2018 with the approval of caplacizumab, the world's first Nb-based drug. Currently, Nbs are being investigated in clinical trials for a broad range of treatments, including targeted therapies against PDL1 and Epidermal Growth Factor Receptor (EGFR), cardiovascular diseases, inflammatory conditions, and neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. They are also being studied for their potential for detecting and imaging autoimmune conditions and infectious diseases such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A variety of methods are now available to generate target-specific Nbs quickly and efficiently at low costs, increasing their accessibility. This article examines these diverse applications of Nbs and their promising roles. Only the most recent articles published in the last five years have been used to summarize the most advanced developments in the field.}, }
@article {pmid39454309, year = {2025}, author = {McKechnie, T and Bogdan, RM and Brennan, K and Shi, V and Grewal, S and Eskicioglu, C and Farooq, A and Patel, S}, title = {Fragility index for extended prophylaxis following abdominopelvic surgery: A methodological survey.}, journal = {American journal of surgery}, volume = {239}, number = {}, pages = {116020}, doi = {10.1016/j.amjsurg.2024.116020}, pmid = {39454309}, issn = {1879-1883}, mesh = {Humans ; *Abdomen/surgery ; *Pelvis/surgery ; *Postoperative Complications/epidemiology/etiology/prevention &amp; control ; Randomized Controlled Trials as Topic ; Venous Thromboembolism/epidemiology/etiology/prevention &amp; control ; }, abstract = {BACKGROUND: Fragility Index (FI) is increasingly used to assess robustness of statistically significant p-values reported in randomized controlled trials (RCTs). FI represents the lowest number of non-events changed to events that would make study findings non-significant. This methodological survey was designed to assess the fragility of the evidence for extended VTEp following major abdominopelvic surgery.<br><br>METHODS: MEDLINE, Embase, and CENTRAL were searched from inception to November 2023. RCTs with parallel, double-armed, superiority design comparing extended VTEp for patients undergoing major abdominopelvic surgery to controls with at least one statistically significant dichotomous outcome were included. Walsh et&#xa0;al.'s method of calculating FI was utilized.<br><br>RESULTS: After review of 611 citations, 6 RCTs were identified with 12 statistically significant outcomes between groups. The mean number of patients randomized per RCT was 419 (SD 176). The median FI was 1.5 (range: 1-4). The number of patients lost to follow-up was greater than the FI for 10/12 (83.3&#xa0;&#x200b;%) outcomes.<br><br>CONCLUSIONS: Statistically significant differences reported in RCTs evaluating extended VTEp following major abdominopelvic surgery are not robust.}, }
@article {pmid39451992, year = {2024}, author = {Ozdinler, PH}, title = {Sleep Apnea and Amyotrophic Lateral Sclerosis: Cause, Correlation, Any Relation?.}, journal = {Brain sciences}, volume = {14}, number = {10}, pages = {}, pmid = {39451992}, issn = {2076-3425}, abstract = {Amyotrophic lateral sclerosis (ALS) is a motor neuron disease with progressive neurodegeneration, affecting both the cortical and the spinal component of the motor neuron circuitry in patients. The cellular and molecular basis of selective neuronal vulnerability is beginning to emerge. Yet, there are no effective cures for ALS, which affects more than 200,000 people worldwide each year. Recent studies highlight the importance of the glymphatic system and its proper function for the clearance of the cerebral spinal fluid, which is achieved mostly during the sleep period. Therefore, a potential link between problems with sleep and neurodegenerative diseases has been postulated. This paper discusses the present understanding of this potential correlation.}, }
@article {pmid39451238, year = {2024}, author = {Crescioli, C and Paronetto, MP}, title = {The Emerging Role of Phosphodiesterase 5 Inhibition in Neurological Disorders: The State of the Art.}, journal = {Cells}, volume = {13}, number = {20}, pages = {}, pmid = {39451238}, issn = {2073-4409}, mesh = {Humans ; *Phosphodiesterase 5 Inhibitors/therapeutic use/pharmacology ; *Nervous System Diseases/drug therapy ; Animals ; Cyclic Nucleotide Phosphodiesterases, Type 5/metabolism ; Neuroinflammatory Diseases/drug therapy/metabolism ; }, abstract = {Growing evidence suggests that neuroinflammation is not just a consequence of neurodegeneration in pathologies such as Alzheimer's disease, Parkinson's disease, Huntington's disease or Amyotrophic lateral sclerosis, but it is rather a determinant factor, which plays a pivotal role in the onset and progression of these disorders. Neuroinflammation can affect cells and processes in the central nervous system (CNS) as well as immune cells, and might precede protein aggregation, which is a hallmark of the neurodegenerative process. Standard treatment methods are far from being able to counteract inflammation and delay neurodegeneration. Remarkably, phosphodiesterase 5 inhibitors (PDE5is), which represent potent vasoactive drugs used as a first-line treatment for erectile dysfunction (ED), display important anti-inflammatory effects through cyclic guanosine monophosphate (cGMP) level stabilization. Since PDE5 hydrolyzes cGMP, several studies positioned PDE5 as a therapeutic target, and more specifically, PDE5is as potential alternative strategies for the treatment of a variety of neurological disorders. Indeed, PDE5is can limit neuroinflammation and enhance synaptic plasticity, with beneficial effects on cognitive function and memory. The aim of this review is to provide an overview of some of the main processes underlying neuroinflammation and neurodegeneration which may be potential targets for PDE5is, focusing on sildenafil, the most extensively studied. Current strategies using PDEis for the treatment of neurodegenerative diseases will be summarized.}, }
@article {pmid39449457, year = {2024}, author = {Rosa, D and Ingrande, L and Marcomini, I and Poliani, A and Villa, G and Sodano, M and Manara, DF}, title = {Perceived Pain in People Living with Amyotrophic Lateral Sclerosis-A Scoping Review.}, journal = {Nursing reports (Pavia, Italy)}, volume = {14}, number = {4}, pages = {3023-3039}, pmid = {39449457}, issn = {2039-4403}, abstract = {(1) Background: Pain is a common symptom in patients with Amyotrophic Lateral Sclerosis (ALS). There are no evidence-based pharmacological treatments for pain in ALS; recommendations are based on guidelines for chronic non-oncological pain and clinical experience. The aim is to map the literature on how people with ALS experience pain, and how this affects their daily activities and social relationships. (2) Methods: This scoping review included studies concerning patients with spinal/bulbar ALS aged ≥ 18 years who experience pain, focusing on perception, characteristics, treatment, and impact on quality of life. Temporal and linguistic criteria were applied when searching the MEDLINE, CINAHL, and SCOPUS databases. (3) Results: The management of pain in these patients is complex and involves the use of anti-inflammatory drugs, analgesics, and opioids. Pain is associated with other conditions such as depression and anxiety, which contribute to a deterioration in the quality of life. Moreover, pain may also negatively influence patient compliance with prescribed treatment regimens and the quality of care they perceive themselves to be receiving. (4) Conclusions: It is of the most importance to identify effective ways to assess and treat this issue, with health care professionals taking an active role in this process.}, }
@article {pmid39441150, year = {2024}, author = {Hamad, AA and Alkhawaldeh, IM and Abbas, A and Elaraby, A and Meshref, M}, title = {Incidence and risk factors of venous thromboembolism in patients with amyotrophic lateral sclerosis: a systematic review and meta-analysis.}, journal = {La Tunisie medicale}, volume = {102}, number = {10}, pages = {610-515}, pmid = {39441150}, issn = {2724-7031}, mesh = {*Amyotrophic Lateral Sclerosis/epidemiology/complications ; Humans ; *Venous Thromboembolism/epidemiology/etiology ; Incidence ; Risk Factors ; Male ; Female ; }, abstract = {AIMS: This systematic review and meta-analysis aimed to determine the annual incidence rate of venous thromboembolism (VTE) and identify risk factors of VTE in amyotrophic lateral sclerosis (ALS) patients.<br><br>METHODS: A comprehensive search of three databases was conducted up to April 8, 2024, to identify longitudinal studies reporting VTE incidence in ALS patients. The included studies were either prospective or retrospective, following up with ALS patients. Quality assessment was performed using the NIH tool for observational cohort studies. Meta-analysis was conducted using Open Meta Analyst, employing a random-effect model. Subgroup, Meta-regression, and sensitivity analyses were also carried out.<br><br>RESULTS: Our analysis included eight studies comprising a total of 26,758 ALS patients that met the inclusion criteria. The pooled annual incidence of VTE across all studies was found to be 22 cases per 1,000 person-year (95% CI = 18 to 27). Subgroup analysis revealed that the annual incidence of VTE in males was 19 cases per 1,000 person-year (95% CI = 15 to 22), while in females, it was 20 cases per 1,000 person-year (95% CI = 16 to 25). Leave-one-out analysis demonstrated that the incidence ranged from 21 to 28 cases per 1,000 person-year when excluding each study individually. Meta-regression analysis did not find a significant association between age and the risk of VTE (P = 0.079). Based on the included studies, risk factors of VTE in ALS patients included a history of VTE, non-invasive ventilation, immobility, and decreased functional status.<br><br>CONCLUSION: Patients with ALS face a higher risk of developing VTE compared to individuals of the same age. These findings underscore the importance of implementing preventive measures and closely monitoring VTE in ALS patients.}, }
@article {pmid39441015, year = {2025}, author = {Liu, Y and Li, Y and Zhang, P}, title = {Stress granules and organelles: coordinating cellular responses in health and disease.}, journal = {Protein &amp; cell}, volume = {16}, number = {6}, pages = {418-438}, pmid = {39441015}, issn = {1674-8018}, support = {2023YFC3505000//National Key Research and Development Project of China/ ; 7244365//Beijing Natural Science Foundation of China/ ; }, mesh = {Humans ; *Stress Granules/metabolism/pathology ; *Organelles/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism/pathology ; Animals ; *Stress, Physiological ; *Cytoplasmic Granules/metabolism ; }, abstract = {Membrane-bound organelles and membraneless organelles (MLOs) coordinate various biological processes within eukaryotic cells. Among these, stress granules (SGs) are significant cytoplasmic MLOs that form in response to cellular stress, exhibiting liquid-like properties alongside stable substructures. SGs interact with diverse organelles, thereby influencing cellular pathways that are critical in both health and disease contexts. This review discusses the interplay between SGs and organelles and explores the methodologies employed to analyze interactions between SGs and other MLOs. Furthermore, it highlights the pivotal roles SGs play in regulating cellular responses and the pathogenesis of amyotrophic lateral sclerosis. Gaining insights into these interactions is essential for deciphering the mechanisms underlying both physiological processes and pathological conditions.}, }
@article {pmid39440770, year = {2025}, author = {Allowitz, K and Taylor, J and Harames, K and Yoo, J and Baloch, O and Ramana, KV}, title = {Oxidative Stress-mediated Lipid Peroxidation-derived Lipid Aldehydes in the Pathophysiology of Neurodegenerative Diseases.}, journal = {Current neuropharmacology}, volume = {23}, number = {6}, pages = {671-685}, pmid = {39440770}, issn = {1875-6190}, mesh = {Humans ; *Oxidative Stress/physiology ; *Neurodegenerative Diseases/metabolism/physiopathology ; *Lipid Peroxidation/physiology ; *Aldehydes/metabolism ; Animals ; }, abstract = {Neurodegenerative diseases such as Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis cause damage and gradual loss of neurons affecting the central nervous system. Neurodegenerative diseases are most commonly seen in the ageing process. Ageing causes increased reactive oxygen species and decreased mitochondrial ATP generation, resulting in redox imbalance and oxidative stress. Oxidative stress-generated free radicals cause damage to membrane lipids containing polyunsaturated fatty acids, leading to the formation of toxic lipid aldehyde products such as 4- hydroxynonenal and malondialdehyde. Several studies have shown that lipid peroxidation-derived aldehyde products form adducts with cellular proteins, altering their structure and function. Thus, these lipid aldehydes could act as secondary signaling intermediates, modifying important metabolic pathways, and contributing to the pathophysiology of several human diseases, including neurodegenerative disorders. Additionally, they could serve as biomarkers for disease progression. This narrative review article discusses the biological and clinical significance of oxidative stress-mediated lipid peroxidation-derived lipid aldehydes in the pathophysiology of various neurodegenerative diseases.}, }
@article {pmid39439710, year = {2024}, author = {Kelser, BM and Teichner, EM and Subtirelu, RC and Hoss, KN}, title = {A review of proposed mechanisms for neurodegenerative disease.}, journal = {Frontiers in aging neuroscience}, volume = {16}, number = {}, pages = {1370580}, pmid = {39439710}, issn = {1663-4365}, abstract = {Neurodegenerative diseases, such as Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis (ALS) affect millions and present significant challenges in healthcare and treatment costs. The debate in the field pivots around two hypotheses: synaptic spread and selective vulnerability. Pioneers like Virginia Lee and John Trojanowski have been instrumental in identifying key proteins (tau, alpha-synuclein, TDP-43) central to these diseases. The synaptic spread hypothesis suggests a cell-to-cell propagation of pathogenic proteins across neuronal synapses, influencing disease progression, with studies highlighting the role of proteins like alpha-synuclein and amyloid-beta in this process. In contrast, the selective vulnerability hypothesis proposes inherent susceptibility of certain neurons to degeneration due to factors like metabolic stress, leading to protein aggregation. Recent advancements in neuroimaging, especially PET/MRI hybrid imaging, offer new insights into these mechanisms. While both hypotheses offer substantial evidence, their relative contributions to neurodegenerative processes remain to be fully elucidated. This uncertainty underscores the necessity for continued research, with a focus on these hypotheses, to develop effective treatments for these devastating diseases.}, }
@article {pmid39436867, year = {2025}, author = {Firozjae, AA and Shiran, MR and Rashidi, M}, title = {The neuropharmacological and clinical effects of lutein: a systematic review.}, journal = {Hormone molecular biology and clinical investigation}, volume = {46}, number = {1}, pages = {27-38}, pmid = {39436867}, issn = {1868-1891}, mesh = {*Lutein/therapeutic use/pharmacology ; Humans ; *Neurodegenerative Diseases/drug therapy/metabolism ; Animals ; }, abstract = {OBJECTIVES: Neurodegenerative diseases are defined by specific protein accumulation and anatomic vulnerability leading to neuronal loss. Some studies have shown that lutein may have an effect on neurodegenerative diseases. As most of the neurodegenerative diseases don't have certain cure and therapies focus on symptom control, Lutein may be a complementary treatment. Due to controversies in studies investigating lutein effect on neurodegenerative diseases, we decided to perform a systematic review on these studies.<br><br>METHODS: A systematic search was carried out in the available databases. We used all MeSH terms and relevant keywords. Studies that reported relationship between lutein and any neurodegenerative disease were included.<br><br>RESULTS: We found 278 studies. After removing duplicates, screening by titles and abstracts and excluding irrelevant papers, 17 articles were included in this study. Fourteen studies investigated Alzheimer's disease, 2 studies Parkinson's disease and 1 study Amyotrophic lateral sclerosis. 1/17 study found that high serum levels of lutein at baseline were associated with a lower risk of AD mortality and lutein effect on lipid profile have been investigated in 2/17 studies. Also, 1/17 study has been shown that high intake of lutein may reduce the risk of ALS progression.<br><br>CONCLUSIONS: 4/17 studies confirm that lutein can improve cognitive function. 8/17 studies demonstrate a reduction in&#xa0;the progression of AD, and 2/17 studies indicate an improvement in lipid profiles. However, some studies did not find any significant associations. Additionally, there is a limited number of studies investigating the effects of lutein on other neurodegenerative diseases.}, }
@article {pmid39434139, year = {2024}, author = {Agah, E and Mojtabavi, H and Behkar, A and Heidari, A and Ajdari, A and Shaka, Z and Mousavi, SV and Firoozeh, N and Tafakhori, A and Rezaei, N}, title = {CSF and blood levels of Neurofilaments, T-Tau, P-Tau, and Abeta-42 in amyotrophic lateral sclerosis: a systematic review and meta-analysis.}, journal = {Journal of translational medicine}, volume = {22}, number = {1}, pages = {953}, pmid = {39434139}, issn = {1479-5876}, mesh = {Humans ; *Amyloid beta-Peptides/cerebrospinal fluid/blood ; *Amyotrophic Lateral Sclerosis/blood/cerebrospinal fluid/diagnosis ; Biomarkers/blood/cerebrospinal fluid ; Neurofilament Proteins/blood/cerebrospinal fluid ; Peptide Fragments/cerebrospinal fluid/blood ; Phosphorylation ; Publication Bias ; *tau Proteins/cerebrospinal fluid/blood ; }, abstract = {Recent literature suggests that markers of neuroaxonal damage, such as neurofilaments and tau protein, might serve as potential biomarkers for ALS. We conducted this systematic review and meta-analysis study to compare cerebrospinal fluid (CSF) and blood levels of total tau (t-tau), phosphorylated tau (p-tau), amyloid beta peptide 42 (Abeta-42), and neurofilaments in ALS patients and controls. A systematic search of Cochrane Library, PubMed, Embase, and ISI Web of Science was conducted on March 18, 2022, and updated on January 26, 2023. Observational studies that compared the concentrations of neurofilament light chain (NfL), neurofilament heavy chain (NFH), t-tau, p-tau, or Abeta-42 in CSF or peripheral blood of ALS patients and controls were included. Data from relevant studies were independently extracted and screened for quality using a standard tool, by at least two authors. Meta-analysis was conducted when a minimum of 3 studies reported the same biomarker within the same biofluid. A total of 100 studies were eligible for at least one meta-analysis. CSF and blood levels of NfL (standardized mean difference (SMD) [95% CI]; CSF: 1.46 [1.25-1.68]; blood: 1.35 [1.09-1.60]) and NFH (CSF: 1.32 [1.13-1.50], blood: 0.90 [0.58-1.22]) were significantly higher in ALS patients compared with controls. The pooled differences between ALS patients and controls were not significant for CSF t-tau, blood t-tau, and CSF Abeta-42, but CSF p-tau was lower in ALS patients (-0.27 [-0.47- -0.07]). Significantly decreased p-tau/t-tau ratios were found in ALS patients compared with controls (-0.84 [-1.16- -0.53]). Heterogeneity was considerable in most of our meta-analyses. CSF and blood neurofilament levels, as well as the CSF p-tau/t-tau ratio, might be potential candidates for improving ALS diagnosis. Further research is warranted to better understand the underlying mechanisms and the clinical implications of these biomarker alterations.}, }
@article {pmid39432435, year = {2025}, author = {Anjaneyulu, J and Godbole, A}, title = {Small organism models for mode of action research on anti-ageing and nootropic herbs, foods, and formulations.}, journal = {Nutritional neuroscience}, volume = {28}, number = {6}, pages = {744-762}, doi = {10.1080/1028415X.2024.2409128}, pmid = {39432435}, issn = {1476-8305}, mesh = {Animals ; *Aging/drug effects ; *Neurodegenerative Diseases/prevention &amp; control/drug therapy ; Humans ; *Disease Models, Animal ; Zebrafish ; *Plant Extracts/pharmacology ; }, abstract = {With global increase in ageing population along with increasing age-related neurodegenerative diseases (NDs), development of sustainable, safe and effective solutions for promoting healthy ageing and preventing diseases has become a priority. Traditional healthcare systems/medicines prescribe several herbs, foods and formulations to promote healthy ageing and prevent and/or treat age-related diseases. However, the scientific data elucidating their mechanism of action is very limited and deeper research using different models is warranted for timely and wider use. The clinical studies and research with higher model organisms, although useful, have several practical, technical, and financial limitations. Conversely, small organism models like Yeast, Roundworm, Fruit fly, and Zebrafish, which have genetic similarities to humans, can replicate the disease features and provide behavioural, cellular and molecular insights. The common features of ageing and NDs, like amyloid protein aggregations, oxidative stress, energy dysregulation, inflammation and neurodegeneration can be mimicked in the small organism models for Alzheimer's, Parkinson's, Huntington's diseases, and Amyotrophic Lateral Sclerosis. This review focuses on small organism model- based research unveiling interesting modes of action and synergistic effects of herbal extracts, foods, and formulations, which are indicated especially for healthy ageing and management of NDs. This will provide leads for the quick and sustainable development of scientifically evaluated solutions for clinically relevant, age-related conditions.}, }
@article {pmid39428248, year = {2024}, author = {Luo, N and Wang, J and Zhang, ZY and Zhao, XY and Huang, RR and Wu, QY}, title = {[Research progress on Pb-induced neurotoxicity through glial cells].}, journal = {Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine]}, volume = {58}, number = {10}, pages = {1610-1615}, doi = {10.3760/cma.j.cn112150-20240513-00382}, pmid = {39428248}, issn = {0253-9624}, support = {8217348282, 82173554, 82101593//National Natural Science Foundation of China/ ; }, mesh = {*Neuroglia/drug effects ; Humans ; *Lead/toxicity ; }, abstract = {Lead is one of the most important occupational hazards in China, and occupational exposure is the leading cause of lead poisoning. Lead can be absorbed by the body through air, food, drinking water and skin, and accumulate in multiple organs in the body, posing health risks to humans, especially to lead workers. Many previous studies have shown that lead can affect the function of glial cells such as microglia, astrocytes and oligodendrocytes, resulting in irreversible neurological damage. This article provides an overview of the neurotoxic mechanism induced by lead through glial cells, elucidates that lead can induce neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, and reviews the relationship between lead and glial cells, in order to provide reference for further research on the neurotoxic mechanism of lead on glial cells.}, }
@article {pmid39425065, year = {2024}, author = {Jones, AT and Tremblay, &#xc9; and Costeux, AL and Strus, JA and Barcket, A}, title = {What tools are available to assess climate and environmental health impacts on perinatal families with an equity lens? A rapid review of the Canadian context.}, journal = {BMC pregnancy and childbirth}, volume = {24}, number = {1}, pages = {680}, pmid = {39425065}, issn = {1471-2393}, mesh = {Humans ; Canada ; *Climate Change ; Female ; Pregnancy ; *Perinatal Care ; *Environmental Health ; Health Equity ; Social Determinants of Health ; }, abstract = {OBJECTIVES: This rapid review is designed to identify existing tools in the Canadian literature that assess the impacts of climate change on the health of perinatal families, particularly those who are equity-denied. Addressing the needs of equity-denied perinatal populations in the face of climate change is crucial to promoting equitable and inclusive perinatal care in Canada.<br><br>METHODS: Rapid review methodology was selected to provide evidence in a timely and cost-effective manner. PubMed/MEDLINE and gray literature (Google and Google Scholar) were searched for English and French papers published from 2013 onward. The original research question, focused on climate change and health, yielded very few relevant results. Therefore, the search was broadened to include environmental health. Garrity et al.'s (J Clin Epidemiol 130:13-22, 2021) nine-stage process was used to identify 11 relevant papers, extract the relevant data, and complete the narrative synthesis.<br><br>SYNTHESIS: This review revealed a significant lack of tools for comprehensively assessing climate-health impacts on perinatal families and equity-denied perinatal families. While Canadian perinatal health screenings focus on equity via indicators of several social determinants of health (e.g., income, social support), they largely omit climate considerations. Environmental health factors are more commonly included but remain minimal.<br><br>CONCLUSION: Climate-health screening tools are lacking yet needed in routine perinatal healthcare. Given the seriousness of climate change, urgent engagement of health systems and healthcare workers is essential to help mitigate and adapt to climate-health challenges, particularly for perinatal families experiencing health inequities.}, }
@article {pmid39424648, year = {2024}, author = {Chartier, C and Godard, J and Durand, S and Humeau-Heurtier, A and Menetrier, E and Allain, P and Besnard, J}, title = {Combinations of physical and cognitive training for subcortical neurodegenerative diseases with physical, cognitive and behavioral symptoms: a systematic review.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {12}, pages = {5571-5589}, pmid = {39424648}, issn = {1590-3478}, mesh = {Humans ; *Neurodegenerative Diseases/therapy ; Behavioral Symptoms/therapy/etiology ; Cognitive Behavioral Therapy/methods ; Exercise Therapy/methods ; Cognitive Dysfunction/therapy/rehabilitation/etiology ; Cognitive Training ; }, abstract = {BACKGROUND: The onset of the symptoms of subcortical NDs is due to a unique part of the brain which strengthens the idea of reciprocal influence of physical activity and cognitive training in improving clinical symptoms. Consequently, protocols combining the two stimulations are becoming increasingly popular in NDs. Our threefold aim was to (A) describe the different combinations of physical and cognitive training used to alleviate the motor and cognitive symptoms of patients with subcortical neurodegenerative disorders, (B) compare the effects of these different combinations (sequential, dual tasking, synergical) on symptoms, and (C) recommend approaches for further studies.<br><br>METHODS: We conducted literature searches of PubMed, BASE and ACM, to carry out a systematic review of randomized controlled trials and controlled trials of combined physical and cognitive training among patients with Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, Lewy body dementia, spinocerebellar ataxia, Friedreich's ataxia, and progressive supranuclear palsy. Physical, neuropsychological, behavioral outcomes were considered. The Cochrane risk-of-bias tool was used to verify the critical appraisal.<br><br>RESULTS: Twenty-one studies focused on Parkinson's disease with 940 participants were included. Despites promising benefits on cognitive and physical function, our results revealed discrepant findings for research on combined training.<br><br>DISCUSSION: Inconsistencies were linked to the choice of tests, the functions that were targeted, disease progression, and trainings. There was a dearth of follow-up data.<br><br>CONCLUSIONS: Differences between combined training are unclear, particularly regarding the role of cognitive load. Future studies should focus on comparing the feasibility, tolerability, and effectiveness of different combinations of motor-cognitive training.}, }
@article {pmid39424561, year = {2024}, author = {Crow, YJ}, title = {CNS disease associated with enhanced type I interferon signalling.}, journal = {The Lancet. Neurology}, volume = {23}, number = {11}, pages = {1158-1168}, pmid = {39424561}, issn = {1474-4465}, support = {786142/ERC_/European Research Council/International ; MC_UU_00035/11/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *Interferon Type I/metabolism/immunology ; *Signal Transduction ; Animals ; Central Nervous System Diseases/immunology/metabolism ; }, abstract = {The ability to mount an interferon-mediated innate immune response is essential in protection against neurotropic viruses, but antiviral type I interferons also have neurotoxic potential. The production of type I interferons can be triggered by self-derived nucleic acids, and the brain can be susceptible to inappropriate upregulation of type I interferon signalling. Homoeostatic dysregulation of type I interferons has been implicated in rare inborn errors of immunity (referred to as type I interferonopathies) and more common neurodegenerative disorders (eg, Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis). Recent developments include new insights into the pathogenesis of these disorders that involve dysregulated type I interferon signalling, as well as advances in their diagnosis and management. The role of type I interferons in brain cellular health suggests the future therapeutic potential of approaches that target these interferons and their signalling.}, }
@article {pmid39423873, year = {2024}, author = {Thapa, R and Moglad, E and Afzal, M and Gupta, G and Bhat, AA and Hassan Almalki, W and Kazmi, I and Alzarea, SI and Pant, K and Singh, TG and Singh, SK and Ali, H}, title = {The role of sirtuin 1 in ageing and neurodegenerative disease: A molecular perspective.}, journal = {Ageing research reviews}, volume = {102}, number = {}, pages = {102545}, doi = {10.1016/j.arr.2024.102545}, pmid = {39423873}, issn = {1872-9649}, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Sirtuin 1/metabolism ; *Aging/metabolism/genetics ; Animals ; Oxidative Stress/physiology ; }, abstract = {Sirtuin 1 (SIRT1), an NAD+-dependent deacetylase, has emerged as a key regulator of cellular processes linked to ageing and neurodegeneration. SIRT1 modulates various signalling pathways, including those involved in autophagy, oxidative stress, and mitochondrial function, which are critical in the pathogenesis of neurodegenerative diseases. This review explores the therapeutic potential of SIRT1 in several neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic Lateral Sclerosis (ALS). Preclinical studies have demonstrated that SIRT1 activators, such as resveratrol, SRT1720, and SRT2104, can alleviate disease symptoms by reducing oxidative stress, enhancing autophagic flux, and promoting neuronal survival. Ongoing clinical trials are evaluating the efficacy of these SIRT1 activators, providing hope for future therapeutic strategies targeting SIRT1 in neurodegenerative diseases. This review explores the role of SIRT1 in ageing and neurodegenerative diseases, with a particular focus on its molecular mechanisms, therapeutic potential, and clinical applications.}, }
@article {pmid39422938, year = {2024}, author = {Pappolla, MA and Wu, P and Fang, X and Poeggeler, B and Sambamurti, K and Wisniewski, T and Perry, G}, title = {Stem Cell Interventions in Neurology: From Bench to Bedside.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {101}, number = {s1}, pages = {S395-S416}, doi = {10.3233/JAD-230897}, pmid = {39422938}, issn = {1875-8908}, mesh = {Humans ; Animals ; *Stem Cell Transplantation/methods/trends ; Nervous System Diseases/therapy ; Neurology/trends/methods ; Translational Research, Biomedical/trends ; Neural Stem Cells/transplantation ; }, abstract = {Stem cell therapies are progressively redefining the treatment landscape for a spectrum of neurological and age-related disorders. This review discusses the molecular and functional attributes of stem cells, emphasizing the roles of neural stem cells and mesenchymal stem cells in the context of neurological diseases such as stroke, multiple sclerosis, amyotrophic lateral sclerosis, traumatic brain injury, Parkinson's disease, and Alzheimer's disease. The review also explores the potential of stem cells in addressing the aging process. The paper analyzes stem cells' intrinsic properties of self-renewal, differentiation, and paracrine effects, alongside the importance of laboratory-modified stem cells like induced pluripotent stem cells and transgenic stem cells. Insights into disease-specific stem cell treatments are offered, reviewing both successes and challenges in the field. This includes the translational difficulties from rodent studies to human trials. The review concludes by acknowledging the uncharted territories that warrant further investigation, emphasizing the potential roles of stem cell-derived exosomes and indole-related molecules, and aiming at providing a basic understanding of stem cell therapies.}, }
@article {pmid39418491, year = {2025}, author = {Kumar, R and Ghai, S and Finelli, A and Klotz, L and Kinnaird, A and Mannas, M and Bhindi, B and Sanchez-Salas, R and Anidjar, M and Ahmad, A and Chin, J and Inman, B and Perlis, N}, title = {The use of focal therapy for the treatment of prostate cancer in Canada Where are we, how did we get here, and where are we going?.}, journal = {Canadian Urological Association journal = Journal de l'Association des urologues du Canada}, volume = {19}, number = {2}, pages = {63-72}, pmid = {39418491}, issn = {1911-6470}, abstract = {INTRODUCTION: Focal therapy is an emerging treatment for localized prostate cancer (PCa). The objectives of this review were to: 1) review how focal therapies are regulated and approved; 2) summarize the scope and quality of the literature regarding safety, efficacy, and side-effects; and 3) outline ongoing clinical trials of focal therapy in Canada.<br><br>METHODS: Using the PRISMA framework for scoping reviews, we searched PubMed, Embase, and Cochrane from 2021-2024, complementing Hopstaken et al's search up to 2020. We focused on studies reporting functional and oncologic outcomes. Additionally, we examined the FDA database for regulatory details and ongoing trials in Canada via ClinicalTrials.gov.<br><br>RESULTS: FDA approval for prostate tissue ablation was granted to high-intensity focused ultrasound (HIFU) in 2015 via the de novo pathway; other therapies followed the 510(k) route, citing equivalence to predicate devices. Most studies are in early stages, primarily single-arm, prospective cohort designs. Oncologic outcomes like cancer detection and survival rates, alongside functional data, such as adverse events and erectile function, were assessed. Recurrence-free survival at 48 months ranged from 58-92%, pad-free rates were greater than 95%, and rates of new-onset erectile dysfunction were variable, ranging from no change to 50%. Rates of serious adverse events were low, ranging from 0-14%. Three Canadian clinical trials are actively enrolling participants, and five private clinics were found offering private HIFU, irreversible electroporation, or transurethral ultrasound ablation.<br><br>CONCLUSIONS: Focal therapy technologies have gained regulatory approval for prostate tissue ablation, and aside from provincial support for cryoablation in Alberta, are available to Canadians through private payment or clinical trials. Many studies demonstrate promising cancer control and impressive functional outcomes but are limited by their short followup and lack of comparator group. Clinical trial or registry participation should be prioritized to ensure an evidence-based integration into current prostate cancer treatment approaches.}, }
@article {pmid39405005, year = {2024}, author = {Cheng, JL and Cook, AL and Talbot, J and Perry, S}, title = {How is Excitotoxicity Being Modelled in iPSC-Derived Neurons?.}, journal = {Neurotoxicity research}, volume = {42}, number = {5}, pages = {43}, pmid = {39405005}, issn = {1476-3524}, mesh = {*Induced Pluripotent Stem Cells/drug effects/physiology ; Humans ; *Neurons/drug effects/metabolism ; Animals ; *Amyotrophic Lateral Sclerosis/pathology/metabolism ; Cell Differentiation/drug effects/physiology ; }, abstract = {Excitotoxicity linked either to environmental causes (pesticide and cyanotoxin exposure), excitatory neurotransmitter imbalance, or to intrinsic neuronal hyperexcitability, is a pathological mechanism central to neurodegeneration in amyotrophic lateral sclerosis (ALS). Investigation of excitotoxic mechanisms using in vitro and in vivo animal models has been central to understanding ALS mechanisms of disease. In particular, advances in induced pluripotent stem cell (iPSC) technologies now provide human cell-based models that are readily amenable to environmental and network-based excitotoxic manipulations. The cell-type specific differentiation of iPSC, combined with approaches to modelling excitotoxicity that include editing of disease-associated gene variants, chemogenetics, and environmental risk-associated exposures make iPSC primed to examine gene-environment interactions and disease-associated excitotoxic mechanisms. Critical to this is knowledge of which neurotransmitter receptor subunits are expressed by iPSC-derived neuronal cultures being studied, how their activity responds to antagonists and agonists of these receptors, and how to interpret data derived from multi-parameter electrophysiological recordings. This review explores how iPSC-based studies have contributed to our understanding of ALS-linked excitotoxicity and highlights novel approaches to inducing excitotoxicity in iPSC-derived neurons to further our understanding of its pathological pathways.}, }
@article {pmid39402501, year = {2024}, author = {Madzimbe, P and Maart, S and Corten, L and Dambi, J}, title = {Participation of fathers and siblings in home rehabilitation programmes for children with neuro-developmental delay: a scoping review.}, journal = {BMC pediatrics}, volume = {24}, number = {1}, pages = {659}, pmid = {39402501}, issn = {1471-2431}, mesh = {Humans ; Child ; *Fathers/psychology ; *Developmental Disabilities/rehabilitation ; *Siblings/psychology ; Caregivers/psychology ; Home Care Services ; }, abstract = {BACKGROUND: The role of, and impact on, mothers caring for children with neuro-developmental delay (NDD) is well documented. However, the role of fathers and siblings in families of children with NDD remains significantly understudied, particularly in low- and middle-income countries (LMICs). There has been an increased call for holistic rehabilitation of children with NDD at the family level. This study aimed to explore the involvement of fathers and siblings in the home rehabilitation programmes of children with NDD.<br><br>METHODS: A scoping review was conducted using the Joanna Briggs Institute (JBI) Peters et al.'s methodology and reported according to Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. Articles were retrieved from PUBMED, ScienceDirect, PsycINFO, SCOPUS, PEDro, and Google Scholar. Reference lists of relevant studies were also manually searched.<br><br>RESULTS: Thirty research articles were identified. Father and sibling participation in home-based rehabilitation and caregiving is low in LMICs compared to high-income countries due to economic factors and cultural beliefs. Reduced participation stresses mothers and reduces developmental outcomes in children with NDD.<br><br>CONCLUSIONS: This review highlights the need for rehabilitation professionals to encourage father and sibling participation in caregiving for children with NDD in home rehabilitation programmes.}, }
@article {pmid39402174, year = {2025}, author = {Jellinger, KA}, title = {The spectrum of behavioral disorders in amyotrophic lateral sclerosis: current view.}, journal = {Journal of neural transmission (Vienna, Austria : 1996)}, volume = {132}, number = {2}, pages = {217-236}, pmid = {39402174}, issn = {1435-1463}, support = {Society for the Promotion of Research in Experimental Neurology, Vienna, Austria//Society for the Promotion of Research in Experimental Neurology, Vienna, Austria/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/physiopathology/pathology/psychology ; *Mental Disorders/etiology/physiopathology ; *Brain/physiopathology/pathology ; }, abstract = {Behavioral disorders, with an average prevalence of 30-60% are important non-motor symptoms in amyotrophic lateral sclerosis (ALS) that have a negative impact on prognosis, management and quality of life, yet the underlying neurobiology is poorly understood. Among people with ALS, apathy, fatigue, anxiety, irritability and other behavioral symptoms are the most prominent, although less frequent than cognitive impairment. The present review explores the current understanding of behavioral changes in ALS with particular emphasis on our current knowledge about their structural and functional brain correlates, substantiating a multisystem degeneration with particular dysfunction of frontal-subcortical circuits and dysfunction of fronto-striatal, frontotemporal and other essential brain systems. The natural history of behavioral dysfunctions in ALS and their relationship to frontotemporal lobe degeneration (FTLD) are not fully understood, although they form a clinical continuum, suggesting a differential vulnerability of non-motor brain networks, ALS being considered a brain network disorder. An assessment of risks or the early detection of brain connectivity signatures before structural changes may be helpful in investigating the pathophysiological mechanisms of behavioral impairment in ALS. Treatment of both ALS and co-morbid behavioral disorders is a multidisciplinary task, but whereas no causal or disease-modifying therapies for ALS are available, symptomatic treatment of a variety of behavioral symptoms plays a pivotal role in patient care, although the management of behavioral symptoms in clinical care still remains limited.}, }
@article {pmid39396709, year = {2024}, author = {Wu, J and Wu, J and Chen, T and Cai, J and Ren, R}, title = {Protein aggregation and its affecting mechanisms in neurodegenerative diseases.}, journal = {Neurochemistry international}, volume = {180}, number = {}, pages = {105880}, doi = {10.1016/j.neuint.2024.105880}, pmid = {39396709}, issn = {1872-9754}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/pathology ; Animals ; Protein Aggregation, Pathological/metabolism ; alpha-Synuclein/metabolism ; Amyloid beta-Peptides/metabolism ; Protein Aggregates/physiology ; tau Proteins/metabolism ; }, abstract = {Protein aggregation serves as a critical pathological marker in a spectrum of neurodegenerative diseases (NDs), including the formation of amyloid β (Aβ) and Tau neurofibrillary tangles in Alzheimer's disease, as well as α-Synuclein (α-Syn) aggregates in Parkinson's disease, Parkinson's disease-related dementia (PDD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). A significant proportion of patients with amyotrophic lateral sclerosis (ALS) exhibit TDP-43 aggregates. Moreover, a confluence of brain protein pathologies, such as Aβ, Tau, α-Syn, and TDP-43, has been identified in individual NDs cases, highlighting the intricate interplay among these proteins that is garnering heightened scrutiny. Importantly, protein aggregation is modulated by an array of factors, with burgeoning evidence suggesting that it frequently results from perturbations in protein homeostasis, influenced by the cellular membrane milieu, metal ion concentrations, post-translational modifications, and genetic mutations. This review delves into the pathological underpinnings of protein aggregation across various NDs and elucidates the intercommunication among disparate proteins within the same disease context. Additionally, we examine the pathogenic mechanisms by which diverse factors impinge upon protein aggregation, offering fresh perspectives for the future therapeutic intervention of NDs.}, }
@article {pmid39395841, year = {2024}, author = {Tran, M and Rhee, J and Hu, W and Magin, P and Shulruf, B}, title = {General practice trainee, supervisor and educator perspectives on the transitions in postgraduate training: a scoping review.}, journal = {Family medicine and community health}, volume = {12}, number = {4}, pages = {}, pmid = {39395841}, issn = {2009-8774}, mesh = {Humans ; *General Practice/education ; Education, Medical, Graduate ; General Practitioners/education ; Students, Medical/psychology ; }, abstract = {UNLABELLED: Transitions are a period and a process, through which there is a longitudinal adaptation in response to changing circumstances in clinical practice and responsibilities. While the experience of the transition in medical student learning and in hospital-based specialty training programmes are well described and researched, the experience of the transition in community-based postgraduate general practitioner (GP) training has not been described comprehensively.<br><br>OBJECTIVE: We aimed to identify, and categorise, the formative experiences of transitions in GP training and their impacts on personal and professional development.<br><br>DESIGN: We adopted Levac et al's scoping review methodology. Of 1543 retrieved records, 76 were selected for data extraction. Based on a combined model of the socioecological and multiple and multi-dimensional theories of transitions, data relating to the experiences of transitions were organised into contextual themes: being physical, psychosocial, organisational culture and chronological.<br><br>ELIGIBILITY CRITERIA: Empirical studies focused on general practice trainees or training, that discussed the transitions experienced in general practice training and that were published in English were included.<br><br>INFORMATION SOURCES: PubMed, MEDLINE and Web of Science databases were searched in January 2024 with no date limits for empirical studies on the transition experiences of GP into, and through, training.<br><br>RESULTS: Our findings describe context-dependent formative experiences which advance, or impede, learning and development. Time is a significant modulator of the factors contributing to more negative experiences, with some initially adverse experiences becoming more positive. Identification of the inflection point that represents a shift from initially adverse to more positive experiences of transitions may help moderate expectations for learning and performance at different stages of training.<br><br>CONCLUSION: Challenges in training can either advance development and contribute positively to professional identity formation and clinical competency, or detract from learning and potentially contribute to burnout and attrition from training programmes. These findings will assist future research in identifying predictive factors of positive and adverse experiences of transitions and may strengthen existing and nascent GP training programmes. The findings are transferable to other community-based specialty training programmes.}, }
@article {pmid39395475, year = {2024}, author = {Kim, SY and Kim, M and Park, K and Hong, S}, title = {A systematic review on analytical methods of the neurotoxin β-N-methylamino-L-alanine (BMAA), and its causative microalgae and distribution in the environment.}, journal = {Chemosphere}, volume = {366}, number = {}, pages = {143487}, doi = {10.1016/j.chemosphere.2024.143487}, pmid = {39395475}, issn = {1879-1298}, mesh = {*Amino Acids, Diamino/analysis ; *Microalgae/metabolism ; *Cyanobacteria Toxins ; *Neurotoxins/analysis ; *Cyanobacteria/metabolism ; *Tandem Mass Spectrometry ; *Environmental Monitoring/methods ; Ecosystem ; Chromatography, Liquid ; Diatoms/metabolism ; Water Pollutants, Chemical/analysis/metabolism ; }, abstract = {β-N-Methylamino-L-alanine (BMAA), a neurotoxin produced by various microalgal groups, is associated with neurodegenerative diseases and is considered a major environmental factor potentially linked to sporadic amyotrophic lateral sclerosis. This study systematically reviews the analytical methods used to study BMAA in publications from 2019 to the present. It also investigates the causative microalgae of BMAA and its geographical distributions in aquatic ecosystems based on studies conducted since 2003. A comprehensive search using the Web of Science database revealed that hydrolysis for extraction (67%), followed by quantification using LC-MS/MS (LC: 84%; MS/MS: 88%), is the most commonly employed method in BMAA analysis. Among analytical methods, RPLC-MS/MS had the highest percentage (88%) of BMAA-positive results and included a high number of quality control (QC) assessments. Various genera of cyanobacteria and diatoms have been reported to produce BMAA. The widespread geographical distribution of BMAA across diverse ecosystems highlights significant environmental and public health concerns. Notably, BMAA accumulation and biomagnification are likely more potent in marine or brackish water ecosystems than in freshwater ecosystems, potentially amplifying its ecological impacts. Future research should prioritize advanced, sensitive methods, particularly LC-MS/MS with as many QC assessments as possible, and should expand investigations to identify novel microalgal producers and previously uncharted geographical areas, with a special focus on marine or brackish water ecosystems. This effort will enhance our understanding of the environmental distribution and impacts of BMAA.}, }
@article {pmid39393594, year = {2024}, author = {Coppieters, R and Bouzigues, A and Jiskoot, L and Montembeault, M and Tee, BL and ,  and Rohrer, JD and Bruffaerts, R}, title = {A systematic review of the quantitative markers of speech and language of the frontotemporal degeneration spectrum and their potential for cross-linguistic implementation.}, journal = {Neuroscience and biobehavioral reviews}, volume = {167}, number = {}, pages = {105909}, doi = {10.1016/j.neubiorev.2024.105909}, pmid = {39393594}, issn = {1873-7528}, mesh = {Humans ; *Frontotemporal Dementia/physiopathology/diagnosis ; *Speech/physiology ; Linguistics ; Language ; Biomarkers ; }, abstract = {Frontotemporal dementia (FTD) is a neurodegenerative disease spectrum with an urgent need for reliable biomarkers for early diagnosis and monitoring. Speech and language changes occur in the early stages of FTD and offer a potential non-invasive, early, and accessible diagnostic tool. The use of speech and language markers in this disease spectrum is limited by the fact that most studies investigate English-speaking patients. This systematic review examines the literature on psychoacoustic and linguistic features of speech that occur across the FTD spectrum across as many different languages as possible. 76 papers were identified that investigate psychoacoustic and linguistic markers in discursive speech. 75 % of these papers studied English-speaking patients. The most generalizable features found across different languages, are speech rate, articulation rate, pause frequency, total pause duration, noun-verb ratio, and total number of nouns. While there are clear interlinguistic differences across patient groups, the results show promise for implementation of cross-linguistic markers of speech and language across the FTD spectrum particularly for psychoacoustic features.}, }
@article {pmid39391178, year = {2024}, author = {Morris, C and Donovan, MT and Switzer, EJ}, title = {The Scope of Practice of Applied Behavior Analysis in State Licensure Laws.}, journal = {Behavior analysis in practice}, volume = {17}, number = {3}, pages = {773-782}, pmid = {39391178}, issn = {1998-1929}, abstract = {The scope of applied behavior analysis has historically been defined by behavior analytic publications like Baer et al., Journal of Applied Behavior Analysis, 1, 91, (1968). However, starting in 2009, state legislators began creating licensure laws for behavior analysts that formalized the scope of practice for applied behavior analysis (ABA) within the applicable states. The purpose of this study was twofold: (1) to evaluate the degree scope of practice statements found in state licensure laws aligned with the individual components of Baer et al.'s seven dimensions of ABA and the APBA Model Act and (2) to evaluate the consistency of the scope of practice statements across states. Each licensed state law was identified, and the section that outlined the scope of practice was isolated and coded. The results of this study identified varying degrees of alignment with the individual components of Baer et al.'s seven dimensions and the APBA Model Act, as well as inconsistencies in the scope of practice among states with licensure for ABA. The component scores of each content area will be discussed, along with the implications for practice.}, }
@article {pmid39390661, year = {2024}, author = {Howard, IM and Babu, S and Carter, C and Sakowski, SA and Kurent, JE and Cudkowicz, ME and Feldman, EL}, title = {Priorities and Recommendations to Make ALS a Livable Disease Emanating from the 2024 National Academies of Sciences, Engineering, and Medicine Report Living with ALS.}, journal = {Annals of neurology}, volume = {96}, number = {6}, pages = {1035-1039}, pmid = {39390661}, issn = {1531-8249}, support = {R01 TS000327/TS/ATSDR CDC HHS/United States ; OT2 NS136938/NS/NINDS NIH HHS/United States ; U01 NS077179/NS/NINDS NIH HHS/United States ; U01 NS136020/NS/NINDS NIH HHS/United States ; //Charles H. Abdalian, Jr. ALS Research Fund/ ; OT2 NS136939/NS/NINDS NIH HHS/United States ; //NeuroNetwork for Emerging Therapies/ ; R01 ES030049/ES/NIEHS NIH HHS/United States ; R01TS000344//Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry/ ; //American Academy of Neurology/ ; //ALS One/ ; //ALS Association/ ; UF1 NS131791/NS/NINDS NIH HHS/United States ; R01TS000327//Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry/ ; 1U01NS136021-01/NH/NIH HHS/United States ; 1U01NS136020-01/NH/NIH HHS/United States ; R01NS127188/NH/NIH HHS/United States ; R01ES030049/NH/NIH HHS/United States ; //Scott L. Pranger/ ; //The Sean M. Healey &amp; AMG Center for ALS/ ; 1U01NS077179-01/NH/NIH HHS/United States ; //Muscular Dystrophy Association/ ; U01 NS136021/NS/NINDS NIH HHS/United States ; R01 NS127188/NS/NINDS NIH HHS/United States ; //The Neurological Clinical Research Institute/ ; UF1NS131791-01/NH/NIH HHS/United States ; 1OT2NS136938-1/NH/NIH HHS/United States ; R01 TS000344/TS/ATSDR CDC HHS/United States ; //ALS Finding a Cure/ ; OT2NS136939/NH/NIH HHS/United States ; }, mesh = {*Amyotrophic Lateral Sclerosis/therapy/diagnosis ; Humans ; United States ; Quality of Life ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a relentless, fatal neurodegenerative disease. The progressive loss of voluntary muscle function, diagnostic delays, lack of effective treatments, and challenges accessing multidisciplinary care and resources have tremendous impact on quality of life. The congressionally directed ALS committee of the National Academies of Science, Engineering, and Medicine, in their 2024 report "Living with ALS," recommends critical actions for specific United States stakeholders to make ALS a livable disease over the next decade. This review summarizes the context and recommendations of the report. Advocacy efforts are critical to make these recommendations a reality for the ALS community. ANN NEUROL 2024;96:1035-1039.}, }
@article {pmid39381815, year = {2024}, author = {Vaismoradi, M and Rae, J and Turunen, H and Logan, PA}, title = {Specialized nurses' role in ensuring patient safety within the context of telehealth in home care: A scoping review.}, journal = {Digital health}, volume = {10}, number = {}, pages = {20552076241287272}, pmid = {39381815}, issn = {2055-2076}, abstract = {OBJECTIVES: Specialized nurses are uniquely positioned to implement innovative telehealth solutions to improve the quality and safety of home care, and this has become a focal point of contemporary healthcare research. This review aimed to identify the nature and scope of specialized nurses' roles in ensuring patient safety within the context of telehealth in home care.<br><br>METHODS: A scoping review of the international literature was carried out from January 1, 2013, to August 29, 2024. The review employed Levac et al.'s framework to delineate the research phenomenon and consolidate existing empirical research findings. Through a comparative analysis, the review integrated findings from selected studies, highlighting both similarities and differences related to this phenomenon, which led to the development of distinct categories.<br><br>RESULTS: The search yielded 1127 articles, from which 23 studies met the inclusion criteria for research synthesis and subsequent reporting of results. These studies spanned specialized nurses' roles in telehealth and various fields in which specialized nurses utilized telehealth to deliver high-quality and safe home care. The findings highlighted key outcomes linked to the improvement of patient safety in home care encompassing continuity of care, confidence in care, monitoring and early intervention, medication safety, engagement and adherence, and healthcare costs.<br><br>CONCLUSIONS: The review revealed the crucial role played by specialized nurses in harnessing telehealth in healthcare to meet the highest care standards, creating an environment that prioritizes the well-being and patient safety in home care.}, }
@article {pmid39377567, year = {2025}, author = {Rani, P and Rajak, BK and Mahato, GK and Rathore, RS and Chandra, G and Singh, DV}, title = {Strategic lead compound design and development utilizing computer-aided drug discovery (CADD) to address herbicide-resistant Phalaris minor in wheat fields.}, journal = {Pest management science}, volume = {81}, number = {5}, pages = {2469-2479}, doi = {10.1002/ps.8455}, pmid = {39377567}, issn = {1526-4998}, support = {//Science and Engineering Research Board, India/ ; //Department of Biotechnology, Ministry of Science and Technology, India/ ; //Department of Science and Technology, Ministry of Science and Technology, India/ ; }, mesh = {*Herbicide Resistance ; *Herbicides/pharmacology/chemistry ; *Triticum/growth &amp; development ; *Drug Discovery/methods ; *Weed Control/methods ; *Phalaris/drug effects ; *Drug Design ; Plant Weeds/drug effects ; Computer-Aided Design ; Molecular Docking Simulation ; }, abstract = {Wheat (Triticum aestivum) is a vital cereal crop and a staple food source worldwide. However, wheat grain productivity has significantly declined as a consequence of infestations by Phalaris minor. Traditional weed control methods have proven inadequate owing to the physiological similarities between P. minor and wheat during early growth stages. Consequently, farmers have turned to herbicides, targeting acetyl-CoA carboxylase (ACCase), acetolactate synthase (ALS) and photosystem II (PSII). Isoproturon targeting PSII was introduced in mid-1970s, to manage P. minor infestations. Despite their effectiveness, the repetitive use of these herbicides has led to the development of herbicide-resistant P. minor biotypes, posing a significant challenge to wheat productivity. To address this issue, there is a pressing need for innovative weed management strategies and the discovery of novel herbicide molecules. The integration of computer-aided drug discovery (CADD) techniques has emerged as a promising approach in herbicide research, that facilitates the identification of herbicide targets and enables the screening of large chemical libraries for potential herbicide-like molecules. By employing techniques such as homology modelling, molecular docking, molecular dynamics simulation and pharmacophore modelling, CADD has become a rapid and cost-effective medium to accelerate the herbicide discovery process significantly. This approach not only reduces the dependency on traditional experimental methods, but also enhances the precision and efficacy of herbicide development. This article underscores the critical role of bioinformatics and CADD in developing next-generation herbicides, offering new hope for sustainable weed management and improved wheat cultivation practices. © 2024 Society of Chemical Industry.}, }
@article {pmid39374680, year = {2024}, author = {Tirassa, P and Rosso, P and Fico, E and Marenco, M and Mallone, F and Gharbiya, M and Lambiase, A and Severini, C}, title = {Perspective role of Substance P in Amyotrophic Lateral Sclerosis: From neuronal vulnerability to neuroprotection.}, journal = {Neuroscience and biobehavioral reviews}, volume = {167}, number = {}, pages = {105914}, doi = {10.1016/j.neubiorev.2024.105914}, pmid = {39374680}, issn = {1873-7528}, mesh = {*Substance P/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism/physiopathology ; Humans ; Animals ; Receptors, Neurokinin-1/metabolism ; Neuroprotection/physiology ; Motor Neurons/metabolism/physiology ; }, abstract = {The neuropeptide Substance P (SP) and its preferred Neurokinin1 Receptor (NK1R) are known to participate in the physiopathology of neurodegenerative diseases and mainly exert a neuroprotective role. In the present work, we have described the involvement of SP and NK1R in Amyotrophic Lateral Sclerosis (ALS). This was demonstrated by the detection of altered levels of SP in the brain, spinal cord and cerebrospinal fluid (CSF) of patients and preclinical models of ALS, and by its ability to inhibit excitotoxicity-induced neurodegeneration in ALS animal models. These data are supported by results indicating an excitatory effect of SP at the motor neuron (MN) level, which promotes locomotor activity. ALS patients are characterized by a differential susceptibility to MNs degeneration, since sphincters and extraocular muscles are classically spared. It is hypothesized that SP may play a role in the maintenance of the ocular system and the innervation of the pelvic floor by contributing directly or indirectly to the selective resistance of this subset of MNs.}, }
@article {pmid39372031, year = {2024}, author = {Pillai, M and Jha, SK}, title = {Conformational Enigma of TDP-43 Misfolding in Neurodegenerative Disorders.}, journal = {ACS omega}, volume = {9}, number = {39}, pages = {40286-40297}, pmid = {39372031}, issn = {2470-1343}, abstract = {Misfolding and aggregation of the protein remain some of the most common phenomena observed in neurodegeneration. While there exist multiple neurodegenerative disorders characterized by accumulation of distinct proteins, what remains particularly interesting is the ability of these proteins to undergo a conformational change to form aggregates. TDP-43 is one such nucleic acid binding protein whose misfolding is associated with many neurogenerative diseases including amyotrophic lateral sclerosis (ALS) and fronto-temporal lobar degeneration (FTLD). TDP-43 protein assumes several different conformations and oligomeric states under the diseased condition. In this review, we explore the intrinsic relationship between the conformational variability of TDP-43 protein, with a particular focus on the RRM domains, and its propensity to undergo aggregation. We further emphasize the probable mechanism behind the formation of these conformations and suggest a potential diagnostic and therapeutic strategy in the context of these conformational states of the protein.}, }
@article {pmid39370211, year = {2024}, author = {Kajitani, GS and Xavier, G and Villena-Rueda, BE and Karia, BTR and Santoro, ML}, title = {Extracellular vesicles in neurodegenerative, mental, and other neurological disorders: Perspectives into mechanisms, biomarker potential, and therapeutic implications.}, journal = {Current topics in membranes}, volume = {94}, number = {}, pages = {299-336}, doi = {10.1016/bs.ctm.2024.06.002}, pmid = {39370211}, issn = {1063-5823}, mesh = {Humans ; *Extracellular Vesicles/metabolism ; *Neurodegenerative Diseases/metabolism/pathology/therapy ; *Biomarkers/metabolism ; Mental Disorders/metabolism/drug therapy/therapy ; Animals ; Nervous System Diseases/metabolism/pathology ; }, abstract = {Extracellular vesicles (EVs) are produced, secreted, and targeted by most human cells, including cells that compose nervous system tissues. EVs carry several types of biomolecules, such as lipids, proteins and microRNA, and can function as signaling agents in physiological and pathological processes. In this chapter, we will focus on EVs and their cargo secreted by brain cells, especially neurons and glia, and how these aspects are affected in pathological conditions. The chapter covers neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis, as well as several psychiatric disorders, namely schizophrenia, autism spectrum disorder and major depressive disorder. This chapter also addresses other types of neurological dysfunctions, epilepsy and traumatic brain injury. EVs can cross the blood brain barrier, and thus brain EVs may be detected in more accessible peripheral tissue, such as circulating blood. Alterations in EV composition and contents can therefore impart valuable clues into the molecular etiology of these disorders, and serve biomarkers regarding disease prevalence, progression and treatment. EVs can also be used to carry drugs and biomolecules into brain tissue, considered as a promising drug delivery agent for neurological diseases. Therefore, although this area of research is still in its early development, it offers great potential in further elucidating and in treating neurological disorders.}, }
@article {pmid39366522, year = {2024}, author = {Taylor, N and Boyland, E and Hardman, CA}, title = {Conceptualising food banking in the UK from drivers of use to impacts on health and wellbeing: A systematic review and directed content analysis.}, journal = {Appetite}, volume = {203}, number = {}, pages = {107699}, doi = {10.1016/j.appet.2024.107699}, pmid = {39366522}, issn = {1095-8304}, mesh = {Humans ; United Kingdom ; *Food Insecurity ; Food Assistance ; Female ; Male ; Food Supply ; }, abstract = {Food banks have become commonplace in the UK as an emergency response to food insecurity. However, food banks are not a long-term solution to food insecurity and are often not accessed by those in need. In the context of the cost-of-living crisis, and increased food insecurity, this systematic review applied market/government failure theory, voluntary failure theory, and Radimer et al.'s (1990) domains of food insecurity to explore three important aspects relevant to the food banking experience: the drivers of food bank use; the limitations of the current food bank model; and the impacts of the food banking model for food bank clients. Empirical, peer-reviewed articles written in English with a UK food bank context and reporting relevant data to these aspects were eligible for inclusion. In total, 221 titles were identified using four databases (Web of Science, SCOPUS, PubMed, CINHAL Plus) in July 2022. The final sample of 41 articles (comprising qualitative, quantitative and mixed methods studies), were quality assessed using the Mixed Methods Appraisal Tool. Data were extracted and analysed through directed content analysis. Market and government failures were widely reported to drive food bank use. Insufficiency, paternalism and particularism represented key limitations of the food bank model. Negative health and psychological impacts of food bank use were prominent, yet social impacts were largely positive. Consequently, new solutions are needed to promote positive health and psychological impacts for food bank clients in the UK. The application of these findings to other high-income countries experiencing food insecurity should be determined.}, }
@article {pmid39361871, year = {2025}, author = {Fernandes, JPM and Garcia, LP and Gouhie, FA and Pereira, RC and Santos, DFD}, title = {Association between motor neuron disease and HIV infection: A systematic review of case reports.}, journal = {International journal of STD &amp; AIDS}, volume = {36}, number = {1}, pages = {24-35}, doi = {10.1177/09564624241288283}, pmid = {39361871}, issn = {1758-1052}, mesh = {Humans ; *HIV Infections/drug therapy/complications ; *Motor Neuron Disease/complications ; Adult ; Male ; *Amyotrophic Lateral Sclerosis/drug therapy/complications ; Female ; Middle Aged ; Riluzole/therapeutic use ; }, abstract = {BACKGROUND: Motor neuron disease (MND) is a well-known group of neurodegenerative diseases, with amyotrophic lateral sclerosis (ALS) being the most common form. Since 1985, a possible association between MND/ALS and HIV infection has been described.<br><br>METHODS: We performed a systematic review of case reports and case series involving people living with HIV with MND/ALS through PubMed, Bireme, Embase, and Lilacs databases. The risk of bias was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Tool for Case Reports.<br><br>RESULTS: We analyzed 36 articles presenting 88 cases. The mean age was 41.6&#xa0;years. Antiretroviral therapy (ART) was used by 89.8% and riluzole by 16.9%. First signs and symptoms were similarly present on cervical/upper (25%) and lumbosacral/lower limbs (23.9%), mostly with fasciculations (69.8%) and hyperreflexia (58.8%). MND had a progressive course in 32.9% patients and a clinical improve in 54.6% following ART. The mean survival of the 32 patients who died was 12.3&#xa0;months and the mean survival of the living patients was 62&#xa0;months. Respiratory failure was the main cause of death (35.7%).<br><br>CONCLUSIONS: MND/ALS may present differently in the people living with HIV as a rapidly progressive disease in younger people but with the potential to improve weakness and survival through antiretroviral therapy.}, }
@article {pmid39356431, year = {2024}, author = {Shin, J and Gibson, JS and Jones, RA and Debnam, KJ}, title = {Factors associated with anxiety in colorectal cancer survivors: a scoping review.}, journal = {Journal of cancer survivorship : research and practice}, volume = {}, number = {}, pages = {}, pmid = {39356431}, issn = {1932-2267}, abstract = {PURPOSE: Anxiety is one of the most common psychological issues among colorectal cancer (CRC) survivors. It can interact with physical symptoms, impacting cancer progression, survival, and quality of life. This scoping review aims to explore the factors associated with anxiety in patients with CRC and the instruments used to measure anxiety.<br><br>METHODS: Using Arksey and O'Malley's (2005) framework for the scoping review, studies investigating anxiety in CRC patients published in CINAHL, PubMed, PsycINFO, and Scopus between 2013 and 2024 were included.<br><br>RESULTS: We analyzed fifty-one studies for this review. The review identified several risk factors and consequences of anxiety in CRC patients. The risk factors were classified into six domains using Niedzwiedz et al.'s (2019) framework: individual characteristics, social/ contextual factors, prior psychological factors, psychological responses to diagnosis and treatment, characteristics of cancer, and treatment. The consequences of anxiety were classified into three categories: global health status/quality of life, functions, and symptoms/problems. The most frequently used tool was the Hospital Anxiety and Depression Scale, with International Classification of Diseases codes being the second most used.<br><br>CONCLUSIONS: This scoping review highlighted the intricate interaction between biological and psychosocial aspects in the lives of CRC survivors. It also identified unique factors associated with anxiety among these individuals. However, the review found some inconsistencies in the results related to anxiety-related factors, potentially due to differences in study populations, designs, measurement tools, and analysis methods.<br><br>This review underscores the potential for interventions targeting modifiable factors to prevent or reduce anxiety and enhance the quality of life for CRC survivors.}, }
@article {pmid39355247, year = {2024}, author = {Yang, JL and Wu, JY and Liu, JJ and Zheng, GQ}, title = {Herbal medicines for SOD1[G93A] mice of amyotrophic lateral sclerosis: preclinical evidence and possible immunologic mechanism.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1433929}, pmid = {39355247}, issn = {1664-3224}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/immunology/genetics ; Animals ; Mice ; *Disease Models, Animal ; Mice, Transgenic ; Humans ; Superoxide Dismutase-1/genetics ; Herbal Medicine ; }, abstract = {Currently, there is no cure or effective treatment for Amyotrophic Lateral Sclerosis (ALS). The mechanisms underlying ALS remain unclear, with immunological factors potentially playing a significant role. Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA), a systematic review of preclinical studies was conducted, searching seven databases including PubMed, covering literature from the inception of the databases to April 10, 2024. Methodological quality of the included literature was assessed using CAMARADES, while the risk of bias in the included studies was evaluated using SYRCLE's ROB tool. Review Manager 5.4.1 statistical software was used for meta-analysis of the outcomes. The scoping review followed the Joanna Briggs Institute Methodological Guidelines and reporting of this review followed the PRISMA-extension for Scoping Reviews (PRISMA -ScR) checklist to explore the immunological mechanisms of Herbal Medicine (HM) in treating ALS. This systematic review and meta-analysis involved 18 studies with a total of 443 animals. The studies scored between 4 to 8 for methodological quality and 3 to 7 for risk of bias, both summing up to 10.A remarkable effects of HM in ALS mice, including onset time(Standardized Mean Difference(SMD): 1.75, 95% Confidence Interval(CI) (1.14 ~ 2.36), Z = 5.60, P < 0.01), survival time(SMD = 1.42, 95% CI (0.79 ~ 2.04), Z = 4.44, P < 0.01), stride length(SMD=1.90, 95% CI (1.21 to 2.59), Z = 5.39, P < 0.01) and duration time (Mean Difference(MD)=6.79, 95% CI [-0.28, 13.87], Z=1.88, P =0.06), showing HM's certain efficiency in treating ALS mice. The scoping review ultimately included 35 articles for review. HMs may treat ALS through mechanisms such as combating oxidative stress, excitatory amino acid toxicity, and calcium cytotoxicity, understanding and exploring the mechanisms will bring hope to patients. Individual herbs and their formulations within HM address ALS through a variety of immune pathways, including safeguarding the blood-brain barrier, countering neuroinflammation, impeding complement system activation, mitigating natural killer cell toxicity, and regulating T cell-mediated immune pathways. The preclinical evidence supports the utilization of HM as a conventional treatment for ALS mice. Growing evidence indicates that HM may potentially delay neurological degeneration in ALS by activating diverse signaling pathways, especially immune pathways.}, }
@article {pmid39350404, year = {2025}, author = {Mohan, M and Mannan, A and Kakkar, C and Singh, TG}, title = {Nrf2 and Ferroptosis: Exploring Translational Avenues for Therapeutic Approaches to Neurological Diseases.}, journal = {Current drug targets}, volume = {26}, number = {1}, pages = {33-58}, pmid = {39350404}, issn = {1873-5592}, mesh = {*Ferroptosis/physiology/drug effects ; Humans ; *NF-E2-Related Factor 2/metabolism/genetics ; Animals ; *Nervous System Diseases/metabolism/drug therapy ; Reactive Oxygen Species/metabolism ; Oxidative Stress ; Iron/metabolism ; }, abstract = {Nrf2, a crucial protein involved in defense mechanisms, particularly oxidative stress, plays a significant role in neurological diseases (NDs) by reducing oxidative stress and inflammation. NDs, including Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis, stroke, epilepsy, schizophrenia, depression, and autism, exhibit ferroptosis, iron-dependent regulated cell death resulting from lipid and iron-dependent reactive oxygen species (ROS) accumulation. Nrf2 has been shown to play a critical role in regulating ferroptosis in NDs. Age-related decline in Nrf2 expression and its target genes (HO-1, Nqo-1, and Trx) coincides with increased iron-mediated cell death, leading to ND onset. The modulation of iron-dependent cell death and ferroptosis by Nrf2 through various cellular and molecular mechanisms offers a potential therapeutic pathway for understanding the pathological processes underlying these NDs. This review emphasizes the mechanistic role of Nrf2 and ferroptosis in multiple NDs, providing valuable insights for future research and therapeutic approaches.}, }
@article {pmid39347334, year = {2024}, author = {Aljehani, NS and Al-Gunaid, ST and Hobani, AH and Alhinti, MF and Khubrani, YA and Abu-Hamoud, LM and Alrayes, AA and Alharbi, LB and Sultan, AA and Turkistani, DA and Naiser, SS and Albraik, L and Alakel, AM and Alotaibi, M and Asiri, AY}, title = {Ultrasound Blood-Brain Barrier Opening and Aducanumab in Alzheimer's Disease: A Systematic Review and Meta-Analysis.}, journal = {Cureus}, volume = {16}, number = {8}, pages = {e68008}, pmid = {39347334}, issn = {2168-8184}, abstract = {The blood-brain barrier (BBB) presents a significant challenge in treating Alzheimer's disease, as it restricts the delivery of therapeutic medications to brain tissue. Reversible breaking of the BBB using low-intensity focused ultrasound guided by magnetic resonance imaging (MRI) may benefit patients with Alzheimer's disease and other neurological illnesses, such as brain tumors, amyotrophic lateral sclerosis, and Parkinson's disease. This systematic study and meta-analysis aimed to assess aducanumab and the ultrasonography of BBB opening in Alzheimer's patients. According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), the study was conducted by searching six digital repositories for relevant scholarly literature, focusing on English papers published between 2015 and 2024; the data was extracted using an Excel sheet, and data was analyzed using Revman 5.4.1 software. The study's findings indicate that the groups receiving ultrasound and aducanumab treatment benefited from it; however, overall, the effect was not statistically significant (P=0.29) at 95% CI 0.86 (0.75, 1.00). With regard to side effects, the results indicate that the treatment had fewer side effects compared to the control group; however, the difference was not statistically significant (p=0.94) at 95% CI 0.93 (0.70, 1.22). The study found a positive effect of ultrasound and aducanumab on the treatment groups, but it was not statistically significant. The control group had less side effects than the treatment group. Therefore, future studies should focus on the quantity or combination of the drug that yields more effective results.}, }
@article {pmid39346681, year = {2024}, author = {Fisher, RMA and Torrente, MP}, title = {Histone post-translational modification and heterochromatin alterations in neurodegeneration: revealing novel disease pathways and potential therapeutics.}, journal = {Frontiers in molecular neuroscience}, volume = {17}, number = {}, pages = {1456052}, pmid = {39346681}, issn = {1662-5099}, support = {R15 NS125394/NS/NINDS NIH HHS/United States ; }, abstract = {Alzheimer's disease (AD), Parkinson's disease (PD), Frontotemporal Dementia (FTD), and Amyotrophic lateral sclerosis (ALS) are complex and fatal neurodegenerative diseases. While current treatments for these diseases do alleviate some symptoms, there is an imperative need for novel treatments able to stop their progression. For all of these ailments, most cases occur sporadically and have no known genetic cause. Only a small percentage of patients bear known mutations which occur in a multitude of genes. Hence, it is clear that genetic factors alone do not explain disease occurrence. Chromatin, a DNA-histone complex whose basic unit is the nucleosome, is divided into euchromatin, an open form accessible to the transcriptional machinery, and heterochromatin, which is closed and transcriptionally inactive. Protruding out of the nucleosome, histone tails undergo post-translational modifications (PTMs) including methylation, acetylation, and phosphorylation which occur at specific residues and are connected to different chromatin structural states and regulate access to transcriptional machinery. Epigenetic mechanisms, including histone PTMs and changes in chromatin structure, could help explain neurodegenerative disease processes and illuminate novel treatment targets. Recent research has revealed that changes in histone PTMs and heterochromatin loss or gain are connected to neurodegeneration. Here, we review evidence for epigenetic changes occurring in AD, PD, and FTD/ALS. We focus specifically on alterations in the histone PTMs landscape, changes in the expression of histone modifying enzymes and chromatin remodelers as well as the consequences of these changes in heterochromatin structure. We also highlight the potential for epigenetic therapies in neurodegenerative disease treatment. Given their reversibility and pharmacological accessibility, epigenetic mechanisms provide a promising avenue for novel treatments. Altogether, these findings underscore the need for thorough characterization of epigenetic mechanisms and chromatin structure in neurodegeneration.}, }
@article {pmid39344228, year = {2024}, author = {Li, P and Tao, Z and Zhao, X}, title = {The Role of Osteopontin (OPN) in Regulating Microglia Phagocytosis in Nervous System Diseases.}, journal = {Journal of integrative neuroscience}, volume = {23}, number = {9}, pages = {169}, doi = {10.31083/j.jin2309169}, pmid = {39344228}, issn = {0219-6352}, mesh = {*Osteopontin/metabolism/physiology ; *Microglia/metabolism/physiology ; *Phagocytosis/physiology ; Animals ; Humans ; Nervous System Diseases/metabolism ; }, abstract = {Phagocytosis is the process by which certain cells or organelles internalise foreign substances by engulfing them and then digesting or disposing of them. Microglia are the main resident phagocytic cells in the brain. It is generally believed that microglia/macrophages play a role in guiding the brain's repair and functional recovery processes. However, the resident and invading immune cells of the central nervous system can also exacerbate tissue damage by stimulating inflammation and engulfing viable neurons. The functional consequences of microglial phagocytosis remain largely unexplored. Overall, phagocytosis is considered a beneficial phenomenon in acute brain injury because it eliminates dead cells and induces an anti-inflammatory response. Osteopontin (OPN) is a phosphorylated glycoprotein induced by injury in various tissues, including brain tissue. In acute brain injuries such as hemorrhagic stroke and ischemic stroke, OPN is generally believed to have anti-inflammatory effects. OPN can promote the reconstruction of the blood-brain barrier and up-regulate the scavenger receptor CD36. But in chronic diseases such as Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS), OPN can cause microglia to engulf neurons and worsen disease progression. We explored the role of OPN in promoting microglial phagocytosis in nervous system disorders.}, }
@article {pmid39344189, year = {2025}, author = {Khorshidi, Z and Adibi, I and Ghasemi, M}, title = {Association between cerebrospinal fluid chitotriosidase level and amyotrophic lateral sclerosis: a systematic review.}, journal = {Hormone molecular biology and clinical investigation}, volume = {46}, number = {1}, pages = {13-19}, pmid = {39344189}, issn = {1868-1891}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/cerebrospinal fluid/diagnosis ; *Hexosaminidases/cerebrospinal fluid ; Biomarkers/cerebrospinal fluid ; }, abstract = {INTRODUCTION: One of the fatal and debilitating neurodegenerative diseases is amyotrophic lateral sclerosis (ALS). Increasing age is one of the risk factors of ALS. Considering that the elderly population in the world is increasing, it is very important to identify useful and effective diagnostic and treatment methods. The purpose of this systematic review is to determine the relationship between chitotriosidase (CHIT1) level and ALS disorder.<br><br>CONTENT: Keywords "Amyotrophic Lateral Sclerosis", "Gehrig* Disease", "Charcot Disease", "Guam Disease", ALS, CHIT1 and chitotriosidase were searched in PubMed, Scopus, Web of Science and Science Direct databases without time limit on September 2023. Hundred twenty studies were obtained by searching, and finally, 14 studies were included in this study using the inclusion and exclusion criteria. In all 14 selected studies, the level of biomarker CHIT1 in the CSF of ALS patients was significantly higher than that of healthy control and disease control groups. But, in 8 studies that included 3 groups, no significant difference was observed between the CHIT1 levels in the two control groups. Six studies have reported the amount of CHIT1 level quantitatively. Among these 6 studies, in 5 studies CHIT1 level in disease control was higher than healthy control (not significant) and in only one study CHIT1 level was higher in healthy control compared to disease control (not significant).<br><br>SUMMARY AND OUTLOOK: In all 14 studies, a multifold increase in CHIT1 levels has been observed in patients compared to healthy and disease control groups. Therefore, based on the findings of the studies, this study confirms the relationship between CHIT1 increase and ALS disorder.}, }
@article {pmid39343990, year = {2024}, author = {Xia, L and Qiu, Y and Li, J and Xu, M and Dong, Z}, title = {The Potential Role of Artemisinins Against Neurodegenerative Diseases.}, journal = {The American journal of Chinese medicine}, volume = {52}, number = {6}, pages = {1641-1660}, doi = {10.1142/S0192415X24500642}, pmid = {39343990}, issn = {1793-6853}, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy ; *Artemisinins/pharmacology ; *Neuroprotective Agents/pharmacology ; Alzheimer Disease/drug therapy/metabolism ; Animals ; Oxidative Stress/drug effects ; Signal Transduction/drug effects ; Parkinson Disease/drug therapy/metabolism ; Ferroptosis/drug effects ; Amyotrophic Lateral Sclerosis/drug therapy ; Huntington Disease/drug therapy/metabolism ; Autophagy/drug effects ; }, abstract = {Artemisinin (ART) and its derivatives, collectively referred to as artemisinins (ARTs), have been approved for the treatment of malaria for decades. ARTs are converted into dihydroartemisinin (DHA), the only active form, which is reductive in vivo. In this review, we provide a brief overview of the neuroprotective potential of ARTs and the underlying mechanisms on several of the most common neurodegenerative diseases, particularly considering their potential application in those associated with cognitive and motor impairments including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). ARTs act as autophagy balancers to alleviate AD and PD. They inhibit neuroinflammatory responses by regulating phosphorylation of signal transduction proteins, such as AKT, PI3K, ERK, NF-κB, p38 MAPK, IκBα. In addition, ARTs regulate GABAergic signaling in a dose-dependent manner. Although they competitively inhibit the binding of gephyrin to GABAergic receptors, low doses of ARTs enhance GABAergic signaling. ARTs can also inhibit ferroptosis, activate the Akt/Bcl-2, AMPK, or ERK/CREB pathways to reduce oxidative stress, and maintain mitochondrial homeostasis, protecting neurons from oxidative stress injury. More importantly, ARTs structurally combine with and suppress β-Amyloid (A[Formula: see text]-induced neurotoxicity, reduce P-tau, and maintain O-GlcNAcylation/Phosphorylation balance, leading to relieved pathological changes in neurodegenerative diseases. Collectively, these natural properties endow ARTs with unique potential for application in neurodegenerative diseases.}, }
@article {pmid39343443, year = {2024}, author = {O'Brien, D and Shaw, PJ}, title = {New developments in the diagnosis and management of motor neuron disease.}, journal = {British medical bulletin}, volume = {152}, number = {1}, pages = {4-15}, doi = {10.1093/bmb/ldae010}, pmid = {39343443}, issn = {1471-8391}, support = {NIHR 203321//NIHR Sheffield Biomedical Research Centre/ ; 972-797//AMBRoSIA Biosampling Programme/ ; 764-780//MNDA (Sheffield Care and Research Centre for Motor Neuron Disorders/ ; }, mesh = {Humans ; *Motor Neuron Disease/therapy/diagnosis ; Neuroprotective Agents/therapeutic use ; Riluzole/therapeutic use ; }, abstract = {INTRODUCTION: Motor neuron disease (MND) is a devastating neurodegenerative disease characterized by progressive muscle weakness.<br><br>SOURCES OF DATA: PubMed, MEDLINE, and Cochrane databases were searched for articles to March 2024. Searches involved the terms 'motor neuron disease' or 'amyotrophic lateral sclerosis' and 'epidemiology', 'diagnosis', 'clinical', 'genetic', 'management', 'treatment', or 'trial'.<br><br>AREAS OF AGREEMENT: Evidence-based management involves riluzole, multidisciplinary care, provision of noninvasive ventilation and gastrostomy, and symptomatic treatments. Tofersen should be offered to treat SOD1-MND.<br><br>AREAS OF CONTROVERSY: Edaravone and Relyvrio are approved treatments in the USA, but insufficient evidence was found to support approval in the UK and Europe.<br><br>GROWING POINTS: The discovery of neurofilaments as MND biomarkers, growth of platform trials and development of novel therapies provide optimism for more powerful neuroprotective therapies.<br><br>Further work should focus on the elucidation of environmental causes of MND, gene-environment interactions, and advanced cellular models of disease.}, }
@article {pmid39341656, year = {2024}, author = {Paris, A and Lakatos, A}, title = {Cell and gene therapy for amyotrophic lateral sclerosis.}, journal = {Handbook of clinical neurology}, volume = {205}, number = {}, pages = {217-241}, doi = {10.1016/B978-0-323-90120-8.00017-4}, pmid = {39341656}, issn = {0072-9752}, mesh = {*Amyotrophic Lateral Sclerosis/therapy/genetics ; Humans ; *Genetic Therapy/methods ; Animals ; Cell- and Tissue-Based Therapy/methods/trends ; Disease Models, Animal ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal and incurable neurodegenerative disorder with rapidly progressive skeletal muscle weakness, which can also cause a variable cognitive deficit. Genetic causes are only identified in approximately 10% of all cases, with complex genotype-phenotype associations, making it challenging to identify treatment targets. What further hampers therapeutic development is a broad heterogeneity in mechanisms, possible targets, and disturbances across various cell types, aside from the cortical and spinal motor neurons that lie at the heart of the pathology of ALS. Over the last decade, significant progress in biotechnologic techniques, cell and ribonucleic acid (RNA) engineering, animal models, and patient-specific human stem cell and organoid models have accelerated both mechanistic and therapeutic discoveries. The growing number of clinical trials mirrors this. This chapter reviews the current state of human preclinical models supporting trial strategies as well as recent clinical cell and gene therapy approaches.}, }
@article {pmid39341507, year = {2024}, author = {Sivalingam, AM}, title = {Advances in understanding biomarkers and treating neurological diseases - Role of the cerebellar dysfunction and emerging therapies.}, journal = {Ageing research reviews}, volume = {101}, number = {}, pages = {102519}, doi = {10.1016/j.arr.2024.102519}, pmid = {39341507}, issn = {1872-9649}, mesh = {Humans ; *Biomarkers/metabolism ; Animals ; *Cerebellar Diseases/therapy/diagnosis/metabolism/genetics ; Genetic Therapy/methods/trends ; Nervous System Diseases/therapy/diagnosis/metabolism ; Cerebellum/metabolism/pathology ; }, abstract = {Cerebellar dysfunction is increasingly recognized as a critical factor in various neurological diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Research has revealed distinct cerebellar atrophy patterns in conditions such as AD and multiple system atrophy, and studies in mice have highlighted its impact on motor control and cognitive functions. Emerging research into autism spectrum disorder (ASD) has identified key targets, such as elevated levels of chemokine receptors and ZIC family genes. Biomarkers, including cerebrospinal fluid (CSF), genetic markers, and advances in AI and bioinformatics, are enhancing early diagnosis and personalized treatment across neurodegenerative disorders. Notable advancements include improved diagnostic tools, gene therapy, and novel clinical trials. Despite progress, challenges such as the bloodbrain barrier and neuroinflammation persist. Current therapies for AD, PD, HD, and ALS, including antisense oligonucleotides and stem cell treatments, show promise but require further investigation. A comprehensive approach that integrates diagnostic methods and innovative therapies is essential for effective management and improved patient outcomes.}, }
@article {pmid39340928, year = {2024}, author = {Dahl, R and Bezprozvanny, I}, title = {SERCA pump as a novel therapeutic target for treating neurodegenerative disorders.}, journal = {Biochemical and biophysical research communications}, volume = {734}, number = {}, pages = {150748}, doi = {10.1016/j.bbrc.2024.150748}, pmid = {39340928}, issn = {1090-2104}, support = {R01 AG071310/AG/NIA NIH HHS/United States ; R56 AG078337/AG/NIA NIH HHS/United States ; R42 AG062001/AG/NIA NIH HHS/United States ; }, mesh = {*Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolism ; *Neurodegenerative Diseases/drug therapy/metabolism/pathology ; Humans ; Animals ; Disease Models, Animal ; Allosteric Regulation/drug effects ; Molecular Targeted Therapy/methods ; *Neuroprotective Agents/pharmacology/therapeutic use ; Calcium Signaling/drug effects ; Calcium/metabolism ; }, abstract = {The neurodegenerative disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), Huntington's disease (HD) and Spinocerebellar ataxias (SCAs), present an enormous medical, social, financial and scientific problem. Despite intense research into the causes of these disorders, only marginal progress has been made in the clinic and no cures exist for any of them. Most of the scientific effort has been focused on identification of the major causes of these diseases and on developing ways to target them, such as targeting amyloid accumulation for AD or targeting expression of mutant Huntingtin for HD. Calcium (Ca[2+]) signaling has long been proposed to play an important role in the pathogenesis of neurodegenerative disorders, but blockers of Ca[2+] channels and Ca[2+] signaling proteins have not been translated to clinic primarily due to side effects related to the important roles of target molecules for these compounds at the peripheral tissues. In this review article, we would like to discuss an idea that recently identified positive allosteric modulators (PAMs) of the sarco-endoplasmic reticulum calcium (SERCA) pump may provide a promising approach to develop therapeutic compounds for treatment of these disorders. This hypothesis is supported by the preclinical data obtained with animal models of AD and PD. The first critical test of this idea will be an imminent phase I study that will offer an opportunity to evaluate potential side effects of this class of compounds in humans.}, }
@article {pmid39340590, year = {2024}, author = {Ghiasvand, K and Amirfazli, M and Moghimi, P and Safari, F and Takhshid, MA}, title = {The role of neuron-like cell lines and primary neuron cell models in unraveling the complexity of neurodegenerative diseases: a comprehensive review.}, journal = {Molecular biology reports}, volume = {51}, number = {1}, pages = {1024}, doi = {10.1007/s11033-024-09964-x}, pmid = {39340590}, issn = {1573-4978}, mesh = {Humans ; *Neurodegenerative Diseases/pathology ; *Neurons/metabolism ; Animals ; Coculture Techniques/methods ; Cell Line ; Models, Biological ; Alzheimer Disease/pathology/genetics ; }, abstract = {Neurodegenerative diseases (NDs) are characterized by the progressive loss of neurons. As to developing effective therapeutic interventions, it is crucial to understand the underlying mechanisms of NDs. Cellular models have become invaluable tools for studying the complex pathogenesis of NDs, offering insights into disease mechanisms, determining potential therapeutic targets, and aiding in drug discovery. This review provides a comprehensive overview of various cellular models used in ND research, focusing on Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. Cell lines, such as SH-SY5Y and PC12 cells, have emerged as valuable tools due to their ease of use, reproducibility, and scalability. Additionally, co-culture models, involving the growth of distinct cell types like neurons and astrocytes together, are highlighted for simulating brain interactions and microenvironment. While cell lines cannot fully replicate the complexity of the human brain, they provide a scalable method for examining important aspects of neurodegenerative diseases. Advancements in cell line technologies, including the incorporation of patient-specific genetic variants and improved co-culture models, hold promise for enhancing our understanding and expediting the development of effective treatments. Integrating multiple cellular models and advanced technologies offers the potential for significant progress in unraveling the intricacies of these debilitating diseases and improving patient outcomes.}, }
@article {pmid39338563, year = {2024}, author = {Dow, CT and Pierce, ES and Sechi, LA}, title = {Mycobacterium paratuberculosis: A HERV Turn-On for Autoimmunity, Neurodegeneration, and Cancer?.}, journal = {Microorganisms}, volume = {12}, number = {9}, pages = {}, pmid = {39338563}, issn = {2076-2607}, abstract = {Human endogenous retroviruses (HERVs) are remnants of ancient retroviral infections that, over millions of years, became integrated into the human genome. While normally inactive, environmental stimuli such as infections have contributed to the transcriptional reactivation of HERV-promoting pathological conditions, including the development of autoimmunity, neurodegenerative disease and cancer. What infections trigger HERV activation? Mycobacterium avium subspecies paratuberculosis (MAP) is a pluripotent driver of human disease. Aside from granulomatous diseases, Crohn's disease, sarcoidosis and Blau syndrome, MAP is associated with autoimmune disease: type one diabetes (T1D), multiple sclerosis (MS), rheumatoid arthritis (RA) and autoimmune thyroiditis. MAP is also associated with Alzheimer's disease (AD) and Parkinson's disease (PD). Autoimmune diabetes, MS and RA are the diseases with the strongest MAP/HERV association. There are several other diseases associated with HERV activation, including diseases whose epidemiology and/or pathology would prompt speculation for a causal role of MAP. These include non-solar uveal melanoma, colon cancer, glioblastoma and amyotrophic lateral sclerosis (ALS). This article further points to MAP infection as a contributor to autoimmunity, neurodegenerative disease and cancer via the un-silencing of HERV. We examine the link between the ever-increasing number of MAP-associated diseases and the MAP/HERV intersection with these diverse medical conditions, and propose treatment opportunities based upon this association.}, }
@article {pmid39337908, year = {2024}, author = {Wang, R and Chen, L and Zhang, Y and Sun, B and Liang, M}, title = {Expression Changes of miRNAs in Humans and Animal Models of Amyotrophic Lateral Sclerosis and Their Potential Application for Clinical Diagnosis.}, journal = {Life (Basel, Switzerland)}, volume = {14}, number = {9}, pages = {}, pmid = {39337908}, issn = {2075-1729}, support = {YJXJ-JZ-2021-0014//Scientific Research Project of Beijing Yicheng Cooperative Development Foundation in 2021-Public welfare projects of rare disease related topics/ ; KM202310858001//R&amp;D Program of Beijing Municipal Education Commission/ ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a severe motor neuron disease. Current detection methods can only confirm the diagnosis at the onset of the disease, missing the critical window for early treatment. Recent studies using animal models have found that detecting changes in miRNA sites can predict the onset and severity of the disease in its early stages, facilitating early diagnosis and treatment. miRNAs show expression changes in motor neurons that connect the brain, spinal cord, and brain stem, as well as in the skeletal muscle in mouse models of ALS. Clinically, expression changes in some miRNAs in patients align with those in mouse models, such as the upregulation of miR-29b in the brain and the upregulation of miR-206 in the skeletal muscle. This study provides an overview of some miRNA study findings in humans as well as in animal models, including SOD1, FUS, TDP-43, and C9orf72 transgenic mice and wobbler mice, highlighting the potential of miRNAs as diagnostic markers for ALS. miR-21 and miR-206 are aberrantly expressed in both mouse model and patient samples, positioning them as key potential diagnostic markers in ALS. Additionally, miR-29a, miR-29b, miR-181a, and miR-142-3p have shown aberrant expression in both types of samples and show promise as clinical targets for ALS. Finally, miR-1197 and miR-486b-5p have been recently identified as aberrantly expressed miRNAs in mouse models for ALS, although further studies are needed to determine their viability as diagnostic targets.}, }
@article {pmid39337696, year = {2024}, author = {Niazi, SK}, title = {Bioavailability as Proof to Authorize the Clinical Testing of Neurodegenerative Drugs-Protocols and Advice for the FDA to Meet the ALS Act Vision.}, journal = {International journal of molecular sciences}, volume = {25}, number = {18}, pages = {}, pmid = {39337696}, issn = {1422-0067}, mesh = {Humans ; *United States Food and Drug Administration ; United States ; *Drug Approval ; *Biological Availability ; *Amyotrophic Lateral Sclerosis/drug therapy ; Neurodegenerative Diseases/drug therapy ; Blood-Brain Barrier/metabolism ; Clinical Trials as Topic ; }, abstract = {Although decades of intensive drug discovery efforts to treat neurodegenerative disorders (NDs) have failed, around half a million patients in more than 2000 studies continue being tested, costing over USD 100 billion, despite the conclusion that even those drugs which have been approved have no better effect than a placebo. The US Food and Drug Administration (FDA) has established multiple programs to innovate the treatment of rare diseases, particularly NDs, providing millions of USD in funding primarily by encouraging novel clinical trials to account for issues related to study sizes and adopting multi-arm studies to account for patient dropouts. Instead, the FDA should focus on the primary reason for failure: the poor bioavailability of drugs reaching the brain (generally 0.1% at most) due to the blood-brain barrier (BBB). There are several solutions to enhance entry into the brain, and the FDA must require proof of significant entry into the brain as the prerequisite to approving Investigational New Drug (IND) applications. The FDA should also rely on factors other than biomarkers to confirm efficacy, as these are rarely relevant to clinical use. This study summarizes how the drugs used to treat NDs can be made effective and how the FDA should change its guidelines for IND approval of these drugs.}, }
@article {pmid39337560, year = {2024}, author = {Malaguarnera, M and Cabrera-Pastor, A}, title = {Emerging Role of Extracellular Vesicles as Biomarkers in Neurodegenerative Diseases and Their Clinical and Therapeutic Potential in Central Nervous System Pathologies.}, journal = {International journal of molecular sciences}, volume = {25}, number = {18}, pages = {}, pmid = {39337560}, issn = {1422-0067}, support = {PI23/00204//Instituto de Salud Carlos III (ISCIII) through the project "PI23/00204" and co-funded by the European Union; and Conselleria de Educaci&#xf3;n/Innovaci&#xf3;n, Universidades, Ciencia y Sociedad Digital, subvenciones para la realizaci&#xf3;n de proyectos de I+D+i desarro/ ; CIGE/083//This research was funded by Instituto de Salud Carlos III (ISCIII) through the project "PI23/00204" and co-funded by the European Union; and Conselleria de Educaci&#xf3;n/Innovaci&#xf3;n, Universidades, Ciencia y Sociedad Digital, subvenciones para la realizaci&#xf3;n d/ ; }, mesh = {Humans ; *Extracellular Vesicles/metabolism ; *Biomarkers/metabolism ; *Neurodegenerative Diseases/therapy/metabolism/diagnosis ; Animals ; Central Nervous System Diseases/metabolism/therapy/diagnosis ; Blood-Brain Barrier/metabolism ; }, abstract = {The emerging role of extracellular vesicles (EVs) in central nervous system (CNS) diseases is gaining significant interest, particularly their applications as diagnostic biomarkers and therapeutic agents. EVs are involved in intercellular communication and are secreted by all cell types. They contain specific markers and a diverse cargo such as proteins, lipids, and nucleic acids, reflecting the physiological and pathological state of their originating cells. Their reduced immunogenicity and ability to cross the blood-brain barrier make them promising candidates for both biomarkers and therapeutic agents. In the context of CNS diseases, EVs have shown promise as biomarkers isolable from different body fluids, providing a non-invasive method for diagnosing CNS diseases and monitoring disease progression. This makes them useful for the early detection and monitoring of diseases such as Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis, where specific alterations in EVs content can be detected. Additionally, EVs derived from stem cells show potential in promoting tissue regeneration and repairing damaged tissues. An evaluation has been conducted on the current clinical trials studying EVs for CNS diseases, focusing on their application, treatment protocols, and obtained results. This review aims to explore the potential of EVs as diagnostic markers and therapeutic carriers for CNS diseases, highlighting their significant advantages and ongoing clinical trials evaluating their efficacy.}, }
@article {pmid39337454, year = {2024}, author = {Rizea, RE and Corlatescu, AD and Costin, HP and Dumitru, A and Ciurea, AV}, title = {Understanding Amyotrophic Lateral Sclerosis: Pathophysiology, Diagnosis, and Therapeutic Advances.}, journal = {International journal of molecular sciences}, volume = {25}, number = {18}, pages = {}, pmid = {39337454}, issn = {1422-0067}, mesh = {*Amyotrophic Lateral Sclerosis/therapy/diagnosis/physiopathology/metabolism/genetics ; Humans ; Biomarkers ; Genetic Therapy/methods ; Oxidative Stress ; Animals ; Mitochondria/metabolism ; }, abstract = {This review offers an in-depth examination of amyotrophic lateral sclerosis (ALS), addressing its epidemiology, pathophysiology, clinical presentation, diagnostic techniques, and current as well as emerging treatments. The purpose is to condense key findings and illustrate the complexity of ALS, which is shaped by both genetic and environmental influences. We reviewed the literature to discuss recent advancements in understanding molecular mechanisms such as protein misfolding, mitochondrial dysfunction, oxidative stress, and axonal transport defects, which are critical for identifying potential therapeutic targets. Significant progress has been made in refining diagnostic criteria and identifying biomarkers, leading to earlier and more precise diagnoses. Although current drug treatments provide some benefits, there is a clear need for more effective therapies. Emerging treatments, such as gene therapy and stem cell therapy, show potential in modifying disease progression and improving the quality of life for ALS patients. The review emphasizes the importance of continued research to address challenges such as disease variability and the limited effectiveness of existing treatments. Future research should concentrate on further exploring the molecular foundations of ALS and developing new therapeutic approaches. The implications for clinical practice include ensuring the accessibility of new treatments and that healthcare systems are equipped to support ongoing research and patient care.}, }
@article {pmid39337436, year = {2024}, author = {Guo, D and Liu, Z and Zhou, J and Ke, C and Li, D}, title = {Significance of Programmed Cell Death Pathways in Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {25}, number = {18}, pages = {}, pmid = {39337436}, issn = {1422-0067}, support = {2023Y9415//Joint Funds for the innovation of science and Technology, Fujian province/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/pathology ; *Signal Transduction ; Animals ; *Apoptosis ; Ferroptosis ; Neurons/metabolism/pathology ; }, abstract = {Programmed cell death (PCD) is a form of cell death distinct from accidental cell death (ACD) and is also referred to as regulated cell death (RCD). Typically, PCD signaling events are precisely regulated by various biomolecules in both spatial and temporal contexts to promote neuronal development, establish neural architecture, and shape the central nervous system (CNS), although the role of PCD extends beyond the CNS. Abnormalities in PCD signaling cascades contribute to the irreversible loss of neuronal cells and function, leading to the onset and progression of neurodegenerative diseases. In this review, we summarize the molecular processes and features of different modalities of PCD, including apoptosis, necroptosis, pyroptosis, ferroptosis, cuproptosis, and other novel forms of PCD, and their effects on the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), multiple sclerosis (MS), traumatic brain injury (TBI), and stroke. Additionally, we examine the key factors involved in these PCD signaling pathways and discuss the potential for their development as therapeutic targets and strategies. Therefore, therapeutic strategies targeting the inhibition or facilitation of PCD signaling pathways offer a promising approach for clinical applications in treating neurodegenerative diseases.}, }
@article {pmid39336146, year = {2024}, author = {Duranti, E and Villa, C}, title = {From Brain to Muscle: The Role of Muscle Tissue in Neurodegenerative Disorders.}, journal = {Biology}, volume = {13}, number = {9}, pages = {}, pmid = {39336146}, issn = {2079-7737}, abstract = {Neurodegenerative diseases (NDs), like amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), and Parkinson's disease (PD), primarily affect the central nervous system, leading to progressive neuronal loss and motor and cognitive dysfunction. However, recent studies have revealed that muscle tissue also plays a significant role in these diseases. ALS is characterized by severe muscle wasting as a result of motor neuron degeneration, as well as alterations in gene expression, protein aggregation, and oxidative stress. Muscle atrophy and mitochondrial dysfunction are also observed in AD, which may exacerbate cognitive decline due to systemic metabolic dysregulation. PD patients exhibit muscle fiber atrophy, altered muscle composition, and α-synuclein aggregation within muscle cells, contributing to motor symptoms and disease progression. Systemic inflammation and impaired protein degradation pathways are common among these disorders, highlighting muscle tissue as a key player in disease progression. Understanding these muscle-related changes offers potential therapeutic avenues, such as targeting mitochondrial function, reducing inflammation, and promoting muscle regeneration with exercise and pharmacological interventions. This review emphasizes the importance of considering an integrative approach to neurodegenerative disease research, considering both central and peripheral pathological mechanisms, in order to develop more effective treatments and improve patient outcomes.}, }
@article {pmid39335395, year = {2024}, author = {Ore, A and Angelastro, JM and Giulivi, C}, title = {Integrating Mitochondrial Biology into Innovative Cell Therapies for Neurodegenerative Diseases.}, journal = {Brain sciences}, volume = {14}, number = {9}, pages = {}, pmid = {39335395}, issn = {2076-3425}, support = {R21 NS128751/NS/NINDS NIH HHS/United States ; }, abstract = {The role of mitochondria in neurodegenerative diseases is crucial, and recent developments have highlighted its significance in cell therapy. Mitochondrial dysfunction has been implicated in various neurodegenerative disorders, including Alzheimer's, Parkinson's, amyotrophic lateral sclerosis, and Huntington's diseases. Understanding the impact of mitochondrial biology on these conditions can provide valuable insights for developing targeted cell therapies. This mini-review refocuses on mitochondria and emphasizes the potential of therapies leveraging mesenchymal stem cells, embryonic stem cells, induced pluripotent stem cells, stem cell-derived secretions, and extracellular vesicles. Mesenchymal stem cell-mediated mitochondria transfer is highlighted for restoring mitochondrial health in cells with dysfunctional mitochondria. Additionally, attention is paid to gene-editing techniques such as mito-CRISPR, mitoTALENs, mito-ZNFs, and DdCBEs to ensure the safety and efficacy of stem cell treatments. Challenges and future directions are also discussed, including the possible tumorigenic effects of stem cells, off-target effects, disease targeting, immune rejection, and ethical issues.}, }
@article {pmid39334720, year = {2024}, author = {Munteanu, C and Galaction, AI and Turnea, M and Blendea, CD and Rotariu, M and Poștaru, M}, title = {Redox Homeostasis, Gut Microbiota, and Epigenetics in Neurodegenerative Diseases: A Systematic Review.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {13}, number = {9}, pages = {}, pmid = {39334720}, issn = {2076-3921}, abstract = {Neurodegenerative diseases encompass a spectrum of disorders marked by the progressive degeneration of the structure and function of the nervous system. These conditions, including Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD), Amyotrophic lateral sclerosis (ALS), and Multiple sclerosis (MS), often lead to severe cognitive and motor deficits. A critical component of neurodegenerative disease pathologies is the imbalance between pro-oxidant and antioxidant mechanisms, culminating in oxidative stress. The brain's high oxygen consumption and lipid-rich environment make it particularly vulnerable to oxidative damage. Pro-oxidants such as reactive nitrogen species (RNS) and reactive oxygen species (ROS) are continuously generated during normal metabolism, counteracted by enzymatic and non-enzymatic antioxidant defenses. In neurodegenerative diseases, this balance is disrupted, leading to neuronal damage. This systematic review explores the roles of oxidative stress, gut microbiota, and epigenetic modifications in neurodegenerative diseases, aiming to elucidate the interplay between these factors and identify potential therapeutic strategies. We conducted a comprehensive search of articles published in 2024 across major databases, focusing on studies examining the relationships between redox homeostasis, gut microbiota, and epigenetic changes in neurodegeneration. A total of 161 studies were included, comprising clinical trials, observational studies, and experimental research. Our findings reveal that oxidative stress plays a central role in the pathogenesis of neurodegenerative diseases, with gut microbiota composition and epigenetic modifications significantly influencing redox balance. Specific bacterial taxa and epigenetic markers were identified as potential modulators of oxidative stress, suggesting novel avenues for therapeutic intervention. Moreover, recent evidence from human and animal studies supports the emerging concept of targeting redox homeostasis through microbiota and epigenetic therapies. Future research should focus on validating these targets in clinical settings and exploring the potential for personalized medicine strategies based on individual microbiota and epigenetic profiles.}, }
@article {pmid39332091, year = {2024}, author = {Sharma, O and Kaur Grewal, A and Khan, H and Gurjeet Singh, T}, title = {Exploring the nexus of cGAS STING pathway in neurodegenerative terrain: A therapeutic odyssey.}, journal = {International immunopharmacology}, volume = {142}, number = {Pt B}, pages = {113205}, doi = {10.1016/j.intimp.2024.113205}, pmid = {39332091}, issn = {1878-1705}, mesh = {Humans ; *Membrane Proteins/metabolism/genetics ; Animals ; *Neurodegenerative Diseases/drug therapy/immunology/metabolism ; *Nucleotidyltransferases/metabolism/genetics ; *Signal Transduction ; Immunity, Innate ; }, abstract = {By detecting and responding to cytosolic DNA, the cGAS STING pathway regulates the innate immune responses bymediatinginflammatory reactions and antiviral defense. Thederegulation and modification of this system have been linked to variousneurodegenerative diseases like AD, PD and ALS. Accumulation of tau protein and Aβ aggregates to activate the pathway and releases neuroinflammatory cytokines which accelerates neuronal dysfunction and cognitive impairment as the symptom of AD. Similarly, in PD Alpha-synuclein aggregates activate the cGAS STING pathway and regulate the neuroinflammation and oxidative stress. In ALS, mutation of the genes causes the activation of the pathway which leads to motor neuron degeneration. Alteration of the cGAS STING pathway also leads to mitochondrial dysfunction and impaired autophagy. Preclinical investigations of AD, PD, and ALS animal models showed that STING pathway inhibitors reduced inflammation and improved neurological outcomes and modulators of the cGAS STING pathway may treat these neurodegenerative disorders. In this review we focus on the fact thatneuroinflammation, neuronal dysfunction, and various disease progressions can be treated byaltering the cGAS STING pathway. Understanding the processes and creating specific interventions for this route may offer new treatments for these terrible illnesses.}, }
@article {pmid39330700, year = {2024}, author = {Everett, WH and Bucelli, RC}, title = {Tofersen for SOD1 ALS.}, journal = {Neurodegenerative disease management}, volume = {14}, number = {5}, pages = {149-160}, pmid = {39330700}, issn = {1758-2032}, mesh = {Animals ; Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Oligonucleotides/therapeutic use ; *Superoxide Dismutase-1/antagonists &amp; inhibitors ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition affecting the motor system. The heterogenous nature of ALS complicates trial design. Genetic forms of ALS present an opportunity to intervene in a less heterogeneous population. ALS associated with gain of function mutations in SOD1 make 'knock-down' strategies an attractive therapeutic approach. Tofersen, an antisense oligonucleotide that reduces expression of SOD1 via RNAase mediated degradation of SOD1 mRNA, has shown robust effects on ALS biomarkers. While a Phase III trial of tofersen failed to meet its primary end point, open label extension data suggests that tofersen slows progression of SOD1 ALS.}, }
@article {pmid39323817, year = {2024}, author = {Zeng, A and Huang, Y and Xin, J and Li, J and Qiu, W and Zhang, M}, title = {Progress and recommendations of developing occupational exposure limits for noise-A systematic review.}, journal = {Heliyon}, volume = {10}, number = {18}, pages = {e37878}, pmid = {39323817}, issn = {2405-8440}, abstract = {OBJECTIVE: Noise exposure limit is one of the critical measures to prevent noise-induced hearing loss (NIHL). This review aimed to review the progress and recommendations for developing occupational exposure limits (OELs) for workplace noise.<br><br>METHODS: A systematic review was used. Thirty-eight national or international organizations' noise exposure standards (including OEL) and laws, regulations, and guidelines for noise exposure control were analyzed. Articles on recommendations for revising noise OEL standards between 2000 and 2023 were selected.<br><br>RESULTS: The definition of different noise types (especially for non-steady and impulsive noise) varied worldwide, and the used 8-h OEL varied from 80 to 90&#xa0;dB(A). Maximum sound pressure level (Lmax) and noise dose for industrial noise and peak sound pressure level (Lpeak) for impulsive noise have been incorporated into the OELs. Countries developed noise risk management measures based on OELs, action levels (ALs), and exposure risk ratio or classification. The risk of co-exposure to noise and ototoxic organic substances and the effects of noise on susceptible populations were concerns in EU country standards. Scholars suggested revising the existing noise exposure standards based on noise's temporal structure (expressed by kurtosis), effective noise level, impulsive noise OEL, action level, and key factors of risk assessment.<br><br>CONCLUSIONS: Indicators such as Lmax, noise dose, Lpeak, and action level can be incorporated into noise OELs. Developing noise OEL standards should consider the co-exposure of noise and ototoxic substances, HPD's noise attenuation, susceptible groups, and noise's temporal structure.}, }
@article {pmid39322357, year = {2024}, author = {Mehta, RI and Ranjan, M and Haut, MW and Carpenter, JS and Rezai, AR}, title = {Focused Ultrasound for Neurodegenerative Diseases.}, journal = {Magnetic resonance imaging clinics of North America}, volume = {32}, number = {4}, pages = {681-698}, doi = {10.1016/j.mric.2024.03.001}, pmid = {39322357}, issn = {1557-9786}, mesh = {Humans ; *Neurodegenerative Diseases/diagnostic imaging ; Ultrasonic Therapy/methods ; Brain/diagnostic imaging ; Animals ; }, abstract = {Neurodegenerative diseases are a leading cause of death and disability and pose a looming global public health crisis. Despite progress in understanding biological and molecular factors associated with these disorders and their progression, effective disease modifying treatments are presently limited. Focused ultrasound (FUS) is an emerging therapeutic strategy for Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. In these contexts, applications of FUS include neuroablation, neuromodulation, and/or blood-brain barrier opening with and without facilitated intracerebral drug delivery. Here, the authors review preclinical evidence and current and emerging applications of FUS for neurodegenerative diseases and summarize future directions in the field.}, }
@article {pmid39321879, year = {2024}, author = {Lei, T and Zhang, X and Fu, G and Luo, S and Zhao, Z and Deng, S and Li, C and Cui, Z and Cao, J and Chen, P and Yang, H}, title = {Advances in human cellular mechanistic understanding and drug discovery of brain organoids for neurodegenerative diseases.}, journal = {Ageing research reviews}, volume = {102}, number = {}, pages = {102517}, doi = {10.1016/j.arr.2024.102517}, pmid = {39321879}, issn = {1872-9649}, mesh = {Humans ; *Organoids/drug effects/pathology ; *Neurodegenerative Diseases/pathology/drug therapy ; *Drug Discovery/methods ; *Brain/pathology/drug effects ; Animals ; }, abstract = {The prevalence of neurodegenerative diseases (NDs) is increasing rapidly as the aging population accelerates, and there are still no treatments to halt or reverse the progression of these diseases. While traditional 2D cultures and animal models fail to translate into effective therapies benefit patients, 3D cultured human brain organoids (hBOs) facilitate the use of non-invasive methods to capture patient data. The purpose of this study was to review the research and application of hBO in disease models and drug screening in NDs. The pluripotent stem cells are induced in multiple stages to form cerebral organoids, brain region-specific organoids and their derived brain cells, which exhibit complex brain-like structures and perform electrophysiological activities. The brain region-specific organoids and their derived neurons or glial cells contribute to the understanding of the pathogenesis of NDs and the efficient development of drugs, including Alzheimer's disease, Parkinson's disease, Huntington's disease and Amyotrophic lateral sclerosis. Glial-rich brain organoids facilitate the study of glial function and neuroinflammation, including astrocytes, microglia, and oligodendrocytes. Further research on the maturation enhancement, vascularization and multi-organoid assembly of hBO will help to enhance the research and application of NDs cellular models.}, }
@article {pmid39318842, year = {2024}, author = {Emary, PC and Turner, AJ}, title = {Cervical spondylotic myelopathy in a 68-year-old man diagnosed with amyotrophic lateral sclerosis.}, journal = {The Journal of the Canadian Chiropractic Association}, volume = {68}, number = {2}, pages = {172-176}, pmid = {39318842}, issn = {0008-3194}, abstract = {Owing to similar clinical presentations, cervical spondylotic myelopathy can mimic other neurological disorders. In this imaging case review (ICR), we describe a case of cervical spondylotic myelopathy in a patient diagnosed with amyotrophic lateral sclerosis. The key clinical features, imaging findings and differential diagnoses of cervical spondylotic myelopathy compared with amyotrophic lateral sclerosis are also presented.}, }
@article {pmid39318236, year = {2025}, author = {Majewski, S and Klein, P and Boillée, S and Clarke, BE and Patani, R}, title = {Towards an integrated approach for understanding glia in Amyotrophic Lateral Sclerosis.}, journal = {Glia}, volume = {73}, number = {3}, pages = {591-607}, pmid = {39318236}, issn = {1098-1136}, support = {MR/S006591/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*Amyotrophic Lateral Sclerosis/pathology/metabolism ; Humans ; *Neuroglia/metabolism/pathology ; Animals ; }, abstract = {Substantial advances in technology are permitting a high resolution understanding of the salience of glia, and have helped us to transcend decades of predominantly neuron-centric research. In particular, recent advances in 'omic' technologies have enabled unique insights into glial biology, shedding light on the cellular and molecular aspects of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Here, we review studies using omic techniques to attempt to understand the role of glia in ALS across different model systems and post mortem tissue. We also address caveats that should be considered when interpreting such studies, and how some of these may be mitigated through either using a multi-omic approach and/or careful low throughput, high fidelity orthogonal validation with particular emphasis on functional validation. Finally, we consider emerging technologies and their potential relevance in deepening our understanding of glia in ALS.}, }
@article {pmid39317854, year = {2025}, author = {Khoshdooz, S and Abbasi, H and Abbasi, MM}, title = {Iron-Status Indicators and HFE Gene Polymorphisms in Individuals with Amyotrophic Lateral Sclerosis: An Umbrella Review of Meta-analyses and Systematic Reviews.}, journal = {Biological trace element research}, volume = {203}, number = {6}, pages = {2974-2985}, pmid = {39317854}, issn = {1559-0720}, mesh = {*Amyotrophic Lateral Sclerosis/genetics/blood ; Humans ; *Hemochromatosis Protein/genetics ; *Iron/blood/metabolism ; Systematic Reviews as Topic ; *Polymorphism, Genetic ; Meta-Analysis as Topic ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive loss of motor neurons. Recent meta-analyses and systematic reviews suggest that HFE gene polymorphisms and iron-associated biomarkers may play a key role in the risk and occurrence of ALS. This umbrella study aimed to explore the roles of HFE gene polymorphisms and iron-associated biomarkers in individuals with ALS. A thorough search of three online scientific databases, namely Scopus, Web of Science, and PubMed, was conducted from their inception until September 13, 2024. The screening and selection processes were executed based on the PICO framework and eligibility criteria, followed by two independent reviewers. The Assessment of Multiple Systematic Reviews (AMSTAR)-2 and GRADE tools were utilized to assess the methodological quality and the certainty of evidence. Through an advanced search, 101 records were retrieved, of which eight meta-analyses and systematic reviews were selected for this umbrella review. A significant increase in iron concentrations was found in individuals with ALS compared to healthy controls (SMD, 0.26; 95% CI - 0.05, 0.57). Conversely, selected meta-analyses reported that serum transferrin concentrations in ALS patients were lower compared to healthy controls (SMD, - 0.15; 95% CI - 0.36, 0.05). Furthermore, mutations in H63D polymorphisms resulted in a 13% significant increase in the risk of ALS (OR, 1.13; 95% CI 1.05, 1.22). Our umbrella study of meta-analyses and systematic reviews reveals that individuals with ALS have lower serum concentrations of transferrin compared to healthy controls. Additionally, the H63D polymorphism in the HFE gene is associated with a slight increase in the risk of ALS. Future research should investigate broader aspects of iron-related biomarkers and HFE genes to elucidate their roles in ALS pathogenesis. Registration: Our umbrella study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) with the identification number CRD42024559032 (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024559032).}, }
@article {pmid39317352, year = {2025}, author = {Kleinerova, J and Garcia-Gallardo, A and Tacheva, A and Bede, P}, title = {Subcortical grey matter involvement in ALS and PLS - vulnerable hubs of cortico-cortical and cortico-basal circuits: extrapyramidal, cognitive, bulbar and respiratory correlates.}, journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration}, volume = {26}, number = {1-2}, pages = {1-4}, doi = {10.1080/21678421.2024.2405130}, pmid = {39317352}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnostic imaging/pathology/complications ; *Gray Matter/pathology/diagnostic imaging/physiopathology ; *Cerebral Cortex/pathology/physiopathology/diagnostic imaging ; Neural Pathways/pathology/physiopathology/diagnostic imaging ; *Nerve Net/pathology/physiopathology ; }, abstract = {Evidence from neuroimaging studies suggests that the cardinal clinical manifestations of ALS stem from the dysfunction of specific neural networks. The majority of cortico-cortical and cortico-basal networks are physiologically relayed by deep cerebral and cerebellar grey matter nuclei which have been increasingly implicated in the pathophysiology of ALS. A series of recent human imaging papers revealed volume reductions, shape deformations, metabolic alterations and more recently, susceptibility changes in hippocampal subfields, thalamic, striatal, amygdalar and cerebellar nuclei. Thalamic changes have been identified in presymptomatic mutation carriers long before symptom onset and longitudinal studies have consistently confirmed progressive subcortical degeneration during the symptomatic phase of the disease. The dysfunction of circuits relayed by specific subcortical nuclei has been associated with apathy, amnestic deficits, limbic symptoms, extrapyramidal manifestations, sensory disturbances, pseudobulbar affect and cerebellar deficits. In light of emerging imaging data, the clinical heterogeneity of ALS is probably best approached from a network integrity perspective. Accordingly, the comprehensive assessment of subcortical grey matter nuclei seems imperative to untangle complex clinical phenomena in ALS.}, }
@article {pmid39313512, year = {2024}, author = {Khan, AF and Iturria-Medina, Y}, title = {Beyond the usual suspects: multi-factorial computational models in the search for neurodegenerative disease mechanisms.}, journal = {Translational psychiatry}, volume = {14}, number = {1}, pages = {386}, pmid = {39313512}, issn = {2158-3188}, mesh = {Humans ; *Neurodegenerative Diseases/diagnostic imaging/physiopathology ; *Neuroimaging/methods ; *Brain/diagnostic imaging/physiopathology ; Disease Progression ; Biomarkers ; Alzheimer Disease/diagnostic imaging/physiopathology ; Computer Simulation ; }, abstract = {From Alzheimer's disease to amyotrophic lateral sclerosis, the molecular cascades underlying neurodegenerative disorders remain poorly understood. The clinical view of neurodegeneration is confounded by symptomatic heterogeneity and mixed pathology in almost every patient. While the underlying physiological alterations originate, proliferate, and propagate potentially decades before symptomatic onset, the complexity and inaccessibility of the living brain limit direct observation over a patient's lifespan. Consequently, there is a critical need for robust computational methods to support the search for causal mechanisms of neurodegeneration by distinguishing pathogenic processes from consequential alterations, and inter-individual variability from intra-individual progression. Recently, promising advances have been made by data-driven spatiotemporal modeling of the brain, based on in vivo neuroimaging and biospecimen markers. These methods include disease progression models comparing the temporal evolution of various biomarkers, causal models linking interacting biological processes, network propagation models reproducing the spatial spreading of pathology, and biophysical models spanning cellular- to network-scale phenomena. In this review, we discuss various computational approaches for integrating cross-sectional, longitudinal, and multi-modal data, primarily from large observational neuroimaging studies, to understand (i) the temporal ordering of physiological alterations, i(i) their spatial relationships to the brain's molecular and cellular architecture, (iii) mechanistic interactions between biological processes, and (iv) the macroscopic effects of microscopic factors. We consider the extents to which computational models can evaluate mechanistic hypotheses, explore applications such as improving treatment selection, and discuss how model-informed insights can lay the groundwork for a pathobiological redefinition of neurodegenerative disorders.}, }
@article {pmid39311426, year = {2024}, author = {Azzolino, D and Piras, R and Zulueta, A and Lucchi, T and Lunetta, C}, title = {Amyotrophic lateral sclerosis as a disease model of sarcopenia.}, journal = {Age and ageing}, volume = {53}, number = {9}, pages = {}, doi = {10.1093/ageing/afae209}, pmid = {39311426}, issn = {1468-2834}, mesh = {Humans ; *Sarcopenia/physiopathology/diagnosis ; *Amyotrophic Lateral Sclerosis/physiopathology/complications/diagnosis ; *Muscle, Skeletal/pathology/physiopathology ; Aging/pathology ; Animals ; Age Factors ; Aged ; Risk Factors ; }, abstract = {Sarcopenia, the progressive decline of muscle mass and function, has traditionally been viewed as an age-related process leading to a broad range of adverse outcomes. However, it has been widely reported that sarcopenia can occur earlier in life in association with various conditions (i.e. disease-related sarcopenia), including neuromuscular disorders. As early as 2010, the European Working Group on Sarcopenia in Older People included neurodegenerative diseases characterised by motor neuron loss among the mechanisms underlying sarcopenia. Despite some differences in pathogenetic mechanisms, both amyotrophic lateral sclerosis (ALS) and age-related sarcopenia share common characteristics, such as the loss of motor units and muscle fibre atrophy, oxidative stress, mitochondrial dysfunction and inflammation. The histology of older muscle shows fibre size heterogeneity, fibre grouping and a loss of satellite cells, similar to what is observed in ALS patients. Regrettably, the sarcopenic process in ALS patients has been largely overlooked, and literature on the condition in this patient group is very scarce. Some instruments used for the assessment of sarcopenia in older people could also be applied to ALS patients. At this time, there is no approved specific pharmacological treatment to reverse damage to motor neurons or cure ALS, just as there is none for sarcopenia. However, some agents targeting the muscle, like myostatin and mammalian target of rapamycin inhibitors, are under investigation both in the sarcopenia and ALS context. The development of new therapeutic agents targeting the skeletal muscle may indeed be beneficial to both ALS patients and older people with sarcopenia.}, }
@article {pmid39310519, year = {2024}, author = {Albadawi, EA}, title = {Microstructural Changes in the Corpus Callosum in Neurodegenerative Diseases.}, journal = {Cureus}, volume = {16}, number = {8}, pages = {e67378}, pmid = {39310519}, issn = {2168-8184}, abstract = {The corpus callosum, the largest white matter structure in the brain, plays a crucial role in interhemispheric communication and cognitive function. This review examines the microstructural changes observed in the corpus callosum across various neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis (ALS). New neuroimaging studies, mainly those that use diffusion tensor imaging (DTI) and advanced tractography methods, were put together to show how changes have happened in the organization of white matter and the connections between them. Some of the most common ways the corpus callosum breaks down are discussed, including less fractional anisotropy, higher mean diffusivity, and atrophy in certain regions. The relationship between these microstructural changes and cognitive decline, motor dysfunction, and disease progression is explored. Additionally, we consider the potential of corpus callosum imaging as a biomarker for early disease detection and monitoring. Studies show that people with these disorders have lower fractional anisotropy and higher mean diffusivity in the corpus callosum, often in ways that are specific to the disease. These changes often happen before gray matter atrophy and are linked to symptoms, which suggests that the corpus callosum could be used as an early sign of neurodegeneration. The review also highlights the implications of these findings for understanding disease mechanisms and developing therapeutic strategies. Future directions, including the application of advanced imaging techniques and longitudinal studies, are discussed to elucidate the role of corpus callosum degeneration in neurodegenerative processes. This review underscores the importance of the corpus callosum in understanding the pathophysiology of neurodegenerative diseases and its potential as a target for therapeutic interventions.}, }
@article {pmid39307464, year = {2024}, author = {Kalykaki, M and Rubio-Tomás, T and Tavernarakis, N}, title = {The role of mitochondria in cytokine and chemokine signalling during ageing.}, journal = {Mechanisms of ageing and development}, volume = {222}, number = {}, pages = {111993}, doi = {10.1016/j.mad.2024.111993}, pmid = {39307464}, issn = {1872-6216}, mesh = {Humans ; *Mitochondria/metabolism ; *Aging/metabolism ; *Signal Transduction ; *Inflammation/metabolism ; *Cytokines/metabolism ; Animals ; Chemokines/metabolism ; Cellular Senescence/physiology ; }, abstract = {Ageing is accompanied by a persistent, low-level inflammation, termed "inflammageing", which contributes to the pathogenesis of age-related diseases. Mitochondria fulfil multiple roles in host immune responses, while mitochondrial dysfunction, a hallmark of ageing, has been shown to promote chronic inflammatory states by regulating the production of cytokines and chemokines. In this review, we aim to disentangle the molecular mechanisms underlying this process. We describe the role of mitochondrial signalling components such as mitochondrial DNA, mitochondrial RNA, N-formylated peptides, ROS, cardiolipin, cytochrome c, mitochondrial metabolites, potassium efflux and mitochondrial calcium in the age-related immune system activation. Furthermore, we discuss the effect of age-related decline in mitochondrial quality control mechanisms, including mitochondrial biogenesis, dynamics, mitophagy and UPR[mt], in inflammatory states upon ageing. In addition, we focus on the dynamic relationship between mitochondrial dysfunction and cellular senescence and its role in regulating the secretion of pro-inflammatory molecules by senescent cells. Finally, we review the existing literature regarding mitochondrial dysfunction and inflammation in specific age-related pathological conditions, including neurodegenerative diseases (Alzheimer's and Parkinson's disease, and amyotrophic lateral sclerosis), osteoarthritis and sarcopenia.}, }
@article {pmid39297377, year = {2024}, author = {Akyuz, E and Aslan, FS and Gokce, E and Ilmaz, O and Topcu, F and Kakac, S}, title = {Extracellular vesicle and CRISPR gene therapy: Current applications in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease.}, journal = {The European journal of neuroscience}, volume = {60}, number = {8}, pages = {6057-6090}, doi = {10.1111/ejn.16541}, pmid = {39297377}, issn = {1460-9568}, mesh = {Humans ; *Genetic Therapy/methods ; *Extracellular Vesicles/metabolism/genetics ; *CRISPR-Cas Systems ; *Huntington Disease/therapy/genetics ; *Amyotrophic Lateral Sclerosis/genetics/therapy ; *Parkinson Disease/therapy/genetics ; *Alzheimer Disease/therapy/genetics ; Animals ; Gene Editing/methods ; Neurodegenerative Diseases/therapy/genetics ; }, abstract = {Neurodegenerative diseases are characterized by progressive deterioration of the nervous system. Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD) are prominently life-threatening examples of neurodegenerative diseases. The complexity of the pathophysiology in neurodegenerative diseases causes difficulties in diagnosing. Although the drugs temporarily help to correct specific symptoms including memory loss and degeneration, a complete treatment has not been found yet. New therapeutic approaches have been developed to understand and treat the underlying pathogenesis of neurodegenerative diseases. With this purpose, clustered-regularly interspaced short palindromic repeats/CRISPR-associated protein (CRISPR/Cas) technology has recently suggested a new treatment option. Editing of the genome is carried out by insertion and deletion processes on DNA. Safe delivery of the CRISPR/Cas system to the targeted cells without affecting surrounding cells is frequently investigated. Extracellular vesicles (EVs), that is exosomes, have recently been used in CRISPR/Cas studies. In this review, CRISPR/Cas and EV approaches used for diagnosis and/or treatment in AD, PD, ALS, and HD are reviewed. CRISPR/Cas and EV technologies, which stand out as new therapeutic approaches, may offer a definitive treatment option in neurodegenerative diseases.}, }
@article {pmid39305271, year = {2024}, author = {Panzetta, ME and Valdivia, RH}, title = {Akkermansia in the gastrointestinal tract as a modifier of human health.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2406379}, pmid = {39305271}, issn = {1949-0984}, support = {R01 AI142376/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Akkermansia/physiology ; Animals ; *Gastrointestinal Tract/microbiology ; Gastrointestinal Diseases/microbiology ; }, abstract = {Akkermansia sp are common members of the human gut microbiota. Multiple reports have emerged linking the abundance of A. muciniphila to health benefits and disease risk in humans and animals. This review highlights findings linking Akkermansia species in the gastrointestinal (GI) tract to health outcomes across a spectrum of disorders, encompassing those that affect the digestive, respiratory, urinary, and central nervous systems. The mechanism through which Akkermansia exerts a beneficial versus a detrimental effect on health is likely dependent on the genetic makeup of the host metabolic capacity and immunomodulatory properties of the strain, the competition or cooperation with other members of the host microbiota, as well as synergy with co-administered therapies.}, }
@article {pmid39304878, year = {2024}, author = {Gozzi, P and Persson, M and Nielsen, A and Kilander, H and Kågesten, AE and Iwarsson, KE and Ljungcrantz, D and Bredell, M and Larsson, EC}, title = {Contraceptive access and use among women with migratory experience living in high-income countries: a scoping review.}, journal = {BMC public health}, volume = {24}, number = {1}, pages = {2569}, pmid = {39304878}, issn = {1471-2458}, mesh = {Humans ; Female ; *Health Services Accessibility ; *Developed Countries ; *Contraception Behavior/statistics &amp; numerical data/psychology ; Transients and Migrants/psychology/statistics &amp; numerical data ; Contraception/statistics &amp; numerical data/psychology ; Europe ; North America ; Australasia ; }, abstract = {BACKGROUND: Women who have migrated often encounter difficulties in accessing healthcare and experience inequitable sexual and reproductive health outcomes in destination countries. These health inequities include contraceptive access and use. To better understand what influences contraceptive access and use, this scoping review set out to synthesize the evidence on contraceptive access and use and on associated interventions among women with migratory experience in high-income countries (HICs) in Europe, North America and Australasia.<br><br>METHODS: The scientific databases PubMed, Web of Science and CINAHL were searched for peer-reviewed quantitative, qualitative and mixed method articles published between January 2000 and June 2023. Articles were included if they reported on studies exploring contraceptive use to prevent pregnancies among women of reproductive age with migratory experience living in HICs. Two researchers independently screened and extracted data from the articles. Findings were categorized by patient and health system level factors according to Levesque et al.'s framework of access to health care.<br><br>RESULTS: A total of 68 articles were included, about half (n&#x2009;=&#x2009;32) from North America. The articles focused on the individual level rather than the health system level, including aspects such as women's contraceptive knowledge, the influence of culture and religion on accessing and using contraception, partner involvement, and differing health insurance coverage. On the health system level, the articles highlighted lack of information on contraceptive services, cultural (in)adequacy of services and communication aspects, contraceptives' side effects, as well as geographic availability and cost of services. The review further identified three articles reporting on interventions related to contraceptive counselling.<br><br>CONCLUSIONS: There is a lack of knowledge regarding how health systems impose obstacles to contraceptive services for women with migratory experience on an organizational level, as research has focused heavily on the individual level. This review's findings may serve as a foundation for further research and advances in policy and practice, specifically recommending early provision of health system related information and contraceptive education, engagement of male partners in contraceptive discourses, cultural competency training for healthcare professionals, and strengthening of interpretation services for contraceptive counselling.}, }
@article {pmid39302063, year = {2024}, author = {Khanna, RK and Catanese, S and Mortemousque, G and Mureau, N and Emond, P and Pisella, PJ and Blasco, H and Corcia, P}, title = {Exploring amyotrophic lateral sclerosis through the visual system: A systematic review.}, journal = {European journal of neurology}, volume = {31}, number = {12}, pages = {e16475}, pmid = {39302063}, issn = {1468-1331}, mesh = {*Amyotrophic Lateral Sclerosis/physiopathology/diagnosis ; Humans ; Vision Disorders/etiology/physiopathology ; Visual Pathways/physiopathology ; }, abstract = {BACKGROUND AND PURPOSE: The human visual system relies on neural networks throughout the brain that are easily accessible for tests exploring eye structures and movements. Over the past two decades, investigations have been carried out on both afferent and efferent components of the visual system in people with amyotrophic lateral sclerosis (ALS). This approach might represent an innovative biomarker research strategy to better characterise the phenotypic variability of ALS. The purpose of this review was to determine whether exploring the visual system of patients with ALS (pwALS) is an effective strategy.<br><br>METHODS: The Medline and Web of science databases were searched for studies with terms relating to ALS and vision. Of 1146 references identified, 43 articles were included.<br><br>RESULTS: In this review article, both afferent and efferent components of the visual system were found to be impaired in pwALS in the absence of visual complaint, thereby contributing to the hypothesis that ALS is a multisystem disease with sensory involvement. Of note, some areas of the eye remain unexplored (i.e., tears, and retinal function using electroretinography).<br><br>CONCLUSIONS: According to the findings available in the literature, investigating the oculomotor system and exploring the ocular surface could represent two key promising strategies to identify new diagnostic biomarkers in pwALS. Further longitudinal studies are needed to identify relevant indicators of disease progression and response to therapeutic intervention.}, }
@article {pmid39298990, year = {2024}, author = {Nicholls-Clow, R and Simmonds-Buckley, M and Waller, G}, title = {Avoidant/restrictive food intake disorder: Systematic review and meta-analysis demonstrating the impact of study quality on prevalence rates.}, journal = {Clinical psychology review}, volume = {114}, number = {}, pages = {102502}, doi = {10.1016/j.cpr.2024.102502}, pmid = {39298990}, issn = {1873-7811}, mesh = {Humans ; Prevalence ; *Avoidant Restrictive Food Intake Disorder ; }, abstract = {OBJECTIVES: The prevalence of Avoidant/Restrictive Food Intake Disorder (ARFID) is unclear. This paper is the first to present meta-analysis based estimates of the prevalence of ARFID, and to assess the impact of the quality of the research on these estimates.<br><br>DESIGN: A pre-registered (Prospero: CRD42023487621) systematic review and meta-analysis.<br><br>METHODS: PubMed, PsychInfo, Web of Science and CINAHL were searched (final date of retrieval 30th July 2024) for peer reviewed papers published between 2013 and 2024. Random-effects and quality effects meta-analyses were used to compute and compare prevalence estimates and to evaluate the impact of study quality on prevalence rates. Subgroups were also considered (gender, age group, clinical status). Loney et al.'s (1998) Critical Appraisal of the Health Research Literature: Prevalence or Incidence of a Health Problem scale was used to assign each study a quality score across three categories - methodological validity (six points); interpretation of results (one point); and applicability of the results (one point).<br><br>RESULTS: Twenty-six studies were identified (n&#xa0;=&#xa0;122,861). Meta-analysis using random-effects indicated a prevalence of 11.14&#xa0;% (95&#xa0;% CI 8.16-14.5&#xa0;%), whereas quality effects prevalence was 4.51&#xa0;% (95&#xa0;% CI 0.7-10.68&#xa0;%). Similar contrasts were evident among subgroups.<br><br>CONCLUSIONS: Even taking the more conservative estimate of 4.51&#xa0;%, this review demonstrates that ARFID is a common disorder, meriting further research and clinical and service developments. Future research needs to be more methodologically robust (larger samples; standardised diagnostic measures; clearer data presentation).}, }
@article {pmid39298423, year = {2024}, author = {Roher, SIG and Martin, DH and Yu, Z and Pride, T and Amirault, M and Rand, JR and Benoit, AC}, title = {How Etuaptmumk/Two-Eyed Seeing is used in indigenous health research: A scoping review.}, journal = {PloS one}, volume = {19}, number = {9}, pages = {e0310247}, pmid = {39298423}, issn = {1932-6203}, mesh = {Humans ; *Health Services, Indigenous ; }, abstract = {Our scoping review sought to describe how Etuaptmumk or Two-Eyed Seeing is used and reported on in Indigenous health research. Using the JBI scoping review methodology, we extracted uses of Etuaptmumk/Two-Eyed Seeing from 83 articles and then categorized the reported uses of Etuaptmumk/Two-Eyed Seeing according to Huria et al.'s eight CONSIDER statement domains (governance, prioritization, relationships, methodologies, participation, capacity, analysis and interpretation, and dissemination). We found that while authors used Etuaptmumk/Two-Eyed Seeing in varied ways and at different stages of their research projects, characterizations of the guiding principle were often insufficiently described or overly simplified. This scoping review intends to contribute to a greater dialogue about how Etuaptmumk/Two-Eyed Seeing is conceptualized and used in Indigenous health research with the goal of encouraging more intentional reporting of the guiding principle.}, }
@article {pmid39295118, year = {2024}, author = {Berry, JD and Paganoni, S and Harms, MB and Shneider, N and Andrews, J and Miller, TM and Babu, S and Sherman, AV and Harris, BT and Provenzano, FA and Phatnani, HP and Shefner, J and Garret, MA and Ladha, SS and Tsou, AY and Mohan, P and Igne, C and ,  and Bowser, R}, title = {Access for ALL in ALS: A large-scale, inclusive, collaborative consortium to unlock the molecular and genetic mechanisms of amyotrophic lateral sclerosis.}, journal = {Muscle &amp; nerve}, volume = {70}, number = {6}, pages = {1140-1150}, pmid = {39295118}, issn = {1097-4598}, support = {OT2 NS136938/NS/NINDS NIH HHS/United States ; OT2 NS136939/NS/NINDS NIH HHS/United States ; 1OT2NS136939-01//National Institute of Neurological Disorders and Stroke, NIH/ ; 1OT2NS136938-01//National Institute of Neurological Disorders and Stroke, NIH/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics ; Humans ; United States ; Biomedical Research ; National Institutes of Health (U.S.) ; }, abstract = {Recent progress in therapeutics for amyotrophic lateral sclerosis (ALS) has spurred development and imbued the field of ALS with hope for more breakthroughs, yet substantial scientific gaps persist. This unmet need remains a stark reminder that innovative paradigms are needed to invigorate ALS research. To move toward more informative, targeted, and personalized drug development, the National Institutes of Health (NIH) established a national ALS clinical research consortium called Access for ALL in ALS (ALL ALS). This new consortium is a multi-institutional effort that aims to organize the ALS clinical research landscape in the United States. ALL ALS is operating in partnership with several stakeholders to operationalize the recommendations of the Accelerating Access to Critical Therapies for ALS Act (ACT for ALS) Public Private Partnership. ALL ALS will provide a large-scale, centralized, and readily accessible infrastructure for the collection and storage of a wide range of data from people living with ALS (symptomatic cohort) or who may be at risk of developing ALS (asymptomatic ALS gene carriers). Importantly, ALL ALS is designed to encourage community engagement, equity, and inclusion. The consortium is prioritizing the enrollment of geographically, ethnoculturally, and socioeconomically diverse participants. Collected data include longitudinal clinical data and biofluids, genomic, and digital biomarkers that will be harmonized and linked to the central Accelerating Medicines Partnership for ALS (AMP ALS) portal for sharing with the research community. The aim of ALL ALS is to deliver a comprehensive, inclusive, open-science dataset to help researchers answer important scientific questions of clinical relevance in ALS.}, }
@article {pmid39292414, year = {2024}, author = {Ataman, R and Alhasani, R and Auneau-Enjalbert, L and Quigley, A and Michael, HU and Ahmed, S}, title = {The psychometric properties of the Quality of Life in Neurological Disorders (Neuro-QoL) measurement system in neurorehabilitation populations: a systematic review.}, journal = {Journal of patient-reported outcomes}, volume = {8}, number = {1}, pages = {106}, pmid = {39292414}, issn = {2509-8020}, support = {36053//Canadian Foundation of Innovation and the Ministry of Health of Quebec/ ; }, mesh = {Humans ; *Nervous System Diseases/rehabilitation/psychology/diagnosis ; *Neurological Rehabilitation/methods ; *Psychometrics/methods ; *Quality of Life/psychology ; Reproducibility of Results ; }, abstract = {OBJECTIVE: To systematically review the literature of existing evidence on the measurement properties of the Quality of Life in Neurological Disorders (Neuro-QoL) measurement system among neurorehabilitation populations.<br><br>DATA SOURCES: The Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) guided this systematic review in which we searched nine electronic databases and registries, and hand-searched reference lists of included articles.<br><br>STUDY SELECTION: Two independent reviewers screened selected articles and extracted data from 28 included studies.<br><br>DATA EXTRACTION: COSMIN's approach guided extraction and synthesizing measurement properties evidence (insufficient, sufficient), and the modified GRADE approach guided synthesizing evidence quality (very-low, low, moderate, high) by diagnosis.<br><br>DATA SYNTHESIS: Neuro-QoL has sufficient measurement properties when used by individuals with Huntington's disease, Multiple Sclerosis, Parkinson's disease, stroke, lupus, cognitive decline, and amyotrophic lateral sclerosis. The strongest evidence is for the first four conditions, where test-retest reliability, construct validity, and responsiveness are nearly always sufficient (GRADE: moderate-high). Structural validity is assessed only in multiple sclerosis and stroke but is often insufficient (GRADE: moderate-high). Criterion validity is sufficient in some stroke and Huntington's disease domains (GRADE: high). Item response theory analyses were reported for some stroke domains only. There is limited, mixed evidence for responsiveness and measurement error (GRADE: moderate-high), and no cross-cultural validity evidence CONCLUSIONS: Neuro-QoL domains can describe and evaluate patients with Huntington's disease, multiple sclerosis, Parkinson's disease, and stroke, but predictive validity evidence would be beneficial. In the other conditions captured in this review, a limited number of Neuro-QoL domains have evidence for descriptive use only. For these conditions, further evidence of structural validity, measurement error, cross-cultural validity and predictive validity would enhance the use and interpretation of Neuro-QoL.}, }
@article {pmid39290830, year = {2024}, author = {Noches, V and Campos-Melo, D and Droppelmann, CA and Strong, MJ}, title = {Epigenetics in the formation of pathological aggregates in amyotrophic lateral sclerosis.}, journal = {Frontiers in molecular neuroscience}, volume = {17}, number = {}, pages = {1417961}, pmid = {39290830}, issn = {1662-5099}, abstract = {The progressive degeneration of motor neurons in amyotrophic lateral sclerosis (ALS) is accompanied by the formation of a broad array of cytoplasmic and nuclear neuronal inclusions (protein aggregates) largely containing RNA-binding proteins such as TAR DNA-binding protein 43 (TDP-43) or fused in sarcoma/translocated in liposarcoma (FUS/TLS). This process is driven by a liquid-to-solid phase separation generally from proteins in membrane-less organelles giving rise to pathological biomolecular condensates. The formation of these protein aggregates suggests a fundamental alteration in the mRNA expression or the levels of the proteins involved. Considering the role of the epigenome in gene expression, alterations in DNA methylation, histone modifications, chromatin remodeling, non-coding RNAs, and RNA modifications become highly relevant to understanding how this pathological process takes effect. In this review, we explore the evidence that links epigenetic mechanisms with the formation of protein aggregates in ALS. We propose that a greater understanding of the role of the epigenome and how this inter-relates with the formation of pathological LLPS in ALS will provide an attractive therapeutic target.}, }
@article {pmid39286440, year = {2024}, author = {Kew, SYN and Mok, SY and Goh, CH}, title = {Machine learning and brain-computer interface approaches in prognosis and individualized care strategies for individuals with amyotrophic lateral sclerosis: A systematic review.}, journal = {MethodsX}, volume = {13}, number = {}, pages = {102765}, pmid = {39286440}, issn = {2215-0161}, abstract = {Amyotrophic lateral sclerosis (ALS) characterized by progressive degeneration of motor neurons is a debilitating disease, posing substantial challenges in both prognosis and daily life assistance. However, with the advancement of machine learning (ML) which is renowned for tackling many real-world settings, it can offer unprecedented opportunities in prognostic studies and facilitate individuals with ALS in motor-imagery tasks. ML models, such as random forests (RF), have emerged as the most common and effective algorithms for predicting disease progression and survival time in ALS. The findings revealed that RF models had an excellent predictive performance for ALS, with a testing R2 of 0.524 and minimal treatment effects of 0.0717 for patient survival time. Despite significant limitations in sample size, with a maximum of 18 participants, which may not adequately reflect the population diversity being studied, ML approaches have been effectively applied to ALS datasets, and numerous prognostic models have been tested using neuroimaging data, longitudinal datasets, and core clinical variables. In many literatures, the constraints of ML models are seldom explicitly enunciated. Therefore, the main objective of this research is to provide a review of the most significant studies on the usage of ML models for analyzing ALS. This review covers a variation of ML algorithms involved in applications in ALS prognosis besides, leveraging ML to improve the efficacy of brain-computer interfaces (BCIs) for ALS individuals in later stages with restricted voluntary muscular control. The key future advances in individualized care and ALS prognosis may include the advancement of more personalized care aids that enable real-time input and ongoing validation of ML in diverse healthcare contexts.}, }
@article {pmid39280794, year = {2024}, author = {Ren, K and Wang, Q and Jiang, D and Liu, E and Alsmaan, J and Jiang, R and Rutkove, SB and Tian, F}, title = {A comprehensive review of electrophysiological techniques in amyotrophic lateral sclerosis research.}, journal = {Frontiers in cellular neuroscience}, volume = {18}, number = {}, pages = {1435619}, pmid = {39280794}, issn = {1662-5102}, support = {R01 NS055099/NS/NINDS NIH HHS/United States ; }, abstract = {Amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disease, is characterized by progressive motor neuron degeneration, leading to widespread weakness and respiratory failure. While a variety of mechanisms have been proposed as causes of this disease, a full understanding remains elusive. Electrophysiological alterations, including increased motor axon excitability, likely play an important role in disease progression. There remains a critical need for non-animal disease models that can integrate electrophysiological tools to better understand underlying mechanisms, track disease progression, and evaluate potential therapeutic interventions. This review explores the integration of electrophysiological technologies with ALS disease models. It covers cellular and clinical electrophysiological tools and their applications in ALS research. Additionally, we examine conventional animal models and highlight advancements in humanized models and 3D organoid technologies. By bridging the gap between these models, we aim to enhance our understanding of ALS pathogenesis and facilitate the development of new therapeutic strategies.}, }
@article {pmid39273694, year = {2024}, author = {Evangelisti, C and Ramadan, S and Orlacchio, A and Panza, E}, title = {Experimental Cell Models for Investigating Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {25}, number = {17}, pages = {}, pmid = {39273694}, issn = {1422-0067}, mesh = {Humans ; *Neurodegenerative Diseases/therapy/pathology/metabolism ; Animals ; *Induced Pluripotent Stem Cells/cytology/metabolism ; *Organoids/pathology ; Models, Biological ; }, abstract = {Experimental models play a pivotal role in biomedical research, facilitating the understanding of disease mechanisms and the development of novel therapeutics. This is particularly true for neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and motor neuron disease, which present complex challenges for research and therapy development. In this work, we review the recent literature about experimental models and motor neuron disease. We identified three main categories of models that are highly studied by scientists. In fact, experimental models for investigating these diseases encompass a variety of approaches, including modeling the patient's cell culture, patient-derived induced pluripotent stem cells, and organoids. Each model offers unique advantages and limitations, providing researchers with a range of tools to address complex biological questions. Here, we discuss the characteristics, applications, and recent advancements in terms of each model system, highlighting their contributions to advancing biomedical knowledge and translational research.}, }
@article {pmid39273435, year = {2024}, author = {Di Chiano, M and Sallustio, F and Fiocco, D and Rocchetti, MT and Spano, G and Pontrelli, P and Moschetta, A and Gesualdo, L and Gadaleta, RM and Gallone, A}, title = {Psychobiotic Properties of Lactiplantibacillus plantarum in Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {25}, number = {17}, pages = {}, pmid = {39273435}, issn = {1422-0067}, support = {1062//PON "RICERCA E INNOVAZIONE" 2014-2020-Innovazione/ ; Call for tender No. 341 of 15 March 2022 of Italian Ministry of University and Research funded by the European Union - Next Generation EU//National Recovery and Resilience Plan (NRRP)/ ; Concession Decree No. 1550 of 11 October 2022 adopted by the Italian Ministry of University and Research, CUP D93C22000890001//Italian Ministry of University and Research, CUP D93C22000890001/ ; Codice progetto n. 2022H9MPZ5//MIUR- PRIN Progetti di Ricerca di Rilevante Interesse Nazionale 2022/ ; Id. 23239//AIRC IG 2019/ ; Call for tender No. 3138 of 16/12/2021 of Italian Ministry of University and Research funded by the European Union//National Recovery and Resilience Plan (NRRP)/ ; Project code: CN00000041, CUP H93C22000430007//NextGenerationEU/ ; PNRR-MR1-2022-12376395//European Union - Next Generation EU - PNRR M6C2/ ; "POFACS" - ARS01_00640 -", D.D. 1211/2020 and 1104/2021//Italian Ministry of University and Research (MIUR)/ ; PRA-HE 2021//University of Foggia/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/microbiology/metabolism ; *Gastrointestinal Microbiome ; *Probiotics/therapeutic use ; Dysbiosis/microbiology ; Brain-Gut Axis ; Animals ; }, abstract = {Neurodegenerative disorders are the main cause of cognitive and physical disabilities, affect millions of people worldwide, and their incidence is on the rise. Emerging evidence pinpoints a disturbance of the communication of the gut-brain axis, and in particular to gut microbial dysbiosis, as one of the contributors to the pathogenesis of these diseases. In fact, dysbiosis has been associated with neuro-inflammatory processes, hyperactivation of the neuronal immune system, impaired cognitive functions, aging, depression, sleeping disorders, and anxiety. With the rapid advance in metagenomics, metabolomics, and big data analysis, together with a multidisciplinary approach, a new horizon has just emerged in the fields of translational neurodegenerative disease. In fact, recent studies focusing on taxonomic profiling and leaky gut in the pathogenesis of neurodegenerative disorders are not only shedding light on an overlooked field but are also creating opportunities for biomarker discovery and development of new therapeutic and adjuvant strategies to treat these disorders. Lactiplantibacillus plantarum (LBP) strains are emerging as promising psychobiotics for the treatment of these diseases. In fact, LBP strains are able to promote eubiosis, increase the enrichment of bacteria producing beneficial metabolites such as short-chain fatty acids, boost the production of neurotransmitters, and support the homeostasis of the gut-brain axis. In this review, we summarize the current knowledge on the role of the gut microbiota in the pathogenesis of neurodegenerative disorders with a particular focus on the benefits of LBP strains in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, autism, anxiety, and depression.}, }
@article {pmid39273079, year = {2024}, author = {Lundt, S and Ding, S}, title = {Potential Therapeutic Interventions Targeting NAD[+] Metabolism for ALS.}, journal = {Cells}, volume = {13}, number = {17}, pages = {}, pmid = {39273079}, issn = {2073-4409}, support = {R01NS069726/NS/NINDS NIH HHS/United States ; R01 NS123023/NS/NINDS NIH HHS/United States ; R21 AG080715/AG/NIA NIH HHS/United States ; R01 NS069726/NS/NINDS NIH HHS/United States ; R21AG080715/AG/NIA NIH HHS/United States ; R01NS123023/NS/NINDS NIH HHS/United States ; }, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/drug therapy ; *NAD/metabolism ; Humans ; Animals ; Disease Models, Animal ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting both upper and lower motor neurons. While there have been many potential factors implicated for ALS development, such as oxidative stress and mitochondrial dysfunction, no exact mechanism has been determined at this time. Nicotinamide adenine dinucleotide (NAD[+]) is one of the most abundant metabolites in mammalian cells and is crucial for a broad range of cellular functions from DNA repair to energy homeostasis. NAD[+] can be synthesized from three different intracellular pathways, but it is the NAD[+] salvage pathway that generates the largest proportion of NAD[+]. Impaired NAD[+] homeostasis has been connected to aging and neurodegenerative disease-related dysfunctions. In ALS mice, NAD[+] homeostasis is potentially disrupted prior to the appearance of physical symptoms and is significantly reduced in the nervous system at the end stage. Treatments targeting NAD[+] metabolism, either by administering NAD[+] precursor metabolites or small molecules that alter NAD[+]-dependent enzyme activity, have shown strong beneficial effects in ALS disease models. Here, we review the therapeutic interventions targeting NAD[+] metabolism for ALS and their effects on the most prominent pathological aspects of ALS in animal and cell models.}, }
@article {pmid39271680, year = {2024}, author = {Shan, Y and Zhang, M and Tao, E and Wang, J and Wei, N and Lu, Y and Liu, Q and Hao, K and Zhou, F and Wang, G}, title = {Pharmacokinetic characteristics of mesenchymal stem cells in translational challenges.}, journal = {Signal transduction and targeted therapy}, volume = {9}, number = {1}, pages = {242}, pmid = {39271680}, issn = {2059-3635}, support = {82104184//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82373949//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82073928//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {Humans ; *Mesenchymal Stem Cells/metabolism/cytology ; *Mesenchymal Stem Cell Transplantation ; Graft vs Host Disease/therapy ; Translational Research, Biomedical ; Amyotrophic Lateral Sclerosis/therapy ; }, abstract = {Over the past two decades, mesenchymal stem/stromal cell (MSC) therapy has made substantial strides, transitioning from experimental clinical applications to commercial products. MSC therapies hold considerable promise for treating refractory and critical conditions such as acute graft-versus-host disease, amyotrophic lateral sclerosis, and acute respiratory distress syndrome. Despite recent successes in clinical and commercial applications, MSC therapy still faces challenges when used as a commercial product. Current detection methods have limitations, leaving the dynamic biodistribution, persistence in injured tissues, and ultimate fate of MSCs in patients unclear. Clarifying the relationship between the pharmacokinetic characteristics of MSCs and their therapeutic effects is crucial for patient stratification and the formulation of precise therapeutic regimens. Moreover, the development of advanced imaging and tracking technologies is essential to address these clinical challenges. This review provides a comprehensive analysis of the kinetic properties, key regulatory molecules, different fates, and detection methods relevant to MSCs and discusses concerns in evaluating MSC druggability from the perspective of integrating pharmacokinetics and efficacy. A better understanding of these challenges could improve MSC clinical efficacy and speed up the introduction of MSC therapy products to the market.}, }
@article {pmid39268298, year = {2024}, author = {Contractor, RN and Shah, M and Manwell, W and Dempsey, KJ and Simhadri, P}, title = {Jean-Martin Charcot: Pioneer of Neurology.}, journal = {Cureus}, volume = {16}, number = {8}, pages = {e66762}, pmid = {39268298}, issn = {2168-8184}, abstract = {Jean-Martin Charcot, born on November 29, 1825, in Paris, France, is known as the father of neurology. During a time when neurology was not yet a recognized medical specialty, Charcot's pioneering contributions significantly advanced the field. Charcot's use of the anatomo-clinical method, which correlates clinical symptoms with anatomical findings, led to the discovery and characterization of numerous neurological conditions, including multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Charcot's joint, and Charcot-Marie-Tooth (CMT) disease. His methodical approach to documenting clinical signs and conducting post-mortem examinations revolutionized neurological research and diagnosis, laying the groundwork for modern neurology. The anatomo-clinical methods continue to be a vital tool in neurological research and practice today. Charcot's work extended beyond clinical practice, influencing the study of neurology through his role as an educator and mentor to many, including Sigmund Freud. Despite some controversies and a reputation for being difficult to work with, Charcot's legacy endures, with his initial discoveries fostering greater awareness and the development of therapies for various neurological disorders.}, }
@article {pmid39258740, year = {2025}, author = {O'Connell, C and Kavanaugh, MS and Cummings, C and Genge, A}, title = {How to break the news in amyotrophic lateral sclerosis/motor neuron disease: practical guidelines from experts.}, journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration}, volume = {26}, number = {1-2}, pages = {5-14}, doi = {10.1080/21678421.2024.2397517}, pmid = {39258740}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology/therapy/diagnosis ; Quality of Life/psychology ; *Communication ; *Motor Neuron Disease/psychology ; *Practice Guidelines as Topic/standards ; }, abstract = {In amyotrophic lateral sclerosis/motor neuron disease (ALS/MND), it is necessary to communicate difficult news during the initial diagnosis and throughout the disease trajectory as the condition progresses. However, delivering difficult news to people with ALS/MND is an emotionally demanding task for healthcare and allied health professionals-one for which many feel ill-prepared because of limited training in this area. Ineffective communication of difficult news damages the patient-provider relationship and negatively impacts patient quality of life (QoL). To address this issue, we developed the A-L S-PIKES protocol based on available literature and our extensive clinical experience. It provides easy-to-follow, stepwise guidelines to effectively deliver difficult news to people with ALS/MND (PALS) that includes: Advance Preparation (preparing for the discussion logistically and emotionally); Location &amp; Setting (creating a comfortable setting that fosters rapport); Patient's Perceptions (assessing PALS' understanding and perception of their condition); Invitation (seeking PALS' permission to share information); Knowledge (sharing information in a clear, understandable manner); Emotion/Empathy (addressing emotions with empathy and providing emotional support); and Strategy &amp; Summary (summarizing the discussion and collaboratively developing a plan of action). A-L S-PIKES provides practical guidelines on how to prepare for and conduct these challenging conversations. It emphasizes effective communication tailored to the individual needs of PALS and their families, empathy, sensitivity, and support for PALS' emotional well-being and autonomy. The aim of A-L S-PIKES is to both enhance skills and confidence in delivering difficult news and to improve the QoL of PALS and their families. Future studies should systematically evaluate the feasibility and effectiveness of A-L S-PIKES to establish its utility in clinical practice.}, }
@article {pmid39256473, year = {2024}, author = {Wang, Y and Ji, Z and Xu, B and Li, S and Xie, Y}, title = {The incidence of acute exacerbation of idiopathic pulmonary fibrosis: a systematic review and meta-analysis.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {21080}, pmid = {39256473}, issn = {2045-2322}, support = {No.212300410056//The Natural Science Foundation of Henan Youth Fund/ ; No.81830116//National Natural Science Foundation of China/ ; HSRP-DFCTCM-2023-3-16//Henan Province Scientific Research Project - Double First-Class Traditional Chinese medicine/ ; DFCTCM-2023-4-05//Henan Province Scientific Research Project - Double First-Class Traditional Chinese medicine/ ; 2023ZY2055//Special Project of Traditional Chinese Medicine Research of Henan Province/ ; No. LHGJ20220586//The Henan Province Medical Science and Technology Program/ ; 2021 No. 15//Henan Province Second Batch of Top-notch Chinese Medicine Talent Projects/ ; No. 2023YFC3502601//The National Key Research and development Program/ ; }, mesh = {Humans ; *Disease Progression ; *Idiopathic Pulmonary Fibrosis/epidemiology/therapy ; Incidence ; Prognosis ; Risk Factors ; }, abstract = {Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease with a high incidence of acute exacerbation and an increasing mortality rate. Currently, treatment methods and effects are limited. Therefore, we conducted a meta-analysis of the incidence of acute exacerbation in patients with IPF, hoping to provide reference for the prevention and management of IPF. We systematically searched the PubMed, Embase, Cochrane Library and Web of Science databases. From the creation of the database to the cohort study on April 3, 2023, we collected studies on the incidence of acute exacerbation of IPF patients, and used Stata software (version 16.0) for meta analysis. We used the Newcastle Ottawa Quality Assessment Scale (NOS) to assess the risk of bias for each study. We calculated the incidence of acute exacerbation in IPF patients and analyzed the risk factors for acute exacerbation in IPF patients and prognostic factors for overall survival from the initial IPF diagnosis. A total of ten cohort studies on the incidence of AE-IPF were included, including 11,855 IPF patients. The results showed that the incidence of acute exacerbation within one year was 9%; the incidence of acute exacerbation within 2 years is 13%; the incidence of acute exacerbation within 3 years is 19%; the incidence of acute exacerbation within 4 years is 11%. In addition, one study reported an acute exacerbation rate of 1.9% within 30 days. The incidence of acute exacerbation within ten years reported in one study was 9.8%. Mura et al.'s article included a retrospective cohort study and a prospective cohort study. The prospective cohort study showed that the incidence of acute exacerbation within 3 years was 18.6%, similar to the results of the retrospective cohort study meta-analysis. Our system evaluation and meta-analysis results show that the incidence of AE-IPF is relatively high. Therefore, sufficient attention should be paid to the research results, including the management and prevention of the disease, in order to reduce the risk of AE.Trial registration: PROSPERO, identifier CRD42022341323.}, }
@article {pmid39254482, year = {2025}, author = {García-Parra, B and Guiu, JM and Povedano, M and Modamio, P}, title = {A scoping review of the role of managed entry agreements in upcoming drugs for amyotrophic lateral sclerosis: learning from the case of spinal muscular atrophy.}, journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration}, volume = {26}, number = {1-2}, pages = {48-57}, doi = {10.1080/21678421.2024.2400522}, pmid = {39254482}, issn = {2167-9223}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/economics ; Humans ; *Muscular Atrophy, Spinal/drug therapy/economics ; }, abstract = {INTRODUCTION: The therapeutic options for spinal muscular atrophy (SMA) are encouraging. However, there is currently no cure for amyotrophic lateral sclerosis (ALS). The clinical and economic uncertainty surrounding innovative treatments for rare neurodegenerative diseases makes it necessary to understand managed entry agreements (MEAs). The aim of this study was to review whether models of MEAs in SMA could be extrapolated to ALS.<br><br>METHODS: We performed a scoping review with information on MEAs on SMA in Web of Science (WOS), PubMed, Lyfegen Library, the National Institute for Health and Care Excellence (NICE), and the Canadian Agency for Drugs and Technologies in Health (CADTH).<br><br>RESULTS: We found 45 results in WOS and PubMed. After an initial survey, 10 were reviewed to assess eligibility, and three were selected. We obtained 44 results from Lyfegen Library, and three results each from NICE and CADTH.<br><br>CONCLUSION: The main objective of MEAs is to reduce uncertainty in the financing of drugs with a high budgetary impact and clinical concerns, as is the case with drugs for SMA and ALS. While the information available on MEAs in SMA is scarce, some conceptual models are publicly available. MEAs for long-term treatments for SMA could be used for the design of MEAs in ALS because of their similarities in economic and clinical uncertainty.}, }
@article {pmid39253877, year = {2024}, author = {Thornburg-Suresh, EJC and Summers, DW}, title = {Microtubules, Membranes, and Movement: New Roles for Stathmin-2 in Axon Integrity.}, journal = {Journal of neuroscience research}, volume = {102}, number = {9}, pages = {e25382}, pmid = {39253877}, issn = {1097-4547}, support = {R01 NS126191/NS/NINDS NIH HHS/United States ; R01NS126191/NH/NIH HHS/United States ; }, mesh = {*Stathmin/metabolism ; *Microtubules/metabolism ; Humans ; *Axons/metabolism/physiology ; Animals ; Cell Membrane/metabolism ; Amyotrophic Lateral Sclerosis/metabolism/pathology ; }, abstract = {Neurons establish functional connections responsible for how we perceive and react to the world around us. Communication from a neuron to its target cell occurs through a long projection called an axon. Axon distances can exceed 1 m in length in humans and require a dynamic microtubule cytoskeleton for growth during development and maintenance in adulthood. Stathmins are microtubule-associated proteins that function as relays between kinase signaling and microtubule polymerization. In this review, we describe the prolific role of Stathmins in microtubule homeostasis with an emphasis on emerging roles for Stathmin-2 (Stmn2) in axon integrity and neurodegeneration. Stmn2 levels are altered in Amyotrophic Lateral Sclerosis and loss of Stmn2 provokes motor and sensory neuropathies. There is growing potential for employing Stmn2 as a disease biomarker or even a therapeutic target. Meeting this potential requires a mechanistic understanding of emerging complexity in Stmn2 function. In particular, Stmn2 palmitoylation has a surprising contribution to axon maintenance through undefined mechanisms linking membrane association, tubulin interaction, and axon transport. Exploring these connections will reveal new insight on neuronal cell biology and novel opportunities for disease intervention.}, }
@article {pmid39251203, year = {2025}, author = {Rolf, O and Blana, A and Hagedorn, P}, title = {Implantation of Reverse Shoulder Endoprothesis Using Navigation.}, journal = {Zeitschrift fur Orthopadie und Unfallchirurgie}, volume = {163}, number = {2}, pages = {176-180}, doi = {10.1055/a-2346-9916}, pmid = {39251203}, issn = {1864-6743}, abstract = {Die Implantation einer inversen Schulterendoprothese (TEP) stellt eine bewährte Methode zur Schmerzlinderung und Schulterfunktionsverbesserung dar. Die Ergebnisse variieren je nach Patientenalter, Krankheitsgrad und Erfahrung des Operateurs. Indikationen für eine inverse TEP sind vielfältig, von der Defektarthropathie bis hin zu Frakturen. Aktuelle Studien zeigen verbesserte Überlebensraten und reduzierte Komplikationen nach primärer Implantation. Die präoperative Planung mittels 3-D-CT oder MRT gilt als Goldstandard. Patientenspezifische Instrumente (PSI) wurden eingeführt, sind jedoch mit Kosten und Wartezeit verbunden. Die Navigation mit "Augmented Reality" (AR) bietet eine effizientere Alternative. Die intraoperative Übertragung der Planung auf den Patienten erfolgt über AR-Brillen und ermöglicht Echtzeitinformationen, wodurch der Chirurg den Blick vom Situs nicht abwenden muss. Dies optimiert den Workflow und bietet potenziell präzisere Implantationsresultate. Zusammenfassend bietet die Kombination von 3-D-Planung, Navigation und AR eine vielversprechende Methode für präzise und effiziente Implantationen von inversen Schulterendoprothesen. Allerdings steht der Nachweis verbesserter Standzeiten und Funktionsscores noch aus.}, }
@article {pmid39246238, year = {2024}, author = {Stock, NM and Blaso, D and Hotton, M}, title = {Caring for a Child with a Cleft Lip and/or Palate: A Narrative Review.}, journal = {The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association}, volume = {}, number = {}, pages = {10556656241280071}, doi = {10.1177/10556656241280071}, pmid = {39246238}, issn = {1545-1569}, abstract = {Raising a child with healthcare needs places additional demands on caregivers. In 2012, Nelson and colleagues authored a review of 57 papers pertaining to parents' experiences of caring for a child with cleft lip and/or palate (CL/P). Thanks in large part to this review, available literature on this topic has grown considerably. The aim of the present review was to update and critically appraise recent literature, with the wider goal of assessing progress in the field and setting recommendations for future work. All original, peer-reviewed articles pertaining to the psychological adjustment of parents of children with CL/P living in high-income countries (published May 2009 to May 2024) were examined. A total of 126 articles were included. Findings were narratively synthesised according to three salient themes: Emotional Impact; Social Experiences; and Care Delivery. Recent research has built on Nelson et al.'s recommendations, addressing some prior gaps in knowledge. Nonetheless, some areas remained largely unexplored and critical methodological limitations were still evident. Recommendations for clinical practice include: improved informational resources for parents and non-specialist health professionals, regular audit of services in collaboration with parents and families, routine psychological screening for known risk factors and integrated psychological support from diagnosis onward. Recommendations for future research include the design of multicentre, prospective, longitudinal studies with sufficient sample sizes and appropriate control/reference groups, inclusion of families from diverse ethnic and socioeconomic backgrounds, further examination of factors contributing to psychological growth, the development and evaluation of psychological interventions, and cross-condition learning.}, }
@article {pmid39243983, year = {2025}, author = {Mohan, M and Mannan, A and Nauriyal, A and Singh, TG}, title = {Emerging targets in amyotrophic lateral sclerosis (ALS): The promise of ATP-binding cassette (ABC) transporter modulation.}, journal = {Behavioural brain research}, volume = {476}, number = {}, pages = {115242}, doi = {10.1016/j.bbr.2024.115242}, pmid = {39243983}, issn = {1872-7549}, mesh = {*Amyotrophic Lateral Sclerosis/metabolism ; Humans ; Animals ; *ATP-Binding Cassette Transporters/metabolism ; Signal Transduction/physiology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative primarily affecting motor neurons, leading to disability and neuronal death, and ATP-Binding Cassette (ABC) transporter due to their role in drug efflux and modulation of various cellular pathways contributes to the pathogenesis of ALS. In this article, we extensively investigated various molecular and mechanistic pathways linking ALS transporter to the pathogenesis of ALS; this involves inflammatory pathways such as Mitogen-Activated Protein Kinase (MAPK), Phosphatidylinositol-3-Kinase/Protein Kinase B (PI3K/Akt), Toll-Like Receptor (TLR), Glycogen Synthase Kinase 3β (GSK-3β), Nuclear Factor Kappa-B (NF-κB), and Cyclooxygenase (COX). Oxidative pathways such as Astrocytes, Glutamate, Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), Sirtuin 1 (SIRT-1), Forkhead box protein O (FOXO), Extracellular signal-regulated kinase (ERK). Additionally, we delve into the role of autophagic pathways like TAR DNA-binding protein 43 (TDP-43), AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), and lastly, the apoptotic pathways. Furthermore, by understanding these intricate interactions, we aim to develop novel therapeutic strategies targeting ABC transporters, improving drug delivery, and ultimately offering a promising avenue for treating ALS.}, }
@article {pmid39242576, year = {2024}, author = {Phillips, MCL and Picard, M}, title = {Neurodegenerative disorders, metabolic icebergs, and mitohormesis.}, journal = {Translational neurodegeneration}, volume = {13}, number = {1}, pages = {46}, pmid = {39242576}, issn = {2047-9158}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/genetics ; *Mitochondria/metabolism ; Hormesis/physiology ; Animals ; }, abstract = {Neurodegenerative disorders are typically "split" based on their hallmark clinical, anatomical, and pathological features, but they can also be "lumped" by a shared feature of impaired mitochondrial biology. This leads us to present a scientific framework that conceptualizes Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD) as "metabolic icebergs" comprised of a tip, a bulk, and a base. The visible tip conveys the hallmark neurological symptoms, neurodegenerative regions, and neuronal protein aggregates for each disorder. The hidden bulk depicts impaired mitochondrial biology throughout the body, which is multifaceted and may be subdivided into impaired cellular metabolism, cell-specific mitotypes, and mitochondrial behaviours, functions, activities, and features. The underlying base encompasses environmental factors, especially modern industrial toxins, dietary lifestyles, and cognitive, physical, and psychosocial behaviours, but also accommodates genetic factors specific to familial forms of AD, PD, and ALS, as well as HD. Over years or decades, chronic exposure to a particular suite of environmental and genetic factors at the base elicits a trajectory of impaired mitochondrial biology that maximally impacts particular subsets of mitotypes in the bulk, which eventually surfaces as the hallmark features of a particular neurodegenerative disorder at the tip. We propose that impaired mitochondrial biology can be repaired and recalibrated by activating "mitohormesis", which is optimally achieved using strategies that facilitate a balanced oscillation between mitochondrial stressor and recovery phases. Sustainably harnessing mitohormesis may constitute a potent preventative and therapeutic measure for people at risk of, or suffering with, neurodegenerative disorders.}, }
@article {pmid39236857, year = {2024}, author = {Reiter, RJ and Sharma, RN and Manucha, W and Rosales-Corral, S and Almieda Chuffa, LG and Loh, D and Luchetti, F and Balduini, W and Govitrapong, P}, title = {Dysfunctional mitochondria in age-related neurodegeneration: Utility of melatonin as an antioxidant treatment.}, journal = {Ageing research reviews}, volume = {101}, number = {}, pages = {102480}, doi = {10.1016/j.arr.2024.102480}, pmid = {39236857}, issn = {1872-9649}, mesh = {*Melatonin/metabolism/pharmacology/therapeutic use ; Humans ; *Antioxidants/pharmacology/therapeutic use ; *Mitochondria/metabolism/drug effects ; *Aging/metabolism/drug effects ; Animals ; *Neurodegenerative Diseases/metabolism/drug therapy ; Oxidative Stress/drug effects ; }, abstract = {Mitochondria functionally degrade as neurons age. Degenerative changes cause inefficient oxidative phosphorylation (OXPHOS) and elevated electron leakage from the electron transport chain (ETC) promoting increased intramitochondrial generation of damaging reactive oxygen and reactive nitrogen species (ROS and RNS). The associated progressive accumulation of molecular damage causes an increasingly rapid decline in mitochondrial physiology contributing to aging. Melatonin, a multifunctional free radical scavenger and indirect antioxidant, is synthesized in the mitochondrial matrix of neurons. Melatonin reduces electron leakage from the ETC and elevates ATP production; it also detoxifies ROS/RNS and via the SIRT3/FOXO pathway it upregulates activities of superoxide dismutase 2 and glutathione peroxidase. Melatonin also influences glucose processing by neurons. In neurogenerative diseases, neurons often adopt Warburg-type metabolism which excludes pyruvate from the mitochondria causing reduced intramitochondrial acetyl coenzyme A production. Acetyl coenzyme A supports the citric acid cycle and OXPHOS. Additionally, acetyl coenzyme A is a required co-substrate for arylalkylamine-N-acetyl transferase, which rate limits melatonin synthesis; therefore, melatonin production is diminished in cells that experience Warburg-type metabolism making mitochondria more vulnerable to oxidative stress. Moreover, endogenously produced melatonin diminishes during aging, further increasing oxidative damage to mitochondrial components. More normal mitochondrial physiology is preserved in aging neurons with melatonin supplementation.}, }
@article {pmid39233624, year = {2024}, author = {Garnier, M and Camdessanché, JP and Cassereau, J and Codron, P}, title = {From suspicion to diagnosis: exploration strategy for suspected amyotrophic lateral sclerosis.}, journal = {Annals of medicine}, volume = {56}, number = {1}, pages = {2398199}, pmid = {39233624}, issn = {1365-2060}, mesh = {*Amyotrophic Lateral Sclerosis/diagnosis/physiopathology ; Humans ; Diagnosis, Differential ; Electromyography/methods ; }, abstract = {The diagnosis of amyotrophic lateral sclerosis (ALS) is based on evidence of upper and lower motor neuron degeneration in the bulbar, cervical, thoracic, and lumbar regions in a patient with progressive motor weakness, in the absence of differential diagnosis. Despite these well-defined criteria, ALS can be difficult to diagnose, given the wide variety of clinical phenotypes. Indeed, the central or peripheral location of the disease varies with a spectrum ranging from predominantly central to exclusively peripheral, symptoms can be extensive or limited to the limbs, bulbar area or respiratory muscles, and the duration of the disease may range from a few months to several decades. In the absence of a specific test, the diagnostic strategy relies on clinical, electrophysiological, biological and radiological investigations to confirm the disease and exclude ALS mimics. The main challenge is to establish a diagnosis based on robust clinical and paraclinical evidence without delaying treatment initiation by increasing the number of additional tests. This approach requires a thorough knowledge of the phenotypes of ALS and its main differential diagnoses.}, }
@article {pmid39233146, year = {2024}, author = {Wang, H and Liu, S and Sun, Y and Chen, C and Hu, Z and Li, Q and Long, J and Yan, Q and Liang, J and Lin, Y and Yang, S and Lin, M and Liu, X and Wang, H and Yu, J and Yi, F and Tan, Y and Yang, Y and Chen, N and Ai, Q}, title = {Target modulation of glycolytic pathways as a new strategy for the treatment of neuroinflammatory diseases.}, journal = {Ageing research reviews}, volume = {101}, number = {}, pages = {102472}, doi = {10.1016/j.arr.2024.102472}, pmid = {39233146}, issn = {1872-9649}, mesh = {Humans ; *Glycolysis/physiology ; *Neuroinflammatory Diseases/metabolism/drug therapy ; Animals ; Aging/metabolism ; }, abstract = {Neuroinflammation is an innate and adaptive immune response initiated by the release of inflammatory mediators from various immune cells in response to harmful stimuli. While initially beneficial and protective, prolonged or excessive neuroinflammation has been identified in clinical and experimental studies as a key pathological driver of numerous neurological diseases and an accelerant of the aging process. Glycolysis, the metabolic process that converts glucose to pyruvate or lactate to produce adenosine 5'-triphosphate (ATP), is often dysregulated in many neuroinflammatory disorders and in the affected nerve cells. Enhancing glucose availability and uptake, as well as increasing glycolytic flux through pharmacological or genetic manipulation of glycolytic enzymes, has shown potential protective effects in several animal models of neuroinflammatory diseases. Modulating the glycolytic pathway to improve glucose metabolism and ATP production may help alleviate energy deficiencies associated with these conditions. In this review, we examine six neuroinflammatory diseases-stroke, Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and depression-and provide evidence supporting the role of glycolysis in their treatment. We also explore the potential link between inflammation-induced aging and glycolysis. Additionally, we briefly discuss the critical role of glycolysis in three types of neuronal cells-neurons, microglia, and astrocytes-within physiological processes. This review highlights the significance of glycolysis in the pathology of neuroinflammatory diseases and its relevance to the aging process.}, }
@article {pmid39230722, year = {2024}, author = {Chalitsios, CV and Ley, H and Gao, J and Turner, MR and Thompson, AG}, title = {Apolipoproteins, lipids, lipid-lowering drugs and risk of amyotrophic lateral sclerosis and frontotemporal dementia: a meta-analysis and Mendelian randomisation study.}, journal = {Journal of neurology}, volume = {271}, number = {10}, pages = {6956-6969}, pmid = {39230722}, issn = {1432-1459}, support = {MR/T006927/1/MRC_/Medical Research Council/United Kingdom ; Thompson/Apr23/896-791/MNDA_/Motor Neurone Disease Association/United Kingdom ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/blood/genetics/epidemiology ; *Apolipoproteins/antagonists &amp; inhibitors/blood/genetics ; *Frontotemporal Dementia/blood/genetics/epidemiology ; Hypolipidemic Agents/pharmacology/therapeutic use ; Lipids/blood ; Mendelian Randomization Analysis ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) have clinical, pathological and genetic overlapping. Lipid pathways are implicated in ALS. This study examined the effect of blood lipid levels on ALS, FTD risk, and survival in ALS.<br><br>METHODS: A systematic review and meta-analysis of high and low-density lipoprotein cholesterol (HDL-c and LDL-c), total cholesterol, triglycerides, apolipoproteins B and A1 levels with ALS was performed. Two-sample Mendelian randomisation (MR) analysis sought the causal effects of these exposures on ALS, FTD, and survival in ALS. The effect of lipid-lowering drugs was also examined using genetic proxies for targets of lipid-lowering medications.<br><br>RESULTS: Three cohort studies met the inclusion criteria for meta-analysis. Meta-analysis indicated an association between higher LDL-c (HRper mmol/L&#x2009;=&#x2009;1.07, 95%CI:1.02-1.12; I 2 =18%) and lower HDL-c (HRper mmol/L&#x2009;=&#x2009;0.83, 95%CI:0.74-0.94; I 2 =0%) with an increased risk of ALS. MR suggested causal effects of higher LDL-c (ORIVW&#x2009;=&#x2009;1.085, 95%:CI 1.008-1.168, pFDR&#x2009;=&#x2009;0.0406), total cholesterol (ORIVW&#x2009;=&#x2009;1.081, 95%:CI 1.013-1.154, pFDR&#x2009;=&#x2009;0.0458) and apolipoprotein B (ORIVW&#x2009;=&#x2009;1.104, 95%:CI 1.041-1.171, pFDR&#x2009;=&#x2009;0.0061) increasing ALS risk, and higher apolipoprotein B level increasing FTD risk (ORIVW&#x2009;=&#x2009;1.424, 95%CI 1.072-1.829, pFDR&#x2009;=&#x2009;0.0382). Reducing LDL-c through APOB inhibition was associated with lower ALS (ORIVW&#x2009;=&#x2009;0.84, 95%CI 0.759-0.929, pFDR&#x2009;=&#x2009;0.00275) and FTD risk (ORIVW&#x2009;=&#x2009;0.581, 95%CI 0.387-0.874, pFDR&#x2009;=&#x2009;0.0362).<br><br>CONCLUSION: These data support the influence of LDL-c and total cholesterol on ALS risk and apolipoprotein B on the risk of ALS and FTD. Potential APOB inhibition might decrease the risk of sporadic ALS and FTD. Further work in monogenic forms of ALS and FTD is necessary to determine whether blood lipids influence penetrance and phenotype.}, }
@article {pmid39225243, year = {2024}, author = {Liang, J and Zhu, Y and Liu, S and Kuang, B and Tian, Z and Zhang, L and Yang, S and Lin, M and Chen, N and Liu, X and Ai, Q and Yang, Y}, title = {Progress of Exosomal MicroRNAs and Traditional Chinese Medicine Monomers in Neurodegenerative Diseases.}, journal = {Phytotherapy research : PTR}, volume = {38}, number = {11}, pages = {5323-5349}, doi = {10.1002/ptr.8322}, pmid = {39225243}, issn = {1099-1573}, support = {//The Key Discipline of Biological Engineering of Hunan University of Chinese Medicine [2018] No. 3/ ; 22JBZ052//Hunan University of Chinese Medicine Discipline Construction Project/ ; 202329-2//Key Project of Changsha Hospital for Maternal &amp; Child Health Care Affiliated to Hunan Normal University/ ; 2021JJ30512//Hunan Natural Science Foundation/ ; 2022JJ40313//Hunan Natural Science Foundation/ ; 2022JJ40456//Hunan Natural Science Foundation/ ; 2023JJ60126//Hunan Natural Science Foundation/ ; 2023JJ60471//Hunan Natural Science Foundation/ ; 21B0354//Outstanding Youth Project of Hunan Education Department/ ; B2023061//Scientific Research Project of Hunan Provincial Administration of Traditional Chinese Medicine/ ; //Hunan University of Chinese Medicine First-class Disciple Construction Project of Chinese Material Medica/ ; kq2014091//Changsha Natural Science Foundation/ ; kq2202269//Changsha Natural Science Foundation/ ; //The First-class Discipline Construction Project of Chemical Engineering and Technology of Hunan University of Traditional Chinese Medicine/ ; 212010//Special Scientific and Technological Project for Comprehensive Utilization of Ampelopsis grossedentata Resources of Hunan Qiankun Biotechnology Co., Ltd/ ; 2019xjjj001//Key Project of Hunan University of Chinese Medicine School level Scientific Research Fund/ ; 2021XJJJ028//Key Project of Hunan University of Chinese Medicine School level Scientific Research Fund/ ; U2202214//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Exosomes/metabolism ; *MicroRNAs/genetics ; *Neurodegenerative Diseases/drug therapy ; *Medicine, Chinese Traditional/methods ; Drugs, Chinese Herbal/pharmacology ; Animals ; }, abstract = {Exosomes, extracellular vesicles secreted by various cells, actively participate in intercellular communication by facilitating the exchange of crucial molecular information such as DNA, RNA, and lipids. Within this intricate network, microRNAs, endogenous non-coding small RNAs, emerge as pivotal regulators of post-transcriptional gene expression, significantly influencing the development of neurodegenerative diseases. The historical prominence of traditional Chinese medicine (TCM) in clinical practice in China underscores its enduring significance. Notably, TCM monomers, serving as active constituents within herbal medicine, assume a critical role in the treatment of neurodegenerative diseases, particularly in mitigating oxidative stress, inhibiting apoptosis, and reducing inflammation. This comprehensive review aims to delineate the specific involvement of exosomal microRNAs in various neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, stroke, and amyotrophic lateral sclerosis. Furthermore, the exploration extends to the application of TCM monomers, elucidating their efficacy as therapeutic agents in these conditions. Additionally, the review examines the utilization of exosomes as drug delivery carriers in the context of neurodegenerative diseases, providing a nuanced understanding of the potential synergies between TCM and modern therapeutic approaches. This synthesis of knowledge aims to contribute to the advancement of our comprehension of the intricate molecular mechanisms underlying neurodegeneration and the potential therapeutic avenues offered by TCcom interventions.}, }
@article {pmid39218769, year = {2024}, author = {Sun, J and Zhang, Y}, title = {Microbiome and micronutrient in ALS: From novel mechanisms to new treatments.}, journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics}, volume = {21}, number = {6}, pages = {e00441}, pmid = {39218769}, issn = {1878-7479}, support = {I01 BX004824/BX/BLRD VA/United States ; R01 DK114126/DK/NIDDK NIH HHS/United States ; R01 DK134343/DK/NIDDK NIH HHS/United States ; }, mesh = {*Amyotrophic Lateral Sclerosis/microbiology/metabolism/therapy ; Humans ; *Micronutrients/metabolism ; *Gastrointestinal Microbiome/physiology ; Animals ; Dysbiosis ; Microbiota/physiology ; }, abstract = {Amyotrophic lateral sclerosis is a neurodegenerative disorder. Despite extensive studies, it remains challenging to treat ALS. Recent ALS studies have shown dysbiosis (e.g., loss of microbial diversity and beneficial function in the gut microbiota) is correlated with intestinal inflammation and change of intestinal integrity in ALS. The novel concepts and the roles of microbiome and microbial metabolites through the gut-microbiome-neuron axis in ALS pathogenesis have been slowly recognized by the neurology research field. Here, we will discuss the recent progress of microbiome, including bacteria, fungi, and viruses, in the ALS research. We will discuss our understanding of microbial metabolites in ALS. Micronutrition refers to the intake of essential vitamins, minerals, and other micronutrients. We will summarize the literation related to micronutrition and ALS. Furthermore, we will consider the mutual interactions of microbiome and micronutrition in the ALS progression and treatment. We further propose that the mechanistic and translational studies that shift from suspension of disbelief to cogent ingenuity, and from bench study to bed-side application, should allow new strategies of diagnosis and treatment for ALS.}, }
@article {pmid39217293, year = {2024}, author = {Aljthalin, R and Albalawi, R and Alyahya, A and Alhathlool, R and Alhashemi, M}, title = {Multiple sclerosis and amyotrophic lateral sclerosis: is there an association or a red flag? A case report and literature review.}, journal = {BMC neurology}, volume = {24}, number = {1}, pages = {307}, pmid = {39217293}, issn = {1471-2377}, mesh = {Humans ; Female ; *Amyotrophic Lateral Sclerosis/diagnosis/complications/pathology ; Middle Aged ; *Multiple Sclerosis/complications/diagnosis/pathology ; Magnetic Resonance Imaging ; }, abstract = {BACKGROUND: Multiple sclerosis (MS) is an inflammatory disease of the central nervous system that causes damage to the myelin and axons and is caused by genetic or environmental factors. Amyotrophic lateral sclerosis (ALS) is characterized by rapidly progressive degeneration of the motor neurons resulting in the presence of upper and lower motor-neuron signs and symptoms.<br><br>CASE PRESENTATION: A 46-year-old female patient presented with symmetrical weakness of the lower limbs and numbness that developed over weeks. Magnetic resonance imaging (MRI) of the brain exhibited typical demyelination features, high signal abnormality involving the periventricular and subcortical white matter, and an oval-shaped lesion. The patient was diagnosed with MS based on the clinical presentation and radiological examination. However, there was rapid progression of the symptoms, involvement of bulbar dysfunction, and muscle atrophy. Furthermore, the patient did not respond to acute therapy and immunotherapy, which made the diagnosis of MS less likely or suggested that it could be associated with another diagnosis. Her neurophysiological test met the criteria of ALS, and she was started on riluzole.<br><br>LITERATURE REVIEW: We reviewed all articles from 1986 to 2023, and there were 32 reported cases describing the co-occurrence of ALS and MS in different populations. Our case is the 33rd, and to our knowledge, it is the only case reported in the Middle East and specifically in Saudi Arabia. The main proposed mechanism according to postmortem examinations is a combination of degenerative and inflammatory processes with a cascade of production of reactive oxygen species and nitric oxide, which lead to cell death and apoptosis during concomitant ALS with MS.<br><br>CONCLUSION: The co-occurrence of ALS and MS is extremely rare, but it can be explained by pathogenesis related to neurodegeneration, inflammation, or genetic susceptibility. Rapid progressive motor and bulbar symptoms could be red-flag symptoms, extensive evaluation might be needed for these patients.}, }
@article {pmid39207717, year = {2024}, author = {Ling, Y and Crotti, A}, title = {Emerging Microglial Therapies and Targets in Clinical Trial.}, journal = {Advances in neurobiology}, volume = {37}, number = {}, pages = {623-637}, pmid = {39207717}, issn = {2190-5215}, mesh = {*Microglia/metabolism ; Humans ; Clinical Trials as Topic ; Neurodegenerative Diseases/drug therapy/therapy/metabolism ; Nervous System Diseases/drug therapy/metabolism ; }, abstract = {Modulation of microglia function for treatment of neurodegenerative and neuropsychiatric disorders is an emerging field of neuroscience drug development. This is largely attributed to human genetic association studies combined with biological evidence indicating that the innate immune system acts as a causal contributor superimposed on the reactive component of neuronal loss in neurological dysfunction. The identification of disease risk gene variants that encode immune-modulatory proteins in microglia provides tools to evaluate how microglia cellular function or dysfunction affect neuronal health. The development of clinical stage therapeutic compounds that modify myeloid cell function enables us to investigate how modulating microglia function could become a transformational approach to mitigate neurological disorders. Improving our ability to boost microglia-promoting homeostatic and reparative functions hopefully will translate into achieving a better outcome for patients affected by neurological diseases. In this chapter, we aim to provide an overview of the microglial emerging therapies and targets being studied in current clinical trials.}, }
@article {pmid39207711, year = {2024}, author = {Holtman, IR and Glass, CK and Nott, A}, title = {Interpretation of Neurodegenerative GWAS Risk Alleles in Microglia and their Interplay with Other Cell Types.}, journal = {Advances in neurobiology}, volume = {37}, number = {}, pages = {531-544}, pmid = {39207711}, issn = {2190-5215}, mesh = {Humans ; *Microglia/metabolism ; *Genome-Wide Association Study ; *Neurodegenerative Diseases/genetics ; *Genetic Predisposition to Disease ; Alleles ; Alzheimer Disease/genetics ; }, abstract = {Microglia have been implicated in numerous neurodegenerative and neuroinflammatory disorders; however, the causal contribution of this immune cell type is frequently debated. Genetic studies offer a unique vantage point in that they infer causality over a secondary consequence. Genome-wide association studies (GWASs) have identified hundreds of loci in the genome that are associated with susceptibility to neurodegenerative disorders. GWAS studies implicate microglia in the pathogenesis of Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and to a lesser degree suggest a role for microglia in vascular dementia (VaD), frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS), and other neurodegenerative and neuropsychiatric disorders. The contribution and function of GWAS risk loci on disease progression is an ongoing field of study, in which large genomic datasets, and an extensive framework of computational tools, have proven to be crucial. Several GWAS risk loci are shared between disorders, pointing towards common pleiotropic mechanisms. In this chapter, we introduce key concepts in GWAS and post-GWAS interpretation of neurodegenerative disorders, with a focus on GWAS risk genes implicated in microglia, their interplay with other cell types and shared convergence of GWAS risk loci on microglia.}, }
@article {pmid39207709, year = {2024}, author = {Awogbindin, I and Wanklin, M and Verkhratsky, A and Tremblay, M&#xc8;}, title = {Microglia in Neurodegenerative Diseases.}, journal = {Advances in neurobiology}, volume = {37}, number = {}, pages = {497-512}, pmid = {39207709}, issn = {2190-5215}, mesh = {*Microglia/metabolism/pathology ; Humans ; *Neurodegenerative Diseases/metabolism ; Alzheimer Disease/metabolism/pathology ; Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology/physiopathology ; Animals ; Parkinson Disease/metabolism ; }, abstract = {Neurodegenerative diseases are manifested by a progressive death of neural cells, resulting in the deterioration of central nervous system (CNS) functions, ultimately leading to specific behavioural and cognitive symptoms associated with affected brain regions. Several neurodegenerative disorders are caused by genetic variants or mutations, although the majority of cases are sporadic and linked to various environmental risk factors, with yet an unknown aetiology. Neuroglial changes are fundamental and often lead to the pathophysiology of neurodegenerative diseases. In particular, microglial cells, which are essential for maintaining CNS health, become compromised in their physiological functions with the exposure to environmental risk factors, genetic variants or mutations, as well as disease pathology. In this chapter, we cover the contribution of neuroglia, especially microglia, to several neurodegenerative diseases, including Nasu-Hakola disease, Parkinson's disease, amyotrophic lateral sclerosis, Alzheimer's disease, Huntington's disease, infectious disease-associated neurodegeneration, and metal-precipitated neurodegeneration. Future research perspectives for the field pertaining to the therapeutic targeting of microglia across these disease conditions are also discussed.}, }
@article {pmid39207520, year = {2024}, author = {Bjelica, B and Petri, S}, title = {Narrative review of diagnosis, management and treatment of dysphagia and sialorrhea in amyotrophic lateral sclerosis.}, journal = {Journal of neurology}, volume = {271}, number = {10}, pages = {6508-6513}, pmid = {39207520}, issn = {1432-1459}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/therapy/diagnosis ; *Sialorrhea/etiology/therapy/diagnosis ; *Deglutition Disorders/etiology/therapy/diagnosis/physiopathology ; Disease Management ; }, abstract = {The degenerative motor neuron disorder amyotrophic lateral sclerosis (ALS) frequently leads bulbar symptoms like dysarthria, dysphagia, and sialorrhea, in approximately one-third of cases being the initial symptom. Throughout the disease, more than two-thirds of ALS patients experience dysphagia, regardless of the region of onset. In this review, we aimed to offer an updated overview of dysphagia and sialorrhea in ALS, covering its diagnosis, monitoring, and treatment in clinical practice. Regular assessment of dysphagia and sialorrhea during each patient visit is essential and should be a standard aspect of ALS care. Early discussion of potential treatments such as high-calorie diets or percutaneous endoscopic gastrostomy (PEG) is crucial. Furthermore, this review highlights and discusses potential areas for improvement in both clinical practice and research.}, }
@article {pmid39206899, year = {2024}, author = {Ma, J and Liu, J and Chen, S and Zhang, W and Wang, T and Cao, M and Yang, Y and Du, Y and Cui, G and Du, Z}, title = {Understanding the Mechanism of Ferroptosis in Neurodegenerative Diseases.}, journal = {Frontiers in bioscience (Landmark edition)}, volume = {29}, number = {8}, pages = {291}, doi = {10.31083/j.fbl2908291}, pmid = {39206899}, issn = {2768-6698}, support = {81602893//National Natural Science Foundation of China (NSFC)/ ; ZR2015YL049//Natural Science Foundation of Shandong Province/ ; ZR2021MH218//Natural Science Foundation of Shandong Province/ ; ZR2022MH184//Natural Science Foundation of Shandong Province/ ; 202104020224//Shandong Province Medical and Health Technology Development Plan/ ; 202312010854//Shandong Province Medical and Health Technology Development Plan/ ; Z-2023114//Shandong Province Traditional Chinese Medicine Science and Technology Plan/ ; 202328074//Jinan Science and Technology Plan/ ; }, mesh = {*Ferroptosis/physiology ; Humans ; *Neurodegenerative Diseases/metabolism/physiopathology ; *Iron/metabolism ; Animals ; Neurons/metabolism/pathology ; }, abstract = {Neurodegenerative disorders are typified by the progressive degeneration and subsequent apoptosis of neuronal cells. They encompass a spectrum of conditions, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), epilepsy, brian ischemia, brian injury, and neurodegeneration with brain iron accumulation (NBIA). Despite the considerable heterogeneity in their clinical presentation, pathophysiological underpinning and disease trajectory, a universal feature of these disorders is the functional deterioration of the nervous system concomitant with neuronal apoptosis. Ferroptosis is an iron (Fe)-dependent form of programmed cell death that has been implicated in the pathogenesis of these conditions. It is intricately associated with intracellular Fe metabolism and lipid homeostasis. The accumulation of Fe is observed in a variety of neurodegenerative diseases and has been linked to their etiology and progression, although its precise role in these pathologies has yet to be elucidated. This review aims to elucidate the characteristics and regulatory mechanisms of ferroptosis, its association with neurodegenerative diseases, and recent advances in ferroptosis-targeted therapeutic strategies. Ferroptosis may therefore be a critical area for future research into neurodegenerative diseases.}, }
@article {pmid39204338, year = {2024}, author = {O'Neill, R and Yoo, O and Burcham, P and Lim, LY}, title = {Edaravone for the Treatment of Motor Neurone Disease: A Critical Review of Approved and Alternative Formulations against a Proposed Quality Target Product Profile.}, journal = {Pharmaceutics}, volume = {16}, number = {8}, pages = {}, pmid = {39204338}, issn = {1999-4923}, support = {000990//Australian Government Research Training Program, Stan Perron Charitable Foundation/ ; }, abstract = {Edaravone is one of two main drugs for treating motor neurone disease (MND). This review proposes a specific quality target product profile (QTPP) for edaravone following an appraisal of the issues accounting for the poor clinical uptake of the approved IV and oral liquid edaravone formulations. This is followed by a review of the alternative oral formulations of edaravone described in the published patent and journal literature against the QTPP. A total of 14 texts published by six research groups on 18 novel oral formulations of edaravone for the treatment of MND have been reviewed. The alternative oral formulations included liquid and solid formulations developed with cyclodextrins, lipids, surfactants, co-surfactants, alkalising agents, tablet excipients, and co-solvents. Most were intended to deliver edaravone for drug absorption in the lower gastrointestinal tract (GIT); however, there were also four formulations targeting the oral mucosal absorption of edaravone to avoid first-pass metabolism. All the novel formulations improved the aqueous solubility, stability, and oral bioavailability (BA) of edaravone compared to an aqueous suspension of edaravone. A common limitation of the published formulations is the lack of MND-patient-centred data. Except for TW001, no other formulations have been trialled in MND patients. To meet the QTPP of an oral edaravone formulation for MND patients, it is recommended that a tablet of appropriate size and with acceptable taste and stability be designed for the effective sublingual or buccal absorption of edaravone. This tablet should be designed with input from the MND community.}, }
@article {pmid39201731, year = {2024}, author = {Fang, C and Wu, J and Liang, W}, title = {Systematic Investigation of Aluminum Stress-Related Genes and Their Critical Roles in Plants.}, journal = {International journal of molecular sciences}, volume = {25}, number = {16}, pages = {}, pmid = {39201731}, issn = {1422-0067}, support = {242102111164; 222301420106//Key R&amp;D and Promotion Projects in Henan Province; Henan Science &amp; Technology Research and Development Plan Joint Fund/ ; }, mesh = {*Aluminum/toxicity ; *Stress, Physiological/genetics ; *Gene Expression Regulation, Plant/drug effects ; Plant Proteins/genetics/metabolism ; Zea mays/genetics/growth &amp; development/metabolism/drug effects ; Plants/genetics/metabolism/drug effects ; Genes, Plant ; }, abstract = {Aluminum (Al) stress is a dominant obstacle for plant growth in acidic soil, which accounts for approximately 40-50% of the world's potential arable land. The identification and characterization of Al stress response (Al-SR) genes in Arabidopsis, rice, and other plants have deepened our understanding of Al's molecular mechanisms. However, as a crop sensitive to acidic soil, only eight Al-SR genes have been identified and functionally characterized in maize. In this review, we summarize the Al-SR genes in plants, including their classifications, subcellular localizations, expression organs, functions, and primarily molecular regulatory networks. Moreover, we predict 166 putative Al-SR genes in maize based on orthologue analyses, facilitating a comprehensive understanding of the impact of Al stress on maize growth and development. Finally, we highlight the potential applications of alleviating Al toxicity in crop production. This review deepens our understanding of the Al response in plants and provides a blueprint for alleviating Al toxicity in crop production.}, }
@article {pmid39201350, year = {2024}, author = {Bedja-Iacona, L and Richard, E and Marouillat, S and Brulard, C and Alouane, T and Beltran, S and Andres, CR and Blasco, H and Corcia, P and Veyrat-Durebex, C and Vourc'h, P}, title = {Post-Translational Variants of Major Proteins in Amyotrophic Lateral Sclerosis Provide New Insights into the Pathophysiology of the Disease.}, journal = {International journal of molecular sciences}, volume = {25}, number = {16}, pages = {}, pmid = {39201350}, issn = {1422-0067}, mesh = {*Amyotrophic Lateral Sclerosis/genetics/metabolism ; Humans ; *Protein Processing, Post-Translational ; *Superoxide Dismutase-1/genetics/metabolism ; *RNA-Binding Protein FUS/metabolism/genetics ; DNA-Binding Proteins/metabolism/genetics ; Protein Serine-Threonine Kinases/metabolism/genetics ; Mutation ; Animals ; Phosphorylation ; Acetylation ; }, abstract = {Post-translational modifications (PTMs) affecting proteins during or after their synthesis play a crucial role in their localization and function. The modification of these PTMs under pathophysiological conditions, i.e., their appearance, disappearance, or variation in quantity caused by a pathological environment or a mutation, corresponds to post-translational variants (PTVs). These PTVs can be directly or indirectly involved in the pathophysiology of diseases. Here, we present the PTMs and PTVs of four major amyotrophic lateral sclerosis (ALS) proteins, SOD1, TDP-43, FUS, and TBK1. These modifications involve acetylation, phosphorylation, methylation, ubiquitination, SUMOylation, and enzymatic cleavage. We list the PTM positions known to be mutated in ALS patients and discuss the roles of PTVs in the pathophysiological processes of ALS. In-depth knowledge of the PTMs and PTVs of ALS proteins is needed to better understand their role in the disease. We believe it is also crucial for developing new therapies that may be more effective in ALS.}, }
@article {pmid39199512, year = {2024}, author = {Turner, N and Faull, C and Palmer, J and Armstrong, A and Bedford, J and Turner, MR and Wilson, E}, title = {Understanding Quality of Life for People with Motor Neurone Disease Who Use Tracheostomy Ventilation and Family Members: A Scoping Review.}, journal = {Brain sciences}, volume = {14}, number = {8}, pages = {}, pmid = {39199512}, issn = {2076-3425}, support = {Wilson/Oct21/968-794/MNDA_/Motor Neurone Disease Association/United Kingdom ; }, abstract = {Tracheostomy ventilation (TV) can increase survival time for people living with motor neurone disease (MND); however, the use of TV varies between countries. Concerns regarding anticipated quality of life (QoL) are among the reasons given by healthcare professionals for not recommending this intervention, yet little is known about QoL in this context. This scoping review was conducted to examine the evidence on QoL for those with MND who use TV and family members involved in their care. Using the methodological guidance of the Joanna Briggs Institute, 23 papers were identified for inclusion, and findings were inductively analysed to identify key themes. We found that people living with MND tend to rate QoL post TV more positively than anticipated by healthcare professionals or family members. QoL was found to be related to positive relationships and activities the person could maintain. Feeling able to make a choice and an adequate level of financial resources were also important factors. Family members tended to experience lower QoL, associated with the uncertainty surrounding an emergency procedure and the complexity of subsequently required care. More evidence on QoL from the perspectives of people with MND who use TV is needed to support decision making and inform guidance.}, }
@article {pmid39199454, year = {2024}, author = {Calma, AD and van den Bos, M and Pavey, N and Santos Silva, C and Menon, P and Vucic, S}, title = {Physiological Biomarkers of Upper Motor Neuron Dysfunction in ALS.}, journal = {Brain sciences}, volume = {14}, number = {8}, pages = {}, pmid = {39199454}, issn = {2076-3425}, abstract = {Upper motor neuron (UMN) dysfunction is an important feature of amyotrophic lateral sclerosis (ALS) for the diagnosis and understanding of pathogenesis. The identification of UMN signs forms the basis of ALS diagnosis, although may be difficult to discern, especially in the setting of severe muscle weakness. Transcranial magnetic stimulation (TMS) techniques have yielded objective physiological biomarkers of UMN dysfunction in ALS, enabling the interrogation of cortical and subcortical neuronal networks with diagnostic, pathophysiological, and prognostic implications. Transcranial magnetic stimulation techniques have provided pertinent pathogenic insights and yielded novel diagnostic and prognostic biomarkers. Cortical hyperexcitability, as heralded by a reduction in short interval intracortical inhibition (SICI) and an increase in short interval intracortical facilitation (SICF), has been associated with lower motor neuron degeneration, patterns of disease evolution, as well as the development of specific ALS clinical features including the split hand phenomenon. Reduction in SICI has also emerged as a potential diagnostic aid in ALS. More recently, physiological distinct inhibitory and facilitatory cortical interneuronal circuits have been identified, which have been shown to contribute to ALS pathogenesis. The triple stimulation technique (TST) was shown to enhance the diagnostic utility of conventional TMS measures in detecting UMN dysfunction. Resting-state EEG is a novel neurophysiological technique developed for directly interrogating cortical neuronal networks in ALS, that have yielded potentially useful physiological biomarkers of UMN dysfunction. The present review discusses physiological biomarkers of UMN dysfunction in ALS, encompassing conventional and novel TMS techniques developed to interrogate the functional integrity of the corticomotoneuronal system, focusing on pathogenic, diagnostic, and prognostic utility.}, }
@article {pmid39199129, year = {2024}, author = {Percio, A and Cicchinelli, M and Masci, D and Summo, M and Urbani, A and Greco, V}, title = {Oxidative Cysteine Post Translational Modifications Drive the Redox Code Underlying Neurodegeneration and Amyotrophic Lateral Sclerosis.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {13}, number = {8}, pages = {}, pmid = {39199129}, issn = {2076-3921}, abstract = {Redox dysregulation, an imbalance between oxidants and antioxidants, is crucial in the pathogenesis of various neurodegenerative diseases. Within this context, the "redoxome" encompasses the network of redox molecules collaborating to maintain cellular redox balance and signaling. Among these, cysteine-sensitive proteins are fundamental for this homeostasis. Due to their reactive thiol groups, cysteine (Cys) residues are particularly susceptible to oxidative post-translational modifications (PTMs) induced by free radicals (reactive oxygen, nitrogen, and sulfur species) which profoundly affect protein functions. Cys-PTMs, forming what is referred to as "cysteinet" in the redox proteome, are essential for redox signaling in both physiological and pathological conditions, including neurodegeneration. Such modifications significantly influence protein misfolding and aggregation, key hallmarks of neurodegenerative diseases such as Alzheimer's, Parkinson's, and notably, amyotrophic lateral sclerosis (ALS). This review aims to explore the complex landscape of cysteine PTMs in the cellular redox environment, elucidating their impact on neurodegeneration at protein level. By investigating specific cysteine-sensitive proteins and the regulatory networks involved, particular emphasis is placed on the link between redox dysregulation and ALS, highlighting this pathology as a prime example of a neurodegenerative disease wherein such redox dysregulation is a distinct hallmark.}, }
@article {pmid39198327, year = {2024}, author = {Wang, JY and Speechley, K and Anderson, KK and Gainham, G and Ali, S and Trottier, ED and Sabhaney, V and Heath, A and Sich, C and Forbes, A and Poonai, N}, title = {Intranasal midazolam for procedural distress in children in the emergency department: a systematic review and meta-analysis.}, journal = {CJEM}, volume = {26}, number = {9}, pages = {658-670}, pmid = {39198327}, issn = {1481-8043}, mesh = {Humans ; *Midazolam/administration &amp; dosage ; *Administration, Intranasal ; *Emergency Service, Hospital ; Child ; Hypnotics and Sedatives/administration &amp; dosage ; Pain, Procedural/prevention &amp; control/etiology ; Child, Preschool ; Anti-Anxiety Agents/administration &amp; dosage/therapeutic use ; Adolescent ; Infant ; }, abstract = {OBJECTIVES: Intranasal (IN) midazolam is the most common anxiolytic for children in the emergency department (ED), but evidence of benefit is conflicting. We synthesized the evidence on IN midazolam for procedural distress in children undergoing ED painful procedures.<br><br>METHODS: We included trials involving painful ED procedures in children 0-18&#xa0;years involving IN midazolam. Primary outcome was procedural distress. We summarized results using Tricco et al.'s classification of "neutral" (p&#x2009;&#x2265;&#x2009;0.05), "favorable," and "unfavorable" (p&#x2009;<&#x2009;0.05), supporting IN midazolam or comparator, respectively, or "indeterminate" (unable to judge). Where possible, we pooled results using meta-analysis.&#xa0;Methodologic quality of evidence was evaluated using Cochrane Collaboration's risk of bias tool and GRADE system.<br><br>RESULTS: We included 41 trials (n&#x2009;=&#x2009;2973 participants). Thirty trials involved intravenous insertion. IN midazolam was superior to placebo (RR&#x2009;=&#x2009;7.2; 95% CI: 3.43, 15.25; 3 trials; I[2]&#x2009;=&#x2009;0%). However, 56-90% of the IN midazolam group resisted the procedure. Focusing on the three trials that used validated measures, IN midazolam was "neutral" versus IN ketamine and either "neutral" or "unfavorable" versus IN dexmedetomidine. There was no difference in the proportion of children with a satisfactory distress score between IN midazolam and oral midazolam (RR&#x2009;=&#x2009;1.1; 95% CI: 0.74, 1.73; 2 trials; I[2]&#x2009;=&#x2009;53%), IN ketamine (RR&#x2009;=&#x2009;1.1; 95% CI: 0.91, 1.25; 6 trials; I[2]&#x2009;=&#x2009;0%), or IN dexmedetomidine (RR&#x2009;=&#x2009;0.4; 95% CI: 0.17, 1.05; 3 trials; I[2]&#x2009;=&#x2009;84%). Ten trials involved laceration repair. IN midazolam was "favorable" versus placebo; however, both groups scored in the anxious range. There was no difference in distress between IN midazolam and oral midazolam (SMD&#x2009;=&#x2009;0.01; 95% CI:-0.32, 0.34; 2 trials; I[2]&#x2009;=&#x2009;0%) (Fig.&#xa0;3E) [64,65]. Using validated instruments, IN midazolam was "unfavorable" versus IN dexmedetomidine but "favorable" versus oral diazepam and placebo.<br><br>CONCLUSIONS: There is limited methodologically rigorous evidence that IN midazolam is better than placebo for IV insertion and laceration repair. At the doses studied, preliminary evidence suggests that IN dexmedetomidine may be superior to IN midazolam for both IV insertion and laceration repair.}, }
@article {pmid39193833, year = {2025}, author = {Jalaiei, A and Asadi, MR and Daneshmandpour, Y and Rezazadeh, M and Ghafouri-Fard, S}, title = {Clinical, molecular, physiologic, and therapeutic feature of patients with CHRNA4 and CHRNB2 deficiency: A systematic review.}, journal = {Journal of neurochemistry}, volume = {169}, number = {1}, pages = {e16200}, doi = {10.1111/jnc.16200}, pmid = {39193833}, issn = {1471-4159}, mesh = {Humans ; *Receptors, Nicotinic/genetics ; Mutation/genetics ; Neurodegenerative Diseases/genetics/metabolism ; }, abstract = {The α4β2 nAChRs are crucial ion channels that control neurotransmitter release and play a role in various physiologic and pathologic processes. CHRNA4 encodes the α4-nAChRs, while CHRNB2 encodes the β2-nAChRs. Recent studies have found different variants of α4β2-nAChRs in individuals with conditions such as AD, ADHD, ALS, PD, and brain abnormalities. We conducted a scoping review following a six-stage methodology structure and adhering to PRISMA guidelines. We systematically reviewed articles using relevant keywords up to October 2, 2023. In this summary, we cover the clinical symptoms reported, the genes and protein structure of CHRNA4 and CHRNB2, mutations in these genes, inheritance patterns, the functional impact of mutations and polymorphisms in CHRNA4 and CHRNB2, and the epidemiology of these diseases. Recent research indicates that nAChRs may play a significant role in neurodegenerative disorders, possibly impacting neuronal function through yet undiscovered regulatory pathways. Studying how nAChRs interact with disease-related aggregates in neurodegenerative conditions may lead to new treatment options for these disorders.}, }
@article {pmid39192797, year = {2024}, author = {Luo, RC and Wu, XY and Yu, WW and Zheng, YJ and Wang, D}, title = {[Research progress on the relationship between TRAF6 and neurodegenerative diseases].}, journal = {Sheng li xue bao : [Acta physiologica Sinica]}, volume = {76}, number = {4}, pages = {653-662}, pmid = {39192797}, issn = {0371-0874}, mesh = {Animals ; Humans ; Alzheimer Disease/metabolism/etiology ; Amyotrophic Lateral Sclerosis/metabolism/physiopathology/genetics/etiology ; Multiple Sclerosis/metabolism/physiopathology/etiology ; *Neurodegenerative Diseases/metabolism/etiology ; Parkinson Disease/metabolism/physiopathology ; *TNF Receptor-Associated Factor 6/metabolism/genetics/physiology ; Ubiquitination ; }, abstract = {Given the increasing trend of aging population in the world, neurodegenerative diseases (NDDs), a common type of diseases that mostly occur in the elderly, have attracted much more attention. It has been shown that tumor necrosis factor receptor-associated factor 6 (TRAF6) is involved in the regulation of neuroinflammation, an important pathological feature of NDDs, and affects the occurrence and development of NDDs. Most importantly, the regulatory effect of TRAF6 is related to its ubiquitination. Therefore, in the present paper, the molecular structure, biological function, and ubiquitination mechanism of TRAF6, and its relationship with some common NDDs, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis, were analyzed and summarized. The possible molecular mechanisms by which TRAF6 regulates the occurrence of NDDs were also elucidated, providing a theoretical basis for exploring the etiology and treatment of NDDs.}, }
@article {pmid39191336, year = {2024}, author = {Sirtori, CR and Castiglione, S and Pavanello, C}, title = {Metformin: From diabetes to cancer to prolongation of life.}, journal = {Pharmacological research}, volume = {208}, number = {}, pages = {107367}, doi = {10.1016/j.phrs.2024.107367}, pmid = {39191336}, issn = {1096-1186}, mesh = {Humans ; *Metformin/therapeutic use/pharmacology ; Animals ; *Neoplasms/drug therapy/metabolism ; *Hypoglycemic Agents/therapeutic use/pharmacology ; *Diabetes Mellitus/drug therapy/metabolism ; Longevity/drug effects ; Antineoplastic Agents/therapeutic use/pharmacology ; }, abstract = {The metformin molecule dates back to over a century, but its clinical use started in the '50s. Since then, its use in diabetics has grown constantly, with over 150 million users today. The therapeutic profile also expanded, with improved understanding of novel mechanisms. Metformin has a major activity on insulin resistance, by acting on the insulin receptors and mitochondria, most likely by activation of the adenosine monophosphate-activated kinase. These and associated mechanisms lead to significant lipid lowering and body weight loss. An anti-cancer action has come up in recent years, with mechanisms partly dependent on the mitochondrial activity and also on phosphatidylinositol 3-kinase resistance occurring in some malignant tumors. The potential of metformin to raise life-length is the object of large ongoing studies and of several basic and clinical investigations. The present review article will attempt to investigate the basic mechanisms behind these diverse activities and the potential clinical benefits. Metformin may act on transcriptional activity by histone modification, DNA methylation and miRNAs. An activity on age-associated inflammation (inflammaging) may occur via activation of the nuclear factor erythroid 2 related factor and changes in gut microbiota. A senolytic activity, leading to reduction of cells with the senescent associated secretory phenotype, may be crucial in lifespan prolongation as well as in ancillary properties in age-associated diseases, such as Parkinson's disease. Telomere prolongation may be related to the activity on mitochondrial respiratory factor 1 and on peroxisome gamma proliferator coactivator 1-alpha. Very recent observations on the potential to act on the most severe neurological disorders, such as amyotrophic lateral sclerosis and frontotemporal dementia, have raised considerable hope.}, }
@article {pmid39191031, year = {2024}, author = {He, Q and Wang, Y and Zhao, F and Wei, S and Li, X and Zeng, G}, title = {APE1: A critical focus in neurodegenerative conditions.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {179}, number = {}, pages = {117332}, doi = {10.1016/j.biopha.2024.117332}, pmid = {39191031}, issn = {1950-6007}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism ; *DNA-(Apurinic or Apyrimidinic Site) Lyase/metabolism ; Animals ; }, abstract = {The global growth of the aging population has resulted in an increased prevalence of neurodegenerative diseases, characterized by the progressive loss of central nervous system (CNS) structure and function. Given the high incidence and debilitating nature of neurodegenerative diseases, there is an urgent need to identify potential biomarkers and novel therapeutic targets thereof. Apurinic/apyrimidinic endonuclease 1 (APE1), has been implicated in several neurodegenerative diseases, as having a significant role. Abnormal APE1 expression has been observed in conditions including Alzheimer's disease, stroke, amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease, and epilepsy. However, whether this dysregulation is protective or harmful remains unclear. This review aims to comprehensively review the current understanding of the involvement of APE1 in neurodegenerative diseases.}, }
@article {pmid39190080, year = {2024}, author = {Jensen, BK}, title = {Astrocyte-Neuron Interactions Contributing to Amyotrophic Lateral Sclerosis Progression.}, journal = {Advances in neurobiology}, volume = {39}, number = {}, pages = {285-318}, pmid = {39190080}, issn = {2190-5215}, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/pathology ; Humans ; *Astrocytes/metabolism ; *Disease Progression ; *Motor Neurons/metabolism/pathology ; *Cell Communication/physiology ; Animals ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a complex disease impacting motor neurons of the brain, brainstem, and spinal cord. Disease etiology is quite heterogeneous with over 40 genes causing the disease and a vast ~90% of patients having no prior family history. Astrocytes are major contributors to ALS, particularly through involvement in accelerating disease progression. Through study of genetic forms of disease including SOD1, TDP43, FUS, C9orf72, VCP, TBK1, and more recently patient-derived cells from sporadic individuals, many biological mechanisms have been identified to cause intrinsic or glial-mediated neurotoxicity to motor neurons. Overall, many of the normally supportive and beneficial roles that astrocytes contribute to neuronal health and survival instead switch to become deleterious and neurotoxic. While the exact pathways may differ based on disease-origin, altered astrocyte-neuron communication is a common feature of ALS. Within this chapter, distinct genetic forms are examined in detail, along with what is known from sporadic patient-derived cells. Overall, this chapter highlights the interplay between astrocytes and neurons in this complex disease and describes the key features underlying: astrocyte-mediated motor neuron toxicity, excitotoxicity, oxidative/nitrosative stress, protein dyshomeostasis, metabolic imbalance, inflammation, trophic factor withdrawal, blood-brain/blood-spinal cord barrier involvement, disease spreading, and the extracellular matrix/cell adhesion/TGF-β signaling pathways.}, }
@article {pmid39187176, year = {2025}, author = {Althobaiti, NA}, title = {Heavy metals exposure and Alzheimer's disease: Underlying mechanisms and advancing therapeutic approaches.}, journal = {Behavioural brain research}, volume = {476}, number = {}, pages = {115212}, doi = {10.1016/j.bbr.2024.115212}, pmid = {39187176}, issn = {1872-7549}, mesh = {Humans ; *Alzheimer Disease/chemically induced ; *Metals, Heavy/adverse effects ; Animals ; Oxidative Stress/drug effects/physiology ; Environmental Exposure/adverse effects ; Brain/drug effects/metabolism ; }, abstract = {Heavy metals such as lead, cadmium, mercury, and arsenic are prevalent in the environment due to both natural and anthropogenic sources, leading to significant public health concerns. These heavy metals are known to cause damage to the nervous system, potentially leading to a range of neurological conditions including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and attention-deficit hyperactivity disorder (ADHD). The present study examines the complex relationship between heavy metal exposure and AD, focusing on the underlying mechanisms of toxicity and potential therapeutic approaches. This review article highlights how these metals can impair brain function through mechanisms such as oxidative stress, inflammation, and neurotransmitter disruption, ultimately contributing to neurodegenerative diseases like AD. It also addresses the challenges in diagnosing heavy metal-induced cognitive impairments and emphasizes the need for further research to explore effective treatment strategies and preventive measures against heavy metal exposure.}, }
@article {pmid39187026, year = {2024}, author = {Rezaei, K and Mastali, G and Abbasgholinejad, E and Bafrani, MA and Shahmohammadi, A and Sadri, Z and Zahed, MA}, title = {Cadmium neurotoxicity: Insights into behavioral effect and neurodegenerative diseases.}, journal = {Chemosphere}, volume = {364}, number = {}, pages = {143180}, doi = {10.1016/j.chemosphere.2024.143180}, pmid = {39187026}, issn = {1879-1298}, mesh = {*Cadmium/toxicity ; Humans ; *Neurodegenerative Diseases/chemically induced ; Animals ; Environmental Pollutants/toxicity ; Brain/drug effects/metabolism ; Neurotoxicity Syndromes/etiology ; Neurons/drug effects ; }, abstract = {Cadmium (Cd) induced neurotoxicity has become a growing concern due to its potential adverse effects on the Central Nervous System. Cd is a Heavy Metal (HM) that is released into the environment, through several industrial processes. It poses a risk to the health of the community by polluting air, water, and soil. Cd builds up in the brain and other neural tissues, raising concerns about its effect on the nervous system due to its prolonged biological half-life. Cd can enter into the neurons, hence increasing the production of Reactive Oxygen Species (ROS) in them and impairing their antioxidant defenses. Cd disrupts the Calcium (Ca[2+]) balance in neurons, affects the function of the mitochondria, and triggers cell death pathways. As a result of these pathways, the path to the development of many neurological diseases affected by environmental factors, especially Cd, such as Alzheimer's Disease (AD) and Amyotrophic Lateral Sclerosis (ALS) is facilitated. There are cognitive deficits associated with long exposure to Cd. Memory disorders are present in both animals and humans. Cd alters the brain's function and performance in critical periods. There are lifelong consequences of Cd exposure during critical brain development stages. The susceptibility to neurotoxic effects is increased by interactions with a variety of risk factors. Cd poses risks to neuronal function and behavior, potentially contributing to neurodegenerative diseases like Parkinson's disease (PD) and AD as well as cognitive issues. This article offers a comprehensive overview of Cd-induced neurotoxicity, encompassing risk assessment, adverse effect levels, and illuminating intricate pathways.}, }
@article {pmid39184484, year = {2024}, author = {Ozceylan, O and Sezgin-Bayindir, Z}, title = {Current Overview on the Use of Nanosized Drug Delivery Systems in the Treatment of Neurodegenerative Diseases.}, journal = {ACS omega}, volume = {9}, number = {33}, pages = {35223-35242}, pmid = {39184484}, issn = {2470-1343}, abstract = {Neurodegenerative diseases, encompassing conditions such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, prion disease, and Huntington's disease, present a growing health concern as human life expectancy increases. Despite this, effective treatments to halt disease progression remain elusive due to various factors, including challenges in drug delivery across physiological barriers like the blood-brain barrier and patient compliance issues leading to treatment discontinuation. In response, innovative treatment approaches leveraging noninvasive techniques with higher patient compliance are emerging as promising alternatives. This Review aims to synthesize current treatment options and the challenges encountered in managing neurodegenerative diseases, while also exploring innovative treatment modalities. Specifically, noninvasive strategies such as intranasal administration and nanosized drug delivery systems are gaining prominence for their potential to enhance treatment efficacy and patient adherence. Nanosized drug delivery systems, including liposomes, polymeric micelles, and nanoparticles, are evaluated within the context of outstanding studies. The advantages and disadvantages of these approaches are discussed, providing insights into their therapeutic potential and limitations. Through this comprehensive examination, this Review contributes to the ongoing discourse surrounding the development of effective treatments for neurodegenerative diseases.}, }
@article {pmid39182937, year = {2024}, author = {Silva, ST and Costa, IM and Souza, AA and Pondofe, K and Melo, LP and Resqueti, VR and Valentim, R and Gonçalves, F and Ribeiro, TS}, title = {Physical therapy for the management of global function, fatigue and quality of life in amyotrophic lateral sclerosis: systematic review and meta-analyses.}, journal = {BMJ open}, volume = {14}, number = {8}, pages = {e076541}, pmid = {39182937}, issn = {2044-6055}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/therapy ; *Quality of Life ; *Physical Therapy Modalities ; *Fatigue/therapy/etiology ; Randomized Controlled Trials as Topic ; }, abstract = {OBJECTIVES: To critically evaluate the effectiveness of physical therapy interventions in improving global function, quality of life and fatigue in individuals with amyotrophic lateral sclerosis (ALS).<br><br>DESIGN: Systematic review and meta-analyses.<br><br>DATA SOURCES: MEDLINE, EMBASE, Cochrane Library (CENTRAL) and Physiotherapy Evidence Database (PEDro) were searched through 31 January 2023.<br><br>ELIGIBILITY CRITERIA: We included randomised clinical trials (RCTs) that compared physical therapy interventions that act on global function, fatigue and quality of life in individuals with ALS with any other non-physiotherapeutic methods and techniques, placebo or non-intervention. The primary outcome measure was the evaluation of global function. Secondary outcomes were quality of life, fatigue and adverse events.<br><br>DATA EXTRACTION AND SYNTHESIS: Two independent authors used a researcher-developed extraction form and the Rayyan software to search, screen and code included studies. The risk of bias was assessed using the PEDro scale. Meta-analyses were conducted employing random effects. Outcomes were succinctly presented in Grading of Recommendations, Assessment, Development and Evaluation evidence profiles.<br><br>RESULTS: Our searches identified 39 415 references. After study selection, three studies were included in the review. Such studies involved 62 participants with a mean age of 54.6 years. In the evaluated trials, 40 were male, while 22 participants were female. Regarding the type of onset of the disease, 58 participants had spinal onset of ALS, and four had bulbar.<br><br>CONCLUSIONS: Physical therapy intervention may improve the global function of individuals with ALS in the short term; however, clinically, it was inconclusive. In terms of quality of life and fatigue, physical therapy intervention is not more effective than control in the short term. Adverse events are not increased by physical therapy intervention in the short term. Due to significant methodological flaws, small sample sizes, wide CIs and clinical interpretation, our confidence in the effect estimate is limited.<br><br>PROSPERO REGISTRATION NUMBER: CRD42021251350.}, }
@article {pmid39182146, year = {2024}, author = {Kill, C and Manegold, RK and Fistera, D and Risse, J}, title = {Airway management and ventilation techniques in resuscitation during advanced life support: an update.}, journal = {Journal of anesthesia, analgesia and critical care}, volume = {4}, number = {1}, pages = {58}, pmid = {39182146}, issn = {2731-3786}, abstract = {For many years, ventilation has been an essential part of advanced life support (ALS) in cardiopulmonary resuscitation (CPR). Nevertheless, there is little evidence about the best method of ventilation during resuscitation for both out-of-hospital cardiac arrest (OHCA) and inhospital cardiac arrest (IHCA) patients. Effective ventilation is one of the two main keys to successful resuscitation. In this context, the question always arises as to which airway management, along with which ventilation mode, constitutes the best strategy. Conventional ventilation modes are not designed for cardiac arrest and show important limitations that must be considered when used in CPR. Manual ventilation without the use of an automated transport ventilator (ATV) could be shown to be uncontrolled in applied volumes and pressures and should be avoided. Mechanical ventilation with an ATV is therefore superior to manual ventilation, but both volume- and pressure-controlled ventilation modes are significantly influenced by chest compressions. With the newly designed chest compression synchronized ventilation (CCSV), a special ventilation mode for resuscitation is available. Further research should be conducted to obtain more evidence of the effect of ventilation during CPR on outcomes following OHCA and not only about how to secure the airway for ventilation during CPR.}, }
@article {pmid39181624, year = {2024}, author = {Mousele, C and Holden, D and Gnanapavan, S}, title = {Neurofilaments in neurologic disease.}, journal = {Advances in clinical chemistry}, volume = {123}, number = {}, pages = {65-128}, doi = {10.1016/bs.acc.2024.06.010}, pmid = {39181624}, issn = {2162-9471}, mesh = {Humans ; *Nervous System Diseases/pathology/metabolism/diagnosis ; *Biomarkers ; Neurofilament Proteins/cerebrospinal fluid/metabolism ; Intermediate Filaments/metabolism ; Animals ; }, abstract = {Neurofilaments (NFs), major cytoskeletal constituents of neurons, have emerged as universal biomarkers of neuronal injury. Neuroaxonal damage underlies permanent disability in various neurological conditions. It is crucial to accurately quantify and longitudinally monitor this damage to evaluate disease progression, evaluate treatment effectiveness, contribute to novel treatment development, and offer prognostic insights. Neurofilaments show promise for this purpose, as their levels increase with neuroaxonal damage in both cerebrospinal fluid and blood, independent of specific causal pathways. New assays with high sensitivity allow reliable measurement of neurofilaments in body fluids and open avenues to investigate their role in neurological disorders. This book chapter will delve into the evolving landscape of neurofilaments, starting with their structure and cellular functions within neurons. It will then provide a comprehensive overview of their broad clinical value as biomarkers in diseases affecting the central or peripheral nervous system.}, }
@article {pmid39180957, year = {2024}, author = {Harkins, AL and Ambegaokar, PP and Keeler, AM}, title = {Immune responses to central nervous system directed adeno-associated virus gene therapy: Does direct CNS delivery make a difference?.}, journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics}, volume = {21}, number = {4}, pages = {e00435}, pmid = {39180957}, issn = {1878-7479}, support = {P01 HL158506/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *Dependovirus/genetics/immunology ; *Genetic Therapy/methods ; *Genetic Vectors/immunology/administration &amp; dosage ; Animals ; Central Nervous System/immunology ; Gene Transfer Techniques ; Central Nervous System Diseases/therapy/immunology ; }, abstract = {Adeno-associated virus (AAV) mediated gene therapy is a leading gene delivery platform with potential to transform the landscape of treatment for neurological disorders. While AAV is deemed non-immunogenic compared to other viral vectors, adverse immune reactions have been observed in the clinic, raising concerns. As the central nervous system (CNS) has a tightly regulated immune system, characterized by a degree of tolerance, it has been considered a unique target for AAV gene therapy. AAV vectors have shown promising results for the treatment of several CNS disorders including Spinal Muscular Atrophy, Giant Axonal Neuropathy, Amyotrophic Lateral Sclerosis, Tay Sachs Disease, Parkinson's Disease, and others, demonstrating safety and success. The Food and Drug Administration (FDA) approval of Zolgensma and European Medicines Agency (EMA) approval of Upstaza, for Spinal Muscular Atrophy (SMA) and Aromatic l-amino acid decarboxylase deficiency (AADC) respectively, represent this success, all while highlighting significant differences in immune responses to AAV, particularly with regards to therapeutic administration route. AAV therapies like Upstaza that are injected directly into the immune-specialized brain have been characterized by mild immune response profiles and minor adverse events, whereas therapies like Zolgensma that are injected systemically demonstrate more robust immune stimulation and off-target toxicities. Despite these contrasting parallels, these therapeutics and others in the clinic have demonstrated clinical benefit for patients, warranting further exploration of immune responses to CNS-directed AAV clinical trials. Thus, in this review, we discuss effects of different routes of AAV administration on eliciting local and peripheral immune responses specifically observed in CNS-targeted trials.}, }
@article {pmid39177131, year = {2024}, author = {Sheremeta, CL and Yarlagadda, S and Smythe, ML and Noakes, PG}, title = {Prostaglandins in the Inflamed Central Nervous System: Potential Therapeutic Targets.}, journal = {Current drug targets}, volume = {25}, number = {13}, pages = {885-908}, pmid = {39177131}, issn = {1873-5592}, support = {Project grant,//Muscular Dystrophy Association/ ; }, mesh = {Humans ; *Prostaglandins/metabolism ; Animals ; *Central Nervous System/metabolism/drug effects ; Alzheimer Disease/drug therapy/metabolism ; Signal Transduction/drug effects ; Multiple Sclerosis/drug therapy/metabolism ; Inflammation/drug therapy/metabolism ; Amyotrophic Lateral Sclerosis/drug therapy/metabolism ; Central Nervous System Diseases/drug therapy/metabolism ; }, abstract = {The global burden of neurological disorders is evident, yet there remains limited efficacious therapeutics for their treatment. There is a growing recognition of the role of inflammation in diseases of the central nervous system (CNS); among the numerous inflammatory mediators involved, prostaglandins play a crucial role. Prostaglandins are small lipid mediators derived from arachidonic acid via multi-enzymatic pathways. The actions of prostaglandins are varied, with each prostaglandin having a specific role in maintaining homeostasis. In the CNS, prostaglandins can have neuroprotective or neurotoxic properties depending on their specific G-protein receptor. These G-protein receptors have varying subfamilies, tissue distribution, and signal transduction cascades. Further studies into the impact of prostaglandins in CNS-based diseases may contribute to the clarification of their actions, hopefully leading to the development of efficacious therapeutic strategies. This review focuses on the roles played by prostaglandins in neural degeneration, with a focus on Alzheimer's Disease, Multiple Sclerosis, and Amyotrophic Lateral Sclerosis in both preclinical and clinical settings. We further discuss current prostaglandin-related agonists and antagonists concerning suggestions for their use as future therapeutics.}, }
@article {pmid39176177, year = {2024}, author = {Al Dera, H and AlQahtani, B}, title = {Molecular mechanisms and antisense oligonucleotide therapies of familial amyotrophic lateral sclerosis.}, journal = {Molecular therapy. Nucleic acids}, volume = {35}, number = {3}, pages = {102271}, pmid = {39176177}, issn = {2162-2531}, abstract = {Amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease, presents considerable challenges in both diagnosis and treatment. It is categorized into sporadic and familial amyotrophic lateral sclerosis (fALS); the latter accounts for approximately 10% of cases and is primarily inherited in an autosomal dominant manner. This review summarizes the molecular genetics of fALS, highlighting key mutations that contribute to its pathogenesis, such as mutations in SOD1, FUS, and C9orf72. Central to this discourse is exploring antisense oligonucleotides (ASOs) that target these genetic aberrations, providing a promising therapeutic strategy. This review provides a detailed overview of the molecular mechanisms underlying fALS and the potential therapeutic value of ASOs, offering new insights into treating neurodegenerative diseases.}, }
@article {pmid39175128, year = {2024}, author = {Wu, A and Lee, D and Xiong, WC}, title = {VPS35 or retromer as a potential target for neurodegenerative disorders: barriers to progress.}, journal = {Expert opinion on therapeutic targets}, volume = {28}, number = {8}, pages = {701-712}, pmid = {39175128}, issn = {1744-7631}, support = {R01 AG045781/AG/NIA NIH HHS/United States ; RF1 AG045781/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Neurodegenerative Diseases/physiopathology/drug therapy ; *Vesicular Transport Proteins/metabolism ; Animals ; *Molecular Targeted Therapy ; Protein Transport ; Parkinson Disease/physiopathology/drug therapy ; Mutation, Missense ; Drug Development ; }, abstract = {INTRODUCTION: Vacuolar Protein Sorting 35 (VPS35) is pivotal in the retromer complex, governing transmembrane protein trafficking within cells, and its dysfunction is implicated in neurodegenerative diseases. A missense mutation, Asp620Asn (D620N), specifically ties to familial late-onset Parkinson's, while reduced VPS35 levels are observed in Alzheimer's, amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and tauopathies. VPS35's absence in certain neurons during development can initiate neurodegeneration, highlighting its necessity for neural health. Present therapeutic research mainly targets the clearance of harmful protein aggregates and symptom management. Innovative treatments focusing on VPS35 are under investigation, although fully understanding the mechanisms and optimal targeting strategies remain a challenge.<br><br>AREAS COVERED: This review offers a detailed account of VPS35's discovery, its role in neurodegenerative mechanisms - especially in Parkinson's and Alzheimer's - and its link to other disorders. It shines alight on recent insights into VPS35's function in development, disease, and as a therapeutic target.<br><br>EXPERT OPINION: VPS35 is integral to cellular function and disease association, making it a significant candidate for developing therapies. Progress in modulating VPS35's activity may lead to breakthrough treatments that not only slow disease progression but may also act as biomarkers for neurodegeneration risk, marking a step forward in managing these complex conditions.}, }
@article {pmid39174305, year = {2025}, author = {Mohamed Yusoff, AA and Mohd Khair, SZN}, title = {Unraveling mitochondrial dysfunction: comprehensive perspectives on its impact on neurodegenerative diseases.}, journal = {Reviews in the neurosciences}, volume = {36}, number = {1}, pages = {53-90}, pmid = {39174305}, issn = {2191-0200}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism ; *Mitochondria/metabolism ; Animals ; Mitochondrial Dynamics/physiology ; Mitochondrial Diseases/metabolism ; Mitophagy/physiology ; }, abstract = {Neurodegenerative diseases represent a significant challenge to modern medicine, with their complex etiology and progressive nature posing hurdles to effective treatment strategies. Among the various contributing factors, mitochondrial dysfunction has emerged as a pivotal player in the pathogenesis of several neurodegenerative disorders. This review paper provides a comprehensive overview of how mitochondrial impairment contributes to the development of neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, driven by bioenergetic defects, biogenesis impairment, alterations in mitochondrial dynamics (such as fusion or fission), disruptions in calcium buffering, lipid metabolism dysregulation and mitophagy dysfunction. It also covers current therapeutic interventions targeting mitochondrial dysfunction in these diseases.}, }
@article {pmid39171600, year = {2025}, author = {Nogueira-Machado, JA and das Chagas Lima E Silva, F and Rocha-Silva, F and Gomes, N}, title = {Amyotrophic Lateral Sclerosis (ALS): An Overview of Genetic and Metabolic Signaling Mechanisms.}, journal = {CNS &amp; neurological disorders drug targets}, volume = {24}, number = {2}, pages = {83-90}, pmid = {39171600}, issn = {1996-3181}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; *Signal Transduction/genetics/physiology ; Mutation/genetics ; Animals ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a rare, progressive, and incurable disease. Sporadic (sALS) accounts for ninety percent of ALS cases, while familial ALS (fALS) accounts for around ten percent. Reports have identified over 30 different forms of familial ALS. Multiple types of fALS exhibit comparable symptoms with mutations in different genes and possibly with different predominant metabolic signals. Clinical diagnosis takes into account patient history but not genetic mutations, misfolded proteins, or metabolic signaling. As research on genetics and metabolic pathways advances, it is expected that the intricate complexity of ALS will compound further. Clinicians discuss whether a gene's presence is a cause of the disease or just an association or consequence. They believe that a mutant gene alone is insufficient to diagnose ALS. ALS, often perceived as a single disease, appears to be a complex collection of diseases with similar symptoms. This review highlights gene mutations, metabolic pathways, and muscle-neuron interactions.}, }
@article {pmid39170988, year = {2024}, author = {Baroni, LM and Funari, MP and So Taa Kum, A and Bestetti, AM and de Oliveira, LB and de Carvalho, MF and Franzini, TAP and de Moura, DTH and Bernardo, WM and de Moura, EGH}, title = {Endoscopic Versus Surgical Treatment for Ampullary Lesions: A Systematic Review With Meta-Analysis.}, journal = {Cureus}, volume = {16}, number = {7}, pages = {e65076}, pmid = {39170988}, issn = {2168-8184}, abstract = {Ampullary lesions (ALs) can be treated through either an endoscopic approach (EA) or a surgical approach (SA). However, it is important to note that EAs carry a significant risk of incomplete resection, while opting for surgical interventions can result in substantial morbidity. We performed a systematic review and meta-analysis for R0 resection, recurrence, adverse events in general, major adverse events, mortality, and length of hospital stay between SAs and EAs. Electronic databases were searched from inception to 2023. We identified nine independent studies. The risk difference was -0.32 (95% CI: -0.50, -0.15; p <0.001) for R0, 0.12 (95% CI: 0.06, 0.19; p < 0.001) for recurrence, -0.22 (95% CI: -0.43, 0.00; p 0.05) for overall adverse events, -0.11 (95% CI: -0.32, 0.10; p = 0.31) for major complications, -0.01 (95% CI: -0.02, 0.01; p = 0.43) for mortality, and -14.69 (95% CI: -19.91, -9.47; p < 0.001) for length of hospital stay. As expected, our data suggest a higher complete resection rate and lower recurrence from surgical interventions, but this is associated with an elevated risk of adverse events and a longer hospital stay.}, }
@article {pmid39170125, year = {2024}, author = {Wenzhi, Y and Xiangyi, L and Dongsheng, F}, title = {The prion-like effect and prion-like protein targeting strategy in amyotrophic lateral sclerosis.}, journal = {Heliyon}, volume = {10}, number = {15}, pages = {e34963}, pmid = {39170125}, issn = {2405-8440}, abstract = {Pathological proteins in amyotrophic lateral sclerosis (ALS), such as superoxide dismutase 1, TAR DNA-binding protein 43, and fused in sarcoma, exhibit a prion-like pattern. All these proteins have a low-complexity domain and seeding activity in cells. In this review, we summarize the studies on the prion-like effect of these proteins and list six prion-like protein targeting strategies that we believe have potential for ALS therapy, including antisense oligonucleotides, antibody-based technology, peptide, protein chaperone, autophagy enhancement, and heteromultivalent compounds. Considering the pathological complexity and heterogeneity of ALS, we believe that the final solution to ALS therapy is most likely to be an individualized cocktail therapy, including clearance of toxicity, blockage of pathological progress, and protection of neurons.}, }
@article {pmid39168583, year = {2024}, author = {Memudu, AE and Olukade, BA and Adebayo, OS and Raza, ML}, title = {Coffee and amyotrophic lateral sclerosis (ALS).}, journal = {Progress in brain research}, volume = {289}, number = {}, pages = {81-105}, doi = {10.1016/bs.pbr.2024.06.003}, pmid = {39168583}, issn = {1875-7855}, mesh = {*Amyotrophic Lateral Sclerosis/pathology ; Humans ; *Coffee ; Animals ; Neuroprotective Agents/pharmacology ; Oxidative Stress/physiology/drug effects ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterized by progressive loss of motor neurons. The effective treatments for ALS remain elusive, necessitating exploration into novel preventive strategies. ALS pathogenesis is triggered by oxidative stress which results in neuroinflammation, exicitotoxicity and neuronal cell death. Nutritional mechanism for halting progression of neurodegeneration is through dietary compounds with antioxidants, anti-inflammatory or neuromodulating activity. Coffee is a widely consumed beverage made up of polyphenols, caffeine and other compounds with possible antioxidants and neuro-protective roles. It is important to say that various epidemiological studies have documented association between coffee intake and ALS. This chapter is aimed to present a comprehensive review of existing literature on coffee consumption and ALS, involving epidemiological studies, preclinical research, and its mechanism of actions in animal model of ALS. It highlights key findings regarding the potential neuroprotective properties of coffee constituents such as caffeine, polyphenols, and other bioactive compounds. Furthermore, it discusses possible pathways through which coffee may modulate ALS pathogenesis, including suppressing oxidative stress and neuroinflammation while boosting adenosine function via the adenosine receptor two on the motor neuron cells membrane in the spinal cord to enhance motor function via the corticospinal tract. Overall, this chapter underscores the significance of further research to unravel the specific mechanisms by which coffee exerts its neuroprotective effects in ALS, with the ultimate goal of identifying dietary strategies for ALS prevention and management.}, }
@article {pmid39168577, year = {2024}, author = {Rai, SP and Ansari, AH and Singh, D and Singh, S}, title = {Coffee, antioxidants, and brain inflammation.}, journal = {Progress in brain research}, volume = {289}, number = {}, pages = {123-150}, doi = {10.1016/bs.pbr.2024.06.005}, pmid = {39168577}, issn = {1875-7855}, mesh = {*Coffee/chemistry ; Humans ; *Antioxidants/pharmacology ; Animals ; Neurodegenerative Diseases ; Encephalitis ; Caffeine/pharmacology/administration &amp; dosage ; Neuroinflammatory Diseases ; }, abstract = {Coffee is the most popular beverage in the world and, aside from tea and water, the most often consumed caffeine-containing beverage. Because of its high caffeine concentration, it is typically classified as a stimulant. There are other bioactive ingredients in coffee besides caffeine. The coffee beverage is a blend of several bioactive substances, including diterpenes (cafestol and kahweol), alkaloids (caffeine and trigonelline), and polyphenols (particularly chlorogenic acids in green beans and caffeic acid in roasted coffee beans). Caffeine has also been linked to additional beneficial benefits such as antioxidant and anti-inflammatory properties, which change cellular redox and inflammatory status in a dose-dependent manner. Pyrocatechol, a constituent of roasted coffee that is created when chlorogenic acid is thermally broken down, has anti-inflammatory properties as well. It is postulated that coffee consumption reduces neuroinflammation, which is intimately linked to the onset of neurodegenerative disorders like Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD). This review provides an overview of the most recent studies regarding coffee's possible benefits in preventing brain inflammation and neurodegenerative disorders.}, }
@article {pmid39168358, year = {2024}, author = {Ueno, Y and Morishima, Y and Hata, T and Shindo, A and Murata, H and Saito, T and Nakamura, Y and Shindo, K}, title = {Current progress in microRNA profiling of circulating extracellular vesicles in amyotrophic lateral sclerosis: A systematic review.}, journal = {Neurobiology of disease}, volume = {200}, number = {}, pages = {106639}, doi = {10.1016/j.nbd.2024.106639}, pmid = {39168358}, issn = {1095-953X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/blood/genetics/diagnosis ; Biomarkers/blood ; *Extracellular Vesicles/metabolism/genetics ; *MicroRNAs/blood/genetics ; }, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease affecting upper and lower motor neurons, leading to death resulting mainly from respiratory failure, for which there is currently no curative treatment. Underlying pathological mechanisms for the development of ALS are diverse and have yet to be elucidated. Non-invasive testing to isolate circulating molecules including microRNA to diagnose ALS has been reported, but circulating extracellular vesicle (EV)-derived microRNA has not been fully studied in the ALS population.<br><br>METHODS: A systematic literature review to explore studies investigating the profile of microRNAs in EVs from blood samples of ALS patients was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline.<br><br>RESULTS: Eleven studies including a total of 263 patients with ALS were included in the present systematic review. The majority of patients had sporadic ALS, though a small number of patients with ALS having genetic mutations were included. Seven studies used plasma-derived EVs, and the remaining four studies used serum-derived EVs. RNA sequencing or microarrays were used in eight studies, and quantitative PCR was used in eight studies, of which five studies used RNA sequencing or microarrays for screening and quantitative PCR for validation. There was overlap of miR-199a-3p and miR-199a-5p in three studies.<br><br>CONCLUSIONS: Overall, the systematic review addressed the current advances in the profiling of microRNAs in circulating EVs of ALS patients. Blood samples, isolation of EVs, and microRNA analysis were diverse. Although there was an overlap of miR-199a-3p and miR-199a-5p, collection of further evidence is warranted.}, }
@article {pmid39163164, year = {2025}, author = {Raggi, A and Serretti, A and Ferri, R}, title = {The P300 component of the auditory event-related potential in adult psychiatric and neurologic disorders: a narrative review of clinical and experimental evidence.}, journal = {International clinical psychopharmacology}, volume = {40}, number = {5}, pages = {259-274}, doi = {10.1097/YIC.0000000000000566}, pmid = {39163164}, issn = {1473-5857}, mesh = {Humans ; *Event-Related Potentials, P300/physiology ; *Mental Disorders/physiopathology/diagnosis ; *Nervous System Diseases/physiopathology/diagnosis ; *Evoked Potentials, Auditory/physiology ; Adult ; Electroencephalography ; Neuropsychological Tests ; }, abstract = {The auditory P300 wave, also known as P3b, is an event-related potential component thought to reflect central information processes involved in stimulus evaluation or categorization. It is typically elicited using the oddball paradigm, which involves mixing low-probability target items with high-probability standard stimuli. Its latency is associated with the timing of cognitive processes such as stimulus evaluation and response preparation, while its amplitude is related to the amount of attentional resources engaged during the task. Despite decades of use in research settings, its application in clinical practice has been limited. Prolongation of latencies and reduction of amplitudes in the auditory P3b have been observed in both psychiatric and neurological conditions. This includes cases where traditional neuropsychological tests are challenging due to severe motor or speech dysfunctions, or in conditions characterized by subtle cognitive deficits. Additionally, specific laterality patterns in psychoses and a loss of P300 habituation in migraines have been described. The wealth of experimental evidence supports the use of this evoked potential, which can be elicited through a relatively simple paradigm, for objectively evaluating cognition in psychiatric and neurological patients, particularly in follow-up assessments. Therefore, the auditory P300 appears to be a valuable tool for monitoring the clinical course of patients with mental and neurological disorders in certain circumstances.}, }
@article {pmid39162129, year = {2024}, author = {Mazzini, L and De Marchi, F and Buzanska, L and Follenzi, A and Glover, JC and Gelati, M and Lombardi, I and Maioli, M and Mesa-Herrera, F and Mitrečić, D and Olgasi, C and Pivoriūnas, A and Sanchez-Pernaute, R and Sgromo, C and Zychowicz, M and Vescovi, A and Ferrari, D}, title = {Current status and new avenues of stem cell-based preclinical and therapeutic approaches in amyotrophic lateral sclerosis.}, journal = {Expert opinion on biological therapy}, volume = {24}, number = {9}, pages = {933-954}, doi = {10.1080/14712598.2024.2392307}, pmid = {39162129}, issn = {1744-7682}, mesh = {*Amyotrophic Lateral Sclerosis/therapy/genetics ; Humans ; Animals ; *Stem Cell Transplantation ; Disease Models, Animal ; Clinical Trials as Topic ; }, abstract = {INTRODUCTION: Cell therapy development represents a critical challenge in amyotrophic lateral sclerosis (ALS) research. Despite more than 20 years of basic and clinical research, no definitive safety and efficacy results of cell-based therapies for ALS have been published.<br><br>AREAS COVERED: This review summarizes advances using stem cells (SCs) in pre-clinical studies to promote clinical translation and in clinical trials to treat ALS. New technologies have been developed and new experimental in vitro and animal models are now available to facilitate pre-clinical research in this field and to determine the most promising approaches to pursue in patients. New clinical trial designs aimed at developing personalized SC-based treatment with biological endpoints are being defined.<br><br>EXPERT OPINION: Knowledge of the basic biology of ALS and on the use of SCs to study and potentially treat ALS continues to grow. However, a consensus has yet to emerge on how best to translate these results into therapeutic applications. The selection and follow-up of patients should be based on clinical, biological, and molecular criteria. Planning of SC-based clinical trials should be coordinated with patient profiling genetically and molecularly to achieve personalized treatment. Much work within basic and clinical research is still needed to successfully transition SC therapy in ALS.}, }
@article {pmid39156974, year = {2024}, author = {Fenili, G and Scaricamazza, S and Ferri, A and Valle, C and Paronetto, MP}, title = {Physical exercise in amyotrophic lateral sclerosis: a potential co-adjuvant therapeutic option to counteract disease progression.}, journal = {Frontiers in cell and developmental biology}, volume = {12}, number = {}, pages = {1421566}, pmid = {39156974}, issn = {2296-634X}, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal disorder characterized by the selective degeneration of upper and lower motor neurons, leading to progressive muscle weakness and atrophy. The mean survival time is two to five years. Although the hunt for drugs has greatly advanced over the past decade, no cure is available for ALS yet. The role of intense physical activity in the etiology of ALS has been debated for several decades without reaching a clear conclusion. The benefits of organized physical activity on fitness and mental health have been widely described. Indeed, by acting on specific mechanisms, physical activity can influence the physiology of several chronic conditions. It was shown to improve skeletal muscle metabolism and regeneration, neurogenesis, mitochondrial biogenesis, and antioxidant defense. Interestingly, all these pathways are involved in ALS pathology. This review will provide a broad overview of the effect of different exercise protocols on the onset and progression of ALS, both in humans and in animal models. Furthermore, we will discuss challenges and opportunities to exploit physiological responses of imposed exercise training for therapeutic purposes.}, }
@article {pmid39156432, year = {2024}, author = {Kaye, AD and Sala, KR and Dethloff, D and Norton, M and Moss, C and Plessala, MJ and Derouen, AG and Lopez Torres, Y and Kim, J and Tirumala, S and Shekoohi, S and Varrassi, G}, title = {The Evolving Use of Gold Nanoparticles as a Possible Reversal Agent for the Symptoms of Neurodegenerative Diseases: A Narrative Review.}, journal = {Cureus}, volume = {16}, number = {7}, pages = {e64846}, pmid = {39156432}, issn = {2168-8184}, abstract = {Neurodegenerative diseases are broadly hallmarked by impaired energy metabolism and toxic intracellular accumulations such as damaged organelles or reactive oxygen species (ROS). Gold nanoparticles readily cross the blood-brain barrier and increase nicotinamide adenine dinucleotide + hydrogen (NADH) oxidation to nicotinamide adenine dinucleotide (NAD+), which is vital for intracellular energy generation, cellular repair, and protection from ROS. Thus, the use of gold nanoparticles to treat and potentially reverse cellular injury seen in neurodegenerative disease has been an area of ongoing research. This systematic review explores current literature regarding the use of gold nanoparticle therapy in the treatment of neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). In vitro studies of CNM-Au8 (Clene Nanomedicine, Salt Lake City, UT) have been shown to reduce TDP-43 aggregates associated with ALS. These studies also exhibited the neuroprotective effects of CNM-Au8 in rat primary neurons exposed to amyloid-beta peptides, which are associated with Alzheimer's disease. In animal models of MS, oral delivery of CNM-Au8 was demonstrated to produce robust and significant remyelination activity, oligodendrocyte maturation, and expression of myelin markers. In these same MS animal models, CNM-Au8 improved the motor function of cuprizone-treated mice in both open-field and kinematic gait studies. Recent phase II trials of CNM-Au8 in 13 patients with Parkinson's disease and 11 patients with stable relapsing MS demonstrated a statistically significant increase in the NAD+/NADH ratio across two cohorts. As the current data repeatedly suggest, these gold nanoparticles are efficacious for the treatment and reversal of symptoms across these varying neurodegenerative pathologies. Further opportunities exist for increasing human trials and eventually incorporating this new technology into existing treatment regimens.}, }
@article {pmid39153108, year = {2024}, author = {Hosseini, L and Babaie, S and Shahabi, P and Fekri, K and Shafiee-Kandjani, AR and Mafikandi, V and Maghsoumi-Norouzabad, L and Abolhasanpour, N}, title = {Klotho: molecular mechanisms and emerging therapeutics in central nervous system diseases.}, journal = {Molecular biology reports}, volume = {51}, number = {1}, pages = {913}, pmid = {39153108}, issn = {1573-4978}, mesh = {*Klotho Proteins ; Humans ; *Central Nervous System Diseases/metabolism/drug therapy ; *Signal Transduction ; Animals ; Oxidative Stress ; Glucuronidase/metabolism/genetics ; Autophagy ; Aging/metabolism/genetics ; }, abstract = {Klotho is recognized as an aging-suppressor protein that is implicated in a variety of processes and signaling pathways. The anti-inflammatory, anti-apoptotic, anti-oxidant, and anti-tumor bioactivities of klotho have extended its application in neurosciences and made the protein popular for its lifespan-extending capacity. Furthermore, it has been demonstrated that klotho levels would reduce with aging and numerous pathologies, particularly those related to the central nervous system (CNS). Evidence supports the idea that klotho can be a key therapeutic target in CNS diseases such as amyotrophic lateral sclerosis, Parkinson's disease, stroke, and Alzheimer's disease. Reviewing the literature suggests that the upregulation of klotho expression regulates various signaling pathways related to autophagy, oxidative stress, inflammation, cognition, and ferroptosis in neurological disorders. Therefore, it has been of great interest to develop drugs or agents that boost or restore klotho levels. In this regard, the present review was designed and aimed to gather the delegated documents regarding the therapeutic potential of Klotho in CNS diseases focusing on the molecular and cellular mechanisms.}, }
@article {pmid39143255, year = {2024}, author = {Gehlen, M and Schwarz-Eywill, M and Mahn, K and Pfeiffer, A and Bauer, JM and Maier, A}, title = {[Sonography of muscles : Rheumatology-Neurology-Geriatrics-Sports medicine-Orthopedics].}, journal = {Zeitschrift fur Rheumatologie}, volume = {83}, number = {10}, pages = {829-843}, pmid = {39143255}, issn = {1435-1250}, mesh = {Humans ; *Ultrasonography/methods ; Magnetic Resonance Imaging ; Rheumatology/methods ; Muscle, Skeletal/diagnostic imaging ; Athletic Injuries/diagnostic imaging ; Sarcopenia/diagnostic imaging ; Sports Medicine/methods ; Rheumatic Diseases/diagnostic imaging ; Geriatrics ; Aged ; Neurology ; Muscular Diseases/diagnostic imaging ; Evidence-Based Medicine ; }, abstract = {Muscle sonography is used in rheumatology, neurology, geriatrics, sports medicine and orthopedics. Muscular atrophy with fatty and connective tissue degeneration can be visualized and must be interpreted in conjunction with the sonographic findings of the supplying nerves. Sonography is becoming increasingly more important for the early diagnosis of sarcopenia in rheumatology, geriatrics and osteology. Even if its significance has not yet been conclusively clarified, many publications confirm the high reliability of the method. Sonography can ideally be used in addition to magnetic resonance imaging (MRI) in the diagnostics of myositis as it can speed up the diagnosis, muscle groups that were not imaged by MRI can also be assessed sonographically and all muscle groups can be examined during the course of the procedure. Sonography also helps to make a quick and uncomplicated diagnosis of many sports injuries in addition to MRI and is therefore the basis for a targeted therapeutic approach.}, }
@article {pmid39139642, year = {2024}, author = {Liu, X and Li, Y and Huang, L and Kuang, Y and Wu, X and Ma, X and Zhao, B and Lan, J}, title = {Unlocking the therapeutic potential of P2X7 receptor: a comprehensive review of its role in neurodegenerative disorders.}, journal = {Frontiers in pharmacology}, volume = {15}, number = {}, pages = {1450704}, pmid = {39139642}, issn = {1663-9812}, abstract = {The P2X7 receptor (P2X7R), an ATP-gated ion channel, has emerged as a crucial player in neuroinflammation and a promising therapeutic target for neurodegenerative disorders. This review explores the current understanding of P2X7R's structure, activation, and physiological roles, focusing on its expression and function in microglial cells. The article examines the receptor's involvement in calcium signaling, microglial activation, and polarization, as well as its role in the pathogenesis of Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis. The review highlights the complex nature of P2X7R signaling, discussing its potential neuroprotective and neurotoxic effects depending on the disease stage and context. It also addresses the development of P2X7R antagonists and their progress in clinical trials, identifying key research gaps and future perspectives for P2X7R-targeted therapy development. By providing a comprehensive overview of the current state of knowledge and future directions, this review serves as a valuable resource for researchers and clinicians interested in exploring the therapeutic potential of targeting P2X7R for the treatment of neurodegenerative disorders.}, }
@article {pmid39135084, year = {2024}, author = {Ma, H and Zhu, M and Chen, M and Li, X and Feng, X}, title = {The role of macrophage plasticity in neurodegenerative diseases.}, journal = {Biomarker research}, volume = {12}, number = {1}, pages = {81}, pmid = {39135084}, issn = {2050-7771}, support = {PX2023037//Beijing Municipal Administration of Hospitals Incubating Program/ ; }, abstract = {Tissue-resident macrophages and recruited macrophages play pivotal roles in innate immunity and the maintenance of brain homeostasis. Investigating the involvement of these macrophage populations in eliciting pathological changes associated with neurodegenerative diseases has been a focal point of research. Dysregulated states of macrophages can compromise clearance mechanisms for pathological proteins such as amyloid-β (Aβ) in Alzheimer's disease (AD) and TDP-43 in Amyotrophic lateral sclerosis (ALS). Additionally, recent evidence suggests that abnormalities in the peripheral clearance of pathological proteins are implicated in the pathogenesis and progression of neurodegenerative diseases. Furthermore, numerous genome-wide association studies have linked genetic risk factors, which alter the functionality of various immune cells, to the accumulation of pathological proteins. This review aims to unravel the intricacies of macrophage biology in both homeostatic conditions and neurodegenerative disorders. To this end, we initially provide an overview of the modifications in receptor and gene expression observed in diverse macrophage subsets throughout development. Subsequently, we outlined the roles of resident macrophages and recruited macrophages in neurodegenerative diseases and the progress of targeted therapy. Finally, we describe the latest advances in macrophage imaging methods and measurement of inflammation, which may provide information and related treatment strategies that hold promise for informing the design of future investigations and therapeutic interventions.}, }
@article {pmid39134696, year = {2024}, author = {Visser, BS and Lipiński, WP and Spruijt, E}, title = {The role of biomolecular condensates in protein aggregation.}, journal = {Nature reviews. Chemistry}, volume = {8}, number = {9}, pages = {686-700}, pmid = {39134696}, issn = {2397-3358}, mesh = {Humans ; *Biomolecular Condensates/metabolism/chemistry ; *Protein Aggregates ; Neurodegenerative Diseases/metabolism ; Amyloid/metabolism/chemistry ; Protein Aggregation, Pathological/metabolism ; Proteins/chemistry/metabolism ; }, abstract = {There is an increasing amount of evidence that biomolecular condensates are linked to neurodegenerative diseases associated with protein aggregation, such as Alzheimer's disease and amyotrophic lateral sclerosis, although the mechanisms underlying this link remain elusive. In this Review, we summarize the possible connections between condensates and protein aggregation. We consider both liquid-to-solid transitions of phase-separated proteins and the partitioning of proteins into host condensates. We distinguish five key factors by which the physical and chemical environment of a condensate can influence protein aggregation, and we discuss their relevance in studies of protein aggregation in the presence of biomolecular condensates: increasing the local concentration of proteins, providing a distinct chemical microenvironment, introducing an interface wherein proteins can localize, changing the energy landscape of aggregation pathways, and the presence of chaperones in condensates. Analysing the role of biomolecular condensates in protein aggregation may be essential for a full understanding of amyloid formation and offers a new perspective that can help in developing new therapeutic strategies for the prevention and treatment of neurodegenerative diseases.}, }
@article {pmid39128808, year = {2024}, author = {Farhangian, M and Azarafrouz, F and Valian, N and Dargahi, L}, title = {The role of interferon beta in neurological diseases and its potential therapeutic relevance.}, journal = {European journal of pharmacology}, volume = {981}, number = {}, pages = {176882}, doi = {10.1016/j.ejphar.2024.176882}, pmid = {39128808}, issn = {1879-0712}, mesh = {Humans ; Animals ; *Interferon-beta/therapeutic use/metabolism ; Nervous System Diseases/drug therapy/metabolism ; Signal Transduction/drug effects ; }, abstract = {Interferon beta (IFNβ) is a member of the type-1 interferon family and has various immunomodulatory functions in neuropathological conditions. Although the level of IFNβ is low under healthy conditions, it is increased during inflammatory processes to protect the central nervous system (CNS). In particular, microglia and astrocytes are the main sources of IFNβ upon inflammatory insult in the CNS. The protective effects of IFNβ are well characterized in reducing the progression of multiple sclerosis (MS); however, little is understood about its effects in other neurological/neurodegenerative diseases. In this review, different types of IFNs and their signaling pathways will be described. Then we will focus on the potential role and therapeutic effect of IFNβ in several CNS-related diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, stroke, spinal cord injury, prion disease and spinocerebellar ataxia 7.}, }
@article {pmid39127445, year = {2024}, author = {Wang, MY and Zhou, Y and Li, WL and Zhu, LQ and Liu, D}, title = {Friend or foe: Lactate in neurodegenerative diseases.}, journal = {Ageing research reviews}, volume = {101}, number = {}, pages = {102452}, doi = {10.1016/j.arr.2024.102452}, pmid = {39127445}, issn = {1872-9649}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism ; *Lactic Acid/metabolism ; Animals ; }, abstract = {Lactate, a byproduct of glycolysis, was considered as a metabolic waste until identified by studies on the Warburg effect. Increasing evidence elucidates that lactate functions as energy fuel, signaling molecule, and donor for protein lactylation. Altered lactate utilization is a common metabolic feature of the onset and progression of neurodegenerative diseases, such as Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease and Huntington's disease. This review offers an overview of lactate metabolism from the perspective of production, transportation and clearance, and the role of lactate in neurodegenerative progression, as well as a summary of protein lactylation and the signaling function of lactate in neurodegenerative diseases. Besides, this review delves into the dual roles of changed lactate metabolism during neurodegeneration and explores prospective therapeutic methods targeting lactate. We propose that elucidating the correlation between lactate and neurodegeneration is pivotal for exploring innovative therapeutic interventions for neurodegenerative diseases.}, }
@article {pmid39122453, year = {2024}, author = {Khan, S and Bano, N and Ahamad, S and John, U and Dar, NJ and Bhat, SA}, title = {Excitotoxicity, Oxytosis/Ferroptosis, and Neurodegeneration: Emerging Insights into Mitochondrial Mechanisms.}, journal = {Aging and disease}, volume = {16}, number = {5}, pages = {2504-2543}, pmid = {39122453}, issn = {2152-5250}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/pathology/physiopathology ; *Mitochondria/metabolism/pathology ; Oxidative Stress ; *Ferroptosis/physiology ; Mitophagy ; Animals ; Energy Metabolism ; }, abstract = {Mitochondrial dysfunction plays a pivotal role in the development of age-related diseases, particularly neurodegenerative disorders. The etiology of mitochondrial dysfunction involves a multitude of factors that remain elusive. This review centers on elucidating the role(s) of excitotoxicity, oxytosis/ferroptosis and neurodegeneration within the context of mitochondrial bioenergetics, biogenesis, mitophagy and oxidative stress and explores their intricate interplay in the pathogenesis of neurodegenerative diseases. The effective coordination of mitochondrial turnover processes, notably mitophagy and biogenesis, is assumed to be critically important for cellular resilience and longevity. However, the age-associated decrease in mitophagy impedes the elimination of dysfunctional mitochondria, consequently impairing mitochondrial biogenesis. This deleterious cascade results in the accumulation of damaged mitochondria and deterioration of cellular functions. Both excitotoxicity and oxytosis/ferroptosis have been demonstrated to contribute significantly to the pathophysiology of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's Disease (HD), Amyotrophic Lateral Sclerosis (ALS) and Multiple Sclerosis (MS). Excitotoxicity, characterized by excessive glutamate signaling, initiates a cascade of events involving calcium dysregulation, energy depletion, and oxidative stress and is intricately linked to mitochondrial dysfunction. Furthermore, emerging concepts surrounding oxytosis/ferroptosis underscore the importance of iron-dependent lipid peroxidation and mitochondrial engagement in the pathogenesis of neurodegeneration. This review not only discusses the individual contributions of excitotoxicity and ferroptosis but also emphasizes their convergence with mitochondrial dysfunction, a key driver of neurodegenerative diseases. Understanding the intricate crosstalk between excitotoxicity, oxytosis/ferroptosis, and mitochondrial dysfunction holds potential to pave the way for mitochondrion-targeted therapeutic strategies. Such strategies, with a focus on bioenergetics, biogenesis, mitophagy, and oxidative stress, emerge as promising avenues for therapeutic intervention.}, }
@article {pmid39119436, year = {2024}, author = {Galeazzi, L and Holzman, J and Porporatti, A and Rochefort, J}, title = {Lingual Fasciculation as a Point of Call for the Diagnosis of Amyotrophic Lateral Sclerosis: A Literature Review.}, journal = {Cureus}, volume = {16}, number = {7}, pages = {e64153}, pmid = {39119436}, issn = {2168-8184}, abstract = {BACKGROUND AND AIM: Dental surgeons often play a pivotal role in the initial detection of lingual fasciculations (LFs). These involuntary micro-movements of the tongue can serve as early clinical indicators of neurodegenerative diseases, with amyotrophic lateral sclerosis (ALS) being the most concerning. Therefore, it is imperative to educate dental surgeons on identifying LF and understanding the potential underlying pathologies.<br><br>OBJECTIVES: This study aimed to pinpoint the pathologies in which LFs could emerge as an early clinical marker. Our review focused on articles delineating patient populations exhibiting LF within broader pathological contexts, encompassing neurological and other conditions, with the aim of elucidating their etiologies.<br><br>METHODS: We conducted a comprehensive literature review across four databases (PubMed, Embase, Web of Science, and Scopus). Two authors independently extracted data, with consultation from a third author when necessary. Eligible articles included those describing patients with LFs, detailing the methods of detection, diagnosis, and associated pathologies.<br><br>RESULTS: Our review identified 22 articles encompassing 153 patients with LF, with an average age of 45.8 years and a female prevalence of 43%. Electromyography and ultrasound emerged as the predominant detection methods. ALS constituted the primary diagnosis in the majority of cases (91%). Additionally, other conditions diagnosed included Machado-Joseph disease (0.046%), familial transthyretin amyloid neuropathy (0.013%), Brown-Vialetto-Van-Laere syndrome (0.006%), chronic inflammatory demyelinating polyneuropathy (0.006%), bulbospinal amyotrophy or Kennedy's disease (0.006%), and osmotic demyelination syndrome (0.006%). LF secondary to organophosphate poisoning was also documented. Symptoms associated with LF encompassed taste alterations, dysphagia, difficulty swallowing, and slurred speech.<br><br>CONCLUSION: While primarily indicative of ALS, LFs may also signal diverse underlying pathologies. Healthcare practitioners should be vigilant in their detection and expedite patient referrals to facilitate early integration into care protocols.}, }
@article {pmid39119372, year = {2024}, author = {Maristany, AJ and Sa, BC and Murray, C and Subramaniam, AB and Oldak, SE}, title = {Psychiatric Manifestations of Neurological Diseases: A Narrative Review.}, journal = {Cureus}, volume = {16}, number = {7}, pages = {e64152}, pmid = {39119372}, issn = {2168-8184}, abstract = {Neurological diseases often manifest with psychiatric symptoms, profoundly impacting patients' well-being and treatment outcomes. This comprehensive review examines the psychiatric manifestations associated with Alzheimer's disease, frontotemporal dementia (FTD), Parkinson's disease, multiple sclerosis (MS), stroke, epilepsy, Huntington's disease, amyotrophic lateral sclerosis (ALS), traumatic brain injury (TBI), and multiple system atrophy (MSA). Key psychiatric symptoms include agitation, depression, anxiety, apathy, hallucinations, impulsivity, and aggression across these diseases. In addition, ethical considerations in treating these symptoms are paramount, particularly regarding genetic testing implications, end-of-life discussions, informed consent, and equitable access to innovative treatments. Effective management necessitates interdisciplinary collaboration, personalized interventions, and a focus on patient autonomy. Understanding the psychiatric burden of neurological diseases is crucial for enhancing patients' quality of life. Further research is needed to elucidate underlying mechanisms and develop targeted interventions. This review underscores the importance of comprehensive assessment and ethical treatment practices to address psychiatric manifestations effectively.}, }
@article {pmid39116263, year = {2024}, author = {Aguilar-Vázquez, CA and Aguilar-Castillo, SJ and Raymundo-Carrillo, AD}, title = {[Electrodiagnostic support in an atypical form of amyotrophic lateral sclerosis (Vulpian-Bernhardt syndrome)].}, journal = {Revista medica del Instituto Mexicano del Seguro Social}, volume = {62}, number = {1}, pages = {1-8}, pmid = {39116263}, issn = {2448-5667}, mesh = {Humans ; Male ; *Amyotrophic Lateral Sclerosis/diagnosis/mortality/therapy ; *Electrodiagnosis/methods ; }, abstract = {BACKGROUND: Vulpian-Bernhardt syndrome is an atypical form of the motor neuron disease described since the 19th century. The importance of a timely diagnosis lies in the increased survival present in this variant. Due to the clinical rarity and complex diagnosis we report a clinical case of this disease, which is why we describe the typical clinical presentation, the diagnostic approach, and we make a bibliographic review of this neurodegenerative disorder as well.<br><br>CLINICAL CASE: Latin American man whose clinical case onset was characterized by thoracic asymmetric and increasing limb weakness, showing affection from distal to proximal upper limbs area. Subsequently, symptoms worsened to the point of limiting day-to-day activities and conditioning patient's physical independence. Physical examination was consistent with motor neuron disease. Nerve conduction studies were performed and confirmed findings compatible with motor neuron involvement limited to thoracic limbs.<br><br>CONCLUSION: Vulpian-Bernhardt syndrome is an uncommon form of motor neuron disease. Due to the rarity of its presentation, it is frequent to confuse clinical profile even for trained physicians. The importance of electrodiagnosis relies in identifying the neurogenic origin of the disease, as well as the active denervation and reinnervation data. Considering that with this syndrome patients have a longer survival than with the classic form of amyotrophic lateral sclerosis, it is important to have a clear diagnosis approach in order to provide a better quality of life and supportive treatment.}, }
@article {pmid39115673, year = {2025}, author = {Mishra, Y and Kumar, A and Kaundal, RK}, title = {Mitochondrial Dysfunction is a Crucial Immune Checkpoint for Neuroinflammation and Neurodegeneration: mtDAMPs in Focus.}, journal = {Molecular neurobiology}, volume = {62}, number = {6}, pages = {6715-6747}, pmid = {39115673}, issn = {1559-1182}, support = {EEQ/2021/000875//Science &amp; Engineering Research Board (SERB), Department of Science and Technology, Govt of India/ ; }, mesh = {Humans ; Animals ; *Mitochondria/metabolism/pathology/immunology ; *Neuroinflammatory Diseases/immunology/pathology/metabolism ; *Neurodegenerative Diseases/immunology/pathology/metabolism ; Immunity, Innate ; *Nerve Degeneration/immunology/pathology ; *Inflammation/immunology/pathology ; }, abstract = {Neuroinflammation is a pivotal factor in the progression of both age-related and acute neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, and stroke. Mitochondria, essential for neuronal health due to their roles in energy production, calcium buffering, and oxidative stress regulation, become increasingly susceptible to dysfunction under conditions of metabolic stress, aging, or injury. Impaired mitophagy in aged or injured neurons leads to the accumulation of dysfunctional mitochondria, which release mitochondrial-derived damage-associated molecular patterns (mtDAMPs). These mtDAMPs act as immune checkpoints, activating pattern recognition receptors (PRRs) and triggering innate immune signaling pathways. This activation initiates inflammatory responses in neurons and brain-resident immune cells, releasing cytokines and chemokines that damage adjacent healthy neurons and recruit peripheral immune cells, further amplifying neuroinflammation and neurodegeneration. Long-term mitochondrial dysfunction perpetuates a chronic inflammatory state, exacerbating neuronal injury and contributing additional immunogenic components to the extracellular environment. Emerging evidence highlights the critical role of mtDAMPs in initiating and sustaining neuroinflammation, with circulating levels of these molecules potentially serving as biomarkers for disease progression. This review explores the mechanisms of mtDAMP release due to mitochondrial dysfunction, their interaction with PRRs, and the subsequent activation of inflammatory pathways. We also discuss the role of mtDAMP-triggered innate immune responses in exacerbating both acute and chronic neuroinflammation and neurodegeneration. Targeting dysfunctional mitochondria and mtDAMPs with pharmacological agents presents a promising strategy for mitigating the initiation and progression of neuropathological conditions.}, }
@article {pmid39115327, year = {2024}, author = {Lescouzères, L and Patten, SA}, title = {Promising animal models for amyotrophic lateral sclerosis drug discovery: a comprehensive update.}, journal = {Expert opinion on drug discovery}, volume = {19}, number = {10}, pages = {1213-1233}, doi = {10.1080/17460441.2024.2387791}, pmid = {39115327}, issn = {1746-045X}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/physiopathology ; Animals ; Humans ; *Disease Models, Animal ; *Drug Discovery/methods ; Mice ; Genetic Therapy/methods ; Translational Research, Biomedical/methods ; Induced Pluripotent Stem Cells ; Drug Development/methods ; Caenorhabditis elegans ; Motor Neurons/drug effects ; Zebrafish ; }, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons. Several animal models have been generated to understand ALS pathogenesis. They have provided valuable insight into disease mechanisms and the development of therapeutic strategies.<br><br>AREAS COVERED: In this review, the authors provide a concise overview of simple genetic model organisms, including C. elegans, Drosophila, zebrafish, and mouse genetic models that have been generated to study ALS. They emphasize the benefits of each model and their application in translational research for discovering new chemicals, gene therapy approaches, and antibody-based strategies for treating ALS.<br><br>EXPERT OPINION: Significant progress is being made in identifying new therapeutic targets for ALS. This progress is being enabled by promising animal models of the disease using increasingly effective genetic and pharmacological strategies. There are still challenges to be overcome in order to achieve improved success rates for translating drugs from animal models to clinics for treating ALS. Several promising future directions include the establishment of novel preclinical protocol standards, as well as the combination of animal models with human induced pluripotent stem cells (iPSCs).}, }
@article {pmid39115030, year = {2025}, author = {Mancuso, M and Valentini, I and Basile, M and Bowen, A and Fordell, H and Laurita, R and Möller, MC and Williams, LJ and Zoccolotti, P}, title = {Cost-effectiveness of neuropsychological rehabilitation for acquired brain injuries: Update of Stolwyk et al.'s (2019) review.}, journal = {Journal of neuropsychology}, volume = {19}, number = {1}, pages = {115-139}, pmid = {39115030}, issn = {1748-6653}, mesh = {Humans ; *Cost-Benefit Analysis ; *Brain Injuries/rehabilitation/economics/complications ; *Neurological Rehabilitation/economics ; *Stroke Rehabilitation/economics ; }, abstract = {Acquired brain injuries (ABI), resulting from stroke or traumatic brain injury, cause a range of neuropsychological impairments and many patients continue to experience neuropsychological deficits years after onset. The increasing average age of the population highlights the importance of effective management strategies for the consequences of ABI. Despite the well-documented impact of rehabilitation interventions, the cost-effectiveness of neuropsychological rehabilitation remains largely unknown. This study conducted a scoping review to update the findings of Stolwyk et al. (Neuropsychological Rehabilitation, 2021, 31, 316), focusing on the economic evaluations of neuropsychological rehabilitation for individuals with ABI. Following the PIO framework, PRISMA ScR guidelines, and systematic review reporting checklist, the review screened 1027 articles and included eight studies published between 2019 and 2024. The studies encompassed either language rehabilitation or general neuropsychological programs, including neuropsychological interventions. The economic analyses, including two cost-effectiveness, five cost-utility, and one cost-benefit study, mostly adhered to CHEERS guidelines, enhancing the transparency and methodological rigour of their reporting. These studies demonstrated varying degrees of cost-effectiveness for interventions targeting post-stroke language disorders and neuropsychological rehabilitation for ABI, with significant cost savings and health benefits observed, particularly for home-based rehabilitation interventions. The included studies suffered from a short time horizon, limiting the ability to capture the long-term economic impacts and effectiveness of the interventions. Future research should focus on longer-term follow-up data and include broader search strategies to enhance understanding and optimise health care interventions. A comprehensive implementation of these economic analyses is crucial for informing policymakers, enabling them to introduce rehabilitative interventions based on solid evidence.}, }
@article {pmid39114608, year = {2024}, author = {Koike, Y}, title = {Abnormal Splicing Events due to Loss of Nuclear Function of TDP-43: Pathophysiology and Perspectives.}, journal = {JMA journal}, volume = {7}, number = {3}, pages = {313-318}, pmid = {39114608}, issn = {2433-3298}, abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative diseases with a progressive and fatal course. They are often comorbid and share the same molecular spectrum. Their key pathological features are the formation of the aggregation of TDP-43, an RNA-binding protein, in the cytoplasm and its depletion from the nucleus in the central nervous system. In the nucleus, TDP-43 regulates several aspects of RNA metabolism, ranging from RNA transcription and alternative splicing to RNA transport. Suppressing the aberrant splicing events during RNA processing is one of the significant functions of TDP-43. This function is impaired when TDP-43 becomes depleted from the nucleus. Several critical cryptic splicing targets of TDP-43 have recently emerged, such as STMN2, UNC13A, and others. UNC13A is an important ALS/FTD risk gene, and the genetic variations, single nucleotide polymorphisms, cause disease via the increased susceptibility for cryptic exon inclusion under the TDP-43 dysfunction. Moreover, TDP-43 has an autoregulatory mechanism that regulates the splicing of its mRNA (TARDBP mRNA) in the healthy state. This study provides recent findings on the splicing regulatory function of TDP-43 and discusses the prospects of using these aberrant splicing events as efficient biomarkers.}, }
@article {pmid39104673, year = {2024}, author = {Rezvani, S and Hosseini-Zahraei, SH and Tootchi, A and Guger, C and Chaibakhsh, Y and Saberi, A and Chaibakhsh, A}, title = {A review on the performance of brain-computer interface systems used for patients with locked-in and completely locked-in syndrome.}, journal = {Cognitive neurodynamics}, volume = {18}, number = {4}, pages = {1419-1443}, pmid = {39104673}, issn = {1871-4080}, abstract = {Patients with locked-in syndrome (LIS) and complete locked-in syndrome (CLIS) own a fully functional brain restricted within a non-functional body. In order to help LIS patients stay connected with their surroundings, brain-computer interfaces (BCIs) and related technologies have emerged. BCIs translate brain activity into actions that can be performed by external devices enabling LIS patients to communicate, leading to an increase in their quality of life. The past decade has seen the rapid development of BCIs that have the potential to be used for patients with locked-in syndrome, from which a great deal is tested only on healthy subjects and not on actual patients. This study aims to (1) provide the readers with a comprehensive study that contributes to this growing area of research by exploring the performance of BCIs tested specifically on LIS and CLIS patients, (2) give an overview of different modalities and paradigms used in different stages of the locked-in syndrome, and (3) discuss the contributions and limitations of BCIs introduced for the LIS and CLIS patients in the state-of-the-art and lay a groundwork for researchers interested in this field.}, }
@article {pmid39099373, year = {2024}, author = {Serangeli, I and Diamanti, T and De Jaco, A and Miranda, E}, title = {Role of mitochondria-endoplasmic reticulum contacts in neurodegenerative, neurodevelopmental and neuropsychiatric conditions.}, journal = {The European journal of neuroscience}, volume = {60}, number = {5}, pages = {5040-5068}, doi = {10.1111/ejn.16485}, pmid = {39099373}, issn = {1460-9568}, support = {//Sapienza Universit&#xe0; di Roma/ ; //Sapienza University of Rome/ ; }, mesh = {Humans ; *Mitochondria/metabolism ; *Neurodegenerative Diseases/metabolism/pathology ; *Endoplasmic Reticulum/metabolism ; Animals ; *Neurodevelopmental Disorders/metabolism ; *Mental Disorders/metabolism/physiopathology ; Mitochondria Associated Membranes ; }, abstract = {Mitochondria-endoplasmic reticulum contacts (MERCs) mediate a close and continuous communication between both organelles that is essential for the transfer of calcium and lipids to mitochondria, necessary for cellular signalling and metabolic pathways. Their structural and molecular characterisation has shown the involvement of many proteins that bridge the membranes of the two organelles and maintain the structural stability and function of these contacts. The crosstalk between the two organelles is fundamental for proper neuronal function and is now recognised as a component of many neurological disorders. In fact, an increasing proportion of MERC proteins take part in the molecular and cellular basis of pathologies affecting the nervous system. Here we review the alterations in MERCs that have been reported for these pathologies, from neurodevelopmental and neuropsychiatric disorders to neurodegenerative diseases. Although mitochondrial abnormalities in these debilitating conditions have been extensively attributed to the high energy demand of neurons, a distinct role for MERCs is emerging as a new field of research. Understanding the molecular details of such alterations may open the way to new paths of therapeutic intervention.}, }
@article {pmid39098767, year = {2025}, author = {Endo, F}, title = {Deciphering the spectrum of astrocyte diversity: Insights into molecular, morphological, and functional dimensions in health and neurodegenerative diseases.}, journal = {Neuroscience research}, volume = {210}, number = {}, pages = {1-10}, doi = {10.1016/j.neures.2024.07.008}, pmid = {39098767}, issn = {1872-8111}, mesh = {Humans ; *Astrocytes/pathology/physiology/metabolism ; *Neurodegenerative Diseases/pathology/metabolism/physiopathology ; Animals ; }, abstract = {Astrocytes are the most abundant and morphologically complex glial cells that play active roles in the central nervous system (CNS). Recent research has identified shared and region-specific astrocytic genes and functions, elucidated the cellular origins of their regional diversity, and uncovered the molecular networks for astrocyte morphology, which are essential for their functional complexity. Reactive astrocytes exhibit a wide range of functional diversity in a context-specific manner in CNS disorders. This review discusses recent advances in understanding the molecular and morphological diversity of astrocytes in healthy individuals and those with neurodegenerative diseases, such as Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis.}, }
@article {pmid39097850, year = {2024}, author = {Luan, T and Li, Q and Huang, Z and Feng, Y and Xu, D and Zhou, Y and Hu, Y and Wang, T}, title = {Axonopathy Underlying Amyotrophic Lateral Sclerosis: Unraveling Complex Pathways and Therapeutic Insights.}, journal = {Neuroscience bulletin}, volume = {40}, number = {11}, pages = {1789-1810}, pmid = {39097850}, issn = {1995-8218}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/therapy ; Animals ; *Axons/pathology/metabolism ; Mitochondria/metabolism ; Motor Neurons/metabolism/pathology ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a complex neurodegenerative disorder characterized by progressive axonopathy, jointly leading to the dying back of the motor neuron, disrupting both nerve signaling and motor control. In this review, we highlight the roles of axonopathy in ALS progression, driven by the interplay of multiple factors including defective trafficking machinery, protein aggregation, and mitochondrial dysfunction. Dysfunctional intracellular transport, caused by disruptions in microtubules, molecular motors, and adaptors, has been identified as a key contributor to disease progression. Aberrant protein aggregation involving TDP-43, FUS, SOD1, and dipeptide repeat proteins further amplifies neuronal toxicity. Mitochondrial defects lead to ATP depletion, oxidative stress, and Ca[2+] imbalance, which are regarded as key factors underlying the loss of neuromuscular junctions and axonopathy. Mitigating these defects through interventions including neurotrophic treatments offers therapeutic potential. Collaborative research efforts aim to unravel ALS complexities, opening avenues for holistic interventions that target diverse pathological mechanisms.}, }
@article {pmid39096334, year = {2025}, author = {Paterson, M and Doeltgen, S and Francis, R}, title = {Sensory Changes Related to Swallowing in Motor Neurone Disease.}, journal = {Dysphagia}, volume = {40}, number = {2}, pages = {407-418}, pmid = {39096334}, issn = {1432-0460}, mesh = {Humans ; *Deglutition Disorders/physiopathology/etiology ; *Motor Neuron Disease/complications/physiopathology ; *Deglutition/physiology ; *Sensation Disorders/etiology/physiopathology ; *Sensation/physiology ; }, abstract = {Dysphagia is common in motor neurone disease (MND) and associated with negative health and psychosocial outcomes. Although largely considered a motor disease, a growing body of evidence suggests that MND can also affect the sensory system. As intact sensation is vital for safe swallowing, and sensory changes can influence the clinical management of dysphagia in people living with MND, this review evaluated and summarised the current evidence for sensory changes related to swallowing in MND. Of 3,481 articles originally identified, 29 met the inclusion criteria. Of these, 20 studies reported sensory changes, which included laryngeal sensation, taste, gag reflex, cough reflex, tongue sensation, smell, palatal and pharyngeal sensation, silent aspiration, and undefined sensation of the swallowing mechanism. Sensory changes were either described as decreased (n = 16) or heightened (n = 4). In the remaining nine studies, sensory function was reported as unaffected. The presence of changes to sensory function related to swallowing in MND remains inconclusive, although an increasing number of studies report sensory changes in some sensory domains. Future research is needed to evaluate the prevalence of sensory changes in MND and how such changes may influence dysphagia and its management.}, }
@article {pmid39095145, year = {2024}, author = {Sheers, NL and Andersen, T and Chatwin, M}, title = {Airway Clearance in Neuromuscular Disease.}, journal = {Sleep medicine clinics}, volume = {19}, number = {3}, pages = {485-496}, doi = {10.1016/j.jsmc.2024.04.009}, pmid = {39095145}, issn = {1556-4088}, mesh = {Humans ; *Neuromuscular Diseases/therapy/physiopathology ; Respiratory Therapy/methods ; Cough/therapy/physiopathology ; Airway Management/methods ; }, abstract = {High-quality respiratory care and airway clearance is essential for people with neuromuscular disease (pwNMD) as respiratory tract infections are a major cause of morbidity and mortality. This review expands on published guidelines by highlighting the role of cough peak flow along with other options for cough evaluation, and discusses recent key research findings which have influenced the practice of respiratory therapy for pwNMD.}, }
@article {pmid39093076, year = {2024}, author = {Oriá, RB and Smith, CJ and Ashford, JW and Vitek, MP and Guerrant, RL}, title = {Pros and Cons of APOE4 Homozygosity and Effects on Neuroplasticity, Malnutrition, and Infections in Early Life Adversity, Alzheimer's Disease, and Alzheimer's Prevention.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {100}, number = {s1}, pages = {S179-S185}, doi = {10.3233/JAD-240888}, pmid = {39093076}, issn = {1875-8908}, mesh = {Humans ; *Alzheimer Disease/genetics/prevention &amp; control ; *Apolipoprotein E4/genetics ; *Neuronal Plasticity/genetics ; *Malnutrition/genetics/complications ; Homozygote ; Life Style ; }, abstract = {Fortea et al.'s. (2024) recent data analysis elegantly calls attention to familial late-onset Alzheimer's disease (AD) with APOE4 homozygosity. The article by Grant (2024) reviews the factors associated with AD, particularly the APOE genotype and lifestyle, and the broad implications for prevention, both for individuals with the lifestyles associated with living in resource-rich countries and for those enduring environmental adversity in poverty settings, including high exposure to enteric pathogens and precarious access to healthcare. Grant discusses the issue of APOE genotype and its implications for the benefits of lifestyle modifications. This review highlights that bearing APOE4 could constitute an evolutionary benefit in coping with heavy enteric infections and malnutrition early in life in the critical formative first two years of brain development. However, the critical issue may be that this genotype could be a health concern under shifts in lifestyle and unhealthy diets during aging, leading to severe cognitive impairments and increased risk of AD. This commentary supports the discussions of Grant and the benefits of improving lifestyle for decreasing the risks for AD while providing further understanding and modelling of the early life benefits of APOE4 amidst adversity. This attention to the pathophysiology of AD should help further elucidate these critical, newly appreciated pathogenic pathways for developing approaches to the prevention and management in the context of the APOE genetic variations associated with AD.}, }
@article {pmid39091344, year = {2024}, author = {Goffin, L and Lemoine, D and Clotman, F}, title = {Potential contribution of spinal interneurons to the etiopathogenesis of amyotrophic lateral sclerosis.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1434404}, pmid = {39091344}, issn = {1662-4548}, abstract = {Amyotrophic lateral sclerosis (ALS) consists of a group of adult-onset fatal and incurable neurodegenerative disorders characterized by the progressive death of motor neurons (MNs) throughout the central nervous system (CNS). At first, ALS was considered to be an MN disease, caused by cell-autonomous mechanisms acting specifically in MNs. Accordingly, data from ALS patients and ALS animal models revealed alterations in excitability in multiple neuronal populations, including MNs, which were associated with a variety of cellular perturbations such as protein aggregation, ribonucleic acid (RNA) metabolism defects, calcium dyshomeostasis, modified electrophysiological properties, and autophagy malfunctions. However, experimental evidence rapidly demonstrated the involvement of other types of cells, including glial cells, in the etiopathogenesis of ALS through non-cell autonomous mechanisms. Surprisingly, the contribution of pre-motor interneurons (INs), which regulate MN activity and could therefore critically modulate their excitability at the onset or during the progression of the disease, has to date been severely underestimated. In this article, we review in detail how spinal pre-motor INs are affected in ALS and their possible involvement in the etiopathogenesis of the disease.}, }
@article {pmid39086926, year = {2024}, author = {Tilliole, P and Fix, S and Godin, JD}, title = {hnRNPs: roles in neurodevelopment and implication for brain disorders.}, journal = {Frontiers in molecular neuroscience}, volume = {17}, number = {}, pages = {1411639}, pmid = {39086926}, issn = {1662-5099}, abstract = {Heterogeneous nuclear ribonucleoproteins (hnRNPs) constitute a family of multifunctional RNA-binding proteins able to process nuclear pre-mRNAs into mature mRNAs and regulate gene expression in multiple ways. They comprise at least 20 different members in mammals, named from A (HNRNP A1) to U (HNRNP U). Many of these proteins are components of the spliceosome complex and can modulate alternative splicing in a tissue-specific manner. Notably, while genes encoding hnRNPs exhibit ubiquitous expression, increasing evidence associate these proteins to various neurodevelopmental and neurodegenerative disorders, such as intellectual disability, epilepsy, microcephaly, amyotrophic lateral sclerosis, or dementias, highlighting their crucial role in the central nervous system. This review explores the evolution of the hnRNPs family, highlighting the emergence of numerous new members within this family, and sheds light on their implications for brain development.}, }
@article {pmid39083229, year = {2024}, author = {Kaji, R and Izumi, Y and Oki, R}, title = {Ultra-high dose methylcobalamin and other emerging therapies for amyotrophic lateral sclerosis.}, journal = {Current opinion in neurology}, volume = {37}, number = {5}, pages = {593-602}, doi = {10.1097/WCO.0000000000001311}, pmid = {39083229}, issn = {1473-6551}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Vitamin B 12/analogs &amp; derivatives/therapeutic use/administration &amp; dosage ; Clinical Trials as Topic ; }, abstract = {PURPOSE OF REVIEW: Recent development in understanding the pathophysiology of amyotrophic lateral sclerosis (ALS) has led to increasing number of promising test drugs in the pipeline along with the existing ones. We will review these agents focusing on ultra-high dose methylcobalamin, which is pending approval in Japan. Clinical trial design best suited for ALS will also be discussed.<br><br>RECENT FINDINGS: The most recent phase 3 trial (JETALS) of ultra-high dose methylcobalamin demonstrated significant slowing of ALSFRSR changes (0.5/month), with marked reduction of serum homocysteine levels in the initial double-blind period. The post hoc analysis of the previous phase 2/3 study (E761 trial; Eisai) showed that it prolonged survival of ALS patients, if started within 1&#x200a;year of onset, but the previous studies suggested its efficacy even in later stages, depending upon the rate of progression. Phase 3 trial of AMX0035 or Relyvrio on the other hand showed negative results despite the promising phase 2 data. The latter did not adjust the disease progression rate before entry.<br><br>SUMMARY: Ultra-high dose methylcobalamin is not a vitamin supplement but a novel disease-modifying therapy for ALS, and it emphasizes homocysteine as a key factor in the disease process. Clinical trial design must include entering patients early and with similar rates of progression using pretrial observation periods for meaningful results, since ALS is a chronologically heterogenous condition with similar phenotypes.}, }
@article {pmid39075493, year = {2024}, author = {Mangal, AL and Mücke, M and Rolke, R and Appelmann, I}, title = {Advance directives in amyotrophic lateral sclerosis - a systematic review and meta-analysis.}, journal = {BMC palliative care}, volume = {23}, number = {1}, pages = {191}, pmid = {39075493}, issn = {1472-684X}, mesh = {*Amyotrophic Lateral Sclerosis/psychology/therapy/complications ; Humans ; *Advance Directives/statistics &amp; numerical data/psychology ; Advance Care Planning/statistics &amp; numerical data/standards ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of the upper and lower motoneuron. It is associated with a life expectancy of 2-4 years after diagnosis. Individuals experience paralysis, dysphagia, respiratory failure and loss of communicative function, rendering advance care planning (ACP) critically important. This systematic review primarily aimed to internationally compare the application of advance directives (AD) and ACP in ALS. Its secondary aim was to identify ACP preferences, identify fields for future research and to generate recommendations for improving patient care through ACP.<br><br>METHODS: We conducted a systematic literature review and meta-analysis. Five electronic databases (Embase, Medline, Scopus, PsycInfo and CENTRAL) were searched for qualitative and quantitative primary literature from 1999 to 2024. Cross-references were used to identify additional publications. Study selection was performed based on inclusion criteria. Number and content of AD were extracted systematically. After statistical analysis consecutive meta-analysis was performed for international differences and changes over time. Quality assessment of studies was performed using the MMAT (Mixed Methods Appraisal Tool). PROSPERO Registration (June 07, 2021) : CRD42021248040.<br><br>RESULTS: A total of 998 records was screened of which 26 were included in the synthesis. An increase in publication numbers of 88.9% was observed from 1999 to 2024. Results regarding use and content of AD were heterogeneous and international differences were detected. AD were signed in 60.4% of records (1,629 / 2,696 patients). The number of AD decreased over time when separating the review period in two decades (1st 1999-2011: 78% vs. 2nd 2012-2024: 42%). Study quality was superior in qualitative and mixed method designs compared to quantitative studies.<br><br>CONCLUSION: Further prospective studies should include detailed analyses on preferences regarding ventilation and artificial nutrition in ALS and should encompass countries of the global south. Despite the complexity of ACP with regard to individual patient needs, ACP should be part of each individual support plan for ALS patients and should specifically comprise a discussion on the preferred place of death. The available disease-specific AD documents should be preferred.}, }
@article {pmid39073543, year = {2024}, author = {Litvinov, VV and Freynd, GG}, title = {[Clinical and morphologic characterization of Pick's dementia: case report and review of the literature].}, journal = {Arkhiv patologii}, volume = {86}, number = {4}, pages = {51-57}, doi = {10.17116/patol20248604151}, pmid = {39073543}, issn = {0004-1955}, mesh = {Humans ; *Cerebral Cortex/metabolism/pathology ; *Pick Disease of the Brain/pathology/diagnosis ; tau Proteins/metabolism ; }, abstract = {Diseases morphologically characterized by frontotemporal lobar degeneration have relatively recently been considered as a group of frontotemporal dementias. This group is characterized by a tendency to early clinical onset of dementia, common genetic and morphological features, as well as a possible association with diseases such as amyotrophic lateral sclerosis and atypical parkinsonism syndrome. Historically, Pick's dementia (Pick's disease) was described as the first of the frontotemporal dementias, which is morphologically characterized by the presence of argyrophilic Pick's bodies represented by 3R-tau protein in the neurons of the cerebral cortex. Despite the characteristic clinical and morphological picture due to the relative rarity, the diagnosis of Pick's dementia is infrequently made by both clinicians and pathologists. The article presents current data on frontotemporal dementia. A case of Pick's dementia with characteristic clinical manifestations in the form of early onset of behavioral and personality disorders, as well as specific morphological changes in the brain, is described.}, }
@article {pmid39070547, year = {2024}, author = {Kannan, A and Gangadharan Leela, S and Branzei, D and Gangwani, L}, title = {Role of senataxin in R-loop-mediated neurodegeneration.}, journal = {Brain communications}, volume = {6}, number = {4}, pages = {fcae239}, pmid = {39070547}, issn = {2632-1297}, support = {R01 NS115834/NS/NINDS NIH HHS/United States ; }, abstract = {Senataxin is an RNA:DNA helicase that plays an important role in the resolution of RNA:DNA hybrids (R-loops) formed during transcription. R-loops are involved in the regulation of biological processes such as immunoglobulin class switching, gene expression and DNA repair. Excessive accumulation of R-loops results in DNA damage and loss of genomic integrity. Senataxin is critical for maintaining optimal levels of R-loops to prevent DNA damage and acts as a genome guardian. Within the nucleus, senataxin interacts with various RNA processing factors and DNA damage response and repair proteins. Senataxin interactors include survival motor neuron and zinc finger protein 1, with whom it co-localizes in sub-nuclear bodies. Despite its ubiquitous expression, mutations in senataxin specifically affect neurons and result in distinct neurodegenerative diseases such as amyotrophic lateral sclerosis type 4 and ataxia with oculomotor apraxia type 2, which are attributed to the gain-of-function and the loss-of-function mutations in senataxin, respectively. In addition, low levels of senataxin (loss-of-function) in spinal muscular atrophy result in the accumulation of R-loops causing DNA damage and motor neuron degeneration. Senataxin may play multiple functions in diverse cellular processes; however, its emerging role in R-loop resolution and maintenance of genomic integrity is gaining attention in the field of neurodegenerative diseases. In this review, we highlight the role of senataxin in R-loop resolution and its potential as a therapeutic target to treat neurodegenerative diseases.}, }
@article {pmid39069669, year = {2024}, author = {Abbey, E and Ali, M and Cooper, M and Taylor, P and Mayland, CR}, title = {Recognising dying in motor neurone disease: A scoping review.}, journal = {Palliative medicine}, volume = {38}, number = {9}, pages = {923-934}, pmid = {39069669}, issn = {1477-030X}, mesh = {Humans ; *Motor Neuron Disease/psychology ; *Terminal Care ; Attitude to Death ; Palliative Care ; Aged ; Middle Aged ; Adult ; Aged, 80 and over ; Male ; Female ; }, abstract = {INTRODUCTION: Timely identification of dying in motor neurone disease enables optimal care, yet we know that healthcare professionals can fail to recognise when death is approaching. Clinical factors help predict the end of life in other terminal conditions. Examining these principles in motor neurone disease would help guide more accurate recognition of this critical phase.<br><br>AIM: To examine and map out what is known about dying in patients with motor neurone disease, and the recognition of dying by healthcare professionals.<br><br>DESIGN: A scoping review was conducted following the Arksey and O'Malley methodological framework.<br><br>DATA SOURCES: Four electronic databases (MEDLINE, Scopus, PsycINFO and CINAHL) and grey literature were searched on the 10th May 2023. Reference lists and citations were also reviewed.<br><br>RESULTS: From 1512 articles, 13 studies were included. Dyspnoea, anxiety and pain were the most common symptoms associated with the dying phase. Worsening respiratory function, the development of specific new symptoms and deteriorating symptom control suggested approaching death. No studies reported changes in vital signs or biomarkers associated with dying. Barriers to the recognition of dying by healthcare professionals included a rapid and unpredictable terminal decline.<br><br>CONCLUSIONS: Dying in motor neurone disease is associated with patterns of symptoms and signs, however evidence is limited compared with other terminal conditions and requires further exploration. The characteristic sudden and unpredictable terminal decline is a key barrier to recognition of dying by healthcare professionals. Optimising advance care planning is one approach to navigate these complex, unpredictable clinical situations.}, }
@article {pmid39069095, year = {2024}, author = {Ho, PC and Hsieh, TC and Tsai, KJ}, title = {TDP-43 proteinopathy in frontotemporal lobar degeneration and amyotrophic lateral sclerosis: From pathomechanisms to therapeutic strategies.}, journal = {Ageing research reviews}, volume = {100}, number = {}, pages = {102441}, doi = {10.1016/j.arr.2024.102441}, pmid = {39069095}, issn = {1872-9649}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics/therapy ; *Frontotemporal Lobar Degeneration/metabolism/pathology/therapy/genetics ; *TDP-43 Proteinopathies/metabolism/pathology/genetics ; *DNA-Binding Proteins/metabolism/genetics ; Animals ; Autophagy/physiology ; }, abstract = {Proteostasis failure is a common pathological characteristic in neurodegenerative diseases. Revitalizing clearance systems could effectively mitigate these diseases. The transactivation response (TAR) DNA-binding protein 43 (TDP-43) plays a critical role as an RNA/DNA-binding protein in RNA metabolism and synaptic function. Accumulation of TDP-43 aggregates in the central nervous system is a hallmark of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). Autophagy, a major and highly conserved degradation pathway, holds the potential for degrading aggregated TDP-43 and alleviating FTLD/ALS. This review explores the causes of TDP-43 aggregation, FTLD/ALS-related genes, key autophagy factors, and autophagy-based therapeutic strategies targeting TDP-43 proteinopathy. Understanding the underlying pathological mechanisms of TDP-43 proteinopathy can facilitate therapeutic interventions.}, }
@article {pmid39062967, year = {2024}, author = {Kisielewska, M and Filipski, M and Sebastianka, K and Karaś, D and Molik, K and Choromańska, A}, title = {Investigation into the Neuroprotective and Therapeutic Potential of Plant-Derived Chk2 Inhibitors.}, journal = {International journal of molecular sciences}, volume = {25}, number = {14}, pages = {}, pmid = {39062967}, issn = {1422-0067}, mesh = {*Checkpoint Kinase 2/metabolism/antagonists &amp; inhibitors ; Humans ; Animals ; Protein Kinase Inhibitors/pharmacology/therapeutic use/chemistry ; Neuroprotective Agents/pharmacology/therapeutic use ; Neoplasms/drug therapy ; DNA Damage/drug effects ; DNA Repair/drug effects ; }, abstract = {Nature provides us with a rich source of compounds with a wide range of applications, including the creation of innovative drugs. Despite advancements in chemically synthesized therapeutics, natural compounds are increasingly significant, especially in cancer treatment, a leading cause of death globally. One promising approach involves the use of natural inhibitors of checkpoint kinase 2 (Chk2), a critical regulator of DNA repair, cell cycle arrest, and apoptosis. Chk2's activation in response to DNA damage can lead to apoptosis or DNA repair, influencing glycolysis and mitochondrial function. In cancer therapy, inhibiting Chk2 can disrupt DNA repair and cell cycle progression, promoting cancer cell death and enhancing the efficacy of radiotherapy and chemotherapy. Additionally, Chk2 inhibitors can safeguard non-cancerous cells during these treatments by inhibiting p53-dependent apoptosis. Beyond oncology, Chk2 inhibition shows potential in treating hepatitis C virus (HCV) infections, as the virus relies on Chk2 for RNA replication in neurodegenerative diseases like amyotrophic lateral sclerosis (ALS), in which DNA damage plays a crucial role. Plant-derived Chk2 inhibitors, such as artemetin, rhamnetin, and curcumin, offer a promising future for treating various diseases with potentially milder side effects and broader metabolic impacts compared to conventional therapies. The review aims to underscore the immense potential of natural Chk2 inhibitors in various therapeutic contexts, particularly in oncology and the treatment of other diseases involving DNA damage and repair mechanisms. These natural Chk2 inhibitors hold significant promise for revolutionizing the landscape of cancer treatment and other diseases. Further research into these compounds could lead to the development of innovative therapies that offer hope for the future with fewer side effects and enhanced efficacy.}, }
@article {pmid39062592, year = {2024}, author = {Gao, J and Sterling, E and Hankin, R and Sikal, A and Yao, Y}, title = {Therapeutics Targeting Skeletal Muscle in Amyotrophic Lateral Sclerosis.}, journal = {Biomolecules}, volume = {14}, number = {7}, pages = {}, pmid = {39062592}, issn = {2218-273X}, support = {W81XWH2210261//United States Department of Defense/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/pathology/therapy ; Humans ; *Muscle, Skeletal/metabolism/pathology ; Animals ; Neuromuscular Junction/metabolism/pathology ; Motor Neurons/metabolism/pathology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a complex neuromuscular disease characterized by progressive motor neuron degeneration, neuromuscular junction dismantling, and muscle wasting. The pathological and therapeutic studies of ALS have long been neurocentric. However, recent insights have highlighted the significance of peripheral tissue, particularly skeletal muscle, in disease pathology and treatment. This is evidenced by restricted ALS-like muscle atrophy, which can retrogradely induce neuromuscular junction and motor neuron degeneration. Moreover, therapeutics targeting skeletal muscles can effectively decelerate disease progression by modulating muscle satellite cells for muscle repair, suppressing inflammation, and promoting the recovery or regeneration of the neuromuscular junction. This review summarizes and discusses therapeutic strategies targeting skeletal muscles for ALS treatment. It aims to provide a comprehensive reference for the development of novel therapeutics targeting skeletal muscles, potentially ameliorating the progression of ALS.}, }
@article {pmid39056295, year = {2025}, author = {Lindamood, HL and Liu, TM and Read, TA and Vitriol, EA}, title = {Using ALS to understand profilin 1's diverse roles in cellular physiology.}, journal = {Cytoskeleton (Hoboken, N.J.)}, volume = {82}, number = {3}, pages = {111-129}, pmid = {39056295}, issn = {1949-3592}, support = {R35 GM137959/GM/NIGMS NIH HHS/United States ; }, mesh = {*Profilins/metabolism/genetics ; Humans ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; Animals ; }, abstract = {Profilin is an actin monomer-binding protein whose role in actin polymerization has been studied for nearly 50 years. While its principal biochemical features are now well understood, many questions remain about how profilin controls diverse processes within the cell. Dysregulation of profilin has been implicated in a broad range of human diseases, including neurodegeneration, inflammatory disorders, cardiac disease, and cancer. For example, mutations in the profilin 1 gene (PFN1) can cause amyotrophic lateral sclerosis (ALS), although the precise mechanisms that drive neurodegeneration remain unclear. While initial work suggested proteostasis and actin cytoskeleton defects as the main pathological pathways, multiple novel functions for PFN1 have since been discovered that may also contribute to ALS, including the regulation of nucleocytoplasmic transport, stress granules, mitochondria, and microtubules. Here, we will review these newly discovered roles for PFN1, speculate on their contribution to ALS, and discuss how defects in actin can contribute to these processes. By understanding profilin 1's involvement in ALS pathogenesis, we hope to gain insight into this functionally complex protein with significant influence over cellular physiology.}, }
@article {pmid39054501, year = {2024}, author = {Rahimi Darehbagh, R and Seyedoshohadaei, SA and Ramezani, R and Rezaei, N}, title = {Stem cell therapies for neurological disorders: current progress, challenges, and future perspectives.}, journal = {European journal of medical research}, volume = {29}, number = {1}, pages = {386}, pmid = {39054501}, issn = {2047-783X}, mesh = {Humans ; *Nervous System Diseases/therapy ; *Stem Cell Transplantation/methods/trends ; Animals ; Cell- and Tissue-Based Therapy/methods/trends ; Neural Stem Cells/transplantation/physiology ; }, abstract = {Stem cell-based therapies have emerged as a promising approach for treating various neurological disorders by harnessing the regenerative potential of stem cells to restore damaged neural tissue and circuitry. This comprehensive review provides an in-depth analysis of the current state of stem cell applications in primary neurological conditions, including Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), stroke, spinal cord injury (SCI), and other related disorders. The review begins with a detailed introduction to stem cell biology, discussing the types, sources, and mechanisms of action of stem cells in neurological therapies. It then critically examines the preclinical evidence from animal models and early human trials investigating the safety, feasibility, and efficacy of different stem cell types, such as embryonic stem cells (ESCs), mesenchymal stem cells (MSCs), neural stem cells (NSCs), and induced pluripotent stem cells (iPSCs). While ESCs have been studied extensively in preclinical models, clinical trials have primarily focused on adult stem cells such as MSCs and NSCs, as well as iPSCs and their derivatives. We critically assess the current state of research for each cell type, highlighting their potential applications and limitations in different neurological conditions. The review synthesizes key findings from recent, high-quality studies for each neurological condition, discussing cell manufacturing, delivery methods, and therapeutic outcomes. While the potential of stem cells to replace lost neurons and directly reconstruct neural circuits is highlighted, the review emphasizes the critical role of paracrine and immunomodulatory mechanisms in mediating the therapeutic effects of stem cells in most neurological disorders. The article also explores the challenges and limitations associated with translating stem cell therapies into clinical practice, including issues related to cell sourcing, scalability, safety, and regulatory considerations. Furthermore, it discusses future directions and opportunities for advancing stem cell-based treatments, such as gene editing, biomaterials, personalized iPSC-derived therapies, and novel delivery strategies. The review concludes by emphasizing the transformative potential of stem cell therapies in revolutionizing the treatment of neurological disorders while acknowledging the need for rigorous clinical trials, standardized protocols, and multidisciplinary collaboration to realize their full therapeutic promise.}, }
@article {pmid39050823, year = {2024}, author = {Min, JH and Sarlus, H and Harris, RA}, title = {Copper toxicity and deficiency: the vicious cycle at the core of protein aggregation in ALS.}, journal = {Frontiers in molecular neuroscience}, volume = {17}, number = {}, pages = {1408159}, pmid = {39050823}, issn = {1662-5099}, abstract = {The pathophysiology of ALS involves many signs of a disruption in copper homeostasis, with both excess free levels and functional deficiency likely occurring simultaneously. This is crucial, as many important physiological functions are performed by cuproenzymes. While it is unsurprising that many ALS symptoms are related to signs of copper deficiency, resulting in vascular, antioxidant system and mitochondrial oxidative respiration deficiencies, there are also signs of copper toxicity such as ROS generation and enhanced protein aggregation. We discuss how copper also plays a key role in proteostasis and interacts either directly or indirectly with many of the key aggregate-prone proteins implicated in ALS, such as TDP-43, C9ORF72, SOD1 and FUS as well as the effect of their aggregation on copper homeostasis. We suggest that loss of cuproprotein function is at the core of ALS pathology, a condition that is driven by a combination of unbound copper and ROS that can either initiate and/or accelerate protein aggregation. This could trigger a positive feedback cycle whereby protein aggregates trigger the aggregation of other proteins in a chain reaction that eventually captures elements of the proteostatic mechanisms in place to counteract them. The end result is an abundance of aggregated non-functional cuproproteins and chaperones alongside depleted intracellular copper stores, resulting in a general lack of cuproenzyme function. We then discuss the possible aetiology of ALS and illustrate how strong risk factors including environmental toxins such as BMAA and heavy metals can functionally behave to promote protein aggregation and disturb copper metabolism that likely drives this vicious cycle in sporadic ALS. From this synthesis, we propose restoration of copper balance using copper delivery agents in combination with chaperones/chaperone mimetics, perhaps in conjunction with the neuroprotective amino acid serine, as a promising strategy in the treatment of this incurable disease.}, }
@article {pmid39037015, year = {2024}, author = {Timmins, HC and Thompson, AE and Kiernan, MC}, title = {Diagnostic criteria for amyotrophic lateral sclerosis.}, journal = {Current opinion in neurology}, volume = {37}, number = {5}, pages = {570-576}, doi = {10.1097/WCO.0000000000001302}, pmid = {39037015}, issn = {1473-6551}, mesh = {*Amyotrophic Lateral Sclerosis/diagnosis/genetics ; Humans ; *Biomarkers/analysis ; }, abstract = {PURPOSE OF REVIEW: The present review will discuss the evolution of diagnostic criteria for amyotrophic lateral sclerosis (ALS) and biomarker considerations.<br><br>RECENT FINDINGS: To address the limitations of existing ALS diagnostic criteria, a consortium of key stakeholders developed the Gold Coast consensus criteria (GCC). The GCC has similar or greater sensitivity compared with the revised El Escorial (rEEC) and Awaji criteria (AC), particularly for atypical phenotypes, maintained across disease duration, severity, and site of onset. In addition to improving diagnostic sensitivity, using the GCC in clinical trials may promote an increased enrolment of up to 50% of ALS patients who do not currently meet the full diagnostic eligibility requirements of the rEEC. Future inclusion of genetic biomarkers may mitigate some limitations of the GCC, to further improve diagnostic utility. In advance of such a process, validation of these biomarkers will be required before inclusion as additional criteria.<br><br>SUMMARY: The GCC are simpler to use than previous consensus criteria, with demonstrated greater sensitivity and, enabling an earlier and more definitive ALS diagnosis, thereby facilitating wider enrolment into clinical trials. Broader implementation of the GCC in clinical trial settings is currently underway, globally.}, }
@article {pmid39030740, year = {2024}, author = {Jonson, C and Levine, KS and Lake, J and Hertslet, L and Jones, L and Patel, D and Kim, J and Bandres-Ciga, S and Terry, N and Mata, IF and Blauwendraat, C and Singleton, AB and Nalls, MA and Yokoyama, JS and Leonard, HL}, title = {Assessing the lack of diversity in genetics research across neurodegenerative diseases: A systematic review of the GWAS Catalog and literature.}, journal = {Alzheimer's &amp; dementia : the journal of the Alzheimer's Association}, volume = {20}, number = {8}, pages = {5740-5756}, pmid = {39030740}, issn = {1552-5279}, support = {U19AG079774/NS/NINDS NIH HHS/United States ; R01 AG062588/AG/NIA NIH HHS/United States ; ZO1AG000534/HH/HHS/United States ; U19 AG079774/AG/NIA NIH HHS/United States ; P30 AG062422/AG/NIA NIH HHS/United States ; P01 AG019724/AG/NIA NIH HHS/United States ; R01 AG057234/AG/NIA NIH HHS/United States ; 75N95022C00031/NS/NINDS NIH HHS/United States ; //Intramural Research Program/ ; P01AG019724/NS/NINDS NIH HHS/United States ; P30AG062422/NS/NINDS NIH HHS/United States ; /ALZ/Alzheimer's Association/United States ; U54NS123985/NS/NINDS NIH HHS/United States ; 75N95022C00031/DA/NIDA NIH HHS/United States ; U54 NS123985/NS/NINDS NIH HHS/United States ; R01AG057234/NS/NINDS NIH HHS/United States ; R01AG062588/NS/NINDS NIH HHS/United States ; //Global Brain Health Institute; and the Mary Oakley Foundation/ ; //Rainwater Charitable Foundation/ ; }, mesh = {Humans ; Genetic Predisposition to Disease/genetics ; *Genome-Wide Association Study ; *Neurodegenerative Diseases/genetics ; White People/genetics ; }, abstract = {The under-representation of non-European cohorts in neurodegenerative disease genome-wide association studies (GWAS) hampers precision medicine efforts. Despite the inherent genetic and phenotypic diversity in these diseases, GWAS research consistently exhibits a disproportionate emphasis on participants of European ancestry. This study reviews GWAS up to 2022, focusing on non-European or multi-ancestry neurodegeneration studies. We conducted a systematic review of GWAS results and publications up to 2022, focusing on non-European or multi-ancestry neurodegeneration studies. Rigorous article inclusion and quality assessment methods were employed. Of 123 neurodegenerative disease (NDD) GWAS reviewed, 82% predominantly featured European ancestry participants. A single European study identified over 90 risk loci, compared to a total of 50 novel loci in identified in all non-European or multi-ancestry studies. Notably, only six of the loci have been replicated. The significant under-representation of non-European ancestries in NDD GWAS hinders comprehensive genetic understanding. Prioritizing genomic diversity in future research is crucial for advancing NDD therapies and understanding. HIGHLIGHTS: Eighty-two percent of neurodegenerative genome-wide association studies (GWAS) focus on Europeans. Only 6 of 50 novel neurodegenerative disease (NDD) genetic loci have been replicated. Lack of diversity significantly hampers understanding of NDDs. Increasing diversity in NDD genetic research is urgently required. New initiatives are aiming to enhance diversity in NDD research.}, }
@article {pmid39030617, year = {2024}, author = {Chen, T and Dai, Y and Hu, C and Lin, Z and Wang, S and Yang, J and Zeng, L and Li, S and Li, W}, title = {Cellular and molecular mechanisms of the blood-brain barrier dysfunction in neurodegenerative diseases.}, journal = {Fluids and barriers of the CNS}, volume = {21}, number = {1}, pages = {60}, pmid = {39030617}, issn = {2045-8118}, support = {LGD21H250001 and LGD22H250001//Basic Public Welfare Research Program of Zhejiang Province/ ; LGD21H250001 and LGD22H250001//Basic Public Welfare Research Program of Zhejiang Province/ ; LGD21H250001 and LGD22H250001//Basic Public Welfare Research Program of Zhejiang Province/ ; LGD21H250001 and LGD22H250001//Basic Public Welfare Research Program of Zhejiang Province/ ; LGD21H250001 and LGD22H250001//Basic Public Welfare Research Program of Zhejiang Province/ ; LGD21H250001 and LGD22H250001//Basic Public Welfare Research Program of Zhejiang Province/ ; LGD21H250001 and LGD22H250001//Basic Public Welfare Research Program of Zhejiang Province/ ; LGD21H250001 and LGD22H250001//Basic Public Welfare Research Program of Zhejiang Province/ ; LGD21H250001 and LGD22H250001//Basic Public Welfare Research Program of Zhejiang Province/ ; No.X-202102//Scientific Research Foundation of Zhejiang University City College/ ; }, mesh = {*Blood-Brain Barrier/metabolism/physiopathology ; Humans ; *Neurodegenerative Diseases/metabolism/physiopathology ; Animals ; }, abstract = {BACKGROUND: Maintaining the structural and functional integrity of the blood-brain barrier (BBB) is vital for neuronal equilibrium and optimal brain function. Disruptions to BBB performance are implicated in the pathology of neurodegenerative diseases.<br><br>MAIN BODY: Early indicators of multiple neurodegenerative disorders in humans and animal models include impaired BBB stability, regional cerebral blood flow shortfalls, and vascular inflammation associated with BBB dysfunction. Understanding the cellular and molecular mechanisms of BBB dysfunction in brain disorders is crucial for elucidating the sustenance of neural computations under pathological conditions and for developing treatments for these diseases. This paper initially explores the cellular and molecular definition of the BBB, along with the signaling pathways regulating BBB stability, cerebral blood flow, and vascular inflammation. Subsequently, we review current insights into BBB dynamics in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. The paper concludes by proposing a unified mechanism whereby BBB dysfunction contributes to neurodegenerative disorders, highlights potential BBB-focused therapeutic strategies and targets, and outlines lessons learned and future research directions.<br><br>CONCLUSIONS: BBB breakdown significantly impacts the development and progression of neurodegenerative diseases, and unraveling the cellular and molecular mechanisms underlying BBB dysfunction is vital to elucidate how neural computations are sustained under pathological conditions and to devise therapeutic approaches.}, }
@article {pmid39025824, year = {2024}, author = {Lorenc, T and Khouja, C and Harden, M and Fulbright, H and Thomas, J}, title = {Defensive healthcare practice: systematic review of qualitative evidence.}, journal = {BMJ open}, volume = {14}, number = {7}, pages = {e085673}, pmid = {39025824}, issn = {2044-6055}, mesh = {Humans ; *Qualitative Research ; *Defensive Medicine ; Attitude of Health Personnel ; }, abstract = {OBJECTIVE: To synthesise qualitative evidence on clinicians' views and experiences of defensive practice.<br><br>DESIGN: Systematic review of qualitative data.<br><br>DATA SOURCES: MEDLINE, Embase, PsycINFO, AMED, Maternity and Infant Care, CINAHL, ASSIA, Sociological Abstracts, Proquest Dissertations &amp; Theses and PROSPERO were searched from 2000 to October 2023.<br><br>ELIGIBILITY CRITERIA: We included English-language studies of clinicians which reported qualitative data on the impact of litigation or complaints on clinical practice.<br><br>DATA EXTRACTION AND SYNTHESIS: We coded findings data line by line using a grounded theory approach. We assessed quality using Hawker et al's tool and synthesised data thematically.<br><br>RESULTS: 17 studies were included. Participants identify a range of clinical decisions which may be defensively motivated, relating to diagnosis and documentation as well as to treatment. Defensive practice often relates to a diffuse sense of risk rather than the direct threat of litigation and may overlap with other motivations, such as perceived pressure from patients or the desire to avoid harm. Defensive practice is seen to be harmful in many ways, but again, these perceptions may gain force from broader narratives of mistrust and disempowerment, as much as from the risk of litigation.<br><br>CONCLUSIONS: The idea of defensive practice, as enacted, is more complex than some theoretical accounts suggest and may often function to express broader concerns about the work of clinical care. The qualitative evidence calls into question the view of defensive practice as a key mediator linking litigation risk to inappropriate treatment and excess costs.}, }
@article {pmid39019674, year = {2024}, author = {Georges, M and Perez, T and Rabec, C and Jacquin, L and Finet-Monnier, A and Ramos, C and Patout, M and Attali, V and Amador, M and Gonzalez-Bermejo, J and Salachas, F and Morelot-Panzini, C}, title = {[Proposals from a French expert panel for respiratory care in ALS patients].}, journal = {Revue des maladies respiratoires}, volume = {41}, number = {8}, pages = {620-637}, doi = {10.1016/j.rmr.2024.06.006}, pmid = {39019674}, issn = {1776-2588}, mesh = {*Amyotrophic Lateral Sclerosis/complications/therapy ; Humans ; France/epidemiology ; *Noninvasive Ventilation/methods/standards/instrumentation ; *Respiratory Insufficiency/therapy/etiology ; Respiratory Therapy/methods/standards ; Quality of Life ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive diaphragm weakness and deteriorating lung function. Bulbar involvement and cough weakness contribute to respiratory morbidity and mortality. ALS-related respiratory failure significantly affects quality of life and is the leading cause of death. Non-invasive ventilation (NIV), which is the main recognized treatment for alleviating the symptoms of respiratory failure, prolongs survival and improves quality of life. However, the optimal timing for the initiation of NIV is still a matter of debate. NIV is a complex intervention. Multiple factors influence the efficacy of NIV and patient adherence. The aim of this work was to develop practical evidence-based advices to standardize the respiratory care of ALS patients in French tertiary care centres.<br><br>METHODS: For each proposal, a French expert panel systematically searched an indexed bibliography and prepared a written literature review that was then shared and discussed. A combined draft was prepared by the chairman for further discussion. All of the proposals were unanimously approved by the expert panel.<br><br>RESULTS: The French expert panel updated the criteria for initiating NIV in ALS patients. The most recent criteria were established in 2005. Practical advice for NIV initiation were included and the value of each tool available for NIV monitoring was reviewed. A strategy to optimize NIV parameters was suggested. Revisions were also suggested for the use of mechanically assisted cough devices in ALS patients.<br><br>CONCLUSION: Our French expert panel proposes an evidence-based review to update the respiratory care recommendations for ALS patients in daily practice.}, }
@article {pmid39017652, year = {2024}, author = {Ranta-Aho, J and Johari, M and Udd, B}, title = {Current advance on distal myopathy genetics.}, journal = {Current opinion in neurology}, volume = {37}, number = {5}, pages = {515-522}, pmid = {39017652}, issn = {1473-6551}, mesh = {Humans ; *Distal Myopathies/genetics/pathology ; }, abstract = {PURPOSE OF REVIEW: Distal myopathies are a clinically heterogenous group of rare, genetic muscle diseases, that present with weakness in hands and/or feet at onset. Some of these diseases remain accentuated in the distal muscles whereas others may later progress to the proximal muscles. In this review, the latest findings related to genetic and clinical features of distal myopathies are summarized.<br><br>RECENT FINDINGS: Variants in SMPX , DNAJB2, and HSPB6 have been identified as a novel cause of late-onset distal myopathy and neuromyopathy. In oculopharyngodistal myopathies, repeat expansions were identified in two novel disease-causing genes, RILPL1 and ABCD3. In multisystem proteinopathies, variants in HNRNPA1 and TARDBP , genes previously associated with amyotrophic lateral sclerosis, have been shown to cause late-onset distal myopathy without ALS. In ACTN2 -related distal myopathy, the first recessive forms of the disease have been described, adding it to the growing list of genes were both dominant and recessive forms of myopathy are present.<br><br>SUMMARY: The identification of novel distal myopathy genes and pathogenic variants contribute to our ability to provide a final molecular diagnosis to a larger number of patients and increase our overall understanding of distal myopathy genetics and pathology.}, }
@article {pmid39007083, year = {2024}, author = {Chidambaram, SB and Anand, N and Varma, SR and Ramamurthy, S and Vichitra, C and Sharma, A and Mahalakshmi, AM and Essa, MM}, title = {Superoxide dismutase and neurological disorders.}, journal = {IBRO neuroscience reports}, volume = {16}, number = {}, pages = {373-394}, pmid = {39007083}, issn = {2667-2421}, abstract = {Superoxide dismutase (SOD) is a common antioxidant enzyme found majorly in living cells. The main physiological role of SOD is detoxification and maintain the redox balance, acts as a first line of defence against Reactive nitrogen species (RNS), Reactive oxygen species (ROS), and other such potentially hazardous molecules. SOD catalyses the conversion of superoxide anion free radicals (O 2 -.) into molecular oxygen (O 2) and hydrogen peroxide (H 2O 2) in the cells. Superoxide dismutases (SODs) are expressed in neurons and glial cells throughout the CNS both intracellularly and extracellularly. Endogenous oxidative stress (OS) linked with enlarged production of reactive oxygen metabolites (ROMs), inflammation, deregulation of redox balance, mitochondrial dysfunction and bioenergetic crisis are found to be prerequisite for neuronal loss in neurological diseases. Clinical and genetic studies indicate a direct correlation between mutations in SOD gene and neurodegenerative diseases, like Amyotrophic Lateral Sclerosis (ALS), Huntington's disease (HD), Parkinson's Disease (PD) and Alzheimer's Disease (AD). Therefore, inhibitors of OS are considered as an optimistic approach to prevent neuronal loss. SOD mimetics like Metalloporphyrin Mn (II)-cyclic polyamines, Nitroxides and Mn (III)- Salen complexes are designed and used as therapeutic extensively in the treatment of neurological disorders. SODs and SOD mimetics are promising future therapeutics in the field of various diseases with OS-mediated pathology.}, }
@article {pmid39006764, year = {2024}, author = {Yang, C and Liu, G and Chen, X and Le, W}, title = {Cerebellum in Alzheimer's disease and other neurodegenerative diseases: an emerging research frontier.}, journal = {MedComm}, volume = {5}, number = {7}, pages = {e638}, pmid = {39006764}, issn = {2688-2663}, abstract = {The cerebellum is crucial for both motor and nonmotor functions. Alzheimer's disease (AD), alongside other dementias such as vascular dementia (VaD), Lewy body dementia (DLB), and frontotemporal dementia (FTD), as well as other neurodegenerative diseases (NDs) like Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and spinocerebellar ataxias (SCA), are characterized by specific and non-specific neurodegenerations in central nervous system. Previously, the cerebellum's significance in these conditions was underestimated. However, advancing research has elevated its profile as a critical node in disease pathology. We comprehensively review the existing evidence to elucidate the relationship between cerebellum and the aforementioned diseases. Our findings reveal a growing body of research unequivocally establishing a link between the cerebellum and AD, other forms of dementia, and other NDs, supported by clinical evidence, pathological and biochemical profiles, structural and functional neuroimaging data, and electrophysiological findings. By contrasting cerebellar observations with those from the cerebral cortex and hippocampus, we highlight the cerebellum's distinct role in the disease processes. Furthermore, we also explore the emerging therapeutic potential of targeting cerebellum for the treatment of these diseases. This review underscores the importance of the cerebellum in these diseases, offering new insights into the disease mechanisms and novel therapeutic strategies.}, }
@article {pmid39006715, year = {2024}, author = {Suleiman Khoury, Z and Sohail, F and Wang, J and Mendoza, M and Raake, M and Tahoor Silat, M and Reddy Bathinapatta, M and Sadeghzadegan, A and Meghana, P and Paul, J}, title = {Neuroinflammation: A Critical Factor in Neurodegenerative Disorders.}, journal = {Cureus}, volume = {16}, number = {6}, pages = {e62310}, pmid = {39006715}, issn = {2168-8184}, abstract = {This review offers a comprehensive review of the signals and the paramount role neuroinflammation plays in neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, and amyotrophic lateral sclerosis. The study explores the sophisticated interactions between microglial, astrocytic, and dendritic cells and how neuroinflammation affects long-term neuronal damage and dysfunction. There are specific pathways related to the mentioned inflammatory processes, including Janus kinases/signal transducer and activator of transcriptions, nuclear factor-κB, and mitogen-activated protein kinases pathways. Neuroinflammation is argued to be a double-edged sword, being not only a protective agent that prevents further neuron damage but also the causative factor in more cell injury development. This concept of contrasting inflammation with neuroprotection advocates for the use of therapeutic techniques that seek to modulate neuroinflammatory responses as part of the neurodegeneration treatment. The recent research findings are integrated with the established knowledge to help present a comprehensive image of neuroinflammation's impact on neurodegenerative diseases and its implications for future therapy.}, }
@article {pmid39000336, year = {2024}, author = {Bodai, L and Borosta, R and Ferencz, &#xc1; and Kovács, M and Zsindely, N}, title = {The Role of miR-137 in Neurodegenerative Disorders.}, journal = {International journal of molecular sciences}, volume = {25}, number = {13}, pages = {}, pmid = {39000336}, issn = {1422-0067}, support = {OTKA 145898//National Research, Development and Innovation Office [Hungary]/ ; }, mesh = {*MicroRNAs/genetics/metabolism ; Humans ; *Neurodegenerative Diseases/genetics/metabolism ; Animals ; Gene Expression Regulation ; }, abstract = {Neurodegenerative diseases affect an increasing part of the population of modern societies, burdening healthcare systems and causing immense suffering at the personal level. The pathogenesis of several of these disorders involves dysregulation of gene expression, which depends on several molecular processes ranging from transcription to protein stability. microRNAs (miRNAs) are short non-coding RNA molecules that modulate gene expression by suppressing the translation of partially complementary mRNAs. miR-137 is a conserved, neuronally enriched miRNA that is implicated in neurodegeneration. Here, we review the current body of knowledge about the role that miR-137 plays in five prominent neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis. The presented data indicate that, rather than having a general neuroprotective role, miR-137 modulates the pathology of distinct disorders differently.}, }
@article {pmid38999600, year = {2024}, author = {Chakraborty, N and Das, A and Pal, S and Roy, S and Sil, SK and Adak, MK and Hassanzamman, M}, title = {Exploring Aluminum Tolerance Mechanisms in Plants with Reference to Rice and Arabidopsis: A Comprehensive Review of Genetic, Metabolic, and Physiological Adaptations in Acidic Soils.}, journal = {Plants (Basel, Switzerland)}, volume = {13}, number = {13}, pages = {}, pmid = {38999600}, issn = {2223-7747}, abstract = {Aluminum (Al) makes up a third of the Earth's crust and is a widespread toxic contaminant, particularly in acidic soils. It impacts crops at multiple levels, from cellular to whole plant systems. This review delves into Al's reactivity, including its cellular transport, involvement in oxidative redox reactions, and development of specific metabolites, as well as the influence of genes on the production of membrane channels and transporters, alongside its role in triggering senescence. It discusses the involvement of channel proteins in calcium influx, vacuolar proton pumping, the suppression of mitochondrial respiration, and the initiation of programmed cell death. At the cellular nucleus level, the effects of Al on gene regulation through alterations in nucleic acid modifications, such as methylation and histone acetylation, are examined. In addition, this review outlines the pathways of Al-induced metabolic disruption, specifically citric acid metabolism, the regulation of proton excretion, the induction of specific transcription factors, the modulation of Al-responsive proteins, changes in citrate and nucleotide glucose transporters, and overall metal detoxification pathways in tolerant genotypes. It also considers the expression of phenolic oxidases in response to oxidative stress, their regulatory feedback on mitochondrial cytochrome proteins, and their consequences on root development. Ultimately, this review focuses on the selective metabolic pathways that facilitate Al exclusion and tolerance, emphasizing compartmentalization, antioxidative defense mechanisms, and the control of programmed cell death to manage metal toxicity.}, }
@article {pmid38999371, year = {2024}, author = {Dell'Anna, G and Fanti, L and Fanizza, J and Barà, R and Barchi, A and Fasulo, E and Elmore, U and Rosati, R and Annese, V and Laterza, L and Fuccio, L and Azzolini, F and Danese, S and Mandarino, FV}, title = {VAC-Stent in the Treatment of Post-Esophagectomy Anastomotic Leaks: A New "Kid on the Block" Who Marries the Best of Old Techniques-A Review.}, journal = {Journal of clinical medicine}, volume = {13}, number = {13}, pages = {}, pmid = {38999371}, issn = {2077-0383}, abstract = {Esophagectomy, while a pivotal treatment for esophageal cancer, is not without adverse events. Among these, anastomotic leak (AL) is the most feared complication, threatening patient lives and incurring significant healthcare costs. The management of AL is complex and lacks standardization. Given the high morbidity and mortality rates associated with redo-surgery, which poses risks for already fragile patients, various endoscopic treatments have been developed over time. Self-expandable metallic stents (SEMSs) were the most widely used treatment until the early 2000s. The mechanism of action of SEMSs includes covering the wall defect, protecting it from secretions, and promoting healing. In 2010, endoscopic vacuum therapy (EVT) emerged as a viable alternative for treating ALs, quickly gaining acceptance in clinical practice. EVT involves placing a dedicated sponge under negative pressure inside or adjacent to the wall defect, aiming to clear the leak and promote granulation tissue formation. More recently, the VAC-Stent entered the scenario of endoscopic treatment of post-esophagectomy ALs. This device combines a fully covered SEMS with an integrated EVT sponge, blending the ability of SEMSs to exclude defects and maintain the patency of the esophageal lumen with the capacity of EVT to aspirate secretions and promote the formation of granulation tissue. Although the literature on this new device is not extensive, early results from the application of VAC-Stent have shown promising outcomes. This review aims to synthesize the preliminary efficacy and safety data on the device, thoroughly analyze its advantages over traditional techniques and disadvantages, explore areas for improvement, and propose future directions.}, }
@article {pmid38991324, year = {2024}, author = {Reis, J and Spencer, PS}, title = {An introduction to environmental neurotoxicology: Lessons from a clinical perspective.}, journal = {Journal of the neurological sciences}, volume = {463}, number = {}, pages = {123108}, doi = {10.1016/j.jns.2024.123108}, pmid = {38991324}, issn = {1878-5883}, mesh = {Humans ; *Environmental Exposure/adverse effects ; *Neurotoxicity Syndromes/etiology ; Animals ; }, abstract = {In 1992, the Committee on Neurotoxicology and Models for Assessing Risk of the National Academy of Sciences in Washington DC focused with a scientific perspective on the identification of substances with neurotoxic potential, studies of exposed populations, risk assessment, and biologic markers of disease. This Committee recommended: "all physicians should be trained to take a thorough occupational-exposure history and to be aware of other possible sources of toxic exposure". Although convened after several outbreaks of neurotoxic syndromes, clinical neurological considerations were lacking. After defining keys words, namely Environment, Neurotoxicology and Neurotoxicants, we present some demonstrative cases; e.g., the Epidemic Neuropathy in Cuba, Minamata disease, ALS/PDC on Guam, and the ALS hot spot in the French Alps. Always with a clinical and practical approach, we will then review the milieux that contain and convey potential neurotoxicants, the different exposure routes and the clinical presentations. Drawing lessons from clinical cases, we offer some thoughts concerning the future of Environmental Neurotoxicology (ENT). Pointing notably to the diffuse chemical contamination of ecosystems and living beings, including Homo sapiens, we question the real impact of agents with neurotoxic potential on the human brain, considering the effects, for example, of air pollution, endocrine disruptors and nanoparticles. Concern is expressed over the lack of knowledge of the non-monotonic kinetics of many of these chemicals, the major concern being related to mixtures and low-dose exposures, as well as the delayed appearance in clinical expression of prevalent neurodegenerative diseases.}, }
@article {pmid38988889, year = {2024}, author = {Ansari, U and Alam, M and Nadora, D and Muttalib, Z and Chen, V and Taguinod, I and FitzPatrick, M and Wen, J and Ansari, Z and Lui, F}, title = {Assessing the efficacy of amyotrophic lateral sclerosis drugs in slowing disease progression: A literature review.}, journal = {AIMS neuroscience}, volume = {11}, number = {2}, pages = {166-177}, pmid = {38988889}, issn = {2373-7972}, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal and intricate neurodegenerative disease that impacts upper and lower motor neurons within the central nervous system, leading to their progressive destruction. Despite extensive research, the pathogenesis of this multifaceted disease remains elusive. The United States Food and Drug Administration (FDA) has granted approval for seven medications designed to address ALS and mitigate its associated symptoms. These FDA-sanctioned treatments are Qalsody, Relyvrio, Radicava, Rilutek, Tiglutik, Exservan, and Nuedexta. In this review, the effects of these seven drugs on ALS based on their mechanism of action, dosing, and clinical presentations are comprehensively summarized. Each medication offers a distinct approach to manage ALS, aiming to alleviate the burdensome symptoms and slow the disease's progression, thereby improving the quality of life for individuals affected by this neurological condition. However, despite these advancements in pharmaceutical interventions, finding a definitive cure for ALS remains a significant challenge. Continuous investigation into ALS pathophysiology and therapeutic avenues remains imperative, necessitating further research collaborations and innovative approaches to unravel the complex mechanisms underlying this debilitating condition.}, }
@article {pmid38988765, year = {2024}, author = {Readman, MR and Polden, M and Gibbs, MC and Donohue, A and Chhetri, SK and Crawford, TJ}, title = {Oculomotor atypicalities in motor neurone disease: a systematic review.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1399923}, pmid = {38988765}, issn = {1662-4548}, abstract = {INTRODUCTION: Cognitive dysfunction is commonplace in Motor Neurone Disease (MND). However, due to the prominent motor symptoms in MND, assessing patients' cognitive function through traditional cognitive assessments, which oftentimes require motoric responses, may become increasingly challenging as the disease progresses. Oculomotor pathways are apparently resistant to pathological degeneration in MND. As such, abnormalities in oculomotor functions, largely driven by cognitive processes such as saccades and smooth pursuit eye movement, may be reflective of frontotemporal cognitive deficits in MND. Thus, saccadic and smooth pursuit eye movements may prove to be ideal mechanistic markers of cognitive function in MND.<br><br>METHODS: To ascertain the utility of saccadic and smooth pursuit eye movements as markers of cognitive function in MND, this review summarizes the literature concerning saccadic and smooth pursuit eye movement task performance in people with MND.<br><br>RESULTS AND DISCUSSION: Of the 22 studies identified, noticeable patterns suggest that people with MND can be differentiated from controls based on antisaccade and smooth pursuit task performance, and thus the antisaccade task and smooth pursuit task may be potential candidates for markers of cognition in MND. However, further studies which ascertain the concordance between eye tracking measures and traditional measures of cognition are required before this assumption is extrapolated, and clinical recommendations are made.<br><br>https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=376620, identifier CRD42023376620.}, }
@article {pmid38978024, year = {2024}, author = {Endalamaw, A and Gilks, CF and Ambaw, F and Shiferaw, WS and Assefa, Y}, title = {Explaining inequity in knowledge, attitude, and services related to HIV/AIDS: a systematic review.}, journal = {BMC public health}, volume = {24}, number = {1}, pages = {1815}, pmid = {38978024}, issn = {1471-2458}, mesh = {Humans ; *HIV Infections/psychology ; *Health Knowledge, Attitudes, Practice ; Healthcare Disparities ; }, abstract = {BACKGROUND: Equitable service provision and coverage are important responses to end the threat of the HIV/AIDS pandemic. Understanding inequity supports policies and programmes to deliver tailored interventions. There is continuous evidence generation on inequity in HIV/AIDS services. However, there was a lack of evidence on the global picture of inequity in behavioural and biomedical services related to HIV/AIDS. This systematic review assessed inequities in knowledge, attitude, HIV testing, and ART coverage across individual-level social groups and multiple (dis)advantage categories.<br><br>METHODS: This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline, with a PROSPERO registration number CRD42024521247. The risk of bias was assessed by using Hoy et al's and Joanna Brigg's quality appraisal checklists for cross-sectional quantitative and qualitative studies, respectively. The search date was from inception to the final database search date (May 29, 2023). The included articles were either quantitative or qualitative studies. We used mixed-methods approach to analyse the data from the review articles. Quantitative descriptive analysis was conducted to estimate frequency of articles published from different countries around the world. Qualitative content analysis of the findings from the original studies was conducted using the PROGRESS plus framework which stands for: place of residence, occupation or employment status, gender, religion, education status, socioeconomic status, and social capital.<br><br>RESULTS: Out of 6,029 articles that were accessed and screened, only 72 articles met the inclusion criteria. More articles on HIV-related equity in knowledge, attitude, testing, and ART were published in developed countries than in developing countries. Individuals from higher-income households had better knowledge about HIV/AIDS. Unfavourable attitudes towards people living with HIV and HIV/AIDS-associated stigma were common among women. HIV/AIDS service coverage (HIV testing or ART coverage) was higher among richer and urban residents. HIV/AIDS-associated stigma and lower levels of knowledge about HIV/AIDS were observed among multiple disadvantageous groups due to the intersection of two or more identities.<br><br>CONCLUSIONS: The current review revealed that there have been disparities in HIV/AIDS services between social classes. Ending service disparity towards the global threat of HIV/AIDS demands tailored interventions based on socially disadvantaged groups (e.g., poor, rural dwellers, and women) and intersectional determinants. There is a need to understand the deep-rooted causes of inequity and the challenges that an equity-oriented system faces over time. More studies on inequity are needed, including intersectional inequity, which has been rarely studied in developing countries.}, }
@article {pmid38976599, year = {2024}, author = {Xu, Z and Xu, R}, title = {Current potential diagnostic biomarkers of amyotrophic lateral sclerosis.}, journal = {Reviews in the neurosciences}, volume = {35}, number = {8}, pages = {917-931}, pmid = {38976599}, issn = {2191-0200}, mesh = {*Amyotrophic Lateral Sclerosis/diagnosis/metabolism ; Humans ; *Biomarkers/metabolism ; Oxidative Stress/physiology ; Proteomics/methods ; Animals ; }, abstract = {Amyotrophic lateral sclerosis (ALS) currently lacks the useful diagnostic biomarkers. The current diagnosis of ALS is mainly depended on the clinical manifestations, which contributes to the diagnostic delay and be difficult to make the accurate diagnosis at the early stage of ALS, and hinders the clinical early therapeutics. The more and more pathogenesis of ALS are found at the last 30 years, including excitotoxicity, the oxidative stress, the mitochondrial dysfunction, neuroinflammation, the altered energy metabolism, the RNA misprocessing and the most recent neuroimaging findings. The findings of these pathogenesis bring the new clues for searching the diagnostic biomarkers of ALS. At present, a large number of relevant studies about the diagnostic biomarkers are underway. The ALS pathogenesis related to the diagnostic biomarkers might lessen the diagnostic reliance on the clinical manifestations. Among them, the cortical altered signatures of ALS patients derived from both structural and functional magnetic resonance imaging and the emerging proteomic biomarkers of neuronal loss and glial activation in the cerebrospinal fluid as well as the potential biomarkers in blood, serum, urine, and saliva are leading a new phase of biomarkers. Here, we reviewed these current potential diagnostic biomarkers of ALS.}, }
@article {pmid38975145, year = {2024}, author = {Zhang, J and Xie, D and Jiao, D and Zhou, S and Liu, S and Ju, Z and Hu, L and Qi, L and Yao, C and Zhao, C}, title = {From inflammatory signaling to neuronal damage: Exploring NLR inflammasomes in ageing neurological disorders.}, journal = {Heliyon}, volume = {10}, number = {12}, pages = {e32688}, pmid = {38975145}, issn = {2405-8440}, abstract = {The persistence of neuronal degeneration and damage is a major obstacle in ageing medicine. Nucleotide-binding oligomerization domain (NOD)-like receptors detect environmental stressors and trigger the maturation and secretion of pro-inflammatory cytokines that can cause neuronal damage and accelerate cell death. NLR (NOD-like receptors) inflammasomes are protein complexes that contain NOD-like receptors. Studying the role of NLR inflammasomes in ageing-related neurological disorders can provide valuable insights into the mechanisms of neurodegeneration. This includes investigating their activation of inflammasomes, transcription, and capacity to promote or inhibit inflammatory signaling, as well as exploring strategies to regulate NLR inflammasomes levels. This review summarizes the use of NLR inflammasomes in guiding neuronal degeneration and injury during the ageing process, covering several neurological disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, stroke, and peripheral neuropathies. To improve the quality of life and slow the progression of neurological damage, NLR-based treatment strategies, including inhibitor-related therapies and physical therapy, are presented. Additionally, important connections between age-related neurological disorders and NLR inflammasomes are highlighted to guide future research and facilitate the development of new treatment options.}, }
@article {pmid38973130, year = {2025}, author = {Corcia, P and Guy, N and Pradat, PF and Soriani, MH and Verschueren, A and Couratier, P}, title = {Treatment continuity of amyotrophic lateral sclerosis with available riluzole formulations: state of the art and current challenges in a 'real-world' setting.}, journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration}, volume = {26}, number = {1-2}, pages = {15-21}, doi = {10.1080/21678421.2024.2375330}, pmid = {38973130}, issn = {2167-9223}, mesh = {*Riluzole/therapeutic use/administration &amp; dosage ; Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/complications ; *Neuroprotective Agents/administration &amp; dosage/therapeutic use ; Deglutition Disorders/drug therapy/etiology ; Treatment Outcome ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a rare multisystem neurodegenerative disease leading to death due to respiratory failure. Riluzole was the first disease modifying treatment approved in ALS. Randomized clinical trials showed a significant benefit of riluzole on survival in the months following randomization, with a good safety profile. 'Real-world' studies suggested that the survival benefit of riluzole is substantially greater, with an extended survival ranging between 6 and 19 months. The main limiting associated adverse effects of riluzole are non-severe gastrointestinal complications and an elevation of liver enzymes, observed in 10% of patients. While different classes of drugs have been approved in some countries, riluzole remains the gold standard of therapy. Dysphagia induced by ALS is a major challenge for food intake and riluzole administration. Tablet crushing is associated with a loss of drug intake and a risk of powder aspiration, which jeopardizes the benefits of riluzole. Riluzole oral suspension (ROS) and oral film (ROF) allow riluzole intake in patients with dysphagia. Both formulations are bioequivalent to riluzole tablets with a good safety profile albeit transient oral hypoaesthesia. In case of severe dysphagia, ROS can be used with percutaneous endoscopic gastrostomy. ROF, the last approved formulation, requires low swallowing capacities and may contribute to maintain the efficacy of riluzole when tablets are inadequate according to patient's status and/or preferences. To optimize treatment continuity in newly diagnosed patients, the expected psychological impact of formulation switching that may be perceived as the sign of disease progression should be anticipated.}, }
@article {pmid38969143, year = {2024}, author = {Jha, SK and Nelson, VK and Suryadevara, PR and Panda, SP and Pullaiah, CP and Nuli, MV and Kamal, M and Imran, M and Ausali, S and Abomughaid, MM and Srivastava, R and Deka, R and Pritam, P and Gupta, N and Shyam, H and Singh, IK and Pandey, BW and Dewanjee, S and Jha, NK and Jafari, SM}, title = {Cannabidiol and neurodegeneration: From molecular mechanisms to clinical benefits.}, journal = {Ageing research reviews}, volume = {100}, number = {}, pages = {102386}, doi = {10.1016/j.arr.2024.102386}, pmid = {38969143}, issn = {1872-9649}, mesh = {Humans ; *Cannabidiol/therapeutic use/pharmacology ; *Neurodegenerative Diseases/drug therapy/metabolism ; Animals ; Neuroprotective Agents/therapeutic use/pharmacology ; Oxidative Stress/drug effects ; }, abstract = {Neurodegenerative disorders (NDs) such as Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, and amyotrophic lateral sclerosis are severe and life-threatening conditions in which significant damage of functional neurons occurs to produce psycho-motor malfunctions. NDs are an important cause of death in the elderly population worldwide. These disorders are commonly associated with the progression of age, oxidative stress, and environmental pollutants, which are the major etiological factors. Abnormal aggregation of specific proteins such as α-synuclein, amyloid-β, huntingtin, and tau, and accumulation of the associated oligomers in neurons are the hallmark pathological features of NDs. Existing therapeutic options for NDs are only symptomatic relief and do not address root-causing factors, such as protein aggregation, oxidative stress, and neuroinflammation. Cannabidiol (CBD) is a non-psychotic natural cannabinoid obtained from Cannabis sativa that possesses multiple pharmacological actions, including antioxidant, anti-inflammatory, and neuroprotective effects in various NDs and other neurological disorders both in vitro and in vivo. CBD has gained attention as a promising drug candidate for the management of neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease, by inhibiting protein aggregation, free radicals, and neuroinflammation. In parallel, CBD has shown positive results in other neurological disorders, such as epilepsy, depression, schizophrenia, and anxiety, as well as adjuvant treatment with existing standard therapeutic agents. Hence, the present review focuses on exploring the possible molecular mechanisms in controlling various neurological disorders as well as the clinical applications of CBD in NDs including epilepsy, depression and anxiety. In this way, the current review will serve as a standalone reference for the researchers working in this area.}, }
@article {pmid38968328, year = {2024}, author = {Gowrishankar, S and Smith, ME and Creber, N and Muzaffar, J and Borsetto, D}, title = {Immunosuppression in stem cell clinical trials of neural and retinal cell types: A systematic review.}, journal = {PloS one}, volume = {19}, number = {7}, pages = {e0304073}, pmid = {38968328}, issn = {1932-6203}, mesh = {Humans ; *Stem Cell Transplantation/methods ; *Immunosuppression Therapy/methods ; Retina/immunology ; Immunosuppressive Agents/therapeutic use ; Clinical Trials as Topic ; }, abstract = {BACKGROUND: Pharmacologic immunosuppression regimes are commonly employed in stem cell clinical trials to mitigate host immune rejection and promote survival and viability of transplanted cells. Immunosuppression and cell survival has been extensively studied in retinal and spinal tissues. The applicability of stem cell therapy is rapidly expanding to other sensory organs such as the ear and hearing. As regenerative therapy is directed to new areas, a greater understanding of immunosuppression strategies and their efficacy is required to facilitate translation to organ-specific biologic microenvironments.<br><br>OBJECTIVE: This systematic review appraises the current literature regarding immunosuppression strategies employed in stem cell trials of retinal and neural cells.<br><br>METHODS: This systematic review was performed in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria included studies presenting data on neural or retinal cells as part of an in-human clinical trial that detailed the immunosuppression regime used. Exclusion criteria included non-English language studies, animal studies, review articles, case reports, editorials, and letters. The databases Medline, Embase, Scopus, Web of Science, and the Cochrane Library were searched from inception to February 2024. Risk of bias was evaluated using the ROBINS-I tool.<br><br>RESULTS: Eighteen articles fit the inclusion criteria. Nine articles concerned retinal cells, 5 concerned spinal cord injury, and 4 concerned amyotrophic lateral sclerosis. A multi-drug and short-term immunosuppression regime were commonly employed in the identified studies. Detected immune responses in treated patients were rare. Common immunosuppression paradigms included tacrolimus, mycophenolate mofetil and tapering doses of steroids. Local immunosuppression with steroids was employed in some studies concerning retinal diseases.<br><br>DISCUSSION: A short-term course of systemic immunosuppression seemed efficacious for most included studies, with some showing grafted cells viable months to years after immunosuppression had stopped. Longer-term follow-up is required to see if this remains the case. Side effects related to immunosuppression were uncommon.}, }
@article {pmid38967881, year = {2024}, author = {Rojas-López, JC and Estrada-Gualdron, PI and Ramírez-Guerrero, S and Velásquez-Cárdenas, MJ and Redondo-Escobar, J and Vargas-Arenas, S and Palacios-Sánchez, L and Palacios-Espinosa, X}, title = {Efficacy of pain management strategies in adults with Amyotrophic Lateral Sclerosis (ALS): A Systematic Review.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {12}, pages = {5591-5604}, pmid = {38967881}, issn = {1590-3478}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/therapy ; *Pain Management/methods ; Adult ; Pain/etiology/drug therapy ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive muscle weakness. Presence of pain in ALS patients is heterogeneously reported in studies, and mostly underrepresented in symptom scales. The aim of this study is to evaluate the efficacy of pharmacological and non-pharmacological therapeutic modalities for pain management in patients with ALS. A systematic review was conducted in four databases; PubMed, Scopus, Clinicaltrials.gov, and Cochrane-Ovid. Five randomized controlled clinical trials were included regarding pharmacological and non-pharmacological pain management interventions in adult patients with confirmed diagnosis of ALS in whom pain was objectively evaluated. Risk of bias assessment was evaluated using the RoB2.0 tool. Eligible studies were reported as a descriptive analysis. This systematic review was registered with PROSPERO ID: CRD42024495009. Five clinical trials regarding pain management strategies in ALS were eligible for analysis. Two out of five were non-pharmacological approaches whilst the remaining three provided pharmacological therapies. Of these, Mexiletine was efficient in terms of pain relief, particularly between 600 and 900 mg per day, whereas Mecasin showed no pain relief at both, high and low doses. Non-pharmacological therapies, such as exercise and osteopathic manual treatment also lacked efficacy in regard to pain management. Clinical trials focusing on pain management strategies for ALS patients are limited. Medical professionals, understandably focused on immediate life-threatening aspects, may inadvertently sideline the nuanced and intricate dimension of pain experienced by patients with ALS.}, }
@article {pmid38967655, year = {2024}, author = {Müller, P and Draguhn, A and Egorov, AV}, title = {Persistent sodium currents in neurons: potential mechanisms and pharmacological blockers.}, journal = {Pflugers Archiv : European journal of physiology}, volume = {476}, number = {10}, pages = {1445-1473}, pmid = {38967655}, issn = {1432-2013}, support = {HE8155/1-2//Deutsche Forschungsgemeinschaft/ ; EG134/2-1//Deutsche Forschungsgemeinschaft/ ; Treat-ION01GM1907A//Bundesministerium f&#xfc;r Bildung und Forschung/ ; College for Clinician Scientists//Else Kr&#xf6;ner-Fresenius-Stiftung/ ; }, mesh = {Humans ; Animals ; *Neurons/metabolism/drug effects/physiology ; Sodium Channel Blockers/pharmacology ; Sodium Channels/metabolism/drug effects ; }, abstract = {Persistent sodium current (INaP) is an important activity-dependent regulator of neuronal excitability. It is involved in a variety of physiological and pathological processes, including pacemaking, prolongation of sensory potentials, neuronal injury, chronic pain and diseases such as epilepsy and amyotrophic lateral sclerosis. Despite its importance, neither the molecular basis nor the regulation of INaP are sufficiently understood. Of particular significance is a solid knowledge and widely accepted consensus about pharmacological tools for analysing the function of INaP and for developing new therapeutic strategies. However, the literature on INaP is heterogeneous, with varying definitions and methodologies used across studies. To address these issues, we provide a systematic review of the current state of knowledge on INaP, with focus on mechanisms and effects of this current in the central nervous system. We provide an overview of the specificity and efficacy of the most widely used INaP blockers: amiodarone, cannabidiol, carbamazepine, cenobamate, eslicarbazepine, ethosuximide, gabapentin, GS967, lacosamide, lamotrigine, lidocaine, NBI-921352, oxcarbazepine, phenytoine, PRAX-562, propofol, ranolazine, riluzole, rufinamide, topiramate, valproaic acid and zonisamide. We conclude that there is strong variance in the pharmacological effects of these drugs, and in the available information. At present, GS967 and riluzole can be regarded bona fide INaP blockers, while phenytoin and lacosamide are blockers that only act on the slowly inactivating component of sodium currents.}, }
@article {pmid38967083, year = {2024}, author = {Nijs, M and Van Damme, P}, title = {The genetics of amyotrophic lateral sclerosis.}, journal = {Current opinion in neurology}, volume = {37}, number = {5}, pages = {560-569}, pmid = {38967083}, issn = {1473-6551}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/diagnosis ; *C9orf72 Protein/genetics ; *Genetic Predisposition to Disease/genetics ; *RNA-Binding Protein FUS/genetics ; Superoxide Dismutase-1/genetics ; Superoxide Dismutase/genetics ; Proteins/genetics ; DNA-Binding Proteins/genetics ; Genetic Testing ; }, abstract = {PURPOSE OF REVIEW: Amyotrophic lateral sclerosis (ALS) has a strong genetic basis, but the genetic landscape of ALS appears to be complex. The purpose of this article is to review recent developments in the genetics of ALS.<br><br>RECENT FINDINGS: Large-scale genetic studies have uncovered more than 40 genes contributing to ALS susceptibility. Both rare variants with variable effect size and more common variants with small effect size have been identified. The most common ALS genes are C9orf72 , SOD1 , TARDBP and FUS . Some of the causative genes of ALS are shared with frontotemporal dementia, confirming the molecular link between both diseases. Access to diagnostic gene testing for ALS has to improve, as effective gene silencing therapies for some genetic subtypes of ALS are emerging, but there is no consensus about which genes to test for.<br><br>SUMMARY: Our knowledge about the genetic basis of ALS has improved and the first effective gene silencing therapies for specific genetic subtypes of ALS are underway. These therapeutic advances underline the need for better access to gene testing for people with ALS. Further research is needed to further map the genetic heterogeneity of ALS and to establish the best strategy for gene testing in a clinical setting.}, }
@article {pmid38966756, year = {2024}, author = {Garg, V and Geurten, BRH}, title = {Diving deep: zebrafish models in motor neuron degeneration research.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1424025}, pmid = {38966756}, issn = {1662-4548}, abstract = {In the dynamic landscape of biomedical science, the pursuit of effective treatments for motor neuron disorders like hereditary spastic paraplegia (HSP), amyotrophic lateral sclerosis (ALS), and spinal muscular atrophy (SMA) remains a key priority. Central to this endeavor is the development of robust animal models, with the zebrafish emerging as a prime candidate. Exhibiting embryonic transparency, a swift life cycle, and significant genetic and neuroanatomical congruencies with humans, zebrafish offer substantial potential for research. Despite the difference in locomotion-zebrafish undulate while humans use limbs, the zebrafish presents relevant phenotypic parallels to human motor control disorders, providing valuable insights into neurodegenerative diseases. This review explores the zebrafish's inherent traits and how they facilitate profound insights into the complex behavioral and cellular phenotypes associated with these disorders. Furthermore, we examine recent advancements in high-throughput drug screening using the zebrafish model, a promising avenue for identifying therapeutically potent compounds.}, }
@article {pmid38965379, year = {2024}, author = {Jacob, SM and Lee, S and Kim, SH and Sharkey, KA and Pfeffer, G and Nguyen, MD}, title = {Brain-body mechanisms contribute to sexual dimorphism in amyotrophic lateral sclerosis.}, journal = {Nature reviews. Neurology}, volume = {20}, number = {8}, pages = {475-494}, pmid = {38965379}, issn = {1759-4766}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/physiopathology/epidemiology/metabolism ; *Sex Characteristics ; Male ; Female ; Animals ; Brain/metabolism/physiopathology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is the most common form of human motor neuron disease. It is characterized by the progressive degeneration of upper and lower motor neurons, leading to generalized motor weakness and, ultimately, respiratory paralysis and death within 3-5 years. The disease is shaped by genetics, age, sex and environmental stressors, but no cure or routine biomarkers exist for the disease. Male individuals have a higher propensity to develop ALS, and a different manifestation of the disease phenotype, than female individuals. However, the mechanisms underlying these sex differences remain a mystery. In this Review, we summarize the epidemiology of ALS, examine the sexually dimorphic presentation of the disease and highlight the genetic variants and molecular pathways that might contribute to sex differences in humans and animal models of ALS. We advance the idea that sexual dimorphism in ALS arises from the interactions between the CNS and peripheral organs, involving vascular, metabolic, endocrine, musculoskeletal and immune systems, which are strikingly different between male and female individuals. Finally, we review the response to treatments in ALS and discuss the potential to implement future personalized therapeutic strategies for the disease.}, }
@article {pmid38963497, year = {2024}, author = {Yu, G and Bai, Y and Zhang, ZY}, title = {Valosin-Containing Protein (VCP)/p97 Oligomerization.}, journal = {Sub-cellular biochemistry}, volume = {104}, number = {}, pages = {485-501}, pmid = {38963497}, issn = {0306-0225}, mesh = {*Valosin Containing Protein/metabolism/genetics/chemistry ; Humans ; Protein Multimerization ; Animals ; Mutation ; Frontotemporal Dementia/genetics/metabolism ; Adenosine Triphosphatases/metabolism/genetics/chemistry ; Osteitis Deformans/genetics/metabolism ; Cell Cycle Proteins/metabolism/genetics/chemistry ; Myositis, Inclusion Body/genetics/metabolism ; Muscular Dystrophies, Limb-Girdle ; }, abstract = {Valosin-containing protein (VCP), also known as p97, is an evolutionarily conserved AAA+ ATPase essential for cellular homeostasis. Cooperating with different sets of cofactors, VCP is involved in multiple cellular processes through either the ubiquitin-proteasome system (UPS) or the autophagy/lysosomal route. Pathogenic mutations frequently found at the interface between the NTD domain and D1 ATPase domain have been shown to cause malfunction of VCP, leading to degenerative disorders including the inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia (IBMPFD), amyotrophic lateral sclerosis (ALS), and cancers. Therefore, VCP has been considered as a potential therapeutic target for neurodegeneration and cancer. Most of previous studies found VCP predominantly exists and functions as a hexamer, which unfolds and extracts ubiquitinated substrates from protein complexes for degradation. However, recent studies have characterized a new VCP dodecameric state and revealed a controlling mechanism of VCP oligomeric states mediated by the D2 domain nucleotide occupancy. Here, we summarize our recent knowledge on VCP oligomerization, regulation, and potential implications of VCP in cellular function and pathogenic progression.}, }
@article {pmid38960099, year = {2024}, author = {Bhandari, UR and Danish, SM and Ahmad, S and Ikram, M and Nadaf, A and Hasan, N and Kesharwani, P and Ahmad, FJ}, title = {New opportunities for antioxidants in amelioration of neurodegenerative diseases.}, journal = {Mechanisms of ageing and development}, volume = {221}, number = {}, pages = {111961}, doi = {10.1016/j.mad.2024.111961}, pmid = {38960099}, issn = {1872-6216}, mesh = {Humans ; *Antioxidants/pharmacology/therapeutic use ; *Neurodegenerative Diseases/metabolism/drug therapy ; *Oxidative Stress/drug effects ; Animals ; Neuroprotective Agents/pharmacology/therapeutic use ; Signal Transduction/drug effects ; Reactive Oxygen Species/metabolism ; }, abstract = {This comprehensive review elucidates the critical role of antioxidants to mitigate oxidative stress, a common denominator in an array of neurodegenerative disorders. Oxidative stress-induced damage has been linked to the development of diseases such as Alzheimer's, Parkinson's, Huntington's disease and amyotrophic lateral sclerosis. This article examines a wide range of scientific literature and methodically delineates the several methods by which antioxidants exercise their neuroprotective benefits. It also explores into the complex relationship between oxidative stress and neuroinflammation, focusing on how antioxidants can alter signaling pathways and transcription factors to slow neurodegenerative processes. Key antioxidants, such as vitamins C and E, glutathione, and polyphenolic compounds, are tested for their ability to combat reactive oxygen and nitrogen species. The dual character of antioxidants, which operate as both direct free radical scavengers and regulators of cellular redox homeostasis, is investigated in terms of therapeutic potential. Furthermore, the study focuses on new antioxidant-based therapy techniques and their mechanisms including Nrf-2, PCG1α, Thioredoxin etc., which range from dietary interventions to targeted antioxidant molecules. Insights into ongoing clinical studies evaluating antioxidant therapies in neurodegenerative illnesses offer an insight into the translational potential of antioxidant research. Finally, this review summarizes our present understanding of antioxidant processes in neurodegenerative illnesses, providing important possibilities for future study and treatment development.}, }
@article {pmid38958608, year = {2024}, author = {Lang, R and Hodgson, RE and Shelkovnikova, TA}, title = {TDP-43 in nuclear condensates: where, how, and why.}, journal = {Biochemical Society transactions}, volume = {52}, number = {4}, pages = {1809-1825}, pmid = {38958608}, issn = {1470-8752}, mesh = {Humans ; *DNA-Binding Proteins/metabolism ; *Cell Nucleus/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism ; Biomolecular Condensates/metabolism ; Animals ; Neurodegenerative Diseases/metabolism ; }, abstract = {TDP-43 is an abundant and ubiquitously expressed nuclear protein that becomes dysfunctional in a spectrum of neurodegenerative diseases. TDP-43's ability to phase separate and form/enter biomolecular condensates of varying size and composition is critical for its functionality. Despite the high density of phase-separated assemblies in the nucleus and the nuclear abundance of TDP-43, our understanding of the condensate-TDP-43 relationship in this cellular compartment is only emerging. Recent studies have also suggested that misregulation of nuclear TDP-43 condensation is an early event in the neurodegenerative disease amyotrophic lateral sclerosis. This review aims to draw attention to the nuclear facet of functional and aberrant TDP-43 condensation. We will summarise the current knowledge on how TDP-43 containing nuclear condensates form and function and how their homeostasis is affected in disease.}, }
@article {pmid38958573, year = {2024}, author = {Tu, S and Vucic, S and Kiernan, MC}, title = {Pathological insights derived from neuroimaging in amyotrophic lateral sclerosis: emerging clinical applications.}, journal = {Current opinion in neurology}, volume = {37}, number = {5}, pages = {577-584}, doi = {10.1097/WCO.0000000000001295}, pmid = {38958573}, issn = {1473-6551}, mesh = {*Amyotrophic Lateral Sclerosis/diagnostic imaging/pathology ; Humans ; *Neuroimaging/methods ; Brain/diagnostic imaging/pathology ; }, abstract = {PURPOSE OF REVIEW: Neuroimaging has been instrumental in shaping current understanding of the pathoanatomical signature of amyotrophic lateral sclerosis (ALS) across clinically well defined patient cohorts. The potential utility of imaging as an objective disease marker, however, remains poorly defined.<br><br>RECENT FINDINGS: Increasingly advanced quantitative and computational imaging studies have highlighted emerging clinical applications for neuroimaging as a complementary clinical modality for diagnosis, monitoring, and modelling disease propagation. Multimodal neuroimaging has demonstrated novel approaches for capturing primary motor disease. Extra-motor subcortical dysfunction is increasingly recognized as key modulators of disease propagation.<br><br>SUMMARY: The neural signature of cortical and subcortical dysfunction in ALS has been well defined at the population level. Objective metrics of focal primary motor dysfunction are increasingly sensitive and translatable to the individual patient level. Integrity of extra-motor subcortical abnormalities are recognized to represent critical pathways of the ALS disease 'connectome', predicting pathological spread. Neuroimaging plays a pivotal role in capturing upper motor neuron pathology in ALS. Their potential clinical role as objective disease markers for disease classification, longitudinal monitoring, and prognosis in ALS have become increasingly well defined.}, }
@article {pmid38947464, year = {2024}, author = {Yaşar Dinçer, FC and Yirmibeşoğlu, G and Bilişli, Y and Arık, E and Akgün, H}, title = {Trends and emerging research directions of sustainable aviation: A bibliometric analysis.}, journal = {Heliyon}, volume = {10}, number = {11}, pages = {e32306}, pmid = {38947464}, issn = {2405-8440}, abstract = {This study aims to conduct a bibliometric analysis to determine trends and emerging research directions of sustainable aviation between 2001 and 2023. 726 studies indexed in the Web of Science were examined through VOSviewer software. Science mapping and performance analyses were implemented to demonstrate a systematic quantitative review and the characteristics of the research area. Moreover, by using co-occurrence of keywords, citation, bibliographic coupling, co-authorship, and co-citation analyses, the trends of the research area were revealed in detail. Findings indicated that the publications on sustainable aviation literature were mainly conducted between 2020 and 2023. Research areas of the publications were mainly on "engineering" and "energy fuels". In terms of number of the publications, "International Journal of Sustainable Aviation Fuel" was the most productive source and Heyne was the most productive author. Co-occurrence analysis demonstrated that "sustainable aviation fuel" was the most frequently used keyword. Furthermore, sustainable aviation research has shifted in focus toward more challenging and technology-oriented research over time. Citation analysis indicated that the most cited author was Heyne, the most cited study was Ma et al.'s study on "Aviation biofuel from renewable resources: routes, opportunities and challenges" and the most cited sources was "Energy". Among countries, the U.S.A was the most cited country and Chinese Academy of Sciences was the most cited organization. Bibliographic analysis showed that Heyne was the author with the highest connection strength. Co-authorship analysis demonstrated that Washington State University was the most collaborative organization. Finally, co-citation analysis of cited references indicated that fundamental subjects and related references were mainly sustainable aviation fuel, production of sustainable aviation fuel and its use in aviation studies. It is anticipated that results of this study would contribute to sustainable aviation research and ensure guidance and new perspectives for future research topics and directions on sustainable aviation.}, }
@article {pmid38946579, year = {2024}, author = {Trucco, AP and Backhouse, T and Mioshi, E}, title = {Describing and assessing behavioural symptoms in amyotrophic lateral sclerosis with and without frontotemporal dementia: a scoping review.}, journal = {Current opinion in neurology}, volume = {37}, number = {5}, pages = {603-610}, pmid = {38946579}, issn = {1473-6551}, mesh = {Humans ; *Frontotemporal Dementia/psychology/physiopathology/diagnosis ; *Amyotrophic Lateral Sclerosis/psychology/complications/diagnosis ; Behavioral Symptoms/etiology/diagnosis ; }, abstract = {PURPOSE OF REVIEW: Alongside motor and cognitive symptoms, amyotrophic lateral sclerosis (ALS) and ALS with frontotemporal dementia (ALSFTD) present with behavioural symptoms, which can be challenging for all affected by the disease. A scoping review of studies published between 2011 and 2024 was conducted to present the breadth of behavioural symptoms in ALS and ALSFTD, explore how they are described and assessed, and identify patterns in the literature.<br><br>FINDINGS: This scoping review identified 3939 articles, with 111/3939 meeting eligibility criteria. Most studies were from Australia (23.22%), Italy (16.94%) and the UK (14.29%); 75.67% were cross-sectional. Sample size ranged from 1 to 1013, as case studies were included. Overall mean age (100/111 studies) was 61.32 (SD&#x200a;=&#x200a;4.15). Proportion of male patients (reported 102/111 studies) was 61.49%; mean disease duration (reported in 86/111 records) was 32.63&#x200a;months (SD&#x200a;=&#x200a;24.72). Papers described a broad range of behavioural symptoms (465 examples), which were thematically collated into seven categories: disinhibition (27.74%), apathy (25.16%), perseverative/compulsive behaviours (17.42%), hyperorality (10.53%), loss of sympathy or empathy (8.6%), psychotic symptoms (7.74%), and loss of insight about disease and changes (2.8%). Most studies (78.37%) used validated behavioural assessments that elicited carer's perspectives.<br><br>SUMMARY: Despite extensive evidence of behavioural symptoms in ALS, implementation of assessments and management of behavioural symptoms in clinical care remain limited. Clinicians must assess behavioural symptoms, as these can negatively affect disease prognosis, patient treatment engagement and increase family distress. Measures capturing carers' perspectives through interviews are ideal as they can reveal anosognosia, lack of sympathy and lack of empathy.}, }
@article {pmid38944367, year = {2024}, author = {Wankhede, NL and Rajendra Kopalli, S and Dhokne, MD and Badnag, DJ and Chandurkar, PA and Mangrulkar, SV and Shende, PV and Taksande, BG and Upaganlawar, AB and Umekar, MJ and Koppula, S and Kale, MB}, title = {Decoding mitochondrial quality control mechanisms: Identifying treatment targets for enhanced cellular health.}, journal = {Mitochondrion}, volume = {78}, number = {}, pages = {101926}, doi = {10.1016/j.mito.2024.101926}, pmid = {38944367}, issn = {1872-8278}, mesh = {Humans ; *Mitochondria/metabolism ; *Neurodegenerative Diseases/metabolism/therapy ; Animals ; }, abstract = {Mitochondria are singular cell organelles essential for many cellular functions, which includes responding to stress, regulating calcium levels, maintaining protein homeostasis, and coordinating apoptosis response. The vitality of cells, therefore, hinges on the optimal functioning of these dynamic organelles. Mitochondrial Quality Control Mechanisms (MQCM) play a pivotal role in ensuring the integrity and functionality of mitochondria. Perturbations in these mechanisms have been closely associated with the pathogenesis of neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis. Compelling evidence suggests that targeting specific pathways within the MQCM could potentially offer a therapeutic avenue for rescuing mitochondrial integrity and mitigating the progression of neurodegenerative diseases. The intricate interplay of cellular stress, protein misfolding, and impaired quality control mechanisms provides a nuanced understanding of the underlying pathology. Consequently, unravelling the specific MQCM dysregulation in neurodegenerative disorders becomes paramount for developing targeted therapeutic strategies. This review delves into the impaired MQCM pathways implicated in neurodegenerative disorders and explores emerging therapeutic interventions. By shedding light on pharmaceutical and genetic manipulations aimed at restoring MQCM efficiency, the discussion aims to provide insights into novel strategies for ameliorating the progression of neurodegenerative diseases. Understanding and addressing mitochondrial quality control mechanisms not only underscore their significance in cellular health but also offer a promising frontier for advancing therapeutic approaches in the realm of neurodegenerative disorders.}, }
@article {pmid38942541, year = {2024}, author = {Shukla, H and John, D and Banerjee, S and Tiwari, AK}, title = {Drug repurposing for neurodegenerative diseases.}, journal = {Progress in molecular biology and translational science}, volume = {207}, number = {}, pages = {249-319}, doi = {10.1016/bs.pmbts.2024.03.035}, pmid = {38942541}, issn = {1878-0814}, mesh = {Humans ; *Drug Repositioning ; *Neurodegenerative Diseases/drug therapy ; Animals ; }, abstract = {Neurodegenerative diseases (NDDs) are neuronal problems that include the brain and spinal cord and result in loss of sensory and motor dysfunction. Common NDDs include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Multiple Sclerosis (MS), and Amyotrophic Lateral Sclerosis (ALS) etc. The occurrence of these diseases increases with age and is one of the challenging problems among elderly people. Though, several scientific research has demonstrated the key pathologies associated with NDDs still the underlying mechanisms and molecular details are not well understood and need to be explored and this poses a lack of effective treatments for NDDs. Several lines of evidence have shown that NDDs have a high prevalence and affect more than a billion individuals globally but still, researchers need to work forward in identifying the best therapeutic target for NDDs. Thus, several researchers are working in the directions to find potential therapeutic targets to alter the disease pathology and treat the diseases. Several steps have been taken to identify the early detection of the disease and drug repurposing for effective treatment of NDDs. Moreover, it is logical that current medications are being evaluated for their efficacy in treating such disorders; therefore, drug repurposing would be an efficient, safe, and cost-effective way in finding out better medication. In the current manuscript we discussed the utilization of drugs that have been repurposed for the treatment of AD, PD, HD, MS, and ALS.}, }
@article {pmid38939990, year = {2024}, author = {Song, XY and Fan, CX and Rahman, AU and Choudhary, MI and Wang, XP}, title = {Neuro-regeneration or Repair: Cell Therapy of Neurological Disorders as A Way Forward.}, journal = {Current neuropharmacology}, volume = {22}, number = {14}, pages = {2272-2283}, pmid = {38939990}, issn = {1875-6190}, mesh = {Humans ; *Nervous System Diseases/therapy ; Animals ; *Cell- and Tissue-Based Therapy/methods ; Nerve Regeneration/physiology ; Stem Cell Transplantation/methods ; }, abstract = {The human central nervous system (CNS) has a limited capacity for regeneration and repair, as many other organs do. Partly as a result, neurological diseases are the leading cause of medical burden globally. Most neurological disorders cannot be cured, and primary treatments focus on managing their symptoms and slowing down their progression. Cell therapy for neurological disorders offers several therapeutic potentials and provides hope for many patients. Here we provide a general overview of cell therapy in neurological disorders such as Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Wilson's disease (WD), stroke and traumatic brain injury (TBI), involving many forms of stem cells, including embryonic stem cells and induced pluripotent stem cells. We also address the current concerns and perspectives for the future. Most studies for cell therapy in neurological diseases are in the pre-clinical stage, and there is still a great need for further research to translate neural replacement and regenerative therapies into clinical settings.}, }
@article {pmid38928874, year = {2024}, author = {Szulc, A and Wiśniewska, K and Żabińska, M and Gaffke, L and Szota, M and Olendzka, Z and Węgrzyn, G and Pierzynowska, K}, title = {Effectiveness of Flavonoid-Rich Diet in Alleviating Symptoms of Neurodegenerative Diseases.}, journal = {Foods (Basel, Switzerland)}, volume = {13}, number = {12}, pages = {}, pmid = {38928874}, issn = {2304-8158}, support = {533-0C20-GS0D-24//University of Gdansk/ ; }, abstract = {Over the past decades, there has been a significant increase in the burden of neurological diseases, including neurodegenerative disorders, on a global scale. This is linked to a widespread demographic trend in which developed societies are aging, leading to an increased proportion of elderly individuals and, concurrently, an increase in the number of those afflicted, posing one of the main public health challenges for the coming decades. The complex pathomechanisms of neurodegenerative diseases and resulting varied symptoms, which differ depending on the disease, environment, and lifestyle of the patients, make searching for therapies for this group of disorders a formidable challenge. Currently, most neurodegenerative diseases are considered incurable. An important aspect in the fight against and prevention of neurodegenerative diseases may be broadly understood lifestyle choices, and more specifically, what we will focus on in this review, a diet. One proposal that may help in the fight against the spread of neurodegenerative diseases is a diet rich in flavonoids. Flavonoids are compounds widely found in products considered healthy, such as fruits, vegetables, and herbs. Many studies indicated not only the neuroprotective effects of these compounds but also their ability to reverse changes occurring during the progression of diseases such as Alzheimer's, Parkinson's and amyotrophic lateral sclerosis. Here, we present the main groups of flavonoids, discussing their characteristics and mechanisms of action. The most widely described mechanisms point to neuroprotective functions due to strong antioxidant and anti-inflammatory effects, accompanied with their ability to penetrate the blood-brain barrier, as well as the ability to inhibit the formation of protein aggregates. The latter feature, together with promoting removal of the aggregates is especially important in neurodegenerative diseases. We discuss a therapeutic potential of selected flavonoids in the fight against neurodegenerative diseases, based on in vitro studies, and their impact when included in the diet of animals (laboratory research) and humans (population studies). Thus, this review summarizes flavonoids' actions and impacts on neurodegenerative diseases. Therapeutic use of these compounds in the future is potentially possible but depends on overcoming key challenges such as low bioavailability, determining the therapeutic dose, and defining what a flavonoid-rich diet is and determining its potential negative effects. This review also suggests further research directions to address these challenges.}, }
@article {pmid38928553, year = {2024}, author = {Di Martino, P and Marcozzi, V and Bibbò, S and Ghinassi, B and Di Baldassarre, A and Gaggi, G and Di Credico, A}, title = {Unraveling the Epigenetic Landscape: Insights into Parkinson's Disease, Amyotrophic Lateral Sclerosis, and Multiple Sclerosis.}, journal = {Brain sciences}, volume = {14}, number = {6}, pages = {}, pmid = {38928553}, issn = {2076-3425}, support = {MUR-Fondo Promozione e Sviluppo-DM 737/2021, DEFENDANTs, Developmental Neurotoxi-city of Endocrine Disruptors from Plastic Pollutants.//NextGenerationEU "MUR-Fondo Promozione e Sviluppo-DM 737/2021, DEFENDANTs, De-velopmental Neurotoxicity of Endocrine Disruptors from Plastic Pollutants./ ; }, abstract = {Parkinson's disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS) are examples of neurodegenerative movement disorders (NMDs), which are defined by a gradual loss of motor function that is frequently accompanied by cognitive decline. Although genetic abnormalities have long been acknowledged as significant factors, new research indicates that epigenetic alterations are crucial for the initiation and development of disease. This review delves into the complex interactions that exist between the pathophysiology of NMDs and epigenetic mechanisms such DNA methylation, histone modifications, and non-coding RNAs. Here, we examine how these epigenetic changes could affect protein aggregation, neuroinflammation, and gene expression patterns, thereby influencing the viability and functionality of neurons. Through the clarification of the epigenetic terrain underpinning neurodegenerative movement disorders, this review seeks to enhance comprehension of the underlying mechanisms of the illness and augment the creation of innovative therapeutic strategies.}, }
@article {pmid38927681, year = {2024}, author = {Adler, GL and Le, K and Fu, Y and Kim, WS}, title = {Human Endogenous Retroviruses in Neurodegenerative Diseases.}, journal = {Genes}, volume = {15}, number = {6}, pages = {}, pmid = {38927681}, issn = {2073-4425}, mesh = {Humans ; *Endogenous Retroviruses/genetics/pathogenicity ; *Neurodegenerative Diseases/virology/genetics ; Amyotrophic Lateral Sclerosis/virology/genetics ; Animals ; }, abstract = {Human endogenous retroviruses (HERVs) are DNA transposable elements that have integrated into the human genome via an ancestral germline infection. The potential importance of HERVs is underscored by the fact that they comprise approximately 8% of the human genome. HERVs have been implicated in the pathogenesis of neurodegenerative diseases, a group of CNS diseases characterized by a progressive loss of structure and function of neurons, resulting in cell death and multiple physiological dysfunctions. Much evidence indicates that HERVs are initiators or drivers of neurodegenerative processes in multiple sclerosis and amyotrophic lateral sclerosis, and clinical trials have been designed to target HERVs. In recent years, the role of HERVs has been explored in other major neurodegenerative diseases, including frontotemporal dementia, Alzheimer's disease and Parkinson's disease, with some interesting discoveries. This review summarizes and evaluates the past and current research on HERVs in neurodegenerative diseases. It discusses the potential role of HERVs in disease manifestation and neurodegeneration. It critically reviews antiretroviral strategies used in the therapeutic intervention of neurodegenerative diseases.}, }
@article {pmid38927674, year = {2024}, author = {Gotte, G}, title = {Effects of Pathogenic Mutants of the Neuroprotective RNase 5-Angiogenin in Amyotrophic Lateral Sclerosis (ALS).}, journal = {Genes}, volume = {15}, number = {6}, pages = {}, pmid = {38927674}, issn = {2073-4425}, mesh = {*Amyotrophic Lateral Sclerosis/genetics/pathology ; Humans ; *Ribonuclease, Pancreatic/genetics/metabolism ; *Motor Neurons/metabolism/pathology ; Animals ; Mutation ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease that affects the motoneurons. More than 40 genes are related with ALS, and amyloidogenic proteins like SOD1 and/or TDP-43 mutants are directly involved in the onset of ALS through the formation of polymorphic fibrillogenic aggregates. However, efficacious therapeutic approaches are still lacking. Notably, heterozygous missense mutations affecting the gene coding for RNase 5, an enzyme also called angiogenin (ANG), were found to favor ALS onset. This is also true for the less-studied but angiogenic RNase 4. This review reports the substrate targets and illustrates the neuroprotective role of native ANG in the neo-vascularization of motoneurons. Then, it discusses the molecular determinants of many pathogenic ANG mutants, which almost always cause loss of function related to ALS, resulting in failures in angiogenesis and motoneuron protection. In addition, ANG mutations are sometimes combined with variants of other factors, thereby potentiating ALS effects. However, the activity of the native ANG enzyme should be finely balanced, and not excessive, to avoid possible harmful effects. Considering the interplay of these angiogenic RNases in many cellular processes, this review aims to stimulate further investigations to better elucidate the consequences of mutations in ANG and/or RNase 4 genes, in order to achieve early diagnosis and, possibly, successful therapies against ALS.}, }
@article {pmid38921286, year = {2024}, author = {Katz, L and Gur, A}, title = {Psychosocial Intervention for Family Caregivers of ALS Patients: A Systematic Review.}, journal = {Healthcare (Basel, Switzerland)}, volume = {12}, number = {12}, pages = {}, pmid = {38921286}, issn = {2227-9032}, abstract = {PROPOSAL: This systematic review aims to comprehensively examine all existing knowledge on psychosocial interventions for family caregivers for ALS patients. Also, the study will present the gaps in knowledge, recommendations for future research, and guidelines for psychosocial interventions that are focused and adapted to the needs of family caregivers of ALS patients.<br><br>MATERIALS AND METHODS: The systematic review was conducted according to the PRISMA guidelines and identified studies on psychosocial intervention for family caregivers of ALS patients, using five electronic databases: PsychNET, PubMed, EBSCO, PRIMO, and PROQUEST. Seven articles met the criteria and were included in the review. A thematic analysis was conducted to extract major themes.<br><br>RESULTS: Three major themes emerged from the data: (1) Personal benefits; (2) Interpersonal benefits; and (3) Charting challenges and pathways to improve psychosocial interventions.<br><br>CONCLUSIONS: Based on the findings, practical guidelines were formulated that focus on the group's composition, the facilitator's role, the contents, the relationships within the group, and the opportunities and limitations of online interventions.}, }
@article {pmid38921029, year = {2024}, author = {Carata, E and Muci, M and Di Giulio, S and Di Giulio, T and Mariano, S and Panzarini, E}, title = {The Neuromuscular Disorder Mediated by Extracellular Vesicles in Amyotrophic Lateral Sclerosis.}, journal = {Current issues in molecular biology}, volume = {46}, number = {6}, pages = {5999-6017}, pmid = {38921029}, issn = {1467-3045}, abstract = {Amyotrophic lateral sclerosis (ALS) represents a neurodegenerative disorder characterized by the progressive loss of both upper and lower motor neurons, resulting in muscular atrophy and eventual paralysis. While much research has concentrated on investigating the impact of major mutations associated with ALS on motor neurons and central nervous system (CNS) cells, recent studies have unveiled that ALS pathogenesis extends beyond CNS imbalances, encompassing dysregulation in other tissues such as skeletal muscle. Evidence from animal models and patients supports this broader perspective. Skeletal muscle, once considered solely as an effector organ, is now recognized as possessing significant secretory activity capable of influencing motor neuron survival. However, the precise cellular and molecular mechanisms underlying the detrimental effects observed in muscle and its associated structures in ALS remain poorly understood. Additionally, emerging data suggest that extracellular vesicles (EVs) may play a role in the establishment and function of the neuromuscular junction (NMJ) under both physiological and pathological conditions and in wasting and regeneration of skeletal muscles, particularly in neurodegenerative diseases like ALS. This review aims to explore the key findings about skeletal muscle involvement in ALS, shedding light on the potential underlying mechanisms and contributions of EVs and their possible application for the design of biosensors.}, }
@article {pmid38920997, year = {2024}, author = {Nowak, I and Paździor, M and Sarna, R and Madej, M}, title = {Molecular Mechanisms in the Design of Novel Targeted Therapies for Neurodegenerative Diseases.}, journal = {Current issues in molecular biology}, volume = {46}, number = {6}, pages = {5436-5453}, pmid = {38920997}, issn = {1467-3045}, abstract = {Neurodegenerative diseases are a diverse group of diseases characterized by a progressive loss of neurological function due to damage to nerve cells in the central nervous system. In recent years, there has been a worldwide increase in the expanding associated with increasing human life expectancy. Molecular mechanisms control many of the essential life processes of cells, such as replication, transcription, translation, protein synthesis and gene regulation. These are complex interactions that form the basis for understanding numerous processes in the organism and developing new diagnostic and therapeutic approaches. In the context of neurodegenerative diseases, molecular basis refers to changes at the molecular level that cause damage to or degeneration of nerve cells. These may include protein aggregates leading to pathological structures in brain cells, impaired protein transport in nerve cells, mitochondrial dysfunction, inflammatory processes or genetic mutations that impair nerve cell function. New medical therapies are based on these mechanisms and include gene therapies, reduction in inflammation and oxidative stress, and the use of miRNAs and regenerative medicine. The aim of this study was to bring together the current state of knowledge regarding selected neurodegenerative diseases, presenting the underlying molecular mechanisms involved, which could be potential targets for new forms of treatment.}, }
@article {pmid38920691, year = {2024}, author = {Ilieva, MS}, title = {Non-Coding RNAs in Neurological and Neuropsychiatric Disorders: Unraveling the Hidden Players in Disease Pathogenesis.}, journal = {Cells}, volume = {13}, number = {12}, pages = {}, pmid = {38920691}, issn = {2073-4409}, mesh = {Humans ; *RNA, Untranslated/genetics/metabolism ; *Nervous System Diseases/genetics/metabolism ; *Mental Disorders/genetics/metabolism ; RNA, Circular/genetics/metabolism ; Animals ; RNA, Long Noncoding/genetics/metabolism ; Gene Expression Regulation ; MicroRNAs/genetics/metabolism ; }, abstract = {Neurological and neuropsychiatric disorders pose substantial challenges to public health, necessitating a comprehensive understanding of the molecular mechanisms underlying their pathogenesis. In recent years, the focus has shifted toward the intricate world of non-coding RNAs (ncRNAs), a class of RNA molecules that do not encode proteins but play pivotal roles in gene regulation and cellular processes. This review explores the emerging significance of ncRNAs in the context of neurological and neuropsychiatric disorders, shedding light on their diverse functions and regulatory mechanisms. The dysregulation of various ncRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), has been implicated in the pathophysiology of conditions such as Alzheimer's disease, Parkinson's disease, schizophrenia, and mood disorders. This review delves into the specific roles these ncRNAs play in modulating key cellular processes, including synaptic plasticity, neuroinflammation, and apoptosis, providing a nuanced understanding of their impact on disease progression. Furthermore, it discusses the potential diagnostic and therapeutic implications of targeting ncRNAs in neurological and neuropsychiatric disorders. The identification of specific ncRNA signatures holds promise for the development of novel biomarkers for early disease detection, while the manipulation of ncRNA expression offers innovative therapeutic avenues. Challenges and future directions in the field are also considered, highlighting the need for continued research to unravel the complexities of ncRNA-mediated regulatory networks in the context of neurological and neuropsychiatric disorders. This review aims to provide a comprehensive overview of the current state of knowledge and stimulate further exploration into the fascinating realm of ncRNAs in the brain's intricate landscape.}, }
@article {pmid38918327, year = {2024}, author = {Sharma, V and Sharma, P and Singh, TG}, title = {Mechanistic insights on TLR-4 mediated inflammatory pathway in neurodegenerative diseases.}, journal = {Pharmacological reports : PR}, volume = {76}, number = {4}, pages = {679-692}, pmid = {38918327}, issn = {2299-5684}, mesh = {Humans ; *Toll-Like Receptor 4/metabolism ; *Neurodegenerative Diseases/metabolism/drug therapy ; Animals ; *Signal Transduction ; NF-kappa B/metabolism ; Inflammation/metabolism/drug therapy ; }, abstract = {Neurodegenerative diseases (NDDs) pose a significant issue in healthcare, needing a thorough knowledge of their complex molecular mechanisms. A diverse set of cell signaling mediators and their interactions play critical roles in neuroinflammation. The release of pro-inflammatory mediators in response to neural dysfunction is detrimental to normal cell survival. Moreover, the important role of nuclear factor-κB (NF-κB) in the central nervous system through Toll-like receptor (TLR) activation has been well established. Therefore, through a comprehensive review of current research and experimentation, this investigation elucidates the interactions between novel pharmacological agents (TLR-4/NF-κB inhibitors) and neurodegeneration encompassing Alzheimer's, Parkinson's, Huntington's disease, amyotrophic lateral sclerosis and stroke. Insights garnered from this exploration underscore the potential of TLR-4 as a therapeutic target. Through the revelation of these insights, our aim is to establish a foundation for the development of enhanced and focused therapeutic approaches in the continuous endeavor to combat neurodegeneration. This review thus serves as a roadmap, guiding future research endeavors toward innovative strategies for combatting the complex interplay between TLR-4 signaling and NDDs.}, }
@article {pmid38917863, year = {2024}, author = {Chou, CZ and Everett, EA and McFarlin, J and Ramanathan, U}, title = {End-of-Life and Hospice Care in Neurologic Diseases.}, journal = {Seminars in neurology}, volume = {44}, number = {5}, pages = {523-533}, doi = {10.1055/s-0044-1787809}, pmid = {38917863}, issn = {1098-9021}, mesh = {Humans ; *Nervous System Diseases/therapy ; *Hospice Care ; *Terminal Care/methods ; Advance Care Planning ; }, abstract = {The care of a patient with neurologic disease at end-of-life requires expertise in addressing advance care planning, hospice, symptom management, and caregiver support. Neurologists caring for patients with advanced neurologic disease often identify changes in disease trajectory, functional status, or goals of care that prompt discussions of advance care planning and hospice. Patients nearing end-of-life may develop symptoms such as dyspnea, secretions, delirium, pain, and seizures. Neurologists may be the primary clinicians managing these symptoms, particularly in the hospitalized patient, though they may also lend their expertise to non-neurologists about expected disease trajectories and symptoms in advanced neurologic disease. This article aims to help neurologists guide patients and caregivers through the end-of-life process by focusing on general knowledge that can be applied across diseases as well as specific considerations in severe stroke and traumatic brain injury, amyotrophic lateral sclerosis, Parkinson's disease, and dementia.}, }
@article {pmid38915767, year = {2024}, author = {Ambrosini, A and Dalla Bella, E and Ravasi, M and Melazzini, M and Lauria, G}, title = {New clinical insight in amyotrophic lateral sclerosis and innovative clinical development from the non-profit repurposing trial of the old drug guanabenz.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1407912}, pmid = {38915767}, issn = {2296-858X}, abstract = {Drug repurposing is considered a valid approach to accelerate therapeutic solutions for rare diseases. However, it is not as widely applied as it could be, due to several barriers that discourage both industry and academic institutions from pursuing this path. Herein we present the case of an academic multicentre study that considered the repurposing of the old drug guanabenz as a therapeutic strategy in amyotrophic lateral sclerosis. The difficulties encountered are discussed as an example of the barriers that academics involved in this type of study may face. Although further development of the drug for this target population was hampered for several reasons, the study was successful in many ways. Firstly, because the hypothesis tested was confirmed in a sub-population, leading to alternative innovative solutions that are now under clinical investigation. In addition, the study was informative and provided new insights into the disease, which are now giving new impetus to laboratory research. The message from this example is that even a repurposing study with an old product has the potential to generate innovation and interest from industry partners, provided it is based on a sound rationale, the study design is adequate to ensure meaningful results, and the investigators keep the full clinical development picture in mind.}, }
@article {pmid38914810, year = {2024}, author = {Manchia, M and Paribello, P and Pinna, M and Steardo, L and Carpiniello, B and Pinna, F and Pisanu, C and Squassina, A and Hajek, T}, title = {Lithium and its effects: does dose matter?.}, journal = {International journal of bipolar disorders}, volume = {12}, number = {1}, pages = {23}, pmid = {38914810}, issn = {2194-7511}, abstract = {BACKGROUND: Decades of clinical research have demonstrated the efficacy of lithium in treating acute episodes (both manic and depressive), as well as in preventing recurrences of bipolar disorder (BD). Specific to lithium is its antisuicidal effect, which appears to extend beyond its mood-stabilizing properties. Lithium's clinical effectiveness is, to some extent, counterbalanced by its safety and tolerability profile. Indeed, monitoring of lithium levels is required by its narrow therapeutic index. There is consensus that adequate serum levels should be above 0.6 mEq/L to achieve clinical effectiveness. However, few data support the choice of this threshold, and increasing evidence suggests that lithium might have clinical and molecular effects at much lower concentrations.<br><br>CONTENT: This narrative review is aimed at: (1) reviewing and critically interpreting the clinical evidence supporting the use of the 0.6 mEq/L threshold, (2) reporting a narrative synthesis of the evidence supporting the notion that lithium might be effective in much lower doses. Among these are epidemiological studies of lithium in water, evidence on the antisuicidal, anti-aggressive, and neuroprotective effects, including efficacy in preventing cognitive impairment progression, Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS), of lithium; and (3) revieweing biological data supporting clinically viable uses of lithium at low levels with the delineation of a mechanistic hypothesis surrounding its purported mechanism of action. The study selection was based on the authors' preference, reflecting the varied and extensive expertise on the review subject, further enriched with an extensive pearl-growing strategy for relevant reviews and book sections.<br><br>CONCLUSIONS: Clinical and molecular effects of lithium are numerous, and its effects also appear to have a certain degree of specificity related to the dose administered. In sum, the clinical effects of lithium are maximal for mood stabilisation at concentrations higher than 0.6 mEq/l. However, lower levels may be sufficient for preventing depressive recurrences in older populations of patients, and microdoses could be effective in decreasing suicide risk, especially in patients with BD. Conversely, lithium's ability to counteract cognitive decline appears to be exerted at subtherapeutic doses, possibly corresponding to its molecular neuroprotective effects. Indeed, lithium may reduce inflammation and induce neuroprotection even at doses several folds lower than those commonly used in clinical settings. Nevertheless, findings surrounding its purported mechanism of action are missing, and more research is needed to investigate the molecular targets of low-dose lithium adequately.}, }
@article {pmid38914784, year = {2024}, author = {Sang, A and Zhuo, S and Bochanis, A and Manautou, JE and Bahal, R and Zhong, XB and Rasmussen, TP}, title = {Mechanisms of Action of the US Food and Drug Administration-Approved Antisense Oligonucleotide Drugs.}, journal = {BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy}, volume = {38}, number = {4}, pages = {511-526}, pmid = {38914784}, issn = {1179-190X}, support = {R01 HL147028/HL/NHLBI NIH HHS/United States ; R35 GM140862/GM/NIGMS NIH HHS/United States ; R35GM140862/GM/NIGMS NIH HHS/United States ; R01HL147028/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *Oligonucleotides, Antisense/therapeutic use/pharmacology ; United States ; *United States Food and Drug Administration ; *Drug Approval ; RNA, Messenger/genetics/metabolism ; Animals ; RNA Splicing/drug effects ; }, abstract = {Antisense oligonucleotides (ASOs) are single stranded nucleic acids that target RNA. The US Food and Drug Administration has approved ASOs for several diseases. ASOs utilize three principal modes of action (MOA). The first MOA is initiated by base-pairing between the ASO and its target mRNA, followed by RNase H-dependent mRNA degradation. The second MOA is triggered by ASOs that occlude splice acceptor sites in pre-mRNAs leading to skipping of a mutation-bearing exon. The third MOA involves ASOs that sterically hinder mRNA function, often inhibiting translation. ASOs contain a variety of modifications to the sugar-phosphate backbone and bases that stabilize the ASO or render them resistant to RNase activity. RNase H-dependent ASOs include inotersen and eplontersen (for hereditary transthyretin amyloidosis), fomiversen (for opportunistic cytomegalovirus infection), mipomersen (for familial hypercholesterolemia), and tofersen [for amyotrophic lateral sclerosis (ALS)]. Splice modulating ASOs include nursinersen (for spinal muscular atrophy) and eteplirsen, golodirsen, viltolarsen, and casimersen (all for the treatment of Duchenne muscular dystrophy). In addition, a designer ASO, milasen, was used to treat a single individual afflicted with Batten disease. Since ASO design relies principally upon knowledge of mRNA sequence, the bench to bedside pipeline for ASOs is expedient compared with protein-directed drugs. [Graphical abstract available.].}, }
@article {pmid38909349, year = {2024}, author = {Ketabforoush, A and Faghihi, F and Azedi, F and Ariaei, A and Habibi, MA and Khalili, M and Ashtiani, BH and Joghataei, MT and Arnold, WD}, title = {Sodium Phenylbutyrate and Tauroursodeoxycholic Acid: A Story of Hope Turned to Disappointment in Amyotrophic Lateral Sclerosis Treatment.}, journal = {Clinical drug investigation}, volume = {44}, number = {7}, pages = {495-512}, pmid = {38909349}, issn = {1179-1918}, mesh = {Humans ; *Taurochenodeoxycholic Acid/pharmacology/therapeutic use ; *Amyotrophic Lateral Sclerosis/drug therapy/physiopathology ; *Phenylbutyrates/therapeutic use/pharmacology ; Neuroprotective Agents/therapeutic use/pharmacology ; }, abstract = {The absence of a definitive cure for amyotrophic lateral sclerosis (ALS) emphasizes the crucial need to explore new and improved treatment approaches for this fatal, progressive, and disabling neurodegenerative disorder. As at the end of 2023, five treatments - riluzole, edaravone, dextromethorphan hydrobromide + quinidine sulfate (DHQ), tofersen, and sodium phenylbutyrate-tauroursodeoxycholic acid (PB-TUDCA) - were FDA approved for the treatment of patients with ALS. Among them PB-TUDCA has been shown to impact DNA processing impairments, mitochondria dysfunction, endoplasmic reticulum stress, oxidative stress, and pathologic folded protein agglomeration defects, which have been associated with ALS pathophysiology. The Phase 2 CENTAUR trial demonstrated significant impact of PB-TUDCA on the ALS Functional Rating Scale-Revised (ALSFRS-R) risk of death, hospitalization, and the need for tracheostomy or permanent assisted ventilation in patients with ALS based on post hoc analyses. More recently, contrasting with the CENTAUR trial results, results from the Phase 3 PHOENIX trial (NCT05021536) showed no change in ALSFRS-R total score at 48 weeks. Consequently, the sponsor company initiated the process with the US FDA and Health Canada to voluntarily withdraw the marketing authorizations for PB-TUDCA. In the present article, we review ALS pathophysiology, with a focus on PB-TUDCA's proposed mechanisms of action and recent clinical trial results and discuss the implications of conflicting trial data for ALS and other neurological disorders.}, }
@article {pmid38908196, year = {2024}, author = {Donders, Z and Skorupska, IJ and Willems, E and Mussen, F and Broeckhoven, JV and Carlier, A and Schepers, M and Vanmierlo, T}, title = {Beyond PDE4 inhibition: A comprehensive review on downstream cAMP signaling in the central nervous system.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {177}, number = {}, pages = {117009}, doi = {10.1016/j.biopha.2024.117009}, pmid = {38908196}, issn = {1950-6007}, mesh = {Humans ; *Cyclic AMP/metabolism ; *Phosphodiesterase 4 Inhibitors/pharmacology ; Animals ; *Central Nervous System/drug effects/metabolism ; *Signal Transduction/drug effects ; *Central Nervous System Diseases/drug therapy/metabolism/enzymology ; *Cyclic Nucleotide Phosphodiesterases, Type 4/metabolism ; }, abstract = {Cyclic adenosine monophosphate (cAMP) is a key second messenger that regulates signal transduction pathways pivotal for numerous biological functions. Intracellular cAMP levels are spatiotemporally regulated by their hydrolyzing enzymes called phosphodiesterases (PDEs). It has been shown that increased cAMP levels in the central nervous system (CNS) promote neuroplasticity, neurotransmission, neuronal survival, and myelination while suppressing neuroinflammation. Thus, elevating cAMP levels through PDE inhibition provides a therapeutic approach for multiple CNS disorders, including multiple sclerosis, stroke, spinal cord injury, amyotrophic lateral sclerosis, traumatic brain injury, and Alzheimer's disease. In particular, inhibition of the cAMP-specific PDE4 subfamily is widely studied because of its high expression in the CNS. So far, the clinical translation of full PDE4 inhibitors has been hampered because of dose-limiting side effects. Hence, focusing on signaling cascades downstream activated upon PDE4 inhibition presents a promising strategy, offering novel and pharmacologically safe targets for treating CNS disorders. Yet, the underlying downstream signaling pathways activated upon PDE(4) inhibition remain partially elusive. This review provides a comprehensive overview of the existing knowledge regarding downstream mediators of cAMP signaling induced by PDE4 inhibition or cAMP stimulators. Furthermore, we highlight existing gaps and future perspectives that may incentivize additional downstream research concerning PDE(4) inhibition, thereby providing novel therapeutic approaches for CNS disorders.}, }
@article {pmid38904729, year = {2024}, author = {Portes E Silva, KR and Nogueira, EM and Jesus Mendes, AL and Pena, ALB and Simões E Silva, AC}, title = {The potential role of renin angiotensin system in acute leukemia: a narrative review.}, journal = {Molecular biology reports}, volume = {51}, number = {1}, pages = {775}, pmid = {38904729}, issn = {1573-4978}, support = {304496/2023-5//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; }, mesh = {Humans ; *Renin-Angiotensin System/physiology ; *Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism/pathology ; *Angiotensin II/metabolism ; Leukemia, Myeloid, Acute/metabolism/pathology ; Signal Transduction ; Angiotensin I/metabolism ; Neovascularization, Pathologic/metabolism ; Animals ; Peptide Fragments/metabolism ; }, abstract = {Acute leukemias (ALs) are the most common cancers in pediatric population. There are two types of ALs: acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Some studies suggest that the Renin Angiotensin System (RAS) has a role in ALs. RAS signaling modulates, directly and indirectly, cellular activity in different cancers, affecting tumor cells and angiogenesis. Our review aimed to summarize the role of RAS in ALs and to explore future perspectives for the treatment of these hematological malignancies by modulating RAS molecules. The database including Pubmed, Scopus, Cochrane Library, and Scielo were searched to find articles about RAS molecules in ALL and in pediatric patients. The search terms were "RAS", "Acute Leukemia", "ALL", "Angiotensin-(1-7)", "Pediatric", "Cancer", "Angiotensin II", "AML". In the bone marrow, RAS has been found to play a key role in blood cell formation, affecting several processes including apoptosis, cell proliferation, mobilization, intracellular signaling, angiogenesis, fibrosis, and inflammation. Local tissue RAS modulates tumor growth and metastasis through autocrine and paracrine actions. RAS mainly acts via two molecules, Angiotensin II (Ang II) and Angiotensin (1-7) [Ang-(1-7)]. While Ang II promotes tumor cell growth and stimulates angiogenesis, Ang-(1-7) inhibits the proliferation of neoplastic cells and the angiogenesis, suggesting a potential therapeutic role of this molecule in ALL. The interaction between ALs and RAS reveals a complex network of molecules that can affect the hematopoiesis and the development of hematological cancers. Understanding these interactions could pave the way for innovative therapeutic approaches targeting RAS components.}, }
@article {pmid38903602, year = {2024}, author = {Al-Kuraishy, HM and Jabir, MS and Sulaiman, GM and Mohammed, HA and Al-Gareeb, AI and Albuhadily, AK and Jawad, SF and Swelum, AA and Abomughaid, MM}, title = {The role of statins in amyotrophic lateral sclerosis: protective or not?.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1422912}, pmid = {38903602}, issn = {1662-4548}, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of motor neurons characterized by muscle weakness, muscle twitching, and muscle wasting. ALS is regarded as the third-most frequent neurodegenerative disease, subsequent to Alzheimer's disease (AD) and Parkinson's disease (PD). The World Health Organization (WHO) in 2007 declared that prolonged use of statins may induce development of ALS-like syndrome and may increase ALS risk. Subsequently, different studies have implicated statins in the pathogenesis of ALS. In contrast, results from preclinical and clinical studies highlighted the protective role of statins against ALS neuropathology. Recently, meta-analyses and systematic reviews illustrated no association between long-term use of statins and ALS risk. These findings highlighted controversial points regarding the effects of statins on ALS pathogenesis and risk. The neuroprotective effects of statins against the development and progression of ALS may be mediated by regulating dyslipidemia and inflammatory changes. However, the mechanism for induction of ALS neuropathology by statins may be related to the dysregulation of liver X receptor signaling (LXR) signaling in the motor neurons and reduction of cholesterol, which has a neuroprotective effect against ALS neuropathology. Nevertheless, the exact role of statins on the pathogenesis of ALS was not fully elucidated. Therefore, this narrative review aims to discuss the role of statins in ALS neuropathology.}, }
@article {pmid38898687, year = {2024}, author = {Lee, B and Lee, SM and Song, JW and Choi, JW}, title = {Gut Microbiota Metabolite Messengers in Brain Function and Pathology at a View of Cell Type-Based Receptor and Enzyme Reaction.}, journal = {Biomolecules &amp; therapeutics}, volume = {32}, number = {4}, pages = {403-423}, pmid = {38898687}, issn = {1976-9148}, abstract = {The human gastrointestinal (GI) tract houses a diverse microbial community, known as the gut microbiome comprising bacteria, viruses, fungi, and protozoa. The gut microbiome plays a crucial role in maintaining the body's equilibrium and has recently been discovered to influence the functioning of the central nervous system (CNS). The communication between the nervous system and the GI tract occurs through a two-way network called the gut-brain axis. The nervous system and the GI tract can modulate each other through activated neuronal cells, the immune system, and metabolites produced by the gut microbiome. Extensive research both in preclinical and clinical realms, has highlighted the complex relationship between the gut and diseases associated with the CNS, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This review aims to delineate receptor and target enzymes linked with gut microbiota metabolites and explore their specific roles within the brain, particularly their impact on CNS-related diseases.}, }
@article {pmid38898538, year = {2024}, author = {Bravo-Miana, RDC and Arizaga-Echebarria, JK and Otaegui, D}, title = {Central nervous system-derived extracellular vesicles: the next generation of neural circulating biomarkers?.}, journal = {Translational neurodegeneration}, volume = {13}, number = {1}, pages = {32}, pmid = {38898538}, issn = {2047-9158}, support = {PI20/1253//Instituto de Salud Carlos III/ ; KK-2021/00009//Departamento de Desarrollo Econ&#xf3;mico, Sostenibilidad y Medio Ambiente/ ; ECTRIMS Postdoctoral Research Fellowship 2023//European Committee for Treatment and Research in Multiple Sclerosis/ ; Predoctoral fellowship//Basque Government/ ; }, mesh = {Humans ; *Extracellular Vesicles/metabolism ; *Biomarkers/blood ; *Central Nervous System/metabolism ; *Neurodegenerative Diseases/blood/diagnosis/metabolism ; Animals ; }, abstract = {The central nervous system (CNS) is integrated by glial and neuronal cells, and both release extracellular vesicles (EVs) that participate in CNS homeostasis. EVs could be one of the best candidates to operate as nanosized biological platforms for analysing multidimensional bioactive cargos, which are protected during systemic circulation of EVs. Having a window into the molecular level processes that are happening in the CNS could open a new avenue in CNS research. This raises a particular point of interest: can CNS-derived EVs in blood serve as circulating biomarkers that reflect the pathological status of neurological diseases? L1 cell adhesion molecule (L1CAM) is a widely reported biomarker to identify CNS-derived EVs in peripheral blood. However, it has been demonstrated that L1CAM is also expressed outside the CNS. Given that principal data related to neurodegenerative diseases, such as multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease and Alzheimer's disease were obtained using L1CAM-positive EVs, efforts to overcome present challenges related to its specificity are required. In this sense, other surface biomarkers for CNS-derived EVs, such as glutamate aspartate transporter (GLAST) and myelin oligodendrocyte glycoprotein (MOG), among others, have started to be used. Establishing a panel of EV biomarkers to analyse CNS-derived EVs in blood could increase the specificity and sensitivity necessary for these types of studies. This review covers the main evidence related to CNS-derived EVs in cerebrospinal fluid and blood samples of patients with neurological diseases, focusing on the reported biomarkers and the technical possibilities for their isolation. EVs are emerging as a mirror of brain physiopathology, reflecting both localized and systemic changes. Therefore, when the technical hindrances for EV research and clinical applications are overcome, novel disease-specific panels of EV biomarkers would be discovered to facilitate transformation from traditional medicine to personalized medicine.}, }
@article {pmid38898231, year = {2024}, author = {Gao, J and Gunasekar, S and Xia, ZJ and Shalin, K and Jiang, C and Chen, H and Lee, D and Lee, S and Pisal, ND and Luo, JN and Griciuc, A and Karp, JM and Tanzi, R and Joshi, N}, title = {Gene therapy for CNS disorders: modalities, delivery and translational challenges.}, journal = {Nature reviews. Neuroscience}, volume = {25}, number = {8}, pages = {553-572}, pmid = {38898231}, issn = {1471-0048}, mesh = {Humans ; *Genetic Therapy/methods/trends ; *Central Nervous System Diseases/therapy/genetics ; Animals ; Translational Research, Biomedical/methods ; Gene Transfer Techniques/trends ; }, abstract = {Gene therapy is emerging as a powerful tool to modulate abnormal gene expression, a hallmark of most CNS disorders. The transformative potentials of recently approved gene therapies for the treatment of spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS) and active cerebral adrenoleukodystrophy are encouraging further development of this approach. However, most attempts to translate gene therapy to the clinic have failed to make it to market. There is an urgent need not only to tailor the genes that are targeted to the pathology of interest but to also address delivery challenges and thereby maximize the utility of genetic tools. In this Review, we provide an overview of gene therapy modalities for CNS diseases, emphasizing the interconnectedness of different delivery strategies and routes of administration. Important gaps in understanding that could accelerate the clinical translatability of CNS genetic interventions are addressed, and we present lessons learned from failed clinical trials that may guide the future development of gene therapies for the treatment and management of CNS disorders.}, }
@article {pmid38898006, year = {2024}, author = {Nógrádi, B and Nógrádi-Halmi, D and Erdélyi-Furka, B and Kádár, Z and Csont, T and Gáspár, R}, title = {Mechanism of motoneuronal and pyramidal cell death in amyotrophic lateral sclerosis and its potential therapeutic modulation.}, journal = {Cell death discovery}, volume = {10}, number = {1}, pages = {291}, pmid = {38898006}, issn = {2058-7716}, support = {BO/00574/22//Magyar Tudom&#xe1;nyos Akad&#xe9;mia (Hungarian Academy of Sciences)/ ; &#xda;NKP-23-5 -SZTE-711//Emberi Eroforr&#xe1;sok Miniszt&#xe9;riuma (Ministry of Human Capacities)/ ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder clinically characterized by muscle atrophy and progressive paralysis. Loss of motoneurons and pyramidal cells is thought to be the center piece of the complex and multifaceted ALS pathology, however, the exact mechanisms laying behind motoneuronal cell death in the spinal cord and motor cortex are still unknown. It was originally proposed that apoptosis plays a fundamental role in motoneuronal demise, nonetheless, later it became clear that other forms of regulated cell death, including necroptosis, pyroptosis, ferroptosis, and autophagy-dependent cell death, may also contribute to motoneuron loss. Over the past years, multiple studies aimed to improve our understanding of the contributory role of these mechanisms as well as to offer novel targets for potential therapeutic interventions. The pharmacological inhibition of the ferroptotic pathway and the modulation of the autophagic machinery seem to have particularly promising effects, reducing motoneuron loss and slowing disease progression in transgenic models of ALS. Nevertheless, the potential beneficial effects of necroptosis-targeting interventions were mostly disproven in the latest studies. In this review we aim to summarize the current view on regulated cell death mechanisms that lead to motoneuronal and pyramidal cell degeneration in ALS and showcase their applicability as future drug targets.}, }
@article {pmid38892250, year = {2024}, author = {Cerantonio, A and Citrigno, L and Greco, BM and De Benedittis, S and Passarino, G and Maletta, R and Qualtieri, A and Montesanto, A and Spadafora, P and Cavalcanti, F}, title = {The Role of Mitochondrial Copy Number in Neurodegenerative Diseases: Present Insights and Future Directions.}, journal = {International journal of molecular sciences}, volume = {25}, number = {11}, pages = {}, pmid = {38892250}, issn = {1422-0067}, mesh = {Humans ; *Neurodegenerative Diseases/genetics ; *DNA, Mitochondrial/genetics ; *DNA Copy Number Variations ; *Mitochondria/genetics/metabolism ; Huntington Disease/genetics/pathology ; Animals ; }, abstract = {Neurodegenerative diseases are progressive disorders that affect the central nervous system (CNS) and represent the major cause of premature death in the elderly. One of the possible determinants of neurodegeneration is the change in mitochondrial function and content. Altered levels of mitochondrial DNA copy number (mtDNA-CN) in biological fluids have been reported during both the early stages and progression of the diseases. In patients affected by neurodegenerative diseases, changes in mtDNA-CN levels appear to correlate with mitochondrial dysfunction, cognitive decline, disease progression, and ultimately therapeutic interventions. In this review, we report the main results published up to April 2024, regarding the evaluation of mtDNA-CN levels in blood samples from patients affected by Alzheimer's (AD), Parkinson's (PD), and Huntington's diseases (HD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). The aim is to show a probable link between mtDNA-CN changes and neurodegenerative disorders. Understanding the causes underlying this association could provide useful information on the molecular mechanisms involved in neurodegeneration and offer the development of new diagnostic approaches and therapeutic interventions.}, }
@article {pmid38891774, year = {2024}, author = {Arnold, FJ and Putka, AF and Raychaudhuri, U and Hsu, S and Bedlack, RS and Bennett, CL and La Spada, AR}, title = {Revisiting Glutamate Excitotoxicity in Amyotrophic Lateral Sclerosis and Age-Related Neurodegeneration.}, journal = {International journal of molecular sciences}, volume = {25}, number = {11}, pages = {}, pmid = {38891774}, issn = {1422-0067}, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/pathology ; Humans ; *Glutamic Acid/metabolism ; Animals ; Motor Neurons/metabolism/pathology ; Aging/metabolism ; Receptors, AMPA/metabolism ; Endoplasmic Reticulum Stress ; Mitochondria/metabolism ; Excitatory Amino Acid Transporter 2/metabolism ; Astrocytes/metabolism ; Reactive Oxygen Species/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disorder. While there are five FDA-approved drugs for treating this disease, each has only modest benefits. To design new and more effective therapies for ALS, particularly for sporadic ALS of unknown and diverse etiologies, we must identify key, convergent mechanisms of disease pathogenesis. This review focuses on the origin and effects of glutamate-mediated excitotoxicity in ALS (the cortical hyperexcitability hypothesis), in which increased glutamatergic signaling causes motor neurons to become hyperexcitable and eventually die. We characterize both primary and secondary contributions to excitotoxicity, referring to processes taking place at the synapse and within the cell, respectively. 'Primary pathways' include upregulation of calcium-permeable AMPA receptors, dysfunction of the EAAT2 astrocytic glutamate transporter, increased release of glutamate from the presynaptic terminal, and reduced inhibition by cortical interneurons-all of which have been observed in ALS patients and model systems. 'Secondary pathways' include changes to mitochondrial morphology and function, increased production of reactive oxygen species, and endoplasmic reticulum (ER) stress. By identifying key targets in the excitotoxicity cascade, we emphasize the importance of this pathway in the pathogenesis of ALS and suggest that intervening in this pathway could be effective for developing therapies for this disease.}, }
@article {pmid38891112, year = {2024}, author = {Santos, JR and Park, J}, title = {MATR3's Role beyond the Nuclear Matrix: From Gene Regulation to Its Implications in Amyotrophic Lateral Sclerosis and Other Diseases.}, journal = {Cells}, volume = {13}, number = {11}, pages = {}, pmid = {38891112}, issn = {2073-4409}, support = {n/a//Canada Research Chairs/ ; 202104PJT-462444-NSB-CEAB-275899//CIHR/Canada ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *Nuclear Matrix-Associated Proteins/metabolism/genetics ; *Gene Expression Regulation ; *Nuclear Matrix/metabolism ; Animals ; RNA-Binding Proteins/metabolism/genetics ; }, abstract = {Matrin-3 (MATR3) was initially discovered as a component of the nuclear matrix about thirty years ago. Since then, accumulating studies have provided evidence that MATR3 not only plays a structural role in the nucleus, but that it is also an active protein involved in regulating gene expression at multiple levels, including chromatin organization, DNA transcription, RNA metabolism, and protein translation in the nucleus and cytoplasm. Furthermore, MATR3 may play a critical role in various cellular processes, including DNA damage response, cell proliferation, differentiation, and survival. In addition to the revelation of its biological role, recent studies have reported MATR3's involvement in the context of various diseases, including neurodegenerative and neurodevelopmental diseases, as well as cancer. Moreover, sequencing studies of patients revealed a handful of disease-associated mutations in MATR3 linked to amyotrophic lateral sclerosis (ALS), which further elevated the gene's importance as a topic of study. In this review, we synthesize the current knowledge regarding the diverse functions of MATR3 in DNA- and RNA-related processes, as well as its involvement in various diseases, with a particular emphasis on ALS.}, }
@article {pmid38891099, year = {2024}, author = {Hernan-Godoy, M and Rouaux, C}, title = {From Environment to Gene Expression: Epigenetic Methylations and One-Carbon Metabolism in Amyotrophic Lateral Sclerosis.}, journal = {Cells}, volume = {13}, number = {11}, pages = {}, pmid = {38891099}, issn = {2073-4409}, support = {ANR-21-CE16-0024//Agence Nationale de la Recherche/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics/metabolism ; Humans ; *Epigenesis, Genetic ; *DNA Methylation/genetics ; *Carbon/metabolism ; Animals ; }, abstract = {The etiology of the neurodegenerative disease amyotrophic lateral sclerosis (ALS) is complex and considered multifactorial. The majority of ALS cases are sporadic, but familial cases also exist. Estimates of heritability range from 8% to 61%, indicating that additional factors beyond genetics likely contribute to ALS. Numerous environmental factors are considered, which may add up and synergize throughout an individual's lifetime building its unique exposome. One level of integration between genetic and environmental factors is epigenetics, which results in alterations in gene expression without modification of the genome sequence. Methylation reactions, targeting DNA or histones, represent a large proportion of epigenetic regulations and strongly depend on the availability of methyl donors provided by the ubiquitous one-carbon (1C) metabolism. Thus, understanding the interplay between exposome, 1C metabolism, and epigenetic modifications will likely contribute to elucidating the mechanisms underlying altered gene expression related to ALS and to developing targeted therapeutic interventions. Here, we review evidence for 1C metabolism alterations and epigenetic methylation dysregulations in ALS, with a focus on the impairments reported in neural tissues, and discuss these environmentally driven mechanisms as the consequences of cumulative exposome or late environmental hits, but also as the possible result of early developmental defects.}, }
@article {pmid38891059, year = {2024}, author = {Dashtmian, AR and Darvishi, FB and Arnold, WD}, title = {Chronological and Biological Aging in Amyotrophic Lateral Sclerosis and the Potential of Senolytic Therapies.}, journal = {Cells}, volume = {13}, number = {11}, pages = {}, pmid = {38891059}, issn = {2073-4409}, support = {1R01AG067758, R01AG078129, and R01AG067758-02S2//national institute of health/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism/therapy ; Humans ; *Aging/pathology ; Senotherapeutics/pharmacology/therapeutic use ; Animals ; Cellular Senescence ; Mitochondria/metabolism/pathology ; DNA Damage ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a group of sporadic and genetic neurodegenerative disorders that result in losses of upper and lower motor neurons. Treatment of ALS is limited, and survival is 2-5 years after disease onset. While ALS can occur in younger individuals, the risk significantly increases with advancing age. Notably, both sporadic and genetic forms of ALS share pathophysiological features overlapping hallmarks of aging including genome instability/DNA damage, mitochondrial dysfunction, inflammation, proteostasis, and cellular senescence. This review explores chronological and biological aging in the context of ALS onset and progression. Age-related muscle weakness and motor unit loss mirror aspects of ALS pathology and coincide with peak ALS incidence, suggesting a potential link between aging and disease development. Hallmarks of biological aging, including DNA damage, mitochondrial dysfunction, and cellular senescence, are implicated in both aging and ALS, offering insights into shared mechanisms underlying disease pathogenesis. Furthermore, senescence-associated secretory phenotype and senolytic treatments emerge as promising avenues for ALS intervention, with the potential to mitigate neuroinflammation and modify disease progression.}, }
@article {pmid38891021, year = {2024}, author = {Nguyen, L}, title = {Updates on Disease Mechanisms and Therapeutics for Amyotrophic Lateral Sclerosis.}, journal = {Cells}, volume = {13}, number = {11}, pages = {}, pmid = {38891021}, issn = {2073-4409}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/therapy/pathology/drug therapy ; Animals ; C9orf72 Protein/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS), or Lou Gehrig's disease, is a motor neuron disease. In ALS, upper and lower motor neurons in the brain and spinal cord progressively degenerate during the course of the disease, leading to the loss of the voluntary movement of the arms and legs. Since its first description in 1869 by a French neurologist Jean-Martin Charcot, the scientific discoveries on ALS have increased our understanding of ALS genetics, pathology and mechanisms and provided novel therapeutic strategies. The goal of this review article is to provide a comprehensive summary of the recent findings on ALS mechanisms and related therapeutic strategies to the scientific audience. Several highlighted ALS research topics discussed in this article include the 2023 FDA approved drug for SOD1 ALS, the updated C9orf72 GGGGCC repeat-expansion-related mechanisms and therapeutic targets, TDP-43-mediated cryptic splicing and disease markers and diagnostic and therapeutic options offered by these recent discoveries.}, }
@article {pmid38891002, year = {2024}, author = {Genchi, G and Lauria, G and Catalano, A and Carocci, A and Sinicropi, MS}, title = {Neuroprotective Effects of Curcumin in Neurodegenerative Diseases.}, journal = {Foods (Basel, Switzerland)}, volume = {13}, number = {11}, pages = {}, pmid = {38891002}, issn = {2304-8158}, abstract = {Curcumin, a hydrophobic polyphenol extracted from the rhizome of Curcuma longa, is now considered a candidate drug for the treatment of neurological diseases, including Parkinson's Disease (PD), Alzheimer's Disease (AD), Huntington's Disease (HD), Multiple Sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS), and prion disease, due to its potent anti-inflammatory, antioxidant potential, anticancerous, immunomodulatory, neuroprotective, antiproliferative, and antibacterial activities. Traditionally, curcumin has been used for medicinal and dietary purposes in Asia, India, and China. However, low water solubility, poor stability in the blood, high rate of metabolism, limited bioavailability, and little capability to cross the blood-brain barrier (BBB) have limited the clinical application of curcumin, despite the important pharmacological activities of this drug. A variety of nanocarriers, including liposomes, micelles, dendrimers, cubosome nanoparticles, polymer nanoparticles, and solid lipid nanoparticles have been developed with great success to effectively deliver the active drug to brain cells. Functionalization on the surface of nanoparticles with brain-specific ligands makes them target-specific, which should significantly improve bioavailability and reduce harmful effects. The aim of this review is to summarize the studies on curcumin and/or nanoparticles containing curcumin in the most common neurodegenerative diseases, highlighting the high neuroprotective potential of this nutraceutical.}, }
@article {pmid38890057, year = {2025}, author = {Giommoni, L}, title = {The impact of precursor regulations on illicit drug markets: An analysis of Cunningham et al.'s studies.}, journal = {The International journal on drug policy}, volume = {138}, number = {}, pages = {104498}, doi = {10.1016/j.drugpo.2024.104498}, pmid = {38890057}, issn = {1873-4758}, mesh = {Humans ; *Illicit Drugs/economics/supply &amp; distribution/legislation &amp; jurisprudence ; *Drug and Narcotic Control/legislation &amp; jurisprudence ; *Substance-Related Disorders/prevention &amp; control/epidemiology/economics ; *Drug Trafficking/legislation &amp; jurisprudence/economics ; *Commerce/legislation &amp; jurisprudence ; }, abstract = {This review examines a series of twelve studies led by James K. Cunningham and his team, focusing on the effects of precursor regulation on illicit drug markets. Their research shows that the regulation of chemicals essential for the production of drugs such as heroin, cocaine, and methamphetamine is associated with several positive outcomes. These include a decrease in drug purity, a reduction in seizures, lower demand for treatment and hospitalization, and an increase in drug prices. According to the research, this decrease in harmful outcomes results from a combination of diminished overall consumption and a reduction in harm per dose. However, this review identifies some inconsistencies within their studies. These inconsistencies include premature assumptions about the timing of intervention impacts, uneven influences of similar interventions, variations in the implementation of these interventions, and the disregard of alternate explanations for sudden shifts in drug markets. Cunningham's work can be considered one of the most substantial contributions in this field. However, to secure the full confidence of the drug policy community in the authenticity of their findings, they must effectively address the issues identified in this review.}, }
@article {pmid38889636, year = {2024}, author = {Alkhazaali-Ali, Z and Sahab-Negah, S and Boroumand, AR and Tavakol-Afshari, J}, title = {MicroRNA (miRNA) as a biomarker for diagnosis, prognosis, and therapeutics molecules in neurodegenerative disease.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {177}, number = {}, pages = {116899}, doi = {10.1016/j.biopha.2024.116899}, pmid = {38889636}, issn = {1950-6007}, mesh = {Humans ; *MicroRNAs/genetics ; *Neurodegenerative Diseases/diagnosis/genetics/therapy ; *Biomarkers/metabolism ; Animals ; Prognosis ; }, abstract = {Neurodegenerative diseases that include Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), Huntington's disease (HD), and multiple sclerosis (MS) that arise due to numerous causes like protein accumulation and autoimmunity characterized by neurologic depletion which lead to incapacity in normal physiological function such as thinking and movement in these patients. Glial cells perform an important role in protective neuronal function; in the case of neuroinflammation, glial cell dysfunction can promote the development of neurodegenerative diseases. miRNA that participates in gene regulation and plays a vital role in many biological processes in the body; in the central nervous system (CNS), it can play an essential part in neural maturation and differentiation. In neurodegenerative diseases, miRNA dysregulation occurs, enhancing the development of these diseases. In this review, we discuss neurodegenerative disease (Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS)) and how miRNA is preserved as a diagnostic biomarker or therapeutic agent in these disorders. Finally, we highlight miRNA as therapy.}, }
@article {pmid38889403, year = {2024}, author = {Zhu, Y and Wang, F and Xia, Y and Wang, L and Lin, H and Zhong, T and Wang, X}, title = {Research progress on astrocyte-derived extracellular vesicles in the pathogenesis and treatment of neurodegenerative diseases.}, journal = {Reviews in the neurosciences}, volume = {35}, number = {8}, pages = {855-875}, pmid = {38889403}, issn = {2191-0200}, mesh = {Humans ; *Extracellular Vesicles/metabolism ; *Neurodegenerative Diseases/metabolism/therapy ; *Astrocytes/metabolism ; Animals ; Cell Communication/physiology ; }, abstract = {Neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD), pose significant global health risks and represent a substantial public health concern in the contemporary era. A primary factor in the pathophysiology of these disorders is aberrant accumulation and aggregation of pathogenic proteins within the brain and spinal cord. Recent investigations have identified extracellular vesicles (EVs) in the central nervous system (CNS) as potential carriers for intercellular transport of misfolded proteins associated with neurodegenerative diseases. EVs are involved in pathological processes that contribute to various brain disorders including neurodegenerative disorders. Proteins linked to neurodegenerative disorders are secreted and distributed from cell to cell via EVs, serving as a mechanism for direct intercellular communication through the transfer of biomolecules. Astrocytes, as active participants in CNS intercellular communication, release astrocyte-derived extracellular vesicles (ADEVs) that are capable of interacting with diverse target cells. This review primarily focuses on the involvement of ADEVs in the development of neurological disorders and explores their potential dual roles - both advantageous and disadvantageous in the context of neurological disorders. Furthermore, this review examines the current studies investigating ADEVs as potential biomarkers for the diagnosis and treatment of neurodegenerative diseases. The prospects and challenges associated with the application of ADEVs in clinical settings were also comprehensively reviewed.}, }
@article {pmid38883980, year = {2024}, author = {Azam, HMH and Rößling, RI and Geithe, C and Khan, MM and Dinter, F and Hanack, K and Prüß, H and Husse, B and Roggenbuck, D and Schierack, P and Rödiger, S}, title = {MicroRNA biomarkers as next-generation diagnostic tools for neurodegenerative diseases: a comprehensive review.}, journal = {Frontiers in molecular neuroscience}, volume = {17}, number = {}, pages = {1386735}, pmid = {38883980}, issn = {1662-5099}, abstract = {Neurodegenerative diseases (NDs) are characterized by abnormalities within neurons of the brain or spinal cord that gradually lose function, eventually leading to cell death. Upon examination of affected tissue, pathological changes reveal a loss of synapses, misfolded proteins, and activation of immune cells-all indicative of disease progression-before severe clinical symptoms become apparent. Early detection of NDs is crucial for potentially administering targeted medications that may delay disease advancement. Given their complex pathophysiological features and diverse clinical symptoms, there is a pressing need for sensitive and effective diagnostic methods for NDs. Biomarkers such as microRNAs (miRNAs) have been identified as potential tools for detecting these diseases. We explore the pivotal role of miRNAs in the context of NDs, focusing on Alzheimer's disease, Parkinson's disease, Multiple sclerosis, Huntington's disease, and Amyotrophic Lateral Sclerosis. The review delves into the intricate relationship between aging and NDs, highlighting structural and functional alterations in the aging brain and their implications for disease development. It elucidates how miRNAs and RNA-binding proteins are implicated in the pathogenesis of NDs and underscores the importance of investigating their expression and function in aging. Significantly, miRNAs exert substantial influence on post-translational modifications (PTMs), impacting not just the nervous system but a wide array of tissues and cell types as well. Specific miRNAs have been found to target proteins involved in ubiquitination or de-ubiquitination processes, which play a significant role in regulating protein function and stability. We discuss the link between miRNA, PTM, and NDs. Additionally, the review discusses the significance of miRNAs as biomarkers for early disease detection, offering insights into diagnostic strategies.}, }
@article {pmid38878554, year = {2024}, author = {Mincic, AM and Antal, M and Filip, L and Miere, D}, title = {Modulation of gut microbiome in the treatment of neurodegenerative diseases: A systematic review.}, journal = {Clinical nutrition (Edinburgh, Scotland)}, volume = {43}, number = {7}, pages = {1832-1849}, doi = {10.1016/j.clnu.2024.05.036}, pmid = {38878554}, issn = {1532-1983}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Neurodegenerative Diseases/microbiology/therapy ; *Probiotics/administration &amp; dosage/therapeutic use ; *Prebiotics/administration &amp; dosage ; *Dysbiosis/therapy/microbiology ; Animals ; Fecal Microbiota Transplantation ; }, abstract = {BACKGROUND AND AIMS: Microbiota plays an essential role in maintaining body health, through positive influences on metabolic, defensive, and trophic processes and on intercellular communication. Imbalance in intestinal flora, with the proliferation of harmful bacterial species (dysbiosis) is consistently reported in chronic illnesses, including neurodegenerative diseases (ND). Correcting dysbiosis can have a beneficial impact on the symptoms and evolution of ND. This review examines the effects of microbiota modulation through administration of probiotics, prebiotics, symbiotics, or prebiotics' metabolites (postbiotics) in patients with ND like multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS).<br><br>METHODS: PubMed, Web of Science, Medline databases and ClinicalTrials.gov registry searches were performed using pre-/pro-/postbiotics and ND-related terms. Further references were obtained by checking relevant articles.<br><br>RESULTS: Although few compared to animal studies, the human studies generally show positive effects on disease-specific symptoms, overall health, metabolic parameters, on oxidative stress and immunological markers. Therapy with probiotics in various forms (mixtures of bacterial strains, fecal microbiota transplant, diets rich in fermented foods) exert favorable effects on patients' mental health, cognition, and quality of life, targeting pathogenetic ND mechanisms and inducing reparatory mechanisms at the cellular level. More encouraging results have been observed in prebiotic/postbiotic therapy in some ND.<br><br>CONCLUSIONS: The effects of probiotic-related interventions depend on the patients' ND stage and pre-existing allopathic medication. Further studies on larger cohorts and long term comprehensive neuropsychiatric, metabolic, biochemical testing, and neuroimaging monitoring are necessary to optimize therapeutic protocols in ND.}, }
@article {pmid38877004, year = {2024}, author = {Costa, RG and Conceição, A and Matos, CA and Nóbrega, C}, title = {The polyglutamine protein ATXN2: from its molecular functions to its involvement in disease.}, journal = {Cell death &amp; disease}, volume = {15}, number = {6}, pages = {415}, pmid = {38877004}, issn = {2041-4889}, mesh = {Humans ; *Ataxin-2/metabolism/genetics ; *Peptides/metabolism/genetics ; Animals ; Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; Spinocerebellar Ataxias/metabolism/genetics/pathology ; }, abstract = {A CAG repeat sequence in the ATXN2 gene encodes a polyglutamine (polyQ) tract within the ataxin-2 (ATXN2) protein, showcasing a complex landscape of functions that have been progressively unveiled over recent decades. Despite significant progresses in the field, a comprehensive overview of the mechanisms governed by ATXN2 remains elusive. This multifaceted protein emerges as a key player in RNA metabolism, stress granules dynamics, endocytosis, calcium signaling, and the regulation of the circadian rhythm. The CAG overexpansion within the ATXN2 gene produces a protein with an extended poly(Q) tract, inducing consequential alterations in conformational dynamics which confer a toxic gain and/or partial loss of function. Although overexpanded ATXN2 is predominantly linked to spinocerebellar ataxia type 2 (SCA2), intermediate expansions are also implicated in amyotrophic lateral sclerosis (ALS) and parkinsonism. While the molecular intricacies await full elucidation, SCA2 presents ATXN2-associated pathological features, encompassing autophagy impairment, RNA-mediated toxicity, heightened oxidative stress, and disruption of calcium homeostasis. Presently, SCA2 remains incurable, with patients reliant on symptomatic and supportive treatments. In the pursuit of therapeutic solutions, various studies have explored avenues ranging from pharmacological drugs to advanced therapies, including cell or gene-based approaches. These endeavours aim to address the root causes or counteract distinct pathological features of SCA2. This review is intended to provide an updated compendium of ATXN2 functions, delineate the associated pathological mechanisms, and present current perspectives on the development of innovative therapeutic strategies.}, }
@article {pmid38874845, year = {2024}, author = {Birbaumer, N}, title = {"Your Thoughts are (were) Free!": Brain-Computer-Interfaces, Neurofeedback, Detection of Deception, and the Future of Mind-Reading.}, journal = {Applied psychophysiology and biofeedback}, volume = {}, number = {}, pages = {}, pmid = {38874845}, issn = {1573-3270}, abstract = {This review describes the historical developement and rationale of clinically relevant research on neurophysiological "mind reading" paradims: Brain- Computer-Interfaces, detection of deception, brain stimulation and neurofeedback and the clinical applications in drug resistant epilepsy, chronic stroke, and communication with paralyzed locked-in persons. The emphasis lies on completely locked-in patients with amyotrophic lateral sclerosis using non-invasive and invasive brain computer interfaces and neurofeedback to restore verbal communication with the social environment. In the second part of the article we argue that success and failure of neurophysiological "mind reading" paradigms may be explained with a motor theory of thinking and emotion in combination with learning theory. The ethical implications of brain computer interface and neurofeedback approaches, particularly for severe chronic paralysis and loss of communication diseases and decisions on hastened death and euthanasia are discussed.}, }
@article {pmid38871941, year = {2025}, author = {Naik, B and Sasikumar, J and Das, SP}, title = {From Skin and Gut to the Brain: The Infectious Journey of the Human Commensal Fungus Malassezia and Its Neurological Consequences.}, journal = {Molecular neurobiology}, volume = {62}, number = {1}, pages = {533-556}, pmid = {38871941}, issn = {1559-1182}, support = {GIA/2019/000620/PRCGIA//Indian Council of Medical Research/ ; }, mesh = {Animals ; Humans ; *Brain/microbiology/pathology ; *Malassezia/genetics/isolation &amp; purification/pathogenicity ; *Nervous System Diseases/diagnosis/microbiology/pathology ; *Skin/microbiology ; }, abstract = {The human mycobiome encompasses diverse communities of fungal organisms residing within the body and has emerged as a critical player in shaping health and disease. While extensive research has focused on the skin and gut mycobiome, recent investigations have pointed toward the potential role of fungal organisms in neurological disorders. Among those fungal organisms, the presence of the commensal fungus Malassezia in the brain has created curiosity because of its commensal nature and primary association with the human skin and gut. This budding yeast is responsible for several diseases, such as Seborrheic dermatitis, Atopic dermatitis, Pityriasis versicolor, Malassezia folliculitis, dandruff, and others. However recent findings surprisingly show the presence of Malassezia DNA in the brain and have been linked to diseases like Alzheimer's disease, Parkinson's disease, Multiple sclerosis, and Amyotrophic lateral sclerosis. The exact role of Malassezia in these disorders is unknown, but its ability to infect human cells, travel through the bloodstream, cross the blood-brain barrier, and reside along with the lipid-rich neuronal cells are potential mechanisms responsible for pathogenesis. This also includes the induction of pro-inflammatory cytokines, disruption of the blood-brain barrier, gut-microbe interaction, and accumulation of metabolic changes in the brain environment. In this review, we discuss these key findings from studies linking Malassezia to neurological disorders, emphasizing the complex and multifaceted nature of these cases. Furthermore, we discuss potential mechanisms through which Malassezia might contribute to the development of neurological conditions. Future investigations will open up new avenues for our understanding of the fungal gut-brain axis and how it influences human behavior. Collaborative research efforts among microbiologists, neuroscientists, immunologists, and clinicians hold promise for unraveling the enigmatic connections between human commensal Malassezia and neurological disorders.}, }
@article {pmid38870925, year = {2025}, author = {Hamdi, N and Ocab, O and Soliman, R and Ludolph, A and Anwar, W and Logroscino, G and Fahmy, N}, title = {Motor Neuron Disease Population-Based Registry in Egypt: Where Do We Stand?.}, journal = {Neuroepidemiology}, volume = {59}, number = {3}, pages = {277-289}, doi = {10.1159/000539468}, pmid = {38870925}, issn = {1423-0208}, mesh = {Humans ; Egypt/epidemiology ; *Registries ; *Motor Neuron Disease/epidemiology ; *Amyotrophic Lateral Sclerosis/epidemiology ; Prevalence ; Incidence ; }, abstract = {BACKGROUND: There is a growing body of evidence indicating that the worldwide distribution of amyotrophic lateral sclerosis (ALS) is far from uniform. This is evident through variations in the epidemiology, genetics, and phenotypical characteristics of ALS and other motor neuron diseases (MND) across different regions. However, comprehensive ALS epidemiological studies are still lacking in many parts of the world, especially in Africa. Therefore, we propose the establishment of a population-based register for ALS/MND in Egypt, an important part of Africa with a population of more than 100 millions of people.<br><br>SUMMARY: Given Egypt's distinctive social and demographic characteristics, it is highly recommended to employ specific, recently developed epidemiological techniques for assessing the prevalence and incidence of these diseases within the country. By utilizing these methods, we can gather invaluable data that will contribute to a deeper understanding of ALS and enable us to effectively address its impact on the population of Egypt.<br><br>KEY MESSAGES: Our goal with this pioneering ALS/MND population-based register in Egypt is to define the burden of ALS in this part of Africa and to increase the chances for this consanguineous population to get access to modern individualized genetic therapies. Additionally, we aspire to uncover potential environmental factors and gene-environment interactions that contribute to the development of ALS. This knowledge of MND individual and group risk in Egypt will not only open doors for interventions but also provide opportunities for future research and discovery.}, }
@article {pmid38870470, year = {2024}, author = {McDool, E and Carlton, J and Powell, PA and Coates, E and Knox, L and Mayberry, E and Appleby, N and Griffiths, AW and Hobson, E and McDermott, CJ}, title = {Measuring Health-Related Quality of Life in Amyotrophic Lateral Sclerosis: A Systematic Review and Conceptual Framework.}, journal = {Neurology}, volume = {103}, number = {2}, pages = {e209549}, pmid = {38870470}, issn = {1526-632X}, mesh = {*Amyotrophic Lateral Sclerosis/psychology/physiopathology ; Humans ; *Quality of Life/psychology ; Patient Reported Outcome Measures ; }, abstract = {BACKGROUND AND OBJECTIVES: The assessment of health-related quality of life (HRQoL) in patients with amyotrophic lateral sclerosis (ALS) is heterogeneous and inconsistent. The objectives of this study were (1) to develop a comprehensive conceptual framework of HRQoL in ALS and (2) map the content of existing patient-reported outcome measures (PROMs) used in ALS to this novel framework.<br><br>METHODS: Our model of HRQoL in ALS (Health-related Quality of life in Amyotrophic Lateral Sclerosis, QuALS) was developed from a systematic literature review and consultative input from key stakeholders (patients, carers, and health care professionals). Five electronic databases were searched in April 2022. Primary studies of any design that assessed HRQoL in ALS by using a multi-item PROM and/or qualitative methods were identified. Using an a priori framework, HRQoL themes were extracted and iteratively modified from the content of each PROM and qualitative study quotations identified in the literature. The conceptual framework was ratified by stakeholders with lived experience and clinical experts. The QuALS framework was used to map the content of identified PROMs and qualitative studies based on thematic coverage.<br><br>RESULTS: QuALS covers 3 high-level domains of HRQoL (physical, psychological, and social functioning) and consists of 7 themes (Activities; Physical Health; Autonomy; Cognition; Feelings and Emotions; Self-identity; Relationships), characterized by 42 subthemes. Of 8,220 studies identified, 274 were included in the review that informed QuALS. In these studies, 111 PROMs were used to assess at least 1 aspect of HRQoL, and 11 studies used qualitative methods. Of the 3 high-level domains, physical functioning was the most commonly assessed, particularly within ALS-specific PROMs where almost one-quarter of PROMs exclusively assessed physical functioning. None of the PROMs or qualitative studies identified assessed all aspects of HRQoL in the QuALS framework.<br><br>DISCUSSION: This study presents a new comprehensive conceptual framework of HRQoL in ALS (QuALS), informed by a robust systematic review of existing literature and stakeholder input, incorporating lived experience. QuALS provides a valuable resource for researchers and clinicians interested in taking a holistic approach to assessing and understanding the full impact of ALS on HRQoL and how this may be affected by treatments.}, }
@article {pmid38869826, year = {2024}, author = {Wang, H and Zeng, R}, title = {Aberrant protein aggregation in amyotrophic lateral sclerosis.}, journal = {Journal of neurology}, volume = {271}, number = {8}, pages = {4826-4851}, pmid = {38869826}, issn = {1432-1459}, mesh = {*Amyotrophic Lateral Sclerosis/metabolism ; Humans ; *Protein Aggregation, Pathological/metabolism ; Protein Aggregates/physiology ; Animals ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal disease. As its pathological mechanisms are not well understood, there are no efficient therapeutics for it at present. While it is highly heterogenous both etiologically and clinically, it has a common salient hallmark, i.e., aberrant protein aggregation (APA). The upstream pathogenesis and the downstream effects of APA in ALS are sophisticated and the investigation of this pathology would be of consequence for understanding ALS. In this paper, the pathomechanism of APA in ALS and the candidate treatment strategies for it are discussed.}, }
@article {pmid38864944, year = {2024}, author = {Wang, LY and Zhang, L and Bai, XY and Qiang, RR and Zhang, N and Hu, QQ and Cheng, JZ and Yang, YL and Xiang, Y}, title = {The Role of Ferroptosis in Amyotrophic Lateral Sclerosis Treatment.}, journal = {Neurochemical research}, volume = {49}, number = {10}, pages = {2653-2667}, pmid = {38864944}, issn = {1573-6903}, mesh = {*Ferroptosis/drug effects/physiology ; *Amyotrophic Lateral Sclerosis/metabolism/drug therapy/pathology ; Humans ; Animals ; Oxidative Stress/physiology ; Reactive Oxygen Species/metabolism ; Iron/metabolism ; Antioxidants/therapeutic use ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease with a challenging treatment landscape, due to its complex pathogenesis and limited availability of clinical drugs. Ferroptosis, an iron-dependent form of programmed cell death (PCD), stands distinct from apoptosis, necrosis, autophagy, and other cell death mechanisms. Recent studies have increasingly highlighted the role of iron deposition, reactive oxygen species (ROS) accumulation, oxidative stress, as well as systemic Xc- and glutamate accumulation in the antioxidant system in the pathogenesis of amyotrophic lateral sclerosis. Therefore, targeting ferroptosis emerges as a promising strategy for amyotrophic lateral sclerosis treatment. This review introduces the regulatory mechanism of ferroptosis, the relationship between amyotrophic lateral sclerosis and ferroptosis, and the drugs used in the clinic, then discusses the current status of amyotrophic lateral sclerosis treatment, hoping to provide new directions and targets for its treatment.}, }
@article {pmid38863235, year = {2024}, author = {Priyanka,  and Raymandal, B and Mondal, S}, title = {Native State Stabilization of Amyloidogenic Proteins by Kinetic Stabilizers: Inhibition of Protein Aggregation and Clinical Relevance.}, journal = {ChemMedChem}, volume = {19}, number = {19}, pages = {e202400244}, doi = {10.1002/cmdc.202400244}, pmid = {38863235}, issn = {1860-7187}, support = {SRG/2023/000434//Science and Engineering Research Board, India/ ; }, mesh = {Humans ; Kinetics ; *Amyloidogenic Proteins/metabolism/antagonists &amp; inhibitors/chemistry ; Protein Aggregates/drug effects ; Superoxide Dismutase-1/metabolism/chemistry/antagonists &amp; inhibitors ; Prealbumin/metabolism/chemistry/antagonists &amp; inhibitors ; Amyloidosis/drug therapy/metabolism ; Clinical Relevance ; }, abstract = {Proteinopathies or amyloidoses are a group of life-threatening disorders that result from misfolding of proteins and aggregation into toxic insoluble amyloid aggregates. Amyloid aggregates have low clearance from the body due to the insoluble nature, leading to their deposition in various organs and consequent organ dysfunction. While amyloid deposition in the central nervous system leads to neurodegenerative diseases that mostly cause dementia and difficulty in movement, several other organs, including heart, liver and kidney are also affected by systemic amyloidoses. Regardless of the site of amyloid deposition, misfolding and structural alteration of the precursor proteins play the central role in amyloid formation. Kinetic stabilizers are an emerging class of drugs, which act like pharmacological chaperones to stabilize the native state structure of amyloidogenic proteins and to increase the activation energy barrier that is required for adopting a misfolded structure or conformation, ultimately leading to the inhibition of protein aggregation. In this review, we discuss the kinetic stabilizers that stabilize the native quaternary structure of transthyretin, immunoglobulin light chain and superoxide dismutase 1 that cause transthyretin amyloidoses, light chain amyloidosis and familial amyotrophic lateral sclerosis, respectively.}, }
@article {pmid38859699, year = {2024}, author = {Finsterer, J and Strobl, W}, title = {Gastrointestinal involvement in neuromuscular disorders.}, journal = {Journal of gastroenterology and hepatology}, volume = {39}, number = {10}, pages = {1982-1993}, doi = {10.1111/jgh.16650}, pmid = {38859699}, issn = {1440-1746}, mesh = {Humans ; *Neuromuscular Diseases/complications/etiology ; *Gastrointestinal Diseases/etiology/therapy/diagnosis ; Myotonic Dystrophy/complications/diagnosis/physiopathology ; Mitochondrial Diseases/complications ; }, abstract = {Although not often discussed, many of the neuromuscular disorders (NMDs) affect the gastrointestinal tract (GIT). Depending on the type of NMD, the prevalence of GIT involvement ranges from <5% (e.g. hereditary neuropathies, myofibrillar myopathies) to 100% (e.g. MNGIE, OPMD). Particularly in NMDs with multisystem affection, involvement of the GIT can dominate the clinical presentation or at least make up a significant part of the clinical picture. The most prominent representatives of NMDs with multisystem involvement are the mitochondrial disorders (MIDs) and the myotonic dystrophies. The best known syndromic MIDs with GIT involvement are MNGIE, MELAS, Leigh, and Pearson syndromes. Among neuropathies, GIT involvement is most commonly found in ALS and GBS. GIT involvement may also be a feature of myasthenia. The clinical manifestations of GIT involvement are diverse and can affect the entire GIT, from the teeth to the rectum, including the liver and pancreas. The most well-known clinical manifestations of GIT involvement are dysphagia, nausea, vomiting, reflux, hollow organ dysmotility, hepatopathy, diabetes, diarrhea, constipation, and fecal incontinence. Even if treatment can usually only be symptomatic, the therapeutic options are diverse, are often effective, and can significantly and beneficially influence the course of the underlying NMD.}, }
@article {pmid38856890, year = {2024}, author = {Tripathi, S and Bhawana, }, title = {Epigenetic Orchestration of Neurodegenerative Disorders: A Possible Target for Curcumin as a Therapeutic.}, journal = {Neurochemical research}, volume = {49}, number = {9}, pages = {2319-2335}, pmid = {38856890}, issn = {1573-6903}, mesh = {*Curcumin/therapeutic use/pharmacology ; Humans ; *Epigenesis, Genetic/drug effects ; *Neurodegenerative Diseases/drug therapy/metabolism/genetics ; Animals ; *Neuroprotective Agents/therapeutic use/pharmacology ; Mitochondria/metabolism/drug effects ; Oxidative Stress/drug effects ; }, abstract = {Epigenetic modulations play a major role in gene expression and thus are responsible for various physiological changes including age-associated neurological disorders. Neurodegenerative diseases such as Alzheimer's (AD), Parkinson's (PD), Huntington's disease (HD), although symptomatically different, may share common underlying mechanisms. Most neurodegenerative diseases are associated with increased oxidative stress, aggregation of certain proteins, mitochondrial dysfunction, inactivation/dysregulation of protein degradation machinery, DNA damage and cell excitotoxicity. Epigenetic modulations has been reported to play a significant role in onset and progression of neurodegenerative diseases by regulating these processes. Previous studies have highlighted the marked antioxidant and neuroprotective abilities of polyphenols such as curcumin, by increased activity of detoxification systems like superoxide dismutase (SOD), catalase or glutathione peroxidase. The role of curcumin as an epigenetic modulator in neurological disorders and neuroinflammation apart from other chronic diseases have also been reported by a few groups. Nonetheless, the evidences for the role of curcumin mediated epigenetic modulation in its neuroprotective ability are still limited. This review summarizes the current knowledge of the role of mitochondrial dysfunction, epigenetic modulations and mitoepigenetics in age-associated neurological disorders such as PD, AD, HD, Amyotrophic Lateral Sclerosis (ALS), and Multiple Sclerosis (MS), and describes the neuroprotective effects of curcumin in the treatment and/or prevention of these neurodegenerative diseases by regulation of the epigenetic machinery.}, }
@article {pmid38856793, year = {2025}, author = {Kumari, S and Kamiya, A and Karnik, SS and Rohilla, S and Dubey, SK and Taliyan, R}, title = {Novel Gene Therapy Approaches for Targeting Neurodegenerative Disorders: Focusing on Delivering Neurotrophic Genes.}, journal = {Molecular neurobiology}, volume = {62}, number = {1}, pages = {386-411}, pmid = {38856793}, issn = {1559-1182}, mesh = {Humans ; *Genetic Therapy/methods ; *Neurodegenerative Diseases/therapy/genetics ; Animals ; *Nerve Growth Factors/genetics ; Gene Transfer Techniques ; Genetic Vectors ; }, abstract = {Neurodegenerative illnesses (NDDs) like Alzheimer's, Parkinson's, amyotrophic lateral sclerosis, spinal muscular atrophy, and Huntington's disease have demonstrated considerable potential for gene therapy as a viable therapeutic intervention. NDDs are marked by the decline of neurons, resulting in changes in both behavior and pathology within the body. Strikingly, only symptomatic management is available without a cure for the NDDs. There is an unmet need for a permanent therapeutic approach. Many studies have been going on to target the newer therapeutic molecular targets for NDDs including gene-based therapy. Gene therapy has the potential to provide therapeutic benefits to a large number of patients with NDDs by offering mechanisms including neuroprotection, neuro-restoration, and rectification of pathogenic pathways. Gene therapy is a medical approach that aims to modify the biological characteristics of living cells by controlling the expression of specific genes in certain neurological disorders. Despite being the most complex and well-protected organ in the human body, there is clinical evidence to show that it is possible to specifically target the central nervous system (CNS). This provides hope for the prospective application of gene therapy in treating NDDs in the future. There are several advanced techniques available for using viral or non-viral vectors to deliver the therapeutic gene to the afflicted region. Neurotrophic factors (NTF) in the brain are crucial for the development, differentiation, and survival of neurons in the CNS, making them important in the context of various neurological illnesses. Gene delivery of NTF has the potential to be used as a therapeutic approach for the treatment of neurological problems in the brain. This review primarily focuses on the methodologies employed for delivering the genes of different NTFs to treat neurological disorders. These techniques are currently being explored as a viable therapeutic approach for neurodegenerative diseases. The article exclusively addresses gene delivery approaches and does not cover additional therapy strategies for NDDs. Gene therapy offers a promising alternative treatment for NDDs by stimulating neuronal growth instead of solely relying on symptom relief from drugs and their associated adverse effects. It can serve as a long-lasting and advantageous treatment choice for the management of NDDs. The likelihood of developing NDDs increases with age as a result of neuronal degradation in the brain. Gene therapy is an optimal approach for promoting neuronal growth through the introduction of nerve growth factor genes.}, }
@article {pmid38855322, year = {2024}, author = {Tsekrekou, M and Giannakou, M and Papanikolopoulou, K and Skretas, G}, title = {Protein aggregation and therapeutic strategies in SOD1- and TDP-43- linked ALS.}, journal = {Frontiers in molecular biosciences}, volume = {11}, number = {}, pages = {1383453}, pmid = {38855322}, issn = {2296-889X}, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with severe socio-economic impact. A hallmark of ALS pathology is the presence of aberrant cytoplasmic inclusions composed of misfolded and aggregated proteins, including both wild-type and mutant forms. This review highlights the critical role of misfolded protein species in ALS pathogenesis, particularly focusing on Cu/Zn superoxide dismutase (SOD1) and TAR DNA-binding protein 43 (TDP-43), and emphasizes the urgent need for innovative therapeutic strategies targeting these misfolded proteins directly. Despite significant advancements in understanding ALS mechanisms, the disease remains incurable, with current treatments offering limited clinical benefits. Through a comprehensive analysis, the review focuses on the direct modulation of the misfolded proteins and presents recent discoveries in small molecules and peptides that inhibit SOD1 and TDP-43 aggregation, underscoring their potential as effective treatments to modify disease progression and improve clinical outcomes.}, }
@article {pmid38848023, year = {2024}, author = {Fabi, JP}, title = {The connection between gut microbiota and its metabolites with neurodegenerative diseases in humans.}, journal = {Metabolic brain disease}, volume = {39}, number = {5}, pages = {967-984}, doi = {10.1007/s11011-024-01369-w}, pmid = {38848023}, issn = {1573-7365}, support = {2013/07914-8//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado de S&#xe3;o Paulo/ ; 307842/2022-3//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Neurodegenerative Diseases/metabolism/microbiology ; *Dysbiosis/metabolism ; *Brain-Gut Axis/physiology ; Animals ; Blood-Brain Barrier/metabolism ; Brain/metabolism ; }, abstract = {The aging of populations is a global phenomenon that follows a possible increase in the incidence of neurodegenerative diseases. Alzheimer's, Parkinson's, Multiple Sclerosis, Amyotrophic Lateral Sclerosis, and Huntington's diseases are some neurodegenerative disorders that aging could initiate or aggravate. Recent research has indicated that intestinal microbiota dysbiosis can trigger metabolism and brain functioning, contributing to the etiopathogenesis of those neurodegenerative diseases. The intestinal microbiota and its metabolites show significant functions in various aspects, such as the immune system modulation (development and maturation), the maintenance of the intestinal barrier integrity, the modulation of neuromuscular functions in the intestine, and the facilitation of essential metabolic processes for both the microbiota and humans. The primary evidence supporting the connection between intestinal microbiota and its metabolites with neurodegenerative diseases are epidemiological observations and animal models experimentation. This paper reviews up-to-date evidence on the correlation between the microbiota-gut-brain axis and neurodegenerative diseases, with a specially focus on gut metabolites. Dysbiosis can increase inflammatory cytokines and bacterial metabolites, altering intestinal and blood-brain barrier permeability and causing neuroinflammation, thus facilitating the pathogenesis of neurodegenerative diseases. Clinical data supporting this evidence still needs to be improved. Most of the works found are descriptive and associated with the presence of phyla or species of bacteria with neurodegenerative diseases. Despite the limitations of recent research, the potential for elucidating clinical questions that have thus far eluded clarification within prevailing pathophysiological frameworks of health and disease is promising through investigation of the interplay between the host and microbiota.}, }
@article {pmid38846716, year = {2024}, author = {Bradford, D and Rodgers, KE}, title = {Advancements and challenges in amyotrophic lateral sclerosis.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1401706}, pmid = {38846716}, issn = {1662-4548}, abstract = {Amyotrophic lateral sclerosis (ALS) continues to pose a significant challenge due to the disease complexity and heterogeneous manifestations. Despite recent drug approvals, there remains a critical need for the development of more effective therapies. This review explores the underlying mechanisms involved; including neuroinflammation, glutamate mediated excitotoxicity, mitochondrial dysfunction, and hypermetabolism, and how researchers are trying to develop novel drugs to target these pathways. While progress has been made, the unmet need of ALS patients highlights the urgency for continued research and resource allocation in the pursuit of effective treatments.}, }
@article {pmid38845026, year = {2024}, author = {Kettunen, P and Koistinaho, J and Rolova, T}, title = {Contribution of CNS and extra-CNS infections to neurodegeneration: a narrative review.}, journal = {Journal of neuroinflammation}, volume = {21}, number = {1}, pages = {152}, pmid = {38845026}, issn = {1742-2094}, support = {334525//Research Council of Finland/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/pathology ; *Central Nervous System Infections ; Animals ; }, abstract = {Central nervous system infections have been suggested as a possible cause for neurodegenerative diseases, particularly sporadic cases. They trigger neuroinflammation which is considered integrally involved in neurodegenerative processes. In this review, we will look at data linking a variety of viral, bacterial, fungal, and protozoan infections to Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis and unspecified dementia. This narrative review aims to bring together a broad range of data currently supporting the involvement of central nervous system infections in the development of neurodegenerative diseases. The idea that no single pathogen or pathogen group is responsible for neurodegenerative diseases will be discussed. Instead, we suggest that a wide range of susceptibility factors may make individuals differentially vulnerable to different infectious pathogens and subsequent pathologies.}, }
@article {pmid38844617, year = {2024}, author = {Tyr, A and Heldring, N and Zilg, B}, title = {Examining the use of alternative light sources in medico-legal assessments of blunt-force trauma: a systematic review.}, journal = {International journal of legal medicine}, volume = {138}, number = {5}, pages = {1925-1938}, pmid = {38844617}, issn = {1437-1596}, mesh = {Humans ; *Contusions ; *Wounds, Nonpenetrating ; Light ; Forensic Medicine/methods ; }, abstract = {The ability to analyze blunt-force trauma is crucial for deciphering valuable clues concerning mechanisms of injury and as evidence for medico-legal investigations. The use of alternate light sources (ALS) has been studied over the past decade, and is proposed to outperform conventional white light (CWL) during bruise assessments. In response to the growing interest of the technology worldwide, a systematic review of the literature was conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) to address the ability of ALS to detect and visualize bruising. From an initial 4055 records identified, ten studies met the eligibly criteria and were selected for this review. Evaluation also included a novel framework, referred to as SPICOT, to further systematically assess both scientific evidence and risk of bias in forensic literature. Analysis reveals that narrowband wavelengths within in the infrared or ultraviolet spectral ranges do not significantly outperform CWL in visualizing or detecting bruising. However, wavelengths within the visible spectrum, particularly 415 nm combined with longpass or bandpass yellow filters, are more effective. However, the majority of selected studies only address the sensitivity of ALS, and therefore, results may only be considered valid when the location of a bruise is known. Further investigation is required to understand the specificity of ALS, in particular how the use of topical cosmetic products, previous wounds/scar-tissue, tattoos, moles and freckles may affect detection. The ethical concern regarding the interpretation of enhanced visualized trauma should also be considered in prospect discussions prior to implementing ALS into routine practice. Nevertheless, this review finds that narrowband ALS within the visible spectrum demonstrates potential for improved injury documentation, outperforming CWL in the detection and visualization of bruising.}, }
@article {pmid38839870, year = {2024}, author = {Ye, C and Li, H and Chen, Y and Hao, J and Liu, J and Shan, J and Qiao, SZ}, title = {The role of electrocatalytic materials for developing post-lithium metal||sulfur batteries.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {4797}, pmid = {38839870}, issn = {2041-1723}, abstract = {The exploration of post-Lithium (Li) metals, such as Sodium (Na), Potassium (K), Magnesium (Mg), Calcium (Ca), Aluminum (Al), and Zinc (Zn), for electrochemical energy storage has been driven by the limited availability of Li and the higher theoretical specific energies compared to the state-of-the-art Li-ion batteries. Post-Li metal||S batteries have emerged as a promising system for practical applications. Yet, the insufficient understanding of quantitative cell parameters and the mechanisms of sulfur electrocatalytic conversion hinder the advancement of these battery technologies. This perspective offers a comprehensive analysis of electrode parameters, including S mass loading, S content, electrolyte/S ratio, and negative/positive electrode capacity ratio, in establishing the specific energy (Wh kg[-1]) of post-Li metal||S batteries. Additionally, we critically evaluate the progress in investigating electrochemical sulfur conversion via homogeneous and heterogeneous electrocatalytic approaches in both non-aqueous Na/K/Mg/Ca/Al||S and aqueous Zn||S batteries. Lastly, we provide a critical outlook on potential research directions for designing practical post-Li metal||S batteries.}, }
@article {pmid38837229, year = {2024}, author = {Ó Murchú, SC and O'Halloran, KD}, title = {BREATHE DMD: boosting respiratory efficacy after therapeutic hypoxic episodes in Duchenne muscular dystrophy.}, journal = {The Journal of physiology}, volume = {602}, number = {14}, pages = {3255-3272}, doi = {10.1113/JP280280}, pmid = {38837229}, issn = {1469-7793}, support = {SFI FFP/19/6628 INSPIRE DMD/SFI_/Science Foundation Ireland/Ireland ; }, mesh = {*Muscular Dystrophy, Duchenne/physiopathology/therapy ; Humans ; *Hypoxia/physiopathology ; Animals ; Respiration ; }, abstract = {Duchenne muscular dystrophy (DMD) is a fatal genetic neuromuscular disorder, characterised by progressive decline in skeletal muscle function due to the secondary consequences of dystrophin deficiency. Weakness extends to the respiratory musculature, and cardiorespiratory failure is the leading cause of death in men with DMD. Intermittent hypoxia has emerged as a potential therapy to counteract ventilatory insufficiency by eliciting long-term facilitation of breathing. Mechanisms of sensory and motor facilitation of breathing have been well delineated in animal models. Various paradigms of intermittent hypoxia have been designed and implemented in human trials culminating in clinical trials in people with spinal cord injury and amyotrophic lateral sclerosis. Application of therapeutic intermittent hypoxia to DMD is considered together with discussion of the potential barriers to progression owing to the complexity of this devastating disease. Notwithstanding the considerable challenges and potential pitfalls of intermittent hypoxia-based therapies for DMD, we suggest it is incumbent on the research community to explore the potential benefits in pre-clinical models. Intermittent hypoxia paradigms should be implemented to explore the proclivity to express respiratory plasticity with the longer-term aim of preserving and potentiating ventilation in pre-clinical models and people with DMD.}, }
@article {pmid38834164, year = {2024}, author = {Griñán-Ferré, C and Bellver-Sanchis, A and Guerrero, A and Pallàs, M}, title = {Advancing personalized medicine in neurodegenerative diseases: The role of epigenetics and pharmacoepigenomics in pharmacotherapy.}, journal = {Pharmacological research}, volume = {205}, number = {}, pages = {107247}, doi = {10.1016/j.phrs.2024.107247}, pmid = {38834164}, issn = {1096-1186}, mesh = {Humans ; *Precision Medicine/methods ; *Neurodegenerative Diseases/drug therapy/genetics ; *Pharmacogenetics/methods ; *Epigenesis, Genetic/drug effects ; Animals ; Epigenomics/methods ; }, abstract = {About 80 % of brain disorders have a genetic basis. The pathogenesis of most neurodegenerative diseases is associated with a myriad of genetic defects, epigenetic alterations (DNA methylation, histone/chromatin remodeling, miRNA dysregulation), and environmental factors. The emergence of new sequencing technologies and tools to study the epigenome has led to identifying predictive biomarkers for earlier diagnosis, opening up the possibility of prophylactical interventions. As a result, advances in pharmacogenetics and pharmacoepigenomics now allow for personalized treatments based on the profile of each patient and the specific genetic and epigenetic mechanisms involved. This Review highlights the complexity of neurodegenerative diseases and the variability in patient responses to pharmacotherapy, emphasizing the influence of genetic polymorphisms on the pharmacokinetics and pharmacodynamics of drugs used to treat those conditions. We specifically discuss the potential modulatory effect of several genetic polymorphisms associated with an increased risk of developing different neurodegenerative diseases. We explore genetic and genomic technologies and the potential of analyzing individual-specific drug metabolism to predict and influence drug response and associated clinical outcomes. We also provide insights into the mechanism of action of the drugs under investigation and their potential impact on disease-modifying pathways. Finally, the Review underscores the great potential of this field to enhance the effectiveness and safety of drug treatments through personalized medicine.}, }
@article {pmid38833116, year = {2024}, author = {Mubeen, H and Masood, A and Zafar, A and Khan, ZQ and Khan, MQ and Nisa, AU}, title = {Insights into AlphaFold's breakthrough in neurodegenerative diseases.}, journal = {Irish journal of medical science}, volume = {193}, number = {5}, pages = {2577-2588}, pmid = {38833116}, issn = {1863-4362}, mesh = {Humans ; *Neurodegenerative Diseases/physiopathology ; Artificial Intelligence ; Deep Learning ; Parkinson Disease ; Alzheimer Disease ; Algorithms ; Frontotemporal Dementia/genetics ; }, abstract = {Neurodegenerative diseases (ND) are disorders of the central nervous system (CNS) characterized by impairment in neurons' functions, and complete loss, leading to memory loss, and difficulty in learning, language, and movement processes. The most common among these NDs are Alzheimer's disease (AD) and Parkinson's disease (PD), although several other disorders also exist. These are frontotemporal dementia (FTD), amyotrophic lateral syndrome (ALS), Huntington's disease (HD), and others; the major pathological hallmark of NDs is the proteinopathies, either of amyloid-β (Aβ), tauopathies, or synucleinopathies. Aggregation of proteins that do not undergo normal configuration, either due to mutations or through some disturbance in cellular pathway contributes to the diseases. Artificial Intelligence (AI) and deep learning (DL) have proven to be successful in the diagnosis and treatment of various congenital diseases. DL approaches like AlphaFold (AF) are a major leap towards success in CNS disorders. This 3D protein geometry modeling algorithm developed by DeepMind has the potential to revolutionize biology. AF has the potential to predict 3D-protein confirmation at an accuracy level comparable to experimentally predicted one, with the additional advantage of precisely estimating protein interactions. This breakthrough will be beneficial to identify diseases' advancement and the disturbance of signaling pathways stimulating impaired functions of proteins. Though AlphaFold has solved a major problem in structural biology, it cannot predict membrane proteins-a beneficial approach for drug designing.}, }
@article {pmid38831349, year = {2024}, author = {López-Carbonero, JI and García-Toledo, I and Fernández-Hernández, L and Bascuñana, P and Gil-Moreno, MJ and Matías-Guiu, JA and Corrochano, S}, title = {In vivo diagnosis of TDP-43 proteinopathies: in search of biomarkers of clinical use.}, journal = {Translational neurodegeneration}, volume = {13}, number = {1}, pages = {29}, pmid = {38831349}, issn = {2047-9158}, support = {2022-5A/BMD-24221//Consejer&#xed;a de Educaci&#xf3;n, Juventud y Deporte, Comunidad de Madrid/ ; PDI2020-1153-70RB-100/AEI/10.13039/501100011033//Ministerio de Ciencia e Innovaci&#xf3;n/ ; CM23/00094//Instituto de Salud Carlos III/ ; INT20/00079//Instituto de Salud Carlos III/ ; INT23/00017//Instituto de Salud Carlos III/ ; }, mesh = {Humans ; *TDP-43 Proteinopathies/diagnosis/metabolism/genetics ; *Biomarkers/analysis/metabolism ; *DNA-Binding Proteins/metabolism ; Brain/metabolism/pathology ; }, abstract = {TDP-43 proteinopathies are a heterogeneous group of neurodegenerative disorders that share the presence of aberrant, misfolded and mislocalized deposits of the protein TDP-43, as in the case of amyotrophic lateral sclerosis and some, but not all, pathological variants of frontotemporal dementia. In recent years, many other diseases have been reported to have primary or secondary TDP-43 proteinopathy, such as Alzheimer's disease, Huntington's disease or the recently described limbic-predominant age-related TDP-43 encephalopathy, highlighting the need for new and accurate methods for the early detection of TDP-43 proteinopathy to help on the stratification of patients with overlapping clinical diagnosis. Currently, TDP-43 proteinopathy remains a post-mortem pathologic diagnosis. Although the main aim is to determine the pathologic TDP-43 proteinopathy in the central nervous system (CNS), the ubiquitous expression of TDP-43 in biofluids and cells outside the CNS facilitates the use of other accessible target tissues that might reflect the potential TDP-43 alterations in the brain. In this review, we describe the main developments in the early detection of TDP-43 proteinopathies, and their potential implications on diagnosis and future treatments.}, }
@article {pmid38830181, year = {2024}, author = {Weemering, DN and Beelen, A and Kliest, T and van Leeuwen, LAG and van den Berg, LH and van Eijk, RPA}, title = {Trial Participation in Neurodegenerative Diseases: Barriers and Facilitators: A Systematic Review and Meta-Analysis.}, journal = {Neurology}, volume = {103}, number = {1}, pages = {e209503}, pmid = {38830181}, issn = {1526-632X}, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy ; *Clinical Trials as Topic ; *Patient Participation ; Patient Selection ; }, abstract = {BACKGROUND AND OBJECTIVES: Clinical trials in neurodegenerative diseases often encounter selective enrollment and under-representation of certain patient populations. This delays drug development and substantially limits the generalizability of clinical trial results. To inform recruitment and retention strategies, and to better understand the generalizability of clinical trial populations, we investigated which factors drive participation.<br><br>METHODS: We reviewed the literature systematically to identify barriers to and facilitators of trial participation in 4 major neurodegenerative disease areas: Alzheimer disease, Parkinson disease, amyotrophic lateral sclerosis, and Huntington disease. Inclusion criteria included original research articles published in a peer-reviewed journal and evaluating barriers to and/or facilitators of participation in a clinical trial with a drug therapy (either symptomatic or disease-modifying). The Critical Appraisal Skills Program checklist for qualitative studies was used to assess and ensure the quality of the studies. Qualitative thematic analyses were employed to identify key enablers of trial participation. Subsequently, we pooled quantitative data of each enabler using meta-analytical models.<br><br>RESULTS: Overall, we identified 36 studies, enrolling a cumulative sample size of 5,269 patients, caregivers, and health care professionals. In total, the thematic analysis resulted in 31 unique enablers of trial participation; the key factors were patient-related (own health benefit and altruism), study-related (treatment and study burden), and health care professional-related (information availability and patient-physician relationship). When meta-analyzed across studies, responders reported that the reason to participate was mainly driven by (1) the relationship with clinical staff (70% of the respondents; 95% CI 53%-83%), (2) the availability of study information (67%, 95% CI 38%-87%), and (3) the use or absence of a placebo or sham-control arm (53% 95% CI 32%-72%). There was, however, significant heterogeneity between studies (all p < 0.001).<br><br>DISCUSSION: We have provided a comprehensive list of reasons why patients participate in clinical trials for neurodegenerative diseases. These results may help to increase participation rates, better inform patients, and facilitate patient-centric approaches, thereby potentially reducing selection mechanisms and improving generalizability of trial results.}, }
@article {pmid38829511, year = {2025}, author = {Jiang, S and Xu, R}, title = {The Current Potential Pathogenesis of Amyotrophic Lateral Sclerosis.}, journal = {Molecular neurobiology}, volume = {62}, number = {1}, pages = {221-232}, pmid = {38829511}, issn = {1559-1182}, support = {30560042//National Natural Science Foundation of China/ ; 81160161//National Natural Science Foundation of China/ ; 81360198//National Natural Science Foundation of China/ ; 82160255//National Natural Science Foundation of China/ ; GJJ13198//Education Department of Jiangxi Province/ ; GJJ170021//Education Department of Jiangxi Province/ ; 20192BAB205043//Jiangxi Provincial Department of Science and Technology/ ; 20181019//Health and Family Planning Commission of Jiangxi Province/ ; 202210002//Health and Family Planning Commission of Jiangxi Province/ ; 202310119//Health and Family Planning Commission of Jiangxi Province/ ; }, mesh = {Animals ; Humans ; *Amyotrophic Lateral Sclerosis/genetics/microbiology/pathology/physiopathology ; Autophagy/physiology ; Dysbiosis/complications/microbiology/physiopathology ; Extracellular Vesicles/metabolism ; Gastrointestinal Microbiome/physiology ; Mitochondria/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease mainly characterized by the accumulation of ubiquitinated proteins in the affected motor neurons. At present, the accurate pathogenesis of ALS remains unclear and there are still no effective treatment measures for ALS. The potential pathogenesis of ALS mainly includes the misfolding of some pathogenic proteins, the genetic variation, mitochondrial dysfunction, autophagy disorders, neuroinflammation, the misregulation of RNA, the altered axonal transport, and gut microbial dysbiosis. Exploring the pathogenesis of ALS is a critical step in searching for the effective therapeutic approaches. The current studies suggested that the genetic variation, gut microbial dysbiosis, the activation of glial cells, and the transportation disorder of extracellular vesicles may play some important roles in the pathogenesis of ALS. This review conducts a systematic review of these current potential promising topics closely related to the pathogenesis of ALS; it aims to provide some new evidences and clues for searching the novel treatment measures of ALS.}, }
@article {pmid38822985, year = {2024}, author = {Faysal, M and Dehbia, Z and Zehravi, M and Sweilam, SH and Haque, MA and Kumar, KP and Chakole, RD and Shelke, SP and Sirikonda, S and Nafady, MH and Khan, SL and Nainu, F and Ahmad, I and Emran, TB}, title = {Flavonoids as Potential Therapeutics Against Neurodegenerative Disorders: Unlocking the Prospects.}, journal = {Neurochemical research}, volume = {49}, number = {8}, pages = {1926-1944}, pmid = {38822985}, issn = {1573-6903}, mesh = {*Flavonoids/therapeutic use/pharmacology ; Humans ; *Neurodegenerative Diseases/drug therapy ; Animals ; Neuroprotective Agents/therapeutic use/pharmacology ; Oxidative Stress/drug effects ; Antioxidants/therapeutic use/pharmacology ; }, abstract = {Neurodegeneration, the decline of nerve cells in the brain, is a common feature of neurodegenerative disorders (NDDs). Oxidative stress, a key factor in NDDs such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease can lead to neuronal cell death, mitochondria impairment, excitotoxicity, and Ca[2+] stress. Environmental factors compromising stress response lead to cell damage, necessitating novel therapeutics for preventing or treating brain disorders in older individuals and an aging population. Synthetic medications offer symptomatic benefits but can have adverse effects. This research explores the potential of flavonoids derived from plants in treating NDDs. Flavonoids compounds, have been studied for their potential to enter the brain and treat NDDs. These compounds have diverse biological effects and are currently being explored for their potential in the treatment of central nervous system disorders. Flavonoids have various beneficial effects, including antiviral, anti-allergic, antiplatelet, anti-inflammatory, anti-tumor, anti-apoptotic, and antioxidant properties. Their potential to alleviate symptoms of NDDs is significant.}, }
@article {pmid38822416, year = {2024}, author = {Yadav, S and Deepika,  and Moar, K and Kumar, A and Khola, N and Pant, A and Kakde, GS and Maurya, PK}, title = {Reconsidering red blood cells as the diagnostic potential for neurodegenerative disorders.}, journal = {Biology of the cell}, volume = {116}, number = {7}, pages = {e2400019}, doi = {10.1111/boc.202400019}, pmid = {38822416}, issn = {1768-322X}, support = {//Council of Scientific and Industrial Research (CSIR), Government of India/ ; //University Grant Commission (UGC)/ ; HSCIT-3946//Haryana State Council for Science, Innovation, and Technology/ ; //Central University of Haryana, Mahendergarh/ ; //Indian Council of Medical Research (ICMR), Government of India/ ; }, mesh = {Humans ; *Erythrocytes/metabolism ; *Neurodegenerative Diseases/diagnosis/metabolism/blood ; *Biomarkers/metabolism/blood ; Oxidative Stress ; Animals ; Alzheimer Disease/diagnosis/metabolism/blood ; }, abstract = {BACKGROUND: Red blood cells (RBCs) are usually considered simple cells and transporters of gases to tissues.<br><br>HYPOTHESIS: However, recent research has suggested that RBCs may have diagnostic potential in major neurodegenerative disorders (NDDs).<br><br>RESULTS: This review summarizes the current knowledge on changes in RBC in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and other NDDs. It discusses the deposition of neuronal proteins like amyloid-&#x3b2;, tau, and &#x3b1;-synuclein, polyamines, changes in the proteins of RBCs like band-3, membrane transporter proteins, heat shock proteins, oxidative stress biomarkers, and altered metabolic pathways in RBCs during neurodegeneration. It also highlights the comparison of RBC diagnostic markers to other in-market diagnoses and discusses the challenges in utilizing RBCs as diagnostic tools, such as the need for standardized protocols and further validation studies.<br><br>SIGNIFICANCE STATEMENT: The evidence suggests that RBCs have diagnostic potential in neurodegenerative disorders, and this study can pave the foundation for further research which may lead to the development of novel diagnostic approaches and treatments.}, }
@article {pmid38821351, year = {2024}, author = {Pocock, J and Vasilopoulou, F and Svensson, E and Cosker, K}, title = {Microglia and TREM2.}, journal = {Neuropharmacology}, volume = {257}, number = {}, pages = {110020}, doi = {10.1016/j.neuropharm.2024.110020}, pmid = {38821351}, issn = {1873-7064}, mesh = {Humans ; *Microglia/metabolism ; *Receptors, Immunologic/metabolism/genetics ; *Membrane Glycoproteins/metabolism/genetics ; Animals ; Neurodegenerative Diseases/metabolism/pathology/genetics ; Induced Pluripotent Stem Cells/metabolism ; Phagocytosis/physiology ; }, abstract = {TREM2 is a membrane receptor solely expressed on microglia in normal brain. In this review we outline recent advances in TREM2 biology and its implications for microglial function, with particular emphasis on findings from iPSC-derived microglia (iMG) expressing TREM2 loss-of-function mutations. Alterations in receptor proximal and distal signalling underlie TREM2 risk variants linked to neurodegenerative disease, principally NH-linked FTD, and late-onset AD, but emerging data suggest roles for TREM2 in PD, MS and ALS. TREM2 downstream functions include phagocytosis of myelin debris, amyloid beta peptides, and phosphatidylserine-expressing cells (resulting from damage or stress). Microglial survival, migration, DAMP signalling, inflammasome activation, and intercellular signalling including tau spreading via exosomes, as well as roles for sTREM2 in protection and as a biomarker are discussed. The role of TREM2 in metabolic homeostasis, and immunometabolic switching are discussed regarding microglial responses to damage and protection. The use of iPSC models to investigate the role of TREM2 in AD, PD, MS, ALS, and other neurodegenerative diseases could prove invaluable due to their ability to recapitulate human pathology, allowing a full understanding of TREM2 and microglial involvement in the underlying disease mechanisms and progression. This article is part of the Special Issue on "Microglia".}, }
@article {pmid38820331, year = {2025}, author = {Dessie, G and Li, J and Nghiem, S and Doan, T}, title = {Prevalence and Determinants of Stunting-Anemia and Wasting-Anemia Comorbidities and Micronutrient Deficiencies in Children Under 5 in the Least-Developed Countries: A Systematic Review and Meta-analysis.}, journal = {Nutrition reviews}, volume = {83}, number = {2}, pages = {e178-e194}, pmid = {38820331}, issn = {1753-4887}, support = {//Australia National University/ ; }, mesh = {Child, Preschool ; Female ; Humans ; Infant ; *Anemia/epidemiology ; Comorbidity ; *Developing Countries/statistics &amp; numerical data ; *Growth Disorders/epidemiology ; *Micronutrients/deficiency ; Prevalence ; *Wasting Syndrome/epidemiology ; }, abstract = {CONTEXT: Despite shifting from addressing isolated forms of malnutrition to recognizing its multifaceted nature, evidence on the prevalence and determinants of micronutrient deficiencies, and their coexistence with undernutrition in children under 5, remains insufficient, unsystematic, and incohesive.<br><br>OBJECTIVE: The aim of this systematic review and meta-analysis was to assess the prevalence and determinants of stunting-anemia and wasting-anemia comorbidities and micronutrient deficiencies in children under 5 in the least-developed countries (LDCs).<br><br>DATA SOURCES: Electronic searches took place from January 15, 2023, to February 14, 2024, across multiple databases, including PubMed, Embase, Web of Science, SCOPUS, African Index Medicus (AIM), World Health Organization's Institutional Repository for Information Sharing (IRIS), and African Journals Online. The search spanned the years 2000 to 2024, yet it yielded eligible full-text English research articles from only 2005 to 2021 conducted in LDCs. Studies lacking quantitative data on malnutrition types and their determinants were excluded.<br><br>DATA EXTRACTION: Two independent authors assessed articles for bias and quality using Hoy et al's 10-item scale and Newcastle-Ottawa Scale (NOS) criteria. Prevalence and other details were extracted using a Joanna Briggs Institute Excel template. Authors extracted adjusted odds ratios (aORs) for determinant factors such as sex and vitamin&#x2009;A and iron supplementation.<br><br>DATA ANALYSIS: The search yielded 6248 articles from 46 LDCs. Sixty-nine articles, with a total sample size of 181&#x200a;605, met inclusion criteria for the final meta-analysis. Vitamin&#x2009;A deficiency affected 16.32% of children, and iodine deficiency affected 43.41% of children. The pooled prevalence of wasting-anemia and stunting-anemia comorbidity was 5.44% and 19.47%, respectively. Stunting was associated with vitamin&#x2009;A deficiency (aOR: 1.54; 95% CI: 1.01-2.37), and not taking vitamin&#x2009;A supplementation was associated with iron-deficiency anemia (aOR: 1.37; 95% CI: 1.21-1.55).<br><br>CONCLUSION: A significant proportion of children under 5 in LDCs experienced stunting-anemia and wasting-anemia comorbidities and micronutrient deficiencies. This study underscores the urgent need to address factors driving these burdens.<br><br>PROSPERO registration no. CRD42023409483.}, }
@article {pmid38819491, year = {2024}, author = {Juarez, D and Handal-Silva, A and Morán-Perales, JL and Torres-Cifuentes, DM and Flores, G and Treviño, S and Moreno-Rodriguez, A and Guevara, J and Diaz, A}, title = {New insights into sodium phenylbutyrate as a pharmacotherapeutic option for neurological disorders.}, journal = {Synapse (New York, N.Y.)}, volume = {78}, number = {4}, pages = {e22301}, doi = {10.1002/syn.22301}, pmid = {38819491}, issn = {1098-2396}, support = {IN214117//PAPITT-UNAM/ ; DIFA-NAT24-G//Vicerrector&#xed;a de Investigaci&#xf3;n y Estudios de Posgrado, Benem&#xe9;rita Universidad Aut&#xf3;noma de Puebla/ ; TEMS-NAT24-G//Vicerrector&#xed;a de Investigaci&#xf3;n y Estudios de Posgrado, Benem&#xe9;rita Universidad Aut&#xf3;noma de Puebla/ ; }, mesh = {Humans ; *Phenylbutyrates/therapeutic use/pharmacology ; Animals ; *Nervous System Diseases/drug therapy/metabolism ; }, abstract = {Neurological disorders (NDs) are diseases of the central and peripheral nervous systems that affect more than one billion people worldwide. The risk of developing an ND increases with age due to the vulnerability of the different organs and systems to genetic, environmental, and social changes that consequently cause motor and cognitive deficits that disable the person from their daily activities and individual and social productivity. Intrinsic factors (genetic factors, age, gender) and extrinsic factors (addictions, infections, or lifestyle) favor the persistence of systemic inflammatory processes that contribute to the evolution of NDs. Neuroinflammation is recognized as a common etiopathogenic factor of ND. The study of new pharmacological options for the treatment of ND should focus on improving the characteristic symptoms and attacking specific molecular targets that allow the delay of damage processes such as neuroinflammation, oxidative stress, cellular metabolic dysfunction, and deregulation of transcriptional processes. In this review, we describe the possible role of sodium phenylbutyrate (NaPB) in the pathogenesis of Alzheimer's disease, hepatic encephalopathy, aging, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis; in addition, we describe the mechanism of action of NaPB and its beneficial effects that have been shown in various in vivo and in vitro studies to delay the evolution of any ND.}, }
@article {pmid38818523, year = {2024}, author = {Shen, J and Wang, X and Wang, M and Zhang, H}, title = {Potential molecular mechanism of exercise reversing insulin resistance and improving neurodegenerative diseases.}, journal = {Frontiers in physiology}, volume = {15}, number = {}, pages = {1337442}, pmid = {38818523}, issn = {1664-042X}, abstract = {Neurodegenerative diseases are debilitating nervous system disorders attributed to various conditions such as body aging, gene mutations, genetic factors, and immune system disorders. Prominent neurodegenerative diseases include Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis. Insulin resistance refers to the inability of the peripheral and central tissues of the body to respond to insulin and effectively regulate blood sugar levels. Insulin resistance has been observed in various neurodegenerative diseases and has been suggested to induce the occurrence, development, and exacerbation of neurodegenerative diseases. Furthermore, an increasing number of studies have suggested that reversing insulin resistance may be a critical intervention for the treatment of neurodegenerative diseases. Among the numerous measures available to improve insulin sensitivity, exercise is a widely accepted strategy due to its convenience, affordability, and significant impact on increasing insulin sensitivity. This review examines the association between neurodegenerative diseases and insulin resistance and highlights the molecular mechanisms by which exercise can reverse insulin resistance under these conditions. The focus was on regulating insulin resistance through exercise and providing practical ideas and suggestions for future research focused on exercise-induced insulin sensitivity in the context of neurodegenerative diseases.}, }
@article {pmid38816479, year = {2024}, author = {Mathis, S and Beauvais, D and Duval, F and Solé, G and Le Masson, G}, title = {The various forms of hereditary motor neuron disorders and their historical descriptions.}, journal = {Journal of neurology}, volume = {271}, number = {7}, pages = {3978-3990}, pmid = {38816479}, issn = {1432-1459}, mesh = {Humans ; *Motor Neuron Disease/history/genetics ; History, 20th Century ; History, 19th Century ; Spastic Paraplegia, Hereditary/genetics/history ; }, abstract = {Motor neuron disorders comprise a clinically and pathologically heterogeneous group of neurologic diseases characterized by progressive degeneration of motor neurons (including both sporadic and hereditary diseases), affecting the upper motor neurons, lower motor neurons, or both. Hereditary motor neuron disorders themselves represent a vast and heterogeneous group, with numerous clinical and genetic overlaps that can be a source of error. This narrative review aims at providing an overview of the main types of inherited motor neuron disorders by recounting the stages in their historical descriptions. For practical purposes, this review of the literature sets out their various clinical characteristics and updates the list of all the genes involved in the various forms of inherited motor neuron disorders, including spinal muscular atrophy, familial amyotrophic lateral sclerosis, hereditary spastic paraplegia, distal hereditary motor neuropathies/neuronopathies, Kennedy's disease, riboflavin transporter deficiencies, VCPopathy and the neurogenic scapuloperoneal syndrome.}, }
@article {pmid38813817, year = {2024}, author = {Sprunger, ML and Jackrel, ME}, title = {The role of Matrin-3 in physiology and its dysregulation in disease.}, journal = {Biochemical Society transactions}, volume = {52}, number = {3}, pages = {961-972}, pmid = {38813817}, issn = {1470-8752}, support = {F31 NS120512/NS/NINDS NIH HHS/United States ; R21 AG080393/AG/NIA NIH HHS/United States ; R35 GM128772/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *RNA-Binding Proteins/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism/genetics ; *Nuclear Matrix-Associated Proteins/metabolism ; *Frontotemporal Dementia/metabolism/genetics ; DNA-Binding Proteins/metabolism ; Animals ; DNA Damage ; RNA-Binding Protein FUS/metabolism/chemistry ; }, abstract = {The dysfunction of many RNA-binding proteins (RBPs) that are heavily disordered, including TDP-43 and FUS, are implicated in amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD). These proteins serve many important roles in the cell, and their capacity to form biomolecular condensates (BMCs) is key to their function, but also a vulnerability that can lead to misregulation and disease. Matrin-3 (MATR3) is an intrinsically disordered RBP implicated both genetically and pathologically in ALS/FTD, though it is relatively understudied as compared with TDP-43 and FUS. In addition to binding RNA, MATR3 also binds DNA and is implicated in many cellular processes including the DNA damage response, transcription, splicing, and cell differentiation. It is unclear if MATR3 localizes to BMCs under physiological conditions, which is brought further into question due to its lack of a prion-like domain. Here, we review recent studies regarding MATR3 and its roles in numerous physiological processes, as well as its implication in a range of diseases.}, }
@article {pmid38812793, year = {2024}, author = {Jadhav, SP}, title = {MicroRNAs in microglia: deciphering their role in neurodegenerative diseases.}, journal = {Frontiers in cellular neuroscience}, volume = {18}, number = {}, pages = {1391537}, pmid = {38812793}, issn = {1662-5102}, abstract = {This review presents a comprehensive analysis of the role of microRNAs in microglia and their implications in the pathogenesis of neurodegenerative diseases. Microglia, as the resident immune cells of the central nervous system (CNS), are pivotal in maintaining neural homeostasis and responding to pathological changes. Recent studies have highlighted the significance of miRNAs, small non-coding RNA molecules, in regulating microglial functions. In neurodegenerative diseases, such as Alzheimer's Disease (AD), Parkinson's Disease (PD), Amyotrophic Lateral Sclerosis (ALS), and Multiple Sclerosis (MS), dysregulated miRNA expression in microglia contributes to disease progression through various mechanisms such regulation of gene expression, as modulation of cytokine response and phagocytosis. This review synthesizes current knowledge on how miRNAs influence microglial activation, cytokine production, and phagocytic activity. Specific miRNAs, such as miR-155, are explored for their roles in modulating microglial responses in the context of neuroinflammation and neurodegeneration. The study also discusses the impact of miRNA dysregulation on the transition of microglia from a neuroprotective to a neurotoxic phenotype, a critical aspect in the progression of neurodegenerative diseases.}, }
@article {pmid38811997, year = {2024}, author = {Huang, M and Liu, YU and Yao, X and Qin, D and Su, H}, title = {Variability in SOD1-associated amyotrophic lateral sclerosis: geographic patterns, clinical heterogeneity, molecular alterations, and therapeutic implications.}, journal = {Translational neurodegeneration}, volume = {13}, number = {1}, pages = {28}, pmid = {38811997}, issn = {2047-9158}, mesh = {*Amyotrophic Lateral Sclerosis/genetics/therapy/epidemiology/diagnosis ; Humans ; *Superoxide Dismutase-1/genetics ; Mutation/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive loss of motor neurons, resulting in global health burden and limited post-diagnosis life expectancy. Although primarily sporadic, familial ALS (fALS) cases suggest a genetic basis. This review focuses on SOD1, the first gene found to be associated with fALS, which has been more recently confirmed by genome sequencing. While informative, databases such as ALSoD and STRENGTH exhibit regional biases. Through a systematic global examination of SOD1 mutations from 1993 to 2023, we found different geographic distributions and clinical presentations. Even though different SOD1 variants are expressed at different protein levels and have different half-lives and dismutase activities, these alterations lead to loss of function that is not consistently correlated with disease severity. Gain of function of toxic aggregates of SOD1 resulting from mutated SOD1 has emerged as one of the key contributors to ALS. Therapeutic interventions specifically targeting toxic gain of function of mutant SOD1, including RNA interference and antibodies, show promise, but a cure remains elusive. This review provides a comprehensive perspective on SOD1-associated ALS and describes molecular features and the complex genetic landscape of SOD1, highlighting its importance in determining diverse clinical manifestations observed in ALS patients and emphasizing the need for personalized therapeutic strategies.}, }
@article {pmid38807021, year = {2024}, author = {Rahimian, S and Najafi, H and Webber, CA and Jalali, H}, title = {Advances in Exosome-Based Therapies for the Repair of Peripheral Nerve Injuries.}, journal = {Neurochemical research}, volume = {49}, number = {8}, pages = {1905-1925}, pmid = {38807021}, issn = {1573-6903}, mesh = {*Exosomes/metabolism/transplantation ; Humans ; *Peripheral Nerve Injuries/therapy/metabolism ; Animals ; Nerve Regeneration/physiology ; }, abstract = {Peripheral nerve injuries (PNIs) are the term used to describe injuries that occur to the nerve fibers of the peripheral nervous system (PNS). Such injuries may be caused by trauma, infection, or aberrant immunological response. Although the peripheral nervous system has a limited capacity for self-repair, in cases of severe damage, this process is either interrupted entirely or is only partially completed. The evaluation of variables that promote the repair of peripheral nerves has consistently been a focal point. Exosomes are a subtype of extracellular vesicles that originate from cellular sources and possess abundant proteins, lipids, and nucleic acids, play a critical role in facilitating intercellular communication. Due to their modifiable composition, they possess exceptional capabilities as carriers for therapeutic compounds, including but not limited to mRNAs or microRNAs. Exosome-based therapies have gained significant attention in the treatment of several nervous system diseases due to their advantageous properties, such as low toxicity, high stability, and limited immune system activation. The objective of this review article is to provide an overview of exosome-based treatments that have been developed in recent years for a range of PNIs, including nerve trauma, diabetic neuropathy, amyotrophic lateral sclerosis (ALS), glaucoma, and Guillain-Barre syndrome (GBS). It was concluded that exosomes could provide favorable results in the improvement of peripheral PNIs by facilitating the transfer of regenerative factors. The development of bioengineered exosome therapy for PNIs should be given more attention to enhance the efficacy of exosome treatment for PNIs.}, }
@article {pmid38805053, year = {2024}, author = {Bjelica, B and Bartels, MB and Hesebeck-Brinckmann, J and Petri, S}, title = {Non-motor symptoms in patients with amyotrophic lateral sclerosis: current state and future directions.}, journal = {Journal of neurology}, volume = {271}, number = {7}, pages = {3953-3977}, pmid = {38805053}, issn = {1432-1459}, mesh = {*Amyotrophic Lateral Sclerosis/physiopathology/diagnosis/complications ; Humans ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive degeneration of both upper and lower motor neurons. A defining histopathological feature in approximately 97% of all ALS cases is the accumulation of phosphorylated trans-activation response (TAR) DNA-binding protein 43 protein (pTDP-43) aggregates in the cytoplasm of neurons and glial cells within the central nervous system. Traditionally, it was believed that the accumulation of TDP-43 aggregates and subsequent neurodegeneration primarily occurs in motor neurons. However, contemporary evidence suggests that as the disease progresses, other systems and brain regions are also affected. Despite this, there has been a limited number of clinical studies assessing the non-motor symptoms in ALS patients. These studies often employ various outcome measures, resulting in a wide range of reported frequencies of non-motor symptoms in ALS patients. The importance of assessing the non-motor symptoms reflects in a fact that they have a significant impact on patients' quality of life, yet they frequently go underdiagnosed and unreported during clinical evaluations. This review aims to provide an up-to-date overview of the current knowledge concerning non-motor symptoms in ALS. Furthermore, we address their diagnosis and treatment in everyday clinical practice.}, }
@article {pmid38802624, year = {2024}, author = {Riva, N and Domi, T and Pozzi, L and Lunetta, C and Schito, P and Spinelli, EG and Cabras, S and Matteoni, E and Consonni, M and Bella, ED and Agosta, F and Filippi, M and Calvo, A and Quattrini, A}, title = {Update on recent advances in amyotrophic lateral sclerosis.}, journal = {Journal of neurology}, volume = {271}, number = {7}, pages = {4693-4723}, pmid = {38802624}, issn = {1432-1459}, support = {IDEALS//Agenzia di Ricerca per la Sclerosi Laterale Amiotrofica/ ; Marazzina Project//Marazzina Foundation/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/therapy/genetics ; Humans ; Animals ; }, abstract = {In the last few years, our understanding of disease molecular mechanisms underpinning ALS has advanced greatly, allowing the first steps in translating into clinical practice novel research findings, including gene therapy approaches. Similarly, the recent advent of assistive technologies has greatly improved the possibility of a more personalized approach to supportive and symptomatic care, in the context of an increasingly complex multidisciplinary line of actions, which remains the cornerstone of ALS management. Against this rapidly growing background, here we provide an comprehensive update on the most recent studies that have contributed towards our understanding of ALS pathogenesis, the latest results from clinical trials as well as the future directions for improving the clinical management of ALS patients.}, }
@article {pmid38802184, year = {2024}, author = {Vucic, S and de Carvalho, M and Bashford, J and Alix, JJP}, title = {Contribution of neurophysiology to the diagnosis and monitoring of ALS.}, journal = {International review of neurobiology}, volume = {176}, number = {}, pages = {87-118}, doi = {10.1016/bs.irn.2024.04.001}, pmid = {38802184}, issn = {2162-5514}, mesh = {*Amyotrophic Lateral Sclerosis/diagnosis/physiopathology ; Humans ; *Transcranial Magnetic Stimulation/methods ; *Electromyography/methods ; *Neurophysiology/methods ; Disease Progression ; Motor Cortex/physiopathology ; }, abstract = {This chapter describes the role of neurophysiological techniques in diagnosing and monitoring amyotrophic lateral sclerosis (ALS). Despite many advances, electromyography (EMG) remains a keystone investigation from which to build support for a diagnosis of ALS, demonstrating the pathophysiological processes of motor unit hyperexcitability, denervation and reinnervation. We consider development of the different diagnostic criteria and the role of EMG therein. While not formally recognised by established diagnostic criteria, we discuss the pioneering studies that have demonstrated the diagnostic potential of transcranial magnetic stimulation (TMS) of the motor cortex and highlight the growing evidence for TMS in the diagnostic process. Finally, accurately monitoring disease progression is crucial for the successful implementation of clinical trials. Neurophysiological measures of disease state have been incorporated into clinical trials for over 20 years and we review prominent techniques for assessing disease progression.}, }
@article {pmid38802183, year = {2024}, author = {Moll, T and Harvey, C and Alhathli, E and Gornall, S and O'Brien, D and Cooper-Knock, J}, title = {Non-coding genome contribution to ALS.}, journal = {International review of neurobiology}, volume = {176}, number = {}, pages = {75-86}, doi = {10.1016/bs.irn.2024.04.002}, pmid = {38802183}, issn = {2162-5514}, mesh = {*Amyotrophic Lateral Sclerosis/genetics ; Humans ; Animals ; Genetic Predisposition to Disease/genetics ; }, abstract = {The majority of amyotrophic lateral sclerosis (ALS) is caused by a complex gene-environment interaction. Despite high estimates of heritability, the genetic basis of disease in the majority of ALS patients are unknown. This limits the development of targeted genetic therapies which require an understanding of patient-specific genetic drivers. There is good evidence that the majority of these missing genetic risk factors are likely to be found within the non-coding genome. However, a major challenge in the discovery of non-coding risk variants is determining which variants are functional in which specific CNS cell type. We summarise current discoveries of ALS-associated genetic drivers within the non-coding genome and we make the case that improved cell-specific annotation of genomic function is required to advance this field, particularly via single-cell epigenetic profiling and spatial transcriptomics. We highlight the example of TBK1 where an apparent paradox exists between pathogenic coding variants which cause loss of protein function, and protective non-coding variants which cause reduced gene expression; the paradox is resolved when it is understood that the non-coding variants are acting primarily via change in gene expression within microglia, and the effect of coding variants is most prominent in neurons. We propose that cell-specific functional annotation of ALS-associated genetic variants will accelerate discovery of the genetic architecture underpinning disease in the vast majority of patients.}, }
@article {pmid38802182, year = {2024}, author = {Al-Chalabi, A and Andrews, J and Farhan, S}, title = {Recent advances in the genetics of familial and sporadic ALS.}, journal = {International review of neurobiology}, volume = {176}, number = {}, pages = {49-74}, doi = {10.1016/bs.irn.2024.04.007}, pmid = {38802182}, issn = {2162-5514}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *Genetic Predisposition to Disease/genetics ; }, abstract = {ALS shows complex genetic inheritance patterns. In about 5% to 10% of cases, there is a family history of ALS or a related condition such as frontotemporal dementia in a first or second degree relative, and for about 80% of such people a pathogenic gene variant can be identified. Such variants are also seen in people with no family history because of factor influencing the expression of genes, such as age. Genetic susceptibility factors also contribute to risk, and the heritability of ALS is between 40% and 60%. The genetic variants influencing ALS risk include single base changes, repeat expansions, copy number variants, and others. Here we review what is known of the genetic landscape and architecture of ALS.}, }
@article {pmid38802181, year = {2024}, author = {De Cock, L and Bercier, V and Van Den Bosch, L}, title = {New developments in pre-clinical models of ALS to guide translation.}, journal = {International review of neurobiology}, volume = {176}, number = {}, pages = {477-524}, doi = {10.1016/bs.irn.2024.04.008}, pmid = {38802181}, issn = {2162-5514}, mesh = {*Amyotrophic Lateral Sclerosis/genetics/physiopathology/therapy ; Animals ; *Disease Models, Animal ; Humans ; Translational Research, Biomedical/methods ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder in which selective death of motor neurons leads to muscle weakness and paralysis. Most research has focused on understanding and treating monogenic familial forms, most frequently caused by mutations in SOD1, FUS, TARDBP and C9orf72, although ALS is mostly sporadic and without a clear genetic cause. Rodent models have been developed to study monogenic ALS, but despite numerous pre-clinical studies and clinical trials, few disease-modifying therapies are available. ALS is a heterogeneous disease with complex underlying mechanisms where several genes and molecular pathways appear to play a role. One reason for the high failure rate of clinical translation from the current models could be oversimplification in pre-clinical studies. Here, we review advances in pre-clinical models to better capture the heterogeneous nature of ALS and discuss the value of novel model systems to guide translation and aid in the development of precision medicine.}, }
@article {pmid38802180, year = {2024}, author = {Shelkovnikova, TA and Hautbergue, GM}, title = {RNP granules in ALS and neurodegeneration: From multifunctional membraneless organelles to therapeutic opportunities.}, journal = {International review of neurobiology}, volume = {176}, number = {}, pages = {455-479}, doi = {10.1016/bs.irn.2024.04.009}, pmid = {38802180}, issn = {2162-5514}, support = {MR/R024162/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/pathology ; *Ribonucleoproteins/metabolism ; Animals ; *Cytoplasmic Granules/metabolism ; Neurodegenerative Diseases/metabolism ; Organelles/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) and related neurodegenerative diseases are characterised by dysfunction of a host of RNA-binding proteins (RBPs) and a severely disrupted RNA metabolism. Recently, RBP-harbouring phase-separated complexes, ribonucleoprotein (RNP) granules, have come into the limelight as "crucibles" of neuronal pathology in ALS. RNP granules are indispensable for the multitude of regulatory processes underlying cellular RNA metabolism and serve as critical organisers of cellular biochemistry. Neurons, highly specialised cells, heavily rely on RNP granules for efficient trafficking, signalling and stress responses. Multiple RNP granule components, primarily RBPs such as TDP-43 and FUS, are affected by ALS mutations. However, even in the absence of mutations, RBP proteinopathies represent pathophysiological hallmarks of ALS. Given the high local concentrations of RBPs and RNAs, their weakened or enhanced interactions within RNP granules disrupt their homeostasis. Thus, the physiological process of phase separation and RNP granule formation, vital for maintaining the high-functioning state of neuronal cells, becomes their Achilles heel. Here, we will review the recent literature on the causes and consequences of abnormal RNP granule functioning in ALS and related disorders. In particular, we will summarise the evidence for the network-level dysfunction of RNP granules in these conditions and discuss considerations for therapeutic interventions to target RBPs, RNP granules and their network as a whole.}, }
@article {pmid38802179, year = {2024}, author = {Pandya, VA and Patani, R}, title = {The role of glial cells in amyotrophic lateral sclerosis.}, journal = {International review of neurobiology}, volume = {176}, number = {}, pages = {381-450}, doi = {10.1016/bs.irn.2024.04.005}, pmid = {38802179}, issn = {2162-5514}, mesh = {*Amyotrophic Lateral Sclerosis/pathology/physiopathology/therapy ; Humans ; *Neuroglia/physiology ; Animals ; }, abstract = {Amyotrophic lateral sclerosis (ALS) has traditionally been considered a neuron-centric disease. This view is now outdated, with increasing recognition of cell autonomous and non-cell autonomous contributions of central and peripheral nervous system glia to ALS pathomechanisms. With glial research rapidly accelerating, we comprehensively interrogate the roles of astrocytes, microglia, oligodendrocytes, ependymal cells, Schwann cells and satellite glia in nervous system physiology and ALS-associated pathology. Moreover, we highlight the inter-glial, glial-neuronal and inter-system polylogue which constitutes the healthy nervous system and destabilises in disease. We also propose classification based on function for complex glial reactive phenotypes and discuss the pre-requisite for integrative modelling to advance translation. Given the paucity of life-enhancing therapies currently available for ALS patients, we discuss the promising potential of harnessing glia in driving ALS therapeutic discovery.}, }
@article {pmid38802177, year = {2024}, author = {Lee, J and Pye, N and Ellis, L and Vos, K and Mortiboys, H}, title = {Evidence of mitochondrial dysfunction in ALS and methods for measuring in model systems.}, journal = {International review of neurobiology}, volume = {176}, number = {}, pages = {269-325}, doi = {10.1016/bs.irn.2024.04.006}, pmid = {38802177}, issn = {2162-5514}, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/pathology ; Humans ; *Mitochondria/metabolism ; Animals ; Reactive Oxygen Species/metabolism ; Disease Models, Animal ; Oxidative Stress/physiology ; }, abstract = {Metabolic dysfunction is a hallmark of multiple amyotrophic lateral sclerosis (ALS) models with a majority of ALS patients exhibiting hypermetabolism. The central sites of metabolism in the cell are mitochondria, capable of utilising a multitude of cellular substrates in an array of ATP-generating reactions. With reactive oxygen species (ROS) production occurring during some of these reactions, mitochondria can contribute considerably to oxidative stress. Mitochondria are also very dynamic organelles, interacting with other organelles, undergoing fusion/fission in response to changing metabolic states and being turned over by the cell regularly. Disruptions to many of these mitochondrial functions and processes have been reported in ALS models, largely indicating compromised mitochondrial function, increased ROS production by mitochondria, disrupted interactions with the endoplasmic reticulum and reduced turnover. This chapter summarises methods routinely used to assess mitochondria in ALS models and the alterations that have been reported in these models.}, }
@article {pmid38802176, year = {2024}, author = {Castelli, L and Vasta, R and Allen, SP and Waller, R and Chiò, A and Traynor, BJ and Kirby, J}, title = {From use of omics to systems biology: Identifying therapeutic targets for amyotrophic lateral sclerosis.}, journal = {International review of neurobiology}, volume = {176}, number = {}, pages = {209-268}, doi = {10.1016/bs.irn.2024.02.001}, pmid = {38802176}, issn = {2162-5514}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/drug therapy/therapy ; *Systems Biology/methods ; *Genomics/methods ; Proteomics/methods ; Animals ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a heterogeneous progressive neurodegenerative disorder with available treatments such as riluzole and edaravone extending survival by an average of 3-6 months. The lack of highly effective, widely available therapies reflects the complexity of ALS. Omics technologies, including genomics, transcriptomic and proteomics have contributed to the identification of biological pathways dysregulated and targeted by therapeutic strategies in preclinical and clinical trials. Integrating clinical, environmental and neuroimaging information with omics data and applying a systems biology approach can further improve our understanding of the disease with the potential to stratify patients and provide more personalised medicine. This chapter will review the omics technologies that contribute to a systems biology approach and how these components have assisted in identifying therapeutic targets. Current strategies, including the use of genetic screening and biosampling in clinical trials, as well as the future application of additional technological advances, will also be discussed.}, }
@article {pmid38802175, year = {2024}, author = {Malaspina, A}, title = {Use of biomarkers in clinical trials and future developments that will help identify novel biomarkers.}, journal = {International review of neurobiology}, volume = {176}, number = {}, pages = {171-207}, doi = {10.1016/bs.irn.2024.04.010}, pmid = {38802175}, issn = {2162-5514}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/diagnosis/genetics/metabolism/drug therapy ; *Biomarkers ; *Clinical Trials as Topic/methods ; }, abstract = {Engineering new solutions for therapeutic benefit in Amyotrophic Lateral Sclerosis (ALS) has proved a difficult task to accomplish. This is largely the reflection of complexities at multiple levels, that require solutions to improve cost-effectiveness and outcomes. The main obstacle related to the condition's clinical heterogeneity, chiefly the broad difference in survival observed among ALS patients, imposes large populations studies and long follow-up to evaluate any efficacy. The emerging solution is composite clinical and biological parameters enabling prognostic stratification into homogeneous phenotypes for more affordable studies. From a therapeutic development perspective, the choice of a medicinal product requires the availability of treatment-specific biomarkers of target engagement to identify off-target effects based on the compound's putative modality of action. More importantly, there are no established biomarkers of treatment response that can complement clinical outcome measures and support futility and end of treatment analyses of efficacy. Ultimately the onus rests on the development of biomarkers encompassing the unmet needs of clinical trial design, from inclusion to efficacy. These readouts of the pathological process may be used in combination with clinical and paraclinical outcome measured, significantly reducing the time and financial burden of clinical studies. Progress towards a biomarker-driven clinical trial design in ALS has been possible thanks to the accurate detection of neurofilaments and of other immunological mediators in biological fluids with the disease progression, a step change enabling the testing of novel therapeutic agents in a new clinical trial setting. However, further progress remains to be made to find treatment specific target engagement biomarkers along with readouts of treatment response that can be reliably applied to all emerging therapies and clinical studies. Here we will cover the basic notions of biomarker development in ALS clinical trials, the most crucial unanswered questions and the unmet needs in the ALS biomarkers space.}, }
@article {pmid38802174, year = {2024}, author = {Hobson, E and McDermott, C}, title = {Advances in symptom management and in monitoring disease progression in motor neuron disease.}, journal = {International review of neurobiology}, volume = {176}, number = {}, pages = {119-169}, doi = {10.1016/bs.irn.2024.04.004}, pmid = {38802174}, issn = {2162-5514}, mesh = {Humans ; *Motor Neuron Disease/therapy/physiopathology ; *Disease Progression ; Disease Management ; Quality of Life ; }, abstract = {The aim of supportive management of motor neuron disease is to improve survival, promote good quality of life and patient independence and autonomy whilst preparing for future progression and the end of life. Multidisciplinary specialist care aims to address the multifaceted and interacting biopsychosocial problems associated with motor neuron disease that leads to proven benefits in both survival and quality of life. This chapter will explore principles, structure and details of treatment options, and make recommendations for practice and for future research.}, }
@article {pmid38802173, year = {2024}, author = {Van Es, MA}, title = {Amyotrophic lateral sclerosis; clinical features, differential diagnosis and pathology.}, journal = {International review of neurobiology}, volume = {176}, number = {}, pages = {1-47}, doi = {10.1016/bs.irn.2024.04.011}, pmid = {38802173}, issn = {2162-5514}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics/pathology/physiopathology ; Diagnosis, Differential ; Frontotemporal Dementia/diagnosis/genetics/physiopathology/pathology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a late-onset syndrome characterized by the progressive degeneration of both upper motor neurons (UMN) and lower motor neurons (LMN). ALS forms a clinical continuum with frontotemporal dementia (FTD), in which there are progressive language deficits or behavioral changes. The genetics and pathology underlying both ALS and FTD overlap as well, with cytoplasmatic misvocalization of TDP-43 as the hallmark. ALS is diagnosed by exclusion. Over the years several diagnostic criteria have been proposed, which in essence all require a history of slowly progressive motor symptoms, with UMN and LMN signs on neurological examination, clear spread of symptoms through the body, the exclusion of other disorder that cause similar symptoms and an EMG that it is compatible with LMN loss. ALS is heterogeneous disorder that may present in multitude ways, which makes the diagnosis challenging. Therefore, a systematic approach in the diagnostic process is required in line with the most common presentations. Subsequently, assessing whether there are cognitive and/or behavioral changes within the spectrum of FTD and lastly determining the cause is genetic. This chapter, an outline on how to navigate this 3 step process.}, }
@article {pmid38797132, year = {2024}, author = {Wakimoto, Y and Chen, Y and Honda, H and Shibahara, H}, title = {Advancements in the detection and implications of sperm-immobilizing antibodies in female infertility.}, journal = {Journal of reproductive immunology}, volume = {164}, number = {}, pages = {104256}, doi = {10.1016/j.jri.2024.104256}, pmid = {38797132}, issn = {1872-7603}, mesh = {Humans ; Female ; *Spermatozoa/immunology ; Male ; *Infertility, Female/immunology/therapy/diagnosis ; Pregnancy ; *Sperm Motility/immunology ; Autoantibodies/immunology ; Animals ; Fertilization in Vitro/methods ; Fertilization/immunology ; }, abstract = {This review highlights over five decades of research on sperm-immobilizing antibodies (SI-Abs), which are crucial for understanding female infertility due to their effects on sperm motility and fertilization. Since the 1960s, Isojima et al. have made significant strides, notably with the Sperm Immobilization Test (SIT), which revolutionized the quantification of SI-Abs and their roles in infertility. Drawing from a comprehensive PubMed search on "the sperm immobilization test" and "sperm immobilizing antibody," our review underscores the critical insights gained into SI-Abs' impact on reproductive functions. SI-Abs result from the body's response to sperm antigens, potentially leading to infertility by affecting post-intercourse sperm function. However, the presence of anti-sperm antibodies does not guarantee infertility, indicating a complex relationship between these antibodies and reproductive outcomes. Isojima et al.'s pioneering studies paved the way for SIT and sperm immobilization titer (SI50), tools that have clarified the link between SI-Abs and infertility, focusing on disrupted sperm mobility and fertilization as key infertility mechanisms. Clinically, interventions such as in-vitro fertilization (IVF), which bypasses or eliminates SI-Abs, have improved pregnancy rates, whereas Freund's complete adjuvant therapy has deepened our understanding of infertility mechanisms. The SI50 value is crucial for predicting fertility treatment success and guiding therapeutic decisions based on antibody levels. In summary, the evolution of SI-Abs research has provided new hope for addressing infertility, significantly enriching the field of reproductive immunology, and highlighting the need for ongoing investigation.}, }
@article {pmid38795957, year = {2024}, author = {Bhushan, NL and Romano, CD and Gras-Najjar, J and Reno, J and Rockwood, N and Quattrone, W and Adams, ET and Kelly, B and McLeod, L and Bhavnani, SP and Bocell, FD and Campbell, M and Kontson, K and Reasner, D and Zhang, C and Retzky, S}, title = {Remote-Use Applications of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised Clinical Outcome Assessment Tool: A Scoping Review.}, journal = {Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research}, volume = {27}, number = {10}, pages = {1454-1465}, doi = {10.1016/j.jval.2024.05.005}, pmid = {38795957}, issn = {1524-4733}, support = {75F40120A00017/FD/FDA HHS/United States ; }, mesh = {*Amyotrophic Lateral Sclerosis/therapy/physiopathology ; Humans ; *Outcome Assessment, Health Care/methods ; Telemedicine ; Severity of Illness Index ; Videoconferencing ; }, abstract = {OBJECTIVES: In 2021, the US Congress passed the Accelerating Access to Critical Therapies for Amyotrophic Lateral Sclerosis Act. The law encourages development of "tools, methods, and processes" to improve clinical trial efficiency for neurodegenerative diseases. The Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) is an outcome measure administered during in-person clinic visits and used to support investigational studies for persons living with amyotrophic lateral sclerosis. Availability of a standardized, remote-use version of the ALSFRS-R may promote more inclusive, decentralized clinical trials. A scoping literature review was conducted to identify existing remote-use ALSFRS-R tools, synthesize feasibility and comparability of administration modes, and summarize barriers and facilitators to inform development of a standardized remote-use ALSFRS-R tool.<br><br>METHODS: Included studies reported comparisons between remote and in-person, clinician-reported, ALSFRS-R administration and were published in English (2002-2022). References were identified by searching peer-reviewed and gray literature. Twelve studies met the inclusion criteria and were analyzed to compare findings within and across modes of administration.<br><br>RESULTS: Remote modes of ALSFRS-R administration were categorized into 4 nonmutually exclusive categories: telephone (n&#xa0;= 6), videoconferencing (n&#xa0;= 3), computer or online platforms (n&#xa0;= 3), mobile applications and wearables (n&#xa0;= 2), and 1 unspecified telemedicine modality (n&#xa0;= 1). Studies comparing in-person to telephone or videoconferencing administration reported high ALSFRS-R rating correlations and nonsignificant between-mode differences.<br><br>CONCLUSIONS: There is insufficient information in the ALSFRS-R literature to support remote clinician administration for collecting high quality data. Future research should engage persons living with amyotrophic lateral sclerosis, care partners, and providers to develop a standardized remote-use ALSFRS-R version.}, }
@article {pmid38795640, year = {2024}, author = {Li, Z and Zhang, Y and Ji, M and Wu, C and Zhang, Y and Ji, S}, title = {Targeting ferroptosis in neuroimmune and neurodegenerative disorders for the development of novel therapeutics.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {176}, number = {}, pages = {116777}, doi = {10.1016/j.biopha.2024.116777}, pmid = {38795640}, issn = {1950-6007}, mesh = {*Ferroptosis/drug effects/physiology ; Humans ; *Neurodegenerative Diseases/drug therapy/immunology/metabolism/pathology ; Animals ; Neuroimmunomodulation ; }, abstract = {Neuroimmune and neurodegenerative ailments impose a substantial societal burden. Neuroimmune disorders involve the intricate regulatory interactions between the immune system and the central nervous system. Prominent examples of neuroimmune disorders encompass multiple sclerosis and neuromyelitis optica. Neurodegenerative diseases result from neuronal degeneration or demyelination in the brain or spinal cord, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. The precise underlying pathogenesis of these conditions remains incompletely understood. Ferroptosis, a programmed form of cell death characterised by lipid peroxidation and iron overload, plays a pivotal role in neuroimmune and neurodegenerative diseases. In this review, we provide a detailed overview of ferroptosis, its mechanisms, pathways, and regulation during the progression of neuroimmune and neurodegenerative diseases. Furthermore, we summarise the impact of ferroptosis on neuroimmune-related cells (T cells, B cells, neutrophils, and macrophages) and neural cells (glial cells and neurons). Finally, we explore the potential therapeutic implications of ferroptosis inhibitors in diverse neuroimmune and neurodegenerative diseases.}, }
@article {pmid38791160, year = {2024}, author = {Bocheva, G and Bakalov, D and Iliev, P and Tafradjiiska-Hadjiolova, R}, title = {The Vital Role of Melatonin and Its Metabolites in the Neuroprotection and Retardation of Brain Aging.}, journal = {International journal of molecular sciences}, volume = {25}, number = {10}, pages = {}, pmid = {38791160}, issn = {1422-0067}, mesh = {*Melatonin/metabolism/pharmacology/therapeutic use ; Humans ; *Brain/metabolism/drug effects ; *Aging/metabolism/drug effects ; Animals ; *Neurodegenerative Diseases/metabolism/drug therapy ; *Neuroprotection/drug effects ; *Neuroprotective Agents/therapeutic use/pharmacology ; Oxidative Stress/drug effects ; Kynuramine/metabolism/analogs &amp; derivatives ; }, abstract = {While primarily produced in the pineal gland, melatonin's influence goes beyond its well-known role in regulating sleep, nighttime metabolism, and circadian rhythms, in the field of chronobiology. A plethora of new data demonstrates melatonin to be a very powerful molecule, being a potent ROS/RNS scavenger with anti-inflammatory, immunoregulatory, and oncostatic properties. Melatonin and its metabolites exert multiple beneficial effects in cutaneous and systemic aging. This review is focused on the neuroprotective role of melatonin during aging. Melatonin has an anti-aging capacity, retarding the rate of healthy brain aging and the development of age-related neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, amyotrophic lateral sclerosis, etc. Melatonin, as well as its metabolites, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK), can reduce oxidative brain damage by shielding mitochondria from dysfunction during the aging process. Melatonin could also be implicated in the treatment of neurodegenerative conditions, by modifying their characteristic low-grade neuroinflammation. It can either prevent the initiation of inflammatory responses or attenuate the ongoing inflammation. Drawing on the current knowledge, this review discusses the potential benefits of melatonin supplementation in preventing and managing cognitive impairment and neurodegenerative diseases.}, }
@article {pmid38790450, year = {2024}, author = {Eisen, A and Pioro, EP and Goutman, SA and Kiernan, MC}, title = {Nanoplastics and Neurodegeneration in ALS.}, journal = {Brain sciences}, volume = {14}, number = {5}, pages = {}, pmid = {38790450}, issn = {2076-3425}, support = {R01 TS000327/TS/ATSDR CDC HHS/United States ; R01 ES030049/ES/NIEHS NIH HHS/United States ; R01 NS120926/NS/NINDS NIH HHS/United States ; R01 NS127188/NS/NINDS NIH HHS/United States ; R01 TS000344/TS/ATSDR CDC HHS/United States ; }, abstract = {Plastic production, which exceeds one million tons per year, is of global concern. The constituent low-density polymers enable spread over large distances and micro/nano particles (MNPLs) induce organ toxicity via digestion, inhalation, and skin contact. Particles have been documented in all human tissues including breast milk. MNPLs, especially weathered particles, can breach the blood-brain barrier, inducing neurotoxicity. This has been documented in non-human species, and in human-induced pluripotent stem cell lines. Within the brain, MNPLs initiate an inflammatory response with pro-inflammatory cytokine production, oxidative stress with generation of reactive oxygen species, and mitochondrial dysfunction. Glutamate and GABA neurotransmitter dysfunction also ensues with alteration of excitatory/inhibitory balance in favor of reduced inhibition and resultant neuro-excitation. Inflammation and cortical hyperexcitability are key abnormalities involved in the pathogenic cascade of amyotrophic lateral sclerosis (ALS) and are intricately related to the mislocalization and aggregation of TDP-43, a hallmark of ALS. Water and many foods contain MNPLs and in humans, ingestion is the main form of exposure. Digestion of plastics within the gut can alter their properties, rendering them more toxic, and they cause gut microbiome dysbiosis and a dysfunctional gut-brain axis. This is recognized as a trigger and/or aggravating factor for ALS. ALS is associated with a long (years or decades) preclinical period and neonates and infants are exposed to MNPLs through breast milk, milk substitutes, and toys. This endangers a time of intense neurogenesis and establishment of neuronal circuitry, setting the stage for development of neurodegeneration in later life. MNPL neurotoxicity should be considered as a yet unrecognized risk factor for ALS and related diseases.}, }
@article {pmid38788085, year = {2024}, author = {Mohassel, P and Abdullah, M and Eichler, FS and Dunn, TM}, title = {Serine Palmitoyltransferase (SPT)-related Neurodegenerative and Neurodevelopmental Disorders.}, journal = {Journal of neuromuscular diseases}, volume = {11}, number = {4}, pages = {735-747}, pmid = {38788085}, issn = {2214-3602}, mesh = {Humans ; Amyotrophic Lateral Sclerosis/genetics/metabolism ; Hereditary Sensory and Autonomic Neuropathies/genetics/metabolism/physiopathology ; *Neurodegenerative Diseases/metabolism ; *Neurodevelopmental Disorders ; *Serine C-Palmitoyltransferase/metabolism/genetics ; Spastic Paraplegia, Hereditary/genetics/metabolism ; Sphingolipids/metabolism ; }, abstract = {Motor neuron diseases and peripheral neuropathies are heterogeneous groups of neurodegenerative disorders that manifest with distinct symptoms due to progressive dysfunction or loss of specific neuronal subpopulations during different stages of development. A few monogenic, neurodegenerative diseases associated with primary metabolic disruptions of sphingolipid biosynthesis have been recently discovered. Sphingolipids are a subclass of lipids that form critical building blocks of all cellular and subcellular organelle membranes including the membrane components of the nervous system cells. They are especially abundant within the lipid portion of myelin. In this review, we will focus on our current understanding of disease phenotypes in three monogenic, neuromuscular diseases associated with pathogenic variants in components of serine palmitoyltransferase, the first step in sphingolipid biosynthesis. These include hereditary sensory and autonomic neuropathy type 1 (HSAN1), a sensory predominant peripheral neuropathy, and two neurodegenerative disorders: juvenile amyotrophic lateral sclerosis affecting the upper and lower motor neurons with sparing of sensory neurons, and a complicated form of hereditary spastic paraplegia with selective involvement of the upper motor neurons and more broad CNS neurodegeneration. We will also review our current understanding of disease pathomechanisms, therapeutic approaches, and the unanswered questions to explore in future studies.}, }
@article {pmid38786016, year = {2024}, author = {Salzinger, A and Ramesh, V and Das Sharma, S and Chandran, S and Thangaraj Selvaraj, B}, title = {Neuronal Circuit Dysfunction in Amyotrophic Lateral Sclerosis.}, journal = {Cells}, volume = {13}, number = {10}, pages = {}, pmid = {38786016}, issn = {2073-4409}, mesh = {*Amyotrophic Lateral Sclerosis/physiopathology/pathology ; Humans ; *Motor Neurons/pathology/physiology ; Animals ; Nerve Net/physiopathology/pathology ; Neuromuscular Junction/physiopathology/pathology ; Disease Models, Animal ; Motor Cortex/physiopathology/pathology ; }, abstract = {The primary neural circuit affected in Amyotrophic Lateral Sclerosis (ALS) patients is the corticospinal motor circuit, originating in upper motor neurons (UMNs) in the cerebral motor cortex which descend to synapse with the lower motor neurons (LMNs) in the spinal cord to ultimately innervate the skeletal muscle. Perturbation of these neural circuits and consequent loss of both UMNs and LMNs, leading to muscle wastage and impaired movement, is the key pathophysiology observed. Despite decades of research, we are still lacking in ALS disease-modifying treatments. In this review, we document the current research from patient studies, rodent models, and human stem cell models in understanding the mechanisms of corticomotor circuit dysfunction and its implication in ALS. We summarize the current knowledge about cortical UMN dysfunction and degeneration, altered excitability in LMNs, neuromuscular junction degeneration, and the non-cell autonomous role of glial cells in motor circuit dysfunction in relation to ALS. We further highlight the advances in human stem cell technology to model the complex neural circuitry and how these can aid in future studies to better understand the mechanisms of neural circuit dysfunction underpinning ALS.}, }
@article {pmid38785539, year = {2024}, author = {Pribac, M and Motataianu, A and Andone, S and Mardale, E and Nemeth, S}, title = {Bridging the Gap: Harnessing Plant Bioactive Molecules to Target Gut Microbiome Dysfunctions in Amyotrophic Lateral Sclerosis.}, journal = {Current issues in molecular biology}, volume = {46}, number = {5}, pages = {4471-4488}, pmid = {38785539}, issn = {1467-3045}, abstract = {The correlation between neurodegenerative diseases and the gut microbiome is increasingly evident, with amyotrophic lateral sclerosis (ALS) being particularly notable for its severity and lack of therapeutic options. The gut microbiota, implicated in the pathogenesis and development of ALS, plays a crucial role in the disease. Bioactive plant molecules, specifically volatile compounds in essential oils, offer a promising therapeutic avenue due to their anti-inflammatory properties and gut-modulating effects. Our narrative review aimed to identify microbiota-associated bacteria in ALS and analyze the benefits of administering bioactive plant molecules as much-needed therapeutic options in the management of this disease. A comprehensive search of PubMed database articles published before December 2023, encompassing research on cell, human, and animal ALS models, was conducted. After selecting, analyzing, and discussing key articles, bacteria linked to ALS pathogenesis and physiopathology were identified. Notably, positively highlighted bacteria included Akkermansia muciniphila (Verrucomicrobia phylum), Faecalibacterium prausnitzii, and Butyrivibrio spp. (Firmicutes phylum). Conversely, members of the Escherichia coli spp. (Proteobacteria phylum) and Ruminococcus spp. (Firmicutes phylum) stood out negatively in respect to ALS development. These bacteria were associated with molecular changes linked to ALS pathogenesis and evolution. Bioactive plant molecules can be directly associated with improvements in the microbiome, due to their role in reducing inflammation and oxidative stress, emerging as one of the most promising natural agents for enriching present-day ALS treatments.}, }
@article {pmid38784406, year = {2024}, author = {Keselica, M and Peřan, D and Renza, M and Duška, F and Omáčka, D and Schnaubelt, S and Lulic, I and Sýkora, R}, title = {Efficiency of two-member crews in delivering prehospital advanced life support cardiopulmonary resuscitation: A scoping review.}, journal = {Resuscitation plus}, volume = {18}, number = {}, pages = {100661}, pmid = {38784406}, issn = {2666-5204}, abstract = {BACKGROUND: Advanced Life Support (ALS) during cardiopulmonary resuscitation (CPR) for out-of-hospital cardiac arrest (OHCA) is frequently administered by two-member crews. However, ALS CPR is mostly designed for larger crews, and the feasibility and efficacy of implementing ALS guidelines for only two rescuers remain unclear.<br><br>OBJECTIVE: This scoping review aims to examine the existing evidence and identify knowledge gaps in the efficiency of pre-hospital ALS CPR performed by two-member teams.<br><br>DESIGN: A comprehensive search was undertaken across the following databases: PubMed, Web of Science, SCOPUS, Cochrane Library Trials, and ClinicalTrials.gov. The search covered publications in English or German from January 1, 2005, to November 30, 2023. The review included studies that focused on ALS CPR procedures carried out by two-member teams in adult patients in either simulated or clinical settings.<br><br>RESULTS: A total of 22 articles were included in the qualitative synthesis. Seven topics in two-person prehospital ALS/CPR delivery were identified: 1) effect of team configuration on clinical outcome and CPR quality, 2) early airway management and ventilation techniques, 3) mechanical chest compressions, 4) prefilled syringes, 5) additional equipment, 6) adaptation of recommended ALS/CPR protocols, and 7) human factors.<br><br>CONCLUSION: There is a lack of comprehensive data regarding the adaptation of the recommended ALS algorithm in CPR for two-member crews. Although simulation studies indicate potential benefits arising from the employment of mechanical chest compression devices, prefilled syringes, and automation-assisted protocols, the current evidence is too limited to support specific modifications to existing guidelines.}, }
@article {pmid38784093, year = {2024}, author = {Chen, W and Liu, X and Wan, P and Chen, Z and Chen, Y}, title = {Anti-artifacts techniques for neural recording front-ends in closed-loop brain-machine interface ICs.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1393206}, pmid = {38784093}, issn = {1662-4548}, abstract = {In recent years, thanks to the development of integrated circuits, clinical medicine has witnessed significant advancements, enabling more efficient and intelligent treatment approaches. Particularly in the field of neuromedical, the utilization of brain-machine interfaces (BMI) has revolutionized the treatment of neurological diseases such as amyotrophic lateral sclerosis, cerebral palsy, stroke, or spinal cord injury. The BMI acquires neural signals via recording circuits and analyze them to regulate neural stimulator circuits for effective neurological treatment. However, traditional BMI designs, which are often isolated, have given way to closed-loop brain-machine interfaces (CL-BMI) as a contemporary development trend. CL-BMI offers increased integration and accelerated response speed, marking a significant leap forward in neuromedicine. Nonetheless, this advancement comes with its challenges, notably the stimulation artifacts (SA) problem inherent to the structural characteristics of CL-BMI, which poses significant challenges on the neural recording front-ends (NRFE) site. This paper aims to provide a comprehensive overview of technologies addressing artifacts in the NRFE site within CL-BMI. Topics covered will include: (1) understanding and assessing artifacts; (2) exploring the impact of artifacts on traditional neural recording front-ends; (3) reviewing recent technological advancements aimed at addressing artifact-related issues; (4) summarizing and classifying the aforementioned technologies, along with an analysis of future trends.}, }
@article {pmid38782644, year = {2025}, author = {Corcia, P and Couratier, P and Ingre, C}, title = {Could PLS represent a UMN-predominant ALS syndrome?.}, journal = {Revue neurologique}, volume = {181}, number = {1-2}, pages = {52-57}, doi = {10.1016/j.neurol.2024.04.006}, pmid = {38782644}, issn = {0035-3787}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/pathology ; *Motor Neuron Disease/diagnosis/pathology/classification ; *Motor Neurons/pathology/physiology ; Diagnosis, Differential ; Syndrome ; }, abstract = {Primary lateral sclerosis (PLS) is a motor neuron condition marked by pure upper motor neuron (UMN) degeneration. PLS represents around 3% of all motor neuron diseases. Classically the prognosis of PLS is less severe than those of amyotrophic lateral sclerosis (ALS). This explains the necessity to distinguish both conditions as early as possible. The key hallmark between the two diseases is the involvement of the lower motor neuron (LMN) system which is classically considered spared in PLS contrary to ALS. Although it seemed clinically easy to distinguish PLS from ALS with the aid of clinical and complementary examinations, there is a large body of evidence highlighting that the LMN system might be impaired in PLS. This led us to suggest that PLS might be considered as an almost pure UMN ALS phenotype.}, }
@article {pmid38780277, year = {2025}, author = {Essex, R and Booth, L and Sirois, F and Burch, J and Dibley, L}, title = {A scoping review of the qualitative literature reporting experiences of living with a stoma for inflammatory bowel disease.}, journal = {Journal of advanced nursing}, volume = {81}, number = {1}, pages = {53-68}, pmid = {38780277}, issn = {1365-2648}, mesh = {Humans ; *Inflammatory Bowel Diseases/surgery/psychology ; *Surgical Stomas ; *Quality of Life/psychology ; *Qualitative Research ; *Adaptation, Psychological ; Cross-Sectional Studies ; Female ; Adult ; Male ; Middle Aged ; Aged ; }, abstract = {AIMS: Surgical treatment for inflammatory bowel disease (IBD) potentially includes stoma formation. Although positive clinical outcomes are widely reported, patients' responses to stoma surgery, including coming to terms with and adjusting to the stoma, vary widely. This scoping review charts the qualitative literature addressing the question: What is known about any personal psychosocial and quality of life factors that inform adjustment to living well with an intestinal stoma for IBD?<br><br>DESIGN: A scoping review methodology was employed.<br><br>DATA SOURCES: Searches of Scopus, Web of Science, CINAHL, Medline and PsycInfo in August 2023.<br><br>REVIEW METHODS: Levac et&#xa0;al.'s (2010) methodology was followed. PRISMA-ScR guidelines were adhered to.<br><br>RESULTS: Thirteen cross-sectional studies were included, involving a total of 142 participants. Four themes were identified: (1) facilitative factors; (2) barriers to adjustment; (3) personal attributes; and (4) time and temporality. Data indicate that personal and psychological factors influence adjustment, but not how this occurs. Adjustment takes longer to achieve than is conventionally (clinically) expected.<br><br>CONCLUSION: All available evidence is cross-sectional. The identified gap in the evidence is the notable lack of longitudinal research to assess, monitor and understand the complex process of adjustment in people with IBD having stoma-forming surgery. Detailed understanding of the process of adjustment would enable more targeted support for patients preparing for, and learning to live with, a stoma for IBD.<br><br>IMPACT: This paper highlights the need to understand the multiple personal and psychosocial factors that affect adjustment to life with a stoma and identifies that adjustment takes significantly longer than the few weeks required to become competent in managing the stoma.<br><br>Not applicable.}, }
@article {pmid38778614, year = {2025}, author = {Zhou, H and Xia, Y and Zhu, R and Zhang, Y and Zhang, X and Zhang, Y and Wang, J}, title = {Ribosomal DNA and Neurological Disorders.}, journal = {Current molecular medicine}, volume = {25}, number = {5}, pages = {556-566}, pmid = {38778614}, issn = {1875-5666}, support = {G2022027010L//Ministry of Science and Technology of the People's Republic of China/ ; 82061138005//National Natural Science Foundation of China/ ; T2020009, 337/370//Hubei Provincial Department of Education/ ; }, mesh = {Humans ; *Nervous System Diseases/genetics/metabolism/pathology ; *DNA, Ribosomal/genetics/metabolism ; Animals ; Huntington Disease/genetics ; }, abstract = {Ribosomal DNA (rDNA) is important in the nucleolus and nuclear organization of human cells. Defective rDNA repeat maintenance has been reported to be closely associated with neurological disorders, such as Alzheimer's disease, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, frontotemporal dementia, depression, suicide, etc. However, there has not been a comprehensive review on the role of rDNA in these disorders. In this review, we have summarized the role of rDNA in major neurological disorders to sort out the correlation between rDNA and neurological diseases and provided insights for therapy with rDNA as a target.}, }
@article {pmid38778595, year = {2025}, author = {Jayaprakash, B and Savira, M and Mahmood, AAR and Prasanna, M}, title = {The Role of Stem Cell Therapies in the Treatment of Neurodegenerative Diseases.}, journal = {Current stem cell research &amp; therapy}, volume = {20}, number = {2}, pages = {146-165}, doi = {10.2174/011574888X313112240510160102}, pmid = {38778595}, issn = {2212-3946}, mesh = {Humans ; *Neurodegenerative Diseases/therapy ; *Stem Cell Transplantation/methods ; Animals ; Neural Stem Cells/transplantation ; Parkinson Disease/therapy ; }, abstract = {Cellular replacement therapy and genetic transfer in injured brains provide new pathways for treating human neurological illnesses. Current progress in the field focuses on the production of neurons and glial cells from many types of stem cells, such as embryonic, induced pluripotent, mesenchymal, and neural stem cells. This has led to a significant increase in research on brain transplantation treatments. Extended neurodegeneration results in the progressive decline of certain neuronal subtypes or whole neuronal cells. An analysis of the progress made in induced pluripotent and mesenchymal stem cells reveals their significant promise in disease modeling, regeneration, and medication screening. The requirement for stem cells in neurodegenerative disease studies has been crucial in recent years. Stem cells provide the potential for replacing impaired neurons, comprehending disease needs modeling, and creating efficient treatments, but they have many challenges in culturing and acceptability to the host immune cells. The need to use their potential in discovering novel therapies for diseases such as Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis leads to promising therapy. This review examines the function of stem cells in the pathogenesis and treatment of Huntington's disease, Parkinson's disease, Alzheimer's disease, and multiple sclerosis. This review further examines hurdles such as immunological reactions and delivery systems intending to overcome these problems. This article offers a detailed viewpoint on the use of stem cell-based nanotherapies as revolutionary treatments for various neurological illnesses.}, }
@article {pmid38775852, year = {2024}, author = {Ebrahimi, P and Davoudi, E and Sadeghian, R and Zadeh, AZ and Razmi, E and Heidari, R and Morowvat, MH and Sadeghian, I}, title = {In vivo and ex vivo gene therapy for neurodegenerative diseases: a promise for disease modification.}, journal = {Naunyn-Schmiedeberg's archives of pharmacology}, volume = {397}, number = {10}, pages = {7501-7530}, pmid = {38775852}, issn = {1432-1912}, support = {29849//Shiraz University of Medical Sciences/ ; }, mesh = {Humans ; *Genetic Therapy/methods ; Animals ; *Neurodegenerative Diseases/therapy/genetics ; Gene Editing/methods ; }, abstract = {Neurodegenerative diseases (NDDs), including AD, PD, HD, and ALS, represent a growing public health concern linked to aging and lifestyle factors, characterized by progressive nervous system damage leading to motor and cognitive deficits. Current therapeutics offer only symptomatic management, highlighting the urgent need for disease-modifying treatments. Gene therapy has emerged as a promising approach, targeting the underlying pathology of diseases with diverse strategies including gene replacement, gene silencing, and gene editing. This innovative therapeutic approach involves introducing functional genetic material to combat disease mechanisms, potentially offering long-term efficacy and disease modification. With advancements in genomics, structural biology, and gene editing tools such as CRISPR/Cas9, gene therapy holds significant promise for addressing the root causes of NDDs. Significant progress in preclinical and clinical studies has demonstrated the potential of in vivo and ex vivo gene therapy to treat various NDDs, offering a versatile and precise approach in comparison to conventional treatments. The current review describes various gene therapy approaches employed in preclinical and clinical studies for the treatment of NDDs, including AD, PD, HD, and ALS, and addresses some of the key translational challenges in this therapeutic approach.}, }
@article {pmid38775181, year = {2024}, author = {Marriott, H and Spargo, TP and Al Khleifat, A and Andersen, PM and Başak, NA and Cooper-Knock, J and Corcia, P and Couratier, P and de Carvalho, M and Drory, V and Gotkine, M and Landers, JE and McLaughlin, R and Pardina, JSM and Morrison, KE and Pinto, S and Shaw, CE and Shaw, PJ and Silani, V and Ticozzi, N and van Damme, P and van den Berg, LH and Vourc'h, P and Weber, M and Veldink, JH and ,  and Dobson, RJ and Schwab, P and Al-Chalabi, A and Iacoangeli, A}, title = {Mutations in the tail and rod domains of the neurofilament heavy-chain gene increase the risk of ALS.}, journal = {Annals of clinical and translational neurology}, volume = {11}, number = {7}, pages = {1775-1786}, pmid = {38775181}, issn = {2328-9503}, support = {//Maudsley NHS Foundation Trust/ ; 22-PDF-609//ALS Association Milton Safenowitz Research/ ; MR/R024804/1/MRC_/Medical Research Council/United Kingdom ; //BHF British Heart Foundation/ ; //Darby Rimmer MND Foundation/ ; NIHR202421//National Institute for Health Research/ ; Al Khleifat/Oct21/975-799/MNDA_/Motor Neurone Disease Association/United Kingdom ; //MND Scotland/ ; ES/L008238/1//Economic and Social Research Council/ ; //Alan Davidson Foundation/ ; /WT_/Wellcome Trust/United Kingdom ; //Alzheimer's Research UK/ ; //Rosetrees Trust/ ; MR/L501529/1/MRC_/Medical Research Council/United Kingdom ; //My Name'5 Doddie Foundation/ ; //GlaxoSmithKline/ ; //MRC Medical Research Council/ ; //The NIHR Maudsley Biomedical Research Centre/ ; //Spastic Paraplegia Foundation/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/epidemiology ; Genetic Predisposition to Disease/genetics ; Mutation ; Mutation, Missense ; *Neurofilament Proteins/genetics ; Protein Domains/genetics ; }, abstract = {OBJECTIVE: Neurofilament heavy-chain gene (NEFH) variants are associated with multiple neurodegenerative diseases, however, their relationship with ALS has not been robustly explored. Still, NEFH is commonly included in genetic screening panels worldwide. We therefore aimed to determine if NEFH variants modify ALS risk.<br><br>METHODS: Genetic data of 11,130 people with ALS and 7,416 controls from the literature and Project MinE were analysed. We performed meta-analyses of published case-control studies reporting NEFH variants, and variant analysis of NEFH in Project MinE whole-genome sequencing data.<br><br>RESULTS: Fixed-effects meta-analysis found that rare (MAF&#x2009;<1%) missense variants in the tail domain of NEFH increase ALS risk (OR 4.55, 95% CI 2.13-9.71, p&#x2009;<&#x2009;0.0001). In Project MinE, ultrarare NEFH variants increased ALS risk (OR 1.37 95% CI 1.14-1.63, p&#x2009;=&#x2009;0.0007), with rod domain variants (mostly intronic) appearing to drive the association (OR 1.45 95% CI 1.18-1.77, pMadsen-Browning&#x2009;=&#x2009;0.0007, pSKAT-O&#x2009;=&#x2009;0.003). While in the tail domain, ultrarare (MAF&#x2009;<0.1%) pathogenic missense variants were also associated with higher risk of ALS (OR 1.94, 95% CI 0.86-4.37, pMadsen-Browning&#x2009;=&#x2009;0.039), supporting the meta-analysis results. Finally, several tail in-frame deletions were also found to affect disease risk, however, both protective and pathogenic deletions were found in this domain, highlighting an intricate architecture that requires further investigation.<br><br>INTERPRETATION: We showed that NEFH tail missense and in-frame deletion variants, and intronic rod variants are risk factors for ALS. However, they are not variants of large effect, and their functional impact needs to be clarified in further studies. Therefore, their inclusion in routine genetic screening panels should be reconsidered.}, }
@article {pmid38775138, year = {2024}, author = {Calma, AD and Pavey, N and Menon, P and Vucic, S}, title = {Neuroinflammation in amyotrophic lateral sclerosis: pathogenic insights and therapeutic implications.}, journal = {Current opinion in neurology}, volume = {37}, number = {5}, pages = {585-592}, pmid = {38775138}, issn = {1473-6551}, mesh = {*Amyotrophic Lateral Sclerosis/immunology/therapy/genetics ; Humans ; *Neuroinflammatory Diseases/immunology ; Animals ; Immunity, Innate/immunology ; Inflammation/immunology ; }, abstract = {PURPOSE OF REVIEW: Neuroinflammation appears to be an important pathogenic process in amyotrophic lateral sclerosis (ALS). Dysfunction of central immune pathways, including activation of microglia and astrocytes, and peripherally derived immune cells, initiate noncell autonomous inflammatory mechanisms leading to degeneration. Cell autonomous pathways linked to ALS genetic mutations have been recently identified as contributing mechanism for neurodegeneration. The current review provides insights into the pathogenic importance of central and peripheral inflammatory processes in ALS pathogenesis and appraises their potential as therapeutic targets.<br><br>RECENT FINDINGS: ALS is a multistep process mediated by a complex interaction of genetic, epigenetic, and environmental factors. Noncell autonomous inflammatory pathways contribute to neurodegeneration in ALS. Activation of microglia and astrocytes, along with central nervous system infiltration of peripherally derived pro-inflammatory innate (NK-cells/monocytes) and adaptive (cell-mediated/humoral) immune cells, are characteristic of ALS. Dysfunction of regulatory T-cells, elevation of pro-inflammatory cytokines and dysbiosis of gut microbiome towards a pro-inflammatory phenotype, have been reported as pathogenic mechanisms in ALS.<br><br>SUMMARY: Dysregulation of adaptive and innate immunity is pathogenic in ALS, being associated with greater disease burden, more rapid disease course and reduced survival. Strategies aimed at modulating the pro-inflammatory immune components could be of therapeutic utility.}, }
@article {pmid38769202, year = {2024}, author = {Benatar, M and Wuu, J and Huey, ED and McMillan, CT and Petersen, RC and Postuma, R and McHutchison, C and Dratch, L and Arias, JJ and Crawley, A and Houlden, H and McDermott, MP and Cai, X and Thakur, N and Boxer, A and Rosen, H and Boeve, BF and Dacks, P and Cosentino, S and Abrahams, S and Shneider, N and Lingor, P and Shefner, J and Andersen, PM and Al-Chalabi, A and Turner, MR and , }, title = {The Miami Framework for ALS and related neurodegenerative disorders: an integrated view of phenotype and biology.}, journal = {Nature reviews. Neurology}, volume = {20}, number = {6}, pages = {364-376}, pmid = {38769202}, issn = {1759-4766}, support = {U01 AG079850/AG/NIA NIH HHS/United States ; R01 MH120794/MH/NIMH NIH HHS/United States ; K01 AG057796/AG/NIA NIH HHS/United States ; U54 NS092091/NS/NINDS NIH HHS/United States ; R01 NS105479/NS/NINDS NIH HHS/United States ; R01 AG062268/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/diagnosis/metabolism/pathology ; *Phenotype ; *Frontotemporal Dementia/genetics/diagnosis/metabolism ; Neurodegenerative Diseases/diagnosis/metabolism/genetics ; Biomarkers/metabolism ; }, abstract = {Increasing appreciation of the phenotypic and biological overlap between amyotrophic lateral sclerosis (ALS) and frontotemporal dementia, alongside evolving biomarker evidence for a pre-symptomatic stage of disease and observations that this stage of disease might not always be clinically silent, is challenging traditional views of these disorders. These advances have highlighted the need to adapt ingrained notions of these clinical syndromes to include both the full phenotypic continuum - from clinically silent, to prodromal, to clinically manifest - and the expanded phenotypic spectrum that includes ALS, frontotemporal dementia and some movement disorders. The updated clinical paradigms should also align with our understanding of the biology of these disorders, reflected in measurable biomarkers. The Miami Framework, emerging from discussions at the Second International Pre-Symptomatic ALS Workshop in Miami (February 2023; a full list of attendees and their affiliations appears in the Supplementary Information) proposes a classification system built on: first, three parallel phenotypic axes - motor neuron, frontotemporal and extrapyramidal - rather than the unitary approach of combining all phenotypic elements into a single clinical entity; and second, biomarkers that reflect different aspects of the underlying pathology and biology of neurodegeneration. This framework decouples clinical syndromes from biomarker evidence of disease and builds on experiences from other neurodegenerative diseases to offer a unified approach to specifying the pleiotropic clinical manifestations of disease and describing the trajectory of emergent biomarkers.}, }
@article {pmid38767073, year = {2024}, author = {Napoletano, G and Circosta, F and Basile, G}, title = {Access to medically-assisted procreation: the withdrawal of paternal consent in the maze of law n. 40/2004.}, journal = {La Clinica terapeutica}, volume = {175}, number = {3}, pages = {163-167}, doi = {10.7417/CT.2024.5057}, pmid = {38767073}, issn = {1972-6007}, mesh = {Humans ; *Reproductive Techniques, Assisted/legislation &amp; jurisprudence/ethics ; Italy ; Female ; Male ; Health Services Accessibility/legislation &amp; jurisprudence ; Cryopreservation ; Parental Consent/legislation &amp; jurisprudence ; Informed Consent/legislation &amp; jurisprudence ; }, abstract = {The law (No.40/2004) stipulates that consent to Medically Assisted Procreation (MAP) remains irrevocable post ovum fertilization. Cryo-preservation introduces complexities, enabling embryo implantation requests after a couple's separation and the dissolution of the original parenthood plan. Constitutional Court Ruling No.161 in 2023 affirmed that the prohibition of revoking consent to MAP aligns with the Italian Constitution and the jurisprudence of the European Court of Human Rights. This delicate equilibrium of conflicting interests upholds human freedom, allowing consent revocation prior to ovocyte fertilization. Permitting revocation until implantation could inflict more significant harm: the infertile woman can in fact miss the opportunity to become a mother, impacting her psychophysical well-being and freedom of self-determination. Moreover, the embryo loses the chance to live, remaining in cryopreservation, which violates its dignity. Addressing this issue requires thorough communication by medical profession-als to inform couples about the limitations on consent revocation. An element of objectivity in terms of standards and evidence-based guidelines, from which norms must originate, is of utmost importance. Relying on broadly shared rules, especially at the international level, is vital in light of the unremitting scientific advances in MAP, as in other areas of medicine, which will open up new opportunities for which current legal/regulatory frameworks are inadequate.}, }
@article {pmid38766825, year = {2025}, author = {Tedeschi, V and Sapienza, S and Ciancio, R and Canzoniero, LMT and Pannaccione, A and Secondo, A}, title = {Lysosomal Channels as New Molecular Targets in the Pharmacological Therapy of Neurodegenerative Diseases via Autophagy Regulation.}, journal = {Current neuropharmacology}, volume = {23}, number = {4}, pages = {375-383}, pmid = {38766825}, issn = {1875-6190}, support = {PE0000006//National Recovery and Resilience Plan (NRRP), project MNESYS/ ; }, mesh = {Humans ; *Autophagy/drug effects/physiology ; Animals ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Lysosomes/metabolism/drug effects ; *Transient Receptor Potential Channels/metabolism ; *Calcium Channels/metabolism ; Molecular Targeted Therapy ; }, abstract = {Besides controlling several organellar functions, lysosomal channels also guide the catabolic "self-eating" process named autophagy, which is mainly involved in protein and organelle quality control. Neuronal cells are particularly sensitive to the rate of autophagic flux either under physiological conditions or during the degenerative process. Accordingly, neurodegeneration occurring in Parkinson's (PD), Alzheimer's (AD), and Huntington's Diseases (HD), and Amyotrophic Lateral Sclerosis (ALS) as well as Lysosomal Storage Diseases (LSD) is partially due to defective autophagy and accumulation of toxic aggregates. In this regard, dysfunction of lysosomal ionic homeostasis has been identified as a putative cause of aberrant autophagy. From a therapeutic perspective, Transient Receptor Potential Channel Mucolipin 1 (TRPML1) and Two-Pore Channel isoform 2 (TPC2), regulating lysosomal homeostasis, are now considered promising druggable targets in neurodegenerative diseases. Compelling evidence suggests that pharmacological modulation of TRPML1 and TPC2 may rescue the pathological phenotype associated with autophagy dysfunction in AD, PD, HD, ALS, and LSD. Although pharmacological repurposing has identified several already used drugs with the ability to modulate TPC2, and several tools are already available for the modulation of TRPML1, many efforts are necessary to design and test new entities with much higher specificity in order to reduce dysfunctional autophagy during neurodegeneration.}, }
@article {pmid38763702, year = {2024}, author = {Dorrity, TJ and Shin, H and Gertie, JA and Chung, H}, title = {The Sixth Sense: Self-nucleic acid sensing in the brain.}, journal = {Advances in immunology}, volume = {161}, number = {}, pages = {53-83}, pmid = {38763702}, issn = {1557-8445}, support = {R01 AR050026/AR/NIAMS NIH HHS/United States ; R01 NS127802/NS/NINDS NIH HHS/United States ; T32 AR076953/AR/NIAMS NIH HHS/United States ; T32 GM145440/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Brain/metabolism/immunology ; Animals ; *Receptors, Pattern Recognition/metabolism ; *Immunity, Innate ; *Nucleic Acids/immunology/metabolism ; Homeostasis ; Signal Transduction ; }, abstract = {Our innate immune system uses pattern recognition receptors (PRRs) as a first line of defense to detect microbial ligands and initiate an immune response. Viral nucleic acids are key ligands for the activation of many PRRs and the induction of downstream inflammatory and antiviral effects. Initially it was thought that endogenous (self) nucleic acids rarely activated these PRRs, however emerging evidence indicates that endogenous nucleic acids are able to activate host PRRs in homeostasis and disease. In fact, many regulatory mechanisms are in place to finely control and regulate sensing of self-nucleic acids by PRRs. Sensing of self-nucleic acids is particularly important in the brain, as perturbations to nucleic acid sensing commonly leads to neuropathology. This review will highlight the role of nucleic acid sensors in the brain, both in disease and homeostasis. We also indicate the source of endogenous stimulatory nucleic acids where known and summarize future directions for the study of this growing field.}, }
@article {pmid38762656, year = {2024}, author = {Li, Z and Kang, H}, title = {Efficacy of non-pharmacological interventions for individuals with amyotrophic lateral sclerosis: systematic review and network meta-analysis of randomized control trials.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {11365}, pmid = {38762656}, issn = {2045-2322}, mesh = {*Amyotrophic Lateral Sclerosis/therapy/physiopathology ; Humans ; *Randomized Controlled Trials as Topic ; *Quality of Life ; Exercise Therapy/methods ; Treatment Outcome ; Muscle Strength ; }, abstract = {This network meta-analysis (NMA) aimed to compare the efficacy of five non-pharmacological interventions, including exercise intervention (EI), nutritional intervention (NI), respiratory intervention (RI), psychological intervention (PSI), and integrated physical intervention (IPI), on functional status, quality of life, muscle strength, pulmonary function, and safety in patients with amyotrophic lateral sclerosis (ALS). We searched nine databases, PubMed, Cochrane, Embase, Scopus, Web of Science, CNKI, CBM, WFPD, and CSTJ, for randomized controlled trials of ALS patients. The primary outcome was the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score. Secondary outcomes were the McGill Quality of Life Questionnaire (McGill-QoL), Medical Research Council (MRC)-sum score, Forced Vital Capacity (FVC), and Fatigue Severity Scale (FSS) score. This NMA was conducted using random-effect models to calculate the standard mean difference (SMD) and 95% confidence interval (CI). All types of supplemental interventions had some benefit for patients with ALS. EI had a beneficial effect on the ALSFRS-R score (SMD: 1.01; 95% CI 0.50-1.51), FVC (SMD: 0.78; 95% CI 0.02-1.55), McGill-QoL (SMD: 0.71 95% CI 0.33-1.08), and MRC (SMD: 1.11; 95% CI 0.08-2.14). RI had a beneficial effect on the ALSFRS-R score (SMD: 0.83 95% CI 0.12-1.55). IPI had a beneficial effect on the ALSFRS-R score (SMD: 0.65 95% CI 0.06-1.24). NI had a beneficial effect on the McGill-QoL (SMD: 0.63 95% CI 0.02-1.23). The current study findings support a multimodal intervention strategy with an emphasis on EI for slowing disease progression in patients with ALS.}, }
@article {pmid38762243, year = {2024}, author = {Ponzini, E}, title = {Tear biomarkers.}, journal = {Advances in clinical chemistry}, volume = {120}, number = {}, pages = {69-115}, doi = {10.1016/bs.acc.2024.03.002}, pmid = {38762243}, issn = {2162-9471}, mesh = {Humans ; *Tears/metabolism/chemistry ; *Biomarkers/analysis/metabolism ; Eye Diseases/diagnosis/metabolism ; }, abstract = {An extensive exploration of lacrimal fluid molecular biomarkers in understanding and diagnosing a spectrum of ocular and systemic diseases is presented. The chapter provides an overview of lacrimal fluid composition, elucidating the roles of proteins, lipids, metabolites, and nucleic acids within the tear film. Pooled versus single-tear analysis is discussed to underline the benefits and challenges associated with both approaches, offering insights into optimal strategies for tear sample analysis. Subsequently, an in-depth analysis of tear collection methods is presented, with a focus on Schirmer's test strips and microcapillary tubes methods. Alternative tear collection techniques are also explored, shedding light on their applicability and advantages. Variability factors, including age, sex, and diurnal fluctuations, are examined in the context of their impact on tear biomarker analysis. The main body of the chapter is dedicated to discussing specific biomarkers associated with ocular discomfort and a wide array of ocular diseases. From dry eye disease and thyroid-associated ophthalmopathy to keratoconus, age-related macular degeneration, diabetic retinopathy, and glaucoma, the intricate relationship between molecular biomarkers and these conditions is thoroughly dissected. Expanding beyond ocular pathologies, the chapter explores the applicability of tear biomarkers in diagnosing systemic diseases such as multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, and cancer. This broader perspective underscores the potential of lacrimal fluid analysis in offering non-invasive diagnostic tools for conditions with far-reaching implications.}, }
@article {pmid38760935, year = {2024}, author = {Fiadeiro, MB and Diogo, JC and Silva, AA and Kim, YS and Cristóvão, AC}, title = {NADPH Oxidases in Neurodegenerative Disorders: Mechanisms and Therapeutic Opportunities.}, journal = {Antioxidants &amp; redox signaling}, volume = {41}, number = {7-9}, pages = {522-541}, doi = {10.1089/ars.2023.0002}, pmid = {38760935}, issn = {1557-7716}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/drug therapy ; *NADPH Oxidases/metabolism/antagonists &amp; inhibitors ; *Reactive Oxygen Species/metabolism ; Animals ; Oxidative Stress ; }, abstract = {Significance: The nicotinamide adenine dinucleotide phosphate oxidase (NOX) enzyme family, located in the central nervous system, is recognized as a source of reactive oxygen species (ROS) in the brain. Despite its importance in cellular processes, excessive ROS generation leads to cell death and is involved in the pathogenesis of neurodegenerative disorders. Recent advances: NOX enzymes contribute to the development of neurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and stroke, highlighting their potential as targets for future therapeutic development. This review will discuss NOX's contribution and therapeutic targeting potential in neurodegenerative diseases, focusing on PD, AD, ALS, and stroke. Critical issues: Homeostatic and physiological levels of ROS are crucial for regulating several processes, such as development, memory, neuronal signaling, and vascular homeostasis. However, NOX-mediated excessive ROS generation is deeply involved in the damage of DNA, proteins, and lipids, leading to cell death in the pathogenesis of a wide range of diseases, namely neurodegenerative diseases. Future directions: It is essential to understand the role of NOX homologs in neurodegenerative disorders and the pathological mechanisms undergoing neurodegeneration mediated by increased levels of ROS. This further knowledge will allow the development of new specific NOX inhibitors and their application for neurodegenerative disease therapeutics. Antioxid. Redox Signal. 41, 522-541.}, }
@article {pmid38759454, year = {2024}, author = {Wei, Y and Zhong, S and Yang, H and Wang, X and Lv, B and Bian, Y and Pei, Y and Xu, C and Zhao, Q and Wu, Y and Luo, D and Wang, F and Sun, H and Chen, Y}, title = {Current therapy in amyotrophic lateral sclerosis (ALS): A review on past and future therapeutic strategies.}, journal = {European journal of medicinal chemistry}, volume = {272}, number = {}, pages = {116496}, doi = {10.1016/j.ejmech.2024.116496}, pmid = {38759454}, issn = {1768-3254}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy ; Humans ; *Neuroprotective Agents/pharmacology/chemistry/therapeutic use ; Animals ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects the first and second motoneurons (MNs), associated with muscle weakness, paralysis and finally death. The exact etiology of the disease still remains unclear. Currently, efforts to develop novel ALS treatments which target specific pathomechanisms are being studied. The mechanisms of ALS pathogenesis involve multiple factors, such as protein aggregation, glutamate excitotoxicity, oxidative stress, mitochondrial dysfunction, apoptosis, inflammation etc. Unfortunately, to date, there are only two FDA-approved drugs for ALS, riluzole and edavarone, without curative treatment for ALS. Herein, we give an overview of the many pathways and review the recent discovery and preclinical characterization of neuroprotective compounds. Meanwhile, drug combination and other therapeutic approaches are also reviewed. In the last part, we analyze the reasons of clinical failure and propose perspective on the treatment of ALS in the future.}, }
@article {pmid38759021, year = {2024}, author = {Pupillo, E and Al-Chalabi, A and Sassi, S and Arippol, E and Tinti, L and Vitelli, E and Copetti, M and Leone, MA and Bianchi, E}, title = {Methodological Quality of Clinical Trials in Amyotrophic Lateral Sclerosis: A Systematic Review.}, journal = {Journal of neuromuscular diseases}, volume = {11}, number = {4}, pages = {749-765}, pmid = {38759021}, issn = {2214-3602}, mesh = {*Amyotrophic Lateral Sclerosis/therapy ; Humans ; *Clinical Trials as Topic/standards ; *Research Design ; }, abstract = {BACKGROUND: More than 200 clinical trials have been performed worldwide in ALS so far, but no agents with substantial efficacy on disease progression have been found.<br><br>OBJECTIVE: To describe the methodological quality of all clinical trials performed in ALS and published before December 31, 2022.<br><br>METHODS: We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta Analyses.<br><br>RESULTS: 213 trials were included. 47.4% manuscripts described preclinical study evaluation, with a positive effect in all. 67.6% of trials were conducted with a parallel-arm design, while 12.7% were cross-over studies; 77% were randomized, while in 5.6% historical-controls were used for comparison. 70% of trials were double blind. Participant inclusion allowed forced vital capacity (or corresponding slow vital capacity)<50% in 15% cases, between 55-65% in 21.6%, between 70-80% in 14.1% reports, and 49.3% of the evaluated manuscripts did not provide a minimum value for respiratory capacity at inclusion. Disease duration was <&#x200a;6-months in 6 studies, 7-36 months in 68, 37-60 months in 24, 8 trials requested more than 1-month of disease duration, while in 107 reports a disease duration was not described. Dropout rate was &#x2265;20% in 30.5% trials, while it was not reported for 8.5%.<br><br>CONCLUSION: The methodological quality of the included studies was highly variable. Major issues to be addressed in future ALS clinical trials include: the requirement for standard animal toxicology and phase I studies, the resource-intensive nature of phase II-III studies, adequate study methodology and design, a good results reporting.}, }
@article {pmid38758353, year = {2024}, author = {Mavroudis, I and Alexiou, P and Petridis, F and Ciobica, A and Balmus, IM and Gireadă, B and Gurzu, IL and Novac, O and Novac, B}, title = {Patients' and caregivers' attitudes towards patient assisted suicide or euthanasia in amyotrophic lateral sclerosis-a meta-analysis.}, journal = {Acta neurologica Belgica}, volume = {124}, number = {5}, pages = {1489-1498}, pmid = {38758353}, issn = {2240-2993}, mesh = {*Amyotrophic Lateral Sclerosis/psychology ; Humans ; *Suicide, Assisted/psychology ; *Caregivers/psychology ; *Euthanasia/psychology ; Attitude to Death ; }, abstract = {Assisted suicide and euthanasia are long debated topics in amyotrophic lateral sclerosis (ALS) patients care. We conducted a meta-analysis to evaluate the attitudes of ALS patients and their caregivers toward physician-assisted suicide (PAS) and euthanasia. Also, we were interested to identify the factors associated with the positive or negative attitude of patients and caregivers towards PAS/euthanasia. A thorough search of the online databases (PubMed, Cochrane Library, and Web of Science) was conducted and eligibility criteria according to the PRISMA guidelines were used to include the studies in the current meta-analysis. The assessment of the quality of the selected studies was carried out using a pre-specified set of criteria by Cochrane. The studies that were selected for this meta-analysis suggested that the expression of the wish to die is more likely correlated with depression, anxiety, hopelessness, and lack of optimism. The overall prevalence of considering PAS/euthanasia significantly varies in a dependent manner over the cultural, legal, and societal factors. In this context, we found that the opinion on this topic can be deeply personal and may vary widely among individuals and communities. Lower quality of life and lower religiosity were associated with a positive attitude toward PAS/euthanasia. On the other hand, patients who are more religious are less likely to choose PAS/euthanasia. Gender does not appear to play a significant role in determining attitudes towards PAS/euthanasia in ALS patients. Other factors, such as education and psychological state, could also be important. In conclusion, end-of-life decisions in ALS patients are complex and require careful consideration of individual values, beliefs, and preferences. Understanding the factors that influence a patient's attitude towards PAS/euthanasia can help healthcare providers to offer appropriate care and support for these patients and their families.}, }
@article {pmid38758193, year = {2024}, author = {Oliveira Santos, M and de Carvalho, M}, title = {Profiling tofersen as a treatment of superoxide dismutase 1 amyotrophic lateral sclerosis.}, journal = {Expert review of neurotherapeutics}, volume = {24}, number = {6}, pages = {549-553}, doi = {10.1080/14737175.2024.2355983}, pmid = {38758193}, issn = {1744-8360}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics ; *Superoxide Dismutase-1/genetics/metabolism ; Oligonucleotides/therapeutic use ; Oligonucleotides, Antisense/therapeutic use ; Biomarkers/blood ; }, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a rapidly progressive motor neuron disorder with a fatal outcome 3-5 years after disease onset due to respiratory complications. Superoxide dismutase 1 (SOD1) mutations are found in about 2% of all patients. Tofersen is a novel oligonucleotide antisense drug specifically developed to treat SOD1-ALS patients.<br><br>AREAS COVERED: Our review covers and discusses tofersen pharmacological properties and its phase I/II and III clinical trials results. Other available drugs and their limitations are also addressed.<br><br>EXPERT OPINION: VALOR study failed to meet the primary endpoint (change in the revised Amyotrophic Lateral Sclerosis Functional Rating Scale score from baseline to week 28, tofersen arm vs. placebo), but a significant reduction in plasma neurofilament light chain (NfL) levels was observed in tofersen arm (60% vs. 20%). PrefALS study has proposed plasma NfL has a potential biomarker for presymptomatic treatment, since it increases 6-12&#x2009;months before phenoconversion. There is probably a delay between plasma NfL reduction and the clinical benefit. ATLAS study will allow more insights regarding tofersen clinical efficacy in disease progression rate, survival, and even disease onset delay in presymptomatic SOD1 carriers.}, }
@article {pmid38756356, year = {2024}, author = {Rennie, O and Sharma, M and Helwa, N}, title = {Colorectal anastomotic leakage: a narrative review of definitions, grading systems, and consequences of leaks.}, journal = {Frontiers in surgery}, volume = {11}, number = {}, pages = {1371567}, pmid = {38756356}, issn = {2296-875X}, abstract = {BACKGROUND: Anastomotic leaks (ALs) are a significant and feared postoperative complication, with incidence of up to 30% despite advances in surgical techniques. With implications such as additional interventions, prolonged hospital stays, and hospital readmission, ALs have important impacts at the level of individual patients and healthcare providers, as well as healthcare systems as a whole. Challenges in developing unified definitions and grading systems for leaks have proved problematic, despite acknowledgement that colorectal AL is a critical issue in intestinal surgery with serious consequences. The aim of this study was to construct a narrative review of literature surrounding definitions and grading systems for ALs, and consequences of this postoperative complication.<br><br>METHODS: A literature review was conducted by examining databases including PubMed, Web of Science, OVID Embase, Google Scholar, and Cochrane library databases. Searches were performed with the following keywords: anastomosis, anastomotic leak, colorectal, surgery, grading system, complications, risk factors, and consequences. Publications that were retrieved underwent further assessment to ensure other relevant publications were identified and included.<br><br>RESULTS: A universally accepted definition and grading system for ALs continues to be lacking, leading to variability in reported incidence in the literature. Additional factors add to variability in estimates, including differences in the anastomotic site and institutional/individual differences in operative technique. Various groups have worked to publish guidelines for defining and grading AL, with the International Study Group of Rectal Cancer (ISGRC/ISREC) definition the current most recommended universal definition for colorectal AL. The burden of AL on patients, healthcare providers, and hospitals is well documented in evidence from leak consequences, such as increased morbidity and mortality, higher reoperation rates, and increased readmission rates, among others.<br><br>CONCLUSIONS: Colorectal AL remains a significant challenge in intestinal surgery, despite medical advancements. Understanding the progress made in defining and grading leaks, as well as the range of negative outcomes that arise from AL, is crucial in improving patient care, reduce surgical mortality, and drive further advancements in earlier detection and treatment of AL.}, }
@article {pmid38753426, year = {2024}, author = {Johnson, E and Sunil Kumar Sharma, R and Ruiz Cuenca, P and Byrne, I and Salgado-Lynn, M and Suraya Shahar, Z and Col Lin, L and Zulkifli, N and Dilaila Mohd Saidi, N and Drakeley, C and Matthiopoulos, J and Nelli, L and Fornace, K}, title = {Landscape drives zoonotic malaria prevalence in non-human primates.}, journal = {eLife}, volume = {12}, number = {}, pages = {}, pmid = {38753426}, issn = {2050-084X}, support = {/WT_/Wellcome Trust/United Kingdom ; 221963/Z/20/Z/WT_/Wellcome Trust/United Kingdom ; LRGS/1/2018/UM/01/1//Ministry of Higher Education Malaysia/ ; 221963/Z/20/Z//Royal Society/ ; }, mesh = {Animals ; Humans ; Asia, Southeastern/epidemiology ; Ecosystem ; *Malaria/epidemiology/transmission/parasitology ; *Plasmodium knowlesi ; Prevalence ; Primate Diseases/epidemiology/parasitology/transmission ; *Primates/parasitology ; *Zoonoses/epidemiology/parasitology/transmission ; }, abstract = {Zoonotic disease dynamics in wildlife hosts are rarely quantified at macroecological scales due to the lack of systematic surveys. Non-human primates (NHPs) host Plasmodium knowlesi, a zoonotic malaria of public health concern and the main barrier to malaria elimination in Southeast Asia. Understanding of regional P. knowlesi infection dynamics in wildlife is limited. Here, we systematically assemble reports of NHP P. knowlesi and investigate geographic determinants of prevalence in reservoir species. Meta-analysis of 6322 NHPs from 148 sites reveals that prevalence is heterogeneous across Southeast Asia, with low overall prevalence and high estimates for Malaysian Borneo. We find that regions exhibiting higher prevalence in NHPs overlap with human infection hotspots. In wildlife and humans, parasite transmission is linked to land conversion and fragmentation. By assembling remote sensing data and fitting statistical models to prevalence at multiple spatial scales, we identify novel relationships between P. knowlesi in NHPs and forest fragmentation. This suggests that higher prevalence may be contingent on habitat complexity, which would begin to explain observed geographic variation in parasite burden. These findings address critical gaps in understanding regional P. knowlesi epidemiology and indicate that prevalence in simian reservoirs may be a key spatial driver of human spillover risk.}, }
@article {pmid38747014, year = {2024}, author = {Gale, J and Aizenman, E}, title = {The physiological and pathophysiological roles of copper in the nervous system.}, journal = {The European journal of neuroscience}, volume = {60}, number = {1}, pages = {3505-3543}, pmid = {38747014}, issn = {1460-9568}, support = {R01 NS043277/NS/NINDS NIH HHS/United States ; 5T32AG021885/NH/NIH HHS/United States ; R56 NS043277/NS/NINDS NIH HHS/United States ; NS043277/NH/NIH HHS/United States ; T32 GM144300/GM/NIGMS NIH HHS/United States ; T32 AG021885/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Copper/metabolism ; Animals ; Homeostasis/physiology ; Nervous System/metabolism ; }, abstract = {Copper is a critical trace element in biological systems due the vast number of essential enzymes that require the metal as a cofactor, including cytochrome c oxidase, superoxide dismutase and dopamine-β-hydroxylase. Due its key role in oxidative metabolism, antioxidant defence and neurotransmitter synthesis, copper is particularly important for neuronal development and proper neuronal function. Moreover, increasing evidence suggests that copper also serves important functions in synaptic and network activity, the regulation of circadian rhythms, and arousal. However, it is important to note that because of copper's ability to redox cycle and generate reactive species, cellular levels of the metal must be tightly regulated to meet cellular needs while avoiding copper-induced oxidative stress. Therefore, it is essential that the intricate system of copper transporters, exporters, copper chaperones and copper trafficking proteins function properly and in coordinate fashion. Indeed, disorders of copper metabolism such as Menkes disease and Wilson disease, as well as diseases linked to dysfunction of copper-requiring enzymes, such as SOD1-linked amyotrophic lateral sclerosis, demonstrate the dramatic neurological consequences of altered copper homeostasis. In this review, we explore the physiological importance of copper in the nervous system as well as pathologies related to improper copper handling.}, }
@article {pmid38745425, year = {2024}, author = {Nona, RJ and Henderson, RD and McCombe, PA}, title = {Neutrophil-to-lymphocyte ratio at diagnosis as a biomarker for survival of amyotrophic lateral sclerosis.}, journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration}, volume = {25}, number = {5-6}, pages = {452-464}, doi = {10.1080/21678421.2024.2351187}, pmid = {38745425}, issn = {2167-9223}, mesh = {*Amyotrophic Lateral Sclerosis/blood/diagnosis/mortality ; Humans ; *Neutrophils ; *Lymphocytes ; Female ; Male ; Biomarkers/blood ; Middle Aged ; Aged ; }, abstract = {INTRODUCTION: The neutrophil-to-lymphocyte ratio (NLR) has previously been reported to be associated with survival in ALS. To provide further information about the role of NLR as a biomarker in ALS, we performed a systematic review, analyzed data from our local cohort of ALS subjects and performed a meta-analysis.<br><br>METHODS: (1) The systematic review used established methods. (2) Using data from our cohort of subjects, we analyzed the association of NLR with survival. (3) Meta-analysis was performed using previous studies and our local data.<br><br>RESULTS: (1) In the systematic review, higher NLR was associated with shorter survival in all studies. (2) In our subjects, survival was significantly shorter in patients in the highest NLR groups. (3) Meta-analysis showed subjects with highest NLR tertile or with NLR >3 had significantly shorter survival than other subjects.<br><br>DISCUSSION: This study supports NLR as a biomarker in ALS; high NLR is associated with poor survival.}, }
@article {pmid38741492, year = {2024}, author = {Kanda, S and Kanda, T}, title = {[Multifocal Motor Neuropathy].}, journal = {Brain and nerve = Shinkei kenkyu no shinpo}, volume = {76}, number = {5}, pages = {526-533}, doi = {10.11477/mf.1416202639}, pmid = {38741492}, issn = {1881-6096}, mesh = {Humans ; *Polyneuropathies/physiopathology/diagnosis ; Immunoglobulins, Intravenous/therapeutic use/administration &amp; dosage ; }, abstract = {Multifocal motor neuropathy (MMN), an acquired chronic progressive immune-mediated motor neuropathy, is characterized by asymmetrical distal upper limb muscle weakness and muscle atrophy without sensory impairment. Differentiation from amyotrophic lateral sclerosis is usually challenging, and electrophysiological studies show multifocal conduction blocks. Immunoglobulin (Ig)M GM1 antibodies are detected in approximately 50% of patients. In contrast to chronic inflammatory demyelinating polyneuropathy, corticosteroids are ineffective for management of MMN, and IVIg is the sole established treatment.}, }
@article {pmid38739934, year = {2024}, author = {Xin, J and Huang, S and Wen, J and Li, Y and Li, A and Satyanarayanan, SK and Yao, X and Su, H}, title = {Drug Screening and Validation Targeting TDP-43 Proteinopathy for Amyotrophic Lateral Sclerosis.}, journal = {Aging and disease}, volume = {16}, number = {2}, pages = {693-713}, pmid = {38739934}, issn = {2152-5250}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/metabolism ; Humans ; *TDP-43 Proteinopathies/drug therapy/metabolism ; *DNA-Binding Proteins/metabolism ; Animals ; Drug Evaluation, Preclinical/methods ; Drug Discovery/methods ; }, abstract = {Amyotrophic lateral sclerosis (ALS) stands as a rare, yet severely debilitating disorder marked by the deterioration of motor neurons (MNs) within the brain and spinal cord, which is accompanied by degenerated corticobulbar/corticospinal tracts and denervation in skeletal muscles. Despite ongoing research efforts, ALS remains incurable, attributed to its intricate pathogenic mechanisms. A notable feature in the pathology of ALS is the prevalence of TAR DNA-binding protein 43 (TDP-43) proteinopathy, detected in approximately 97% of ALS cases, underscoring its significance in the disease's progression. As a result, strategies targeting the aberrant TDP-43 protein have garnered attention as a potential avenue for ALS therapy. This review delves into the existing drug screening systems aimed at TDP-43 proteinopathy and the models employed for drug efficacy validation. It also explores the hurdles encountered in the quest to develop potent medications against TDP-43 proteinopathy, offering insights into the intricacies of drug discovery and development for ALS. Through this comprehensive analysis, the review sheds light on the critical aspects of identifying and advancing therapeutic solutions for ALS.}, }
@article {pmid38738727, year = {2025}, author = {Bhushan, B and Singh, K and Kumar, S and Bhardwaj, A}, title = {Advancements in CRISPR-Based Therapies for Genetic Modulation in Neurodegenerative Disorders.}, journal = {Current gene therapy}, volume = {25}, number = {1}, pages = {34-45}, pmid = {38738727}, issn = {1875-5631}, mesh = {Humans ; *Neurodegenerative Diseases/therapy/genetics ; *Genetic Therapy/methods ; *CRISPR-Cas Systems/genetics ; *Gene Editing/methods ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics ; Amyotrophic Lateral Sclerosis/therapy/genetics ; Parkinson Disease/therapy/genetics ; Mutation ; Huntington Disease/therapy/genetics ; }, abstract = {Neurodegenerative disorders pose significant challenges in the realm of healthcare, as these conditions manifest in complex, multifaceted ways, often attributed to genetic anomalies. With the emergence of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) technology, a new frontier has been unveiled in the quest for targeted, precise genetic manipulation. This abstract explores the recent advancements and potential applications of CRISPR-based therapies in addressing genetic components contributing to various neurodegenerative disorders. The review delves into the foundational principles of CRISPR technology, highlighting its unparalleled ability to edit genetic sequences with unprecedented precision. In addition, it talks about the latest progress in using CRISPR to target specific genetic mutations linked to neurodegenerative diseases like Huntington's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), and Parkinson's disease. It talks about the most important studies and trials that show how well and safely CRISPR-based therapies work. This shows how this technology can change genetic variants that cause diseases. Notably, the discussion emphasizes the challenges and ethical considerations associated with the implementation of CRISPR in clinical settings, including off-target effects, delivery methods, and long-term implications. Furthermore, the article explores the prospects and potential hurdles in the widespread application of CRISPR technology for treating neurodegenerative disorders. It touches upon the need for continued research, improved delivery mechanisms, and ethical frameworks to ensure responsible and equitable access to these groundbreaking therapies.}, }
@article {pmid38734122, year = {2024}, author = {Panchalingam, S and Kasivelu, G}, title = {Exploring the impact of circular RNA on ALS progression: A systematic review.}, journal = {Brain research}, volume = {1838}, number = {}, pages = {148990}, doi = {10.1016/j.brainres.2024.148990}, pmid = {38734122}, issn = {1872-6240}, mesh = {*Amyotrophic Lateral Sclerosis/genetics/metabolism ; *RNA, Circular/metabolism/genetics ; Humans ; *Disease Progression ; Animals ; Motor Neurons/metabolism ; }, abstract = {Amyotrophic lateral sclerosis is a neurodegenerative disease that damages motor neurons and causes gradual muscular weakening and paralysis. Although studies have linked a number of genetic and environmental factors to ALS, the specific causes and mechanisms of the disease are still unclear. The pivotal role of circular RNA in the pathogenesis of ALS is a newly emerging area of research. The term "circular RNA" describes a particular class of RNA molecule that, in contrast to most RNA molecules, has a closed-loop structure. According to recent research, circular RNA might be essential for the development and progression of ALS. It has been discovered that these circular RNAs support important cellular functions related to ALS, including protein turnover, mitochondrial function, RNA processing, and cellular transport. Gaining knowledge about the precise roles and processes of circular RNA in the development of ALS could assist in understanding the pathophysiology of the disease and possibly pave the way for the development of targeted therapies. However, the understanding of circular RNA in ALS is still limited, and more research is needed to fully elucidate its role. In order to gain a comprehensive understanding of the role of circRNAs in ALS, it is imperative to delve into the various mechanisms through which circRNAs may contribute to the development and progression of the disease. Examining the current status of circRNA research in ALS and offering insights into their potential as therapeutic targets and diagnostic markers are the primary objectives of this review.}, }
@article {pmid38733435, year = {2024}, author = {Liu, S and Hong, Y and Wang, BR and Wei, ZQ and Zhao, HD and Jiang, T and Zhang, YD and Shi, JQ}, title = {The presence and clinical significance of autoantibodies in amyotrophic lateral sclerosis: a narrative review.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {9}, pages = {4133-4149}, pmid = {38733435}, issn = {1590-3478}, mesh = {*Amyotrophic Lateral Sclerosis/immunology/blood ; Humans ; *Autoantibodies/immunology/blood ; Clinical Relevance ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a debilitating and rapidly fatal neurodegenerative disease, which is characterized by the selective loss of the upper and lower motor neurons. The pathogenesis of ALS remains to be elucidated and has been connected to genetic, environmental and immune conditions. Evidence from clinical and experimental studies has suggested that the immune system played an important role in ALS pathophysiology. Autoantibodies are essential components of the immune system. Several autoantibodies directed at antigens associated with ALS pathogenesis have been identified in the serum and/or cerebrospinal fluid of ALS patients. The aim of this review is to summarize the presence and clinical significance of autoantibodies in ALS.}, }
@article {pmid38732027, year = {2024}, author = {Cantara, S and Simoncelli, G and Ricci, C}, title = {Antisense Oligonucleotides (ASOs) in Motor Neuron Diseases: A Road to Cure in Light and Shade.}, journal = {International journal of molecular sciences}, volume = {25}, number = {9}, pages = {}, pmid = {38732027}, issn = {1422-0067}, mesh = {Humans ; *Oligonucleotides, Antisense/therapeutic use ; *Motor Neuron Disease/genetics/therapy ; Animals ; Muscular Atrophy, Spinal/therapy/genetics ; Amyotrophic Lateral Sclerosis/genetics/therapy ; }, abstract = {Antisense oligonucleotides (ASOs) are short oligodeoxynucleotides designed to bind to specific regions of target mRNA. ASOs can modulate pre-mRNA splicing, increase levels of functional proteins, and decrease levels of toxic proteins. ASOs are being developed for the treatment of motor neuron diseases (MNDs), including spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS) and spinal and bulbar muscular atrophy (SBMA). The biggest success has been the ASO known as nusinersen, the first effective therapy for SMA, able to improve symptoms and slow disease progression. Another success is tofersen, an ASO designed to treat ALS patients with SOD1 gene mutations. Both ASOs have been approved by the FDA and EMA. On the other hand, ASO treatment in ALS patients with the C9orf72 gene mutation did not show any improvement in disease progression. The aim of this review is to provide an up-to-date overview of ASO research in MNDs, from preclinical studies to clinical trials and, where available, regulatory approval. We highlight the successes and failures, underline the strengths and limitations of the current ASO research, and suggest possible approaches that could lead to more effective treatments.}, }
@article {pmid38731036, year = {2024}, author = {Ueha, R and Miura, C and Matsumoto, N and Sato, T and Goto, T and Kondo, K}, title = {Vocal Fold Motion Impairment in Neurodegenerative Diseases.}, journal = {Journal of clinical medicine}, volume = {13}, number = {9}, pages = {}, pmid = {38731036}, issn = {2077-0383}, abstract = {Vocal fold motion impairment (VFMI) is the inappropriate movement of the vocal folds during respiration, leading to vocal fold adduction and/or abduction problems and causing respiratory and vocal impairments. Neurodegenerative diseases (NDDs) are a wide range of disorders characterized by progressive loss of neurons and deposition of altered proteins in the brain and peripheral organs. VFMI may be unrecognized in patients with NDDs. VFMI in NDDs is caused by the following: laryngeal muscle weakness due to muscular atrophy, caused by brainstem and motor neuron degeneration in amyotrophic lateral sclerosis; hyperactivity of laryngeal adductors in Parkinson's disease; and varying degrees of laryngeal adductor hypertonia and abductor paralysis in multiple system atrophy. Management of VFMI depends on whether there is a presence of glottic insufficiency or insufficient glottic opening with/without severe dysphagia. VFMI treatment options for glottic insufficiency range from surgical interventions, including injection laryngoplasty and medialization thyroplasty, to behavioral therapies; for insufficient glottic opening, various options are available based on the severity and underlying cause of the condition, including continuous positive airway pressure therapy, botulinum toxin injection, tracheostomy, vocal fold surgery, or a combination of interventions. In this review, we outline the mechanisms, clinical features, and management of VFMI in NDDs and provide a guide for physicians who may encounter these clinical features in their patients. NDDs are always progressive; hence, timely evaluation, proper diagnosis, and appropriate management of the patient will greatly affect their vocal, respiratory, and swallowing functions as well as their quality of life.}, }
@article {pmid38727285, year = {2024}, author = {Gao, Y and Lu, Y and Liang, X and Zhao, M and Yu, X and Fu, H and Yang, W}, title = {CD4[+] T-Cell Senescence in Neurodegenerative Disease: Pathogenesis and Potential Therapeutic Targets.}, journal = {Cells}, volume = {13}, number = {9}, pages = {}, pmid = {38727285}, issn = {2073-4409}, support = {20230505039ZP//Jilin Province Science and Technology Department/ ; }, mesh = {Animals ; Humans ; Aging/immunology/pathology ; *CD4-Positive T-Lymphocytes/immunology ; *Neurodegenerative Diseases/immunology/pathology/therapy ; *T-Cell Senescence ; }, abstract = {With the increasing proportion of the aging population, neurodegenerative diseases have become one of the major health issues in society. Neurodegenerative diseases (NDs), including multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), are characterized by progressive neurodegeneration associated with aging, leading to a gradual decline in cognitive, emotional, and motor functions in patients. The process of aging is a normal physiological process in human life and is accompanied by the aging of the immune system, which is known as immunosenescence. T-cells are an important part of the immune system, and their senescence is the main feature of immunosenescence. The appearance of senescent T-cells has been shown to potentially lead to chronic inflammation and tissue damage, with some studies indicating a direct link between T-cell senescence, inflammation, and neuronal damage. The role of these subsets with different functions in NDs is still under debate. A growing body of evidence suggests that in people with a ND, there is a prevalence of CD4[+] T-cell subsets exhibiting characteristics that are linked to senescence. This underscores the significance of CD4[+] T-cells in NDs. In this review, we summarize the classification and function of CD4[+] T-cell subpopulations, the characteristics of CD4[+] T-cell senescence, the potential roles of these cells in animal models and human studies of NDs, and therapeutic strategies targeting CD4[+] T-cell senescence.}, }
@article {pmid38726604, year = {2024}, author = {López Gómez, JJ and Díaz Marín, C and Castillo-García, T and Larrad-Sainz, A and Gastaldo-Simeón, R and Juarros-Martínez, S and Leunda-Eizmendi, L and Civera Andrés, M and Matía Martín, P}, title = {[Medical nutrition therapy in amyotrophic lateral sclerosis - Do we act or react? A case report and multidisciplinary review].}, journal = {Nutricion hospitalaria}, volume = {41}, number = {3}, pages = {712-723}, doi = {10.20960/nh.05189}, pmid = {38726604}, issn = {1699-5198}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/complications ; *Malnutrition/etiology/therapy ; *Nutrition Therapy/methods ; Nutritional Status ; }, abstract = {Background: amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a progressive course. The current prevalence is between 3 and 6 cases/100,000. Malnutrition is closely related to patient prognosis in ALS. The implications of this conditions have been that we should recommend patient care in a multidisciplinary unit. Case report: the case presented shows the evolution of a patient with ALS. The patient was referred to different clinical departments after neurological evaluation and her nutritional, functional and respiratory status were assessed. There was no nutritional deterioration at diagnosis; however, intake was below energy-protein requirements. The clinical evolution of the patient showed a decrease in muscle mass with preservation of weight and fat mass. "Aggressive" measures to control nutritional status such as gastrostomy were rejected in the initial stages of the disease, but had to be carried out after development of dysphagia and associated malnutrition. This situation of progressive morphofunctional deterioration and the development of disease-related complications made essential the participation of different health services and professionals in its control. Dicussion: the management of ALS in a multidisciplinary manner allows to improve the course of the disease and the quality of life of both the patients and their families. Patient follow-up is based on the adjustment and management of complications. The basis of the relationship with these patients includes maintaining an adequate communication with them and their families, and ensuring joint decision-making about their condition.}, }
@article {pmid38723906, year = {2024}, author = {Koike, Y}, title = {Molecular mechanisms linking loss of TDP-43 function to amyotrophic lateral sclerosis/frontotemporal dementia-related genes.}, journal = {Neuroscience research}, volume = {208}, number = {}, pages = {1-7}, doi = {10.1016/j.neures.2024.05.001}, pmid = {38723906}, issn = {1872-8111}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; *DNA-Binding Proteins/genetics/metabolism ; *Frontotemporal Dementia/genetics/metabolism ; Animals ; Polymorphism, Single Nucleotide ; Aging/genetics/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are characterized by nuclear depletion and cytoplasmic aggregation of TAR DNA-binding protein-43 (TDP-43). TDP-43 plays a key role in regulating the splicing of numerous genes, including TARDBP. This review aims to delineate two aspects of ALS/FTD pathogenesis associated with TDP-43 function. First, we described novel mechanistic insights into the splicing of UNC13A, a TDP-43 target gene. Single nucleotide polymorphisms (SNPs) in UNC13A are the most common risk factors for ALS/FTD. We found that TDP-43 represses "cryptic exon" inclusion during UNC13A RNA splicing. A risk-associated SNP in this exon results in increased RNA levels of UNC13A retaining the cryptic exon. Second, we described the perturbation of the TDP-43 autoregulatory mechanism caused by age-related DNA demethylation. Aging is a major risk factor for sporadic ALS/FTD. Typically, TDP-43 levels are regulated via alternative splicing of TARDBP mRNA. This review focused on that TARDBP methylation is altered by aging, thereby disrupting TDP-43 autoregulation. It was found that demethylation reduces the efficiency of alternative splicing and increases TARDBP mRNA levels. Moreover, we demonstrated that, with aging, this region is demethylated in the human motor cortex and is associated with the early onset of ALS.}, }
@article {pmid38723752, year = {2024}, author = {Singh, K and Sethi, P and Datta, S and Chaudhary, JS and Kumar, S and Jain, D and Gupta, JK and Kumar, S and Guru, A and Panda, SP}, title = {Advances in gene therapy approaches targeting neuro-inflammation in neurodegenerative diseases.}, journal = {Ageing research reviews}, volume = {98}, number = {}, pages = {102321}, doi = {10.1016/j.arr.2024.102321}, pmid = {38723752}, issn = {1872-9649}, mesh = {Humans ; *Genetic Therapy/methods/trends ; *Neurodegenerative Diseases/therapy/genetics ; *Neuroinflammatory Diseases/therapy ; Animals ; }, abstract = {Over the last three decades, neurodegenerative diseases (NDs) have increased in frequency. About 15% of the world's population suffers from NDs in some capacity, which causes cognitive and physical impairment. Neurodegenerative diseases, including Amyotrophic Lateral Sclerosis, Parkinson's disease, Alzheimer's disease, and others represent a significant and growing global health challenge. Neuroinflammation is recognized to be related to all NDs, even though NDs are caused by a complex mix of genetic, environmental, and lifestyle factors. Numerous genes and pathways such as NFκB, p38 MAPK, Akt/mTOR, caspase, nitric oxide, and COX are involved in triggering brain immune cells like astrocytes and microglia to secrete inflammatory cytokines such as tumor necrosis factor-α, interleukin (IL)-1β, and IL-6. In AD, the binding of Aβ with CD36, TLR4, and TLR6 receptors results in activation of microglia which start to produce proinflammatory cytokines and chemokines. Consequently, the pro-inflammatory cytokines worsen and spread neuroinflammation, causing the deterioration of healthy neurons and the impairment of brain functions. Gene therapy has emerged as a promising therapeutic approach to modulate the inflammatory response in NDs, offering potential neuroprotective effects and disease-modifying benefits. This review article focuses on recent advances in gene therapy strategies targeting neuroinflammation pathways in NDs. We discussed the molecular pathways involved in neuroinflammation, highlighted key genes and proteins implicated in these processes, and reviewed the latest preclinical and clinical studies utilizing gene therapy to modulate neuroinflammatory responses. Additionally, this review addressed the prospects and challenges in translating gene therapy approaches into effective treatments for NDs.}, }
@article {pmid38721118, year = {2024}, author = {Lu, L and Deng, Y and Xu, R}, title = {Current potential therapeutics of amyotrophic lateral sclerosis.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1402962}, pmid = {38721118}, issn = {1664-2295}, abstract = {Amyotrophic lateral sclerosis (ALS) is a debilitating motor neurological disorder for which there is still no cure. The disease seriously jeopardizes the health and lifespan of adult populations. The authors extensively retrieved the current literature about clinical and experimental ALS treatments. Based on them, this review primarily focused on summarizing the current potential clinical usage and trialing therapeutics of ALS. Currently, the clinical ALS treatments have focused primarily on relieving symptoms to improve the quality of life yet. There are a number of therapeutic approaches such as medicine, gene therapy, neuron protectants, combination therapy and stem cells. Among them, Stem cells including embryonic stem cells, mesenchymal stem cells, neural stem cells, and many other types of stem cells have been used in ALS treatment, and although the short-term efficacy is good, it is worth exploring whether this improved efficacy leads to prolonged patient survival. In addition, the supportive treatments also exert an important effect on improving the quality of life and prolong the survival of ALS patients in absence of effectively care for stopping or reversing the progression of ALS.}, }
@article {pmid40655970, year = {2023}, author = {Vardheim, EG and Toft, A and Nielsen, JE and Hasselbalch, SG and Simonsen, AH}, title = {Cerebrospinal fluid ubiquitin as a biomarker for neurodegenerative diseases: A systematic review.}, journal = {Neuroscience applied}, volume = {2}, number = {}, pages = {102438}, pmid = {40655970}, issn = {2772-4085}, abstract = {Ubiquitin plays a vital role in neuronal proteostasis, as a major but often overlooked component of neurotoxic protein aggregates across neurodegenerative diseases. Although neuropathological changes can be present for years before clinical onset, early and accurate diagnosis remains an immense challenge in this disease category. The level of ubiquitin in cerebrospinal fluid (CSF) has been assessed as a biomarker for several disease entities. This systematic review compares current findings and evaluates the potential of CSF ubiquitin as a fluid biomarker. A systematic literature search identified studies comparing CSF ubiquitin levels between a control group and patients with one of the following diseases: Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal dementia (FTD), Lewy body dementia (DLB), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). All included studies were reviewed systematically by two independent authors. 171 studies were identified. A total of 17 studies met the eligibility criteria and were included. Nine out of 13 studies found a significant increase of CSF ubiquitin in AD patients compared with control groups. Correlations between CSF ubiquitin and other established biomarkers were demonstrated in seven studies. A single study was included for both HD and DLB respectively, each showing significantly higher CSF ubiquitin in patients compared to controls. In patients with PD, FTD or ALS, CSF ubiquitin levels were generally equal to those of the control groups, with two studies showing significantly decreased concentrations in a PD and an FTD cohort. Presently, the available body of research is insufficient to assess whether CSF ubiquitin could contribute to the clinical setting, alongside established markers of neurodegeneration. The correlation of elevated CSF ubiquitin with AD is well-founded, whilst validation of reduced or unchanged levels in the other neurodegenerative diseases will determine the usefulness of the biomarker in clinical practice.}, }
@article {pmid38933502, year = {2024}, author = {Chen, BR and Wu, T and Chen, TH and Wang, Y}, title = {Neuroimmune interactions and their roles in neurodegenerative diseases.}, journal = {Fundamental research}, volume = {4}, number = {2}, pages = {251-261}, pmid = {38933502}, issn = {2667-3258}, abstract = {The nervous system possesses bidirectional, sophisticated and delicate communications with the immune system. These neuroimmune interactions play a vitally important role in the initiation and development of many disorders, especially neurodegenerative diseases. Although scientific advancements have made tremendous progress in this field during the last few years, neuroimmune communications are still far from being elucidated. By organizing recent research, in this review, we discuss the local and intersystem neuroimmune interactions and their roles in Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. Unveiling these will help us gain a better understanding of the process of interplay inside the body and how the organism maintains homeostasis. It will also facilitate a view of the diseases from a holistic, pluralistic and interconnected perspective, thus providing a basis of developing novel and effective methods to diagnose, intervene and treat diseases.}, }
@article {pmid39291146, year = {2023}, author = {Mathew, AM and Bhuvanendran, S and Nair, RS and K Radhakrishnan, A}, title = {Exploring the anti-inflammatory activities, mechanism of action and prospective drug delivery systems of tocotrienol to target neurodegenerative diseases.}, journal = {F1000Research}, volume = {12}, number = {}, pages = {338}, pmid = {39291146}, issn = {2046-1402}, abstract = {A major cause of death in the elderly worldwide is attributed to neurodegenerative diseases, such as AD (Alzheimer's disease), PD (Parkinson's disease), ALS (Amyotrophic lateral sclerosis), FRDA (Friedreich's ataxia), VaD (Vascular dementia) etc. These can be caused due to multiple factors such as genetic, physiological problems like stroke or tumor, or even external causes like viruses, toxins, or chemicals. T3s (tocotrienols) exhibit various bioactive properties where it acts as an antioxidant, anti-inflammatory, anti-tumorigenic, and cholesterol lowering agent. Since T3 interferes with and influences several anti-inflammatory mechanisms, it aids in combating inflammatory responses that lead to disease progression. T3s are found to have a profound neuroprotective ability, however, due to their poor oral bioavailability, their full potential could not be exploited. Hence there is a need to explore other drug delivery techniques, especially focusing on aspects of nanotechnology. In this review paper we explore the anti-inflammatory mechanisms of T3 to apply it in the treatment of neurodegenerative diseases and also discusses the possibilities of nano methods of administering tocotrienols to target neurodegenerative diseases.}, }
@article {pmid39165755, year = {2023}, author = {Bustos, LM and Sattler, R}, title = {The Fault in Our Astrocytes - cause or casualties of proteinopathies of ALS/FTD and other neurodegenerative diseases?.}, journal = {Frontiers in molecular medicine}, volume = {3}, number = {}, pages = {1075805}, pmid = {39165755}, issn = {2674-0095}, support = {R21 NS125861/NS/NINDS NIH HHS/United States ; }, abstract = {Many neurodegenerative diseases fall under the class of diseases known as proteinopathies, whereby the structure and localization of specific proteins become abnormal. These aberrant proteins often aggregate within cells which disrupts vital homeostatic and physiological cellular functions, ultimately contributing to cell death. Although neurodegenerative disease research is typically neurocentric, there is evidence supporting the role of non-neuronal cells in the pathogenesis of these diseases. Specifically, the role of astrocytes in neurodegenerative diseases has been an ever-growing area of research. Astrocytes are one of the most abundant cell types in the central nervous system (CNS) and provide an array of essential homeostatic functions that are disrupted in neurodegenerative diseases. Astrocytes can exhibit a reactive phenotype that is characterized by molecular changes, as well as changes in morphology and function. In neurodegenerative diseases, there is potential for reactive astrocytes to assume a loss-of-function phenotype in homeostatic operations such as synapse maintenance, neuronal metabolic support, and facilitating cell-cell communication between glia and neurons. They are also able to concurrently exhibit gain-of-function phenotypes that can be destructive to neural networks and the astrocytes themselves. Additionally, astrocytes have been shown to internalize disease related proteins and reflect similar or exacerbated pathology that has been observed in neurons. Here, we review several major neurodegenerative disease-specific proteinopathies and what is known about their presence in astrocytes and the potential consequences regarding cell and non-cell autonomous neurodegeneration.}, }
@article {pmid39086676, year = {2023}, author = {Stoklund Dittlau, K and Van Den Bosch, L}, title = {Why should we care about astrocytes in a motor neuron disease?.}, journal = {Frontiers in molecular medicine}, volume = {3}, number = {}, pages = {1047540}, pmid = {39086676}, issn = {2674-0095}, abstract = {Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease in adults, causing progressive degeneration of motor neurons, which results in muscle atrophy, respiratory failure and ultimately death of the patients. The pathogenesis of ALS is complex, and extensive efforts have focused on unravelling the underlying molecular mechanisms with a large emphasis on the dying motor neurons. However, a recent shift in focus towards the supporting glial population has revealed a large contribution and influence in ALS, which stresses the need to explore this area in more detail. Especially studies into astrocytes, the residential homeostatic supporter cells of neurons, have revealed a remarkable astrocytic dysfunction in ALS, and therefore could present a target for new and promising therapeutic entry points. In this review, we provide an overview of general astrocyte function and summarize the current literature on the role of astrocytes in ALS by categorizing the potentially underlying molecular mechanisms. We discuss the current efforts in astrocyte-targeted therapy, and highlight the potential and shortcomings of available models.}, }
@article {pmid39238808, year = {2022}, author = {Meiling, JB and Barndt, BS and Ha, CT and Eubanks, JE and Schappell, JB and Raum, GM and Khan, SA and Prokop, L and Conger, A and McCormick, ZL and Hunt, CL}, title = {The therapeutic effect of genicular nerve radiofrequency for chronic knee pain after a total knee arthroplasty: A systematic review.}, journal = {Interventional pain medicine}, volume = {1}, number = {1}, pages = {100072}, pmid = {39238808}, issn = {2772-5944}, abstract = {OBJECTIVE: Summarize the therapeutic pain-reducing effects of GnRF for refractory post-TKA knee pain. A secondary objective was to summarize improvements in physical function after GnRF.<br><br>METHODS: A protocol was registered, and a database search conducted by an experienced librarian of all available studies in the English language up until November 3, 2021. Study inclusion criteria were randomized controlled trials (RCTs), prospective and retrospective longitudinal studies, cross-sectional studies, case series, case reports, studies involving adults &#x2265;18 years of age, and studies written about the use of GnRF for the alleviation of chronic knee pain after receiving a TKA. The study quality and risk of bias was assessed using NHLBI Study Quality of Assessment Tools and Murad et&#xa0;al.'s Quality Assessment of Case Reports. Certainty in the evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation approach.<br><br>RESULTS: A total of 229 studies were screened, 11 met the inclusion criteria, and 265 patients underwent GnRF. Study designs included 1 double-blind pragmatic RCT, 5 retrospective cohort studies, 2 retrospective case series, and 3 case reports. The overall study quality assessment demonstrated three studies had "good", six "fair", and two "poor" quality. There have been positive responses to GnRF for post-TKA chronic knee pain in a range of 30-100% of patients.<br><br>CONCLUSIONS: According to GRADE, there is limited evidence, associated with low certainty to support the use of GnRF to ameliorate chronic knee pain after TKA, largely due to inconsistency and risk of bias. The studies included in this review reported positive results in pain and disability, and relatively few adverse events.}, }
@article {pmid39484675, year = {2022}, author = {Chopra, N and Menounos, S and Choi, JP and Hansbro, PM and Diwan, AD and Das, A}, title = {Blood-Spinal Cord Barrier: Its Role in Spinal Disorders and Emerging Therapeutic Strategies.}, journal = {NeuroSci}, volume = {3}, number = {1}, pages = {1-27}, pmid = {39484675}, issn = {2673-4087}, abstract = {The blood-spinal cord barrier (BSCB) has been long thought of as a functional equivalent to the blood-brain barrier (BBB), restricting blood flow into the spinal cord. The spinal cord is supported by various disc tissues that provide agility and has different local immune responses compared to the brain. Though physiologically, structural components of the BSCB and BBB share many similarities, the clinical landscape significantly differs. Thus, it is crucial to understand the composition of BSCB and also to establish the cause-effect relationship with aberrations and spinal cord dysfunctions. Here, we provide a descriptive analysis of the anatomy, current techniques to assess the impairment of BSCB, associated risk factors and impact of spinal disorders such as spinal cord injury (SCI), amyotrophic lateral sclerosis (ALS), peripheral nerve injury (PNI), ischemia reperfusion injury (IRI), degenerative cervical myelopathy (DCM), multiple sclerosis (MS), spinal cavernous malformations (SCM) and cancer on BSCB dysfunction. Along with diagnostic and mechanistic analyses, we also provide an up-to-date account of available therapeutic options for BSCB repair. We emphasize the need to address BSCB as an individual entity and direct future research towards it.}, }
@article {pmid38720896, year = {2024}, author = {Zong, J and Yang, Y and Wang, H and Zhang, H and Yang, X and Yang, X}, title = {The two-directional prospective association between inflammatory bowel disease and neurodegenerative disorders: a systematic review and meta-analysis based on longitudinal studies.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1325908}, pmid = {38720896}, issn = {1664-3224}, mesh = {Humans ; *Inflammatory Bowel Diseases/complications ; *Neurodegenerative Diseases/epidemiology/etiology ; Longitudinal Studies ; Risk Factors ; Prospective Studies ; }, abstract = {OBJECTIVE: Previous studies reported possible connections between inflammatory bowel disease (IBD) and several neurodegenerative disorders. However, the comprehensive relationships between IBD and various neurodegenerative disorders were not summarized. We executed a meta-analysis of longitudinal studies to provide an estimate of the strength of the two-directional prospective association between IBD and neurodegenerative disorders.<br><br>METHODS: We accomplished a thorough bibliographic search of PubMed, Web of Science, Embase, PsycINFO, and Cochrane Library databases until June 2023 to locate relevant longitudinal studies. The extracted data were then analyzed via meta-analysis using either a fixed or random effects model.<br><br>RESULTS: The final analysis encompassed 27 studies. Individuals with IBD faced an increased risk of developing four neurodegenerative disorders than the general public, namely, Alzheimer's disease (hazard ratio[HR] = 1.35, 95% confidence interval [CI]: 1.03-1.77, P=0.031), dementia (HR =1.24, 95% CI: 1.13-1.36, P<0.001), multiple sclerosis (HR =2.07, 95% CI:1.42-3.02, P<0.001) and Parkinson's disease (HR =1.23, 95% CI:1.10-1.38, P<0.001). Two articles reported an increased incidence of amyotrophic lateral sclerosis or multiple system atrophy in IBD patients. Three studies investigated the prospective association between multiple sclerosis and IBD, revealing an elevated risk of the latter in patients with the former. (HR=1.87, 95% CI:1.66-2.10, P<0.001).<br><br>INTERPRETATION: These findings verified the two-directional relationship between the brain-gut axis, specifically demonstrating a heightened risk of various neurodegenerative diseases among IBD patients. It may be profitable to prepare screening strategies for IBD patients to find neurodegenerative diseases during the long-term course of treatment for IBD with a view to potential earlier diagnosis and treatment of neurodegenerative diseases, reducing public health and social burden.<br><br>PROSPERO (CRD42023437553).}, }
@article {pmid38713169, year = {2024}, author = {Nikel, LM and Talbot, K and Vahsen, BF}, title = {Recent insights from human induced pluripotent stem cell models into the role of microglia in amyotrophic lateral sclerosis.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {46}, number = {7}, pages = {e2400054}, doi = {10.1002/bies.202400054}, pmid = {38713169}, issn = {1521-1878}, support = {2023/MNDS/6400/753TALB//MND Scotland/ ; Talbot/Apr22/889-791/MNDA_/Motor Neurone Disease Association/United Kingdom ; }, mesh = {*Amyotrophic Lateral Sclerosis/pathology/metabolism/genetics ; *Induced Pluripotent Stem Cells/metabolism ; Humans ; *Microglia/metabolism/pathology ; *Motor Neurons/pathology/metabolism ; Coculture Techniques ; Animals ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease, primarily leading to the degeneration of motor neurons. The traditional focus on motor neuron-centric mechanisms has recently shifted towards understanding the contribution of non-neuronal cells, such as microglia, in ALS pathophysiology. Advances in induced pluripotent stem cell (iPSC) technology have enabled the generation of iPSC-derived microglia monocultures and co-cultures to investigate their role in ALS pathogenesis. Here, we briefly review the insights gained from these studies into the role of microglia in ALS. While iPSC-derived microglia monocultures have revealed intrinsic cellular dysfunction due to ALS-associated mutations, microglia-motor neuron co-culture studies have demonstrated neurotoxic effects of mutant microglia on motor neurons. Based on these findings, we briefly discuss currently unresolved questions and how they could be addressed in future studies. iPSC models hold promise for uncovering disease-relevant pathways in ALS and identifying potential therapeutic targets.}, }
@article {pmid38711277, year = {2024}, author = {Vakilipour, P and Fekrvand, S}, title = {Brain-to-brain interface technology: A brief history, current state, and future goals.}, journal = {International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience}, volume = {84}, number = {5}, pages = {351-367}, doi = {10.1002/jdn.10334}, pmid = {38711277}, issn = {1873-474X}, mesh = {Humans ; *Brain-Computer Interfaces ; *Brain/physiology ; History, 20th Century ; History, 21st Century ; }, abstract = {A brain-to-brain interface (BBI), defined as a combination of neuroimaging and neurostimulation methods to extract and deliver information between brains directly without the need for the peripheral nervous system, is a budding communication technique. A BBI system is made up of two parts known as the brain-computer interface part, which reads a sender's brain activity and digitalizes it, and the computer-brain interface part, which writes the delivered brain activity to a receiving brain. As with other technologies, BBI systems have gone through an evolutionary process since they first appeared. The BBI systems have been employed for numerous purposes, including rehabilitation for post-stroke patients, communicating with patients suffering from amyotrophic lateral sclerosis, locked-in syndrome and speech problems following stroke. Also, it has been proposed that a BBI system could play an important role on future battlefields. This technology was not only employed for communicating between two human brains but also for making a direct communication path among different species through which motor or sensory commands could be sent and received. However, the application of BBI systems has provoked significant challenges to human rights principles due to their ability to access and manipulate human brain information. In this study, we aimed to review the brain-computer interface and computer-brain interface technologies as components of BBI systems, the development of BBI systems, applications of this technology, arising ethical issues and expectations for future use.}, }
@article {pmid38708921, year = {2024}, author = {Monteiro, KLC and Dos Santos Alcântara, MG and de Aquino, TM and da Silva-Júnior, EF}, title = {Insights on Natural Products Against Amyotrophic Lateral Sclerosis (ALS).}, journal = {Current neuropharmacology}, volume = {22}, number = {7}, pages = {1169-1188}, pmid = {38708921}, issn = {1875-6190}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy ; Humans ; *Biological Products/therapeutic use/pharmacology ; Animals ; Neuroprotective Agents/therapeutic use/pharmacology ; Plants, Medicinal/chemistry ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that causes the death of motor neurons and consequent muscle paralysis. Despite many efforts to address it, current therapy targeting ALS remains limited, increasing the interest in complementary therapies. Over the years, several herbal preparations and medicinal plants have been studied to prevent and treat this disease, which has received remarkable attention due to their blood-brain barrier penetration properties and low toxicity. Thus, this review presents the therapeutic potential of a variety of medicinal herbs and their relationship with ALS and their physiopathological pathways.}, }
@article {pmid38705104, year = {2024}, author = {Dharmadasa, T and Pavey, N and Tu, S and Menon, P and Huynh, W and Mahoney, CJ and Timmins, HC and Higashihara, M and van den Bos, M and Shibuya, K and Kuwabara, S and Grosskreutz, J and Kiernan, MC and Vucic, S}, title = {Novel approaches to assessing upper motor neuron dysfunction in motor neuron disease/amyotrophic lateral sclerosis: IFCN handbook chapter.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {163}, number = {}, pages = {68-89}, doi = {10.1016/j.clinph.2024.04.010}, pmid = {38705104}, issn = {1872-8952}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnosis ; *Transcranial Magnetic Stimulation/methods ; *Motor Neuron Disease/physiopathology/diagnosis ; *Motor Neurons/physiology ; Evoked Potentials, Motor/physiology ; Motor Cortex/physiopathology/diagnostic imaging ; }, abstract = {Identifying upper motor neuron (UMN) dysfunction is fundamental to the diagnosis and understanding of disease pathogenesis in motor neuron disease (MND). The clinical assessment of UMN dysfunction may be difficult, particularly in the setting of severe muscle weakness. From a physiological perspective, transcranial magnetic stimulation (TMS) techniques provide objective biomarkers of UMN dysfunction in MND and may also be useful to interrogate cortical and network function. Single, paired- and triple pulse TMS techniques have yielded novel diagnostic and prognostic biomarkers in MND, and have provided important pathogenic insights, particularly pertaining to site of disease onset. Cortical hyperexcitability, as heralded by reduced short interval intracortical inhibition (SICI) and increased short interval intracortical facilitation, has been associated with the onset of lower motor neuron degeneration, along with patterns of disease spread, development of specific clinical features such as the split hand phenomenon, and may provide an indication about the rate of disease progression. Additionally, reduction of SICI has emerged as a potential diagnostic aid in MND. The triple stimulation technique (TST) was shown to enhance the diagnostic utility of conventional TMS measures in detecting UMN dysfunction in MND. Separately, sophisticated brain imaging techniques have uncovered novel biomarkers of neurodegeneration that have bene associated with progression. The present review will discuss the utility of TMS and brain neuroimaging derived biomarkers of UMN dysfunction in MND, focusing on recently developed TMS techniques and advanced neuroimaging modalities that interrogate structural and functional integrity of the corticomotoneuronal system, with an emphasis on pathogenic, diagnostic, and prognostic utility.}, }
@article {pmid38702287, year = {2024}, author = {Tazir, M and Nouioua, S}, title = {Distal hereditary motor neuropathies.}, journal = {Revue neurologique}, volume = {180}, number = {10}, pages = {1031-1036}, doi = {10.1016/j.neurol.2023.09.005}, pmid = {38702287}, issn = {0035-3787}, mesh = {Humans ; *Hereditary Sensory and Motor Neuropathy/genetics/diagnosis/physiopathology ; Mutation ; Charcot-Marie-Tooth Disease/genetics/diagnosis/physiopathology/epidemiology ; }, abstract = {Distal hereditary motor neuropathies (dHMN) are a group of heterogeneous hereditary disorders characterized by a slowly progressive distal pure motor neuropathy. Electrophysiology, with normal motor and sensory conduction velocities, can suggest the diagnosis of dHMN and guide the genetic study. More than thirty genes are currently associated with HMNs, but around 60 to 70% of cases of dHMN remain uncharacterized genetically. Recent cohort studies showed that HSPB1, GARS, BICB2 and DNAJB2 are among the most frequent dHMN genes and that the prevalence of the disease was calculated as 2.14 and 2.3 per 100,000. The determination of the different genes involved in dHMNs made it possible to observe a genotypic overlap with some other neurogenetic disorders and other hereditary neuropathies such as CMT2, mainly with the HSPB1, HSPB8, BICD2 and TRPV4 genes of AD-inherited transmission and recently observed with SORD gene of AR transmission which seems relatively frequent and potentially curable. Distal hereditary motor neuropathy that predominates in the upper limbs is linked mainly to three genes: GARS, BSCL2 and REEP1, whereas dHMN with vocal cord palsy is associated with SLC5A7, DCTN1 and TRPV4 genes. Among the rare AR forms of dHMN like IGHMBP2 and DNAJB2, the SIGMAR1 gene mutations as well as VRK1 variants are associated with a motor neuropathy phenotype often associated with upper motoneuron involvement. The differential diagnosis of these latter arises with juvenile forms of amyotrophic lateral sclerosis, that could be caused also by variations of these genes, as well as hereditary spastic paraplegia. A differential diagnosis of dHMN related to Brown Vialetto Van Laere syndrome due to riboflavin transporter deficiency is important to consider because of the therapeutic possibility.}, }
@article {pmid38700207, year = {2024}, author = {Keeley, O and Coyne, AN}, title = {Nuclear and degradative functions of the ESCRT-III pathway: implications for neurodegenerative disease.}, journal = {Nucleus (Austin, Tex.)}, volume = {15}, number = {1}, pages = {2349085}, pmid = {38700207}, issn = {1949-1042}, support = {R00 NS123242/NS/NINDS NIH HHS/United States ; R01 NS132836/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Endosomal Sorting Complexes Required for Transport/metabolism ; *Neurodegenerative Diseases/metabolism/pathology/genetics ; Animals ; Cell Nucleus/metabolism ; Frontotemporal Dementia/metabolism/pathology/genetics ; Endosomes/metabolism ; }, abstract = {The ESCRT machinery plays a pivotal role in membrane-remodeling events across multiple cellular processes including nuclear envelope repair and reformation, nuclear pore complex surveillance, endolysosomal trafficking, and neuronal pruning. Alterations in ESCRT-III functionality have been associated with neurodegenerative diseases including Frontotemporal Dementia (FTD), Amyotrophic Lateral Sclerosis (ALS), and Alzheimer's Disease (AD). In addition, mutations in specific ESCRT-III proteins have been identified in FTD/ALS. Thus, understanding how disruptions in the fundamental functions of this pathway and its individual protein components in the human central nervous system (CNS) may offer valuable insights into mechanisms underlying neurodegenerative disease pathogenesis and identification of potential therapeutic targets. In this review, we discuss ESCRT components, dynamics, and functions, with a focus on the ESCRT-III pathway. In addition, we explore the implications of altered ESCRT-III function for neurodegeneration with a primary emphasis on nuclear surveillance and endolysosomal trafficking within the CNS.}, }
@article {pmid38694387, year = {2024}, author = {Arora, H and Javed, B and Kutikuppala, LVS and Chaurasia, M and Khullar, K and Kannan, S and Golla, V}, title = {ST2 levels and neurodegenerative diseases: is this a significant relation?.}, journal = {Annals of medicine and surgery (2012)}, volume = {86}, number = {5}, pages = {2812-2817}, pmid = {38694387}, issn = {2049-0801}, abstract = {Interleukin-33 (IL-33), belonging to the interleukin-1 cytokine family, has a decoy receptor soluble ST2 (sST2). IL-33 is found in oligodendrocytes and astrocytes and is involved in central nervous system healing and repair, whereas ST2 is found in microglia and astrocytes. Some studies have found a link between changes in the IL-33/ST2 pathway and neurodegenerative disorders. This review article investigates the relationship between the interleukin-33 (IL-33)/ST2 pathway and neurodegenerative disorders. It was discovered that soluble st2 levels were increased. Furthermore, IL-33 levels were found to be lower in many neurodegenerative diseases such as Alzheimer's and amyotrophic lateral sclerosis (ALS). The association with other disorders, such as ankylosing spondylitis, multiple sclerosis, and systemic lupus erythematosus (SLE), was also observed. Various studies suggest that ST2/IL-33 signalling may be pivotal in the disease modulation of neurodegenerative disorders. The serum sST2 level test can be useful in determining the inflammatory status and severity of illness in many neurodegenerative disorders. In this review, we will discuss recent findings concerning the interleukin-33 (IL-33)/ST2 pathway and its role in the diagnosis and treatment of diseases with neurodegeneration.}, }
@article {pmid38691665, year = {2024}, author = {Singh, P and Belliveau, P and Towle, J and Neculau, AE and Dima, L}, title = {Edaravone Oral Suspension: A Neuroprotective Agent to Treat Amyotrophic Lateral Sclerosis.}, journal = {American journal of therapeutics}, volume = {31}, number = {3}, pages = {e258-e267}, doi = {10.1097/MJT.0000000000001742}, pmid = {38691665}, issn = {1536-3686}, mesh = {*Edaravone/administration &amp; dosage/pharmacology/therapeutic use ; Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Neuroprotective Agents/administration &amp; dosage/therapeutic use/adverse effects ; Administration, Oral ; Suspensions ; Biological Availability ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is characterized by loss of motor neurons due to degeneration of nerve cells within the brain and spinal cord. Early symptoms include limb weakness, twitching or muscle cramping, and slurred speech. As the disease progresses, difficulty breathing, swallowing, and paralysis can lead to death. Currently, there are no medications that cure ALS, and guidelines recommend treatments focused on symptom management. Intravenous (IV) edaravone was approved by the US Food and Drug Administration (FDA) in 2017 as a treatment to slow the progression of ALS. In May 2022, the FDA approved an oral suspension (ORS) formulation of edaravone.<br><br>MECHANISM OF ACTION: The mechanism of action of edaravone is not well defined. However, its neuroprotective effects are thought to result from antioxidant properties occurring through elimination of free radicals.<br><br>PHARMACOKINETICS: Edaravone ORS (105 mg) has a bioavailability of 57% when compared with edaravone IV (60 mg). The ORS should be taken on an empty stomach in the morning, with water and no food or beverages, for 1 hour. Edaravone is bound to albumin (92%), has a mean volume of distribution of 63.1 L, a half-life of 4.5-9 hours, and a total clearance of 35.9 L/h after intravenous administration. Edaravone is metabolized into nonactive sulfate and glucuronide conjugates.<br><br>CLINICAL TRIALS: The FDA approval was based on studies of the pharmacokinetics, safety, tolerability, and bioavailability of edaravone ORS. A phase III, global, multicenter, open-label safety study was conducted on edaravone ORS in 185 patients with ALS over 48 weeks. The most reported treatment-emergent adverse events were falls, muscular weakness, and constipation. Serious treatment-emergent adverse events included disease worsening, dysphagia, dyspnea, and respiratory failure.<br><br>THERAPEUTIC ADVANCE: Oral edaravone is an ALS treatment that can be self-administered or administered by a caregiver, precluding the need for administration by a health care professional in an institutional setting.}, }
@article {pmid38682227, year = {2024}, author = {Mohammadi, S and Ghaderi, S and Mohammadi, M and Najafi Asli Pashaki, Z and Khatyal, R and Mohammadian, F and Mohammadjani, S}, title = {Thalamic Alterations in Motor Neuron Diseases: A Systematic Review of MRI Findings.}, journal = {Journal of integrative neuroscience}, volume = {23}, number = {4}, pages = {77}, doi = {10.31083/j.jin2304077}, pmid = {38682227}, issn = {0219-6352}, mesh = {Humans ; *Thalamus/diagnostic imaging/pathology/physiopathology ; *Motor Neuron Disease/diagnostic imaging/pathology/physiopathology ; *Magnetic Resonance Imaging ; Amyotrophic Lateral Sclerosis/diagnostic imaging/pathology/physiopathology ; }, abstract = {BACKGROUND: Motor neuron diseases (MNDs) are progressive neurodegenerative disorders characterized by motor impairment and non-motor symptoms. The involvement of the thalamus in MNDs, especially in conditions such as amyotrophic lateral sclerosis (ALS), and its interaction with frontotemporal dementia (FTD), has garnered increasing research interest. This systematic review analyzed magnetic resonance imaging (MRI) studies that focused on thalamic alterations in MNDs to understand the significance of these changes and their correlation with clinical outcomes.<br><br>METHODS: Following PRISMA 2020 guidelines, the PubMed and Scopus databases were searched from inception to June 2023 for studies related to MRI findings in the thalamus of patients with MNDs. Eligible studies included adult patients diagnosed with ALS or other forms of MND who underwent brain MRI, with outcomes related to thalamic alterations. Studies were evaluated for risk of bias using the Newcastle-Ottawa scale.<br><br>RESULTS: A total of 52 studies (including 3009 MND patients and 2181 healthy controls) used various MRI techniques, including volumetric analysis, diffusion tensor imaging, and functional MRI, to measure thalamic volume, connectivity, and other alterations. This review confirmed significant thalamic changes in MNDs, such as atrophy and microstructural degradation, which are associated with disease severity, progression, and functional disability. Thalamic involvement varies across different MND subtypes and is influenced by the presence of cognitive impairment and mutations in genes including chromosome 9 open reading frame 72 (C9orf72). The synthesis of findings across studies indicates that thalamic pathology is a prevalent early biomarker of MNDs that contributes to motor and cognitive deficits. The thalamus is a promising target for monitoring as its dysfunction underpins a variety of clinical symptoms in MNDs.<br><br>CONCLUSIONS: Thalamic alterations provide valuable insights into the pathophysiology and progression of MNDs. Multimodal MRI techniques are potent tools for detecting dynamic thalamic changes, indicating structural integrity, connectivity disruption, and metabolic activity.}, }
@article {pmid38676818, year = {2024}, author = {Kubat, GB and Picone, P}, title = {Skeletal muscle dysfunction in amyotrophic lateral sclerosis: a mitochondrial perspective and therapeutic approaches.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {9}, pages = {4121-4131}, pmid = {38676818}, issn = {1590-3478}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/physiopathology/pathology ; *Muscle, Skeletal/physiopathology/pathology ; Animals ; Mitochondria/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neuromuscular disease that results in the loss of motor neurons and severe skeletal muscle atrophy. The etiology of ALS is linked to skeletal muscle, which can activate a retrograde signaling cascade that destroys motor neurons. This is why satellite cells and mitochondria play a crucial role in the health and performance of skeletal muscles. This review presents current knowledge on the involvement of mitochondrial dysfunction, skeletal muscle atrophy, muscle satellite cells, and neuromuscular junction (NMJ) in ALS. It also discusses current therapeutic strategies, including exercise, drugs, stem cells, gene therapy, and the prospective use of mitochondrial transplantation as a viable therapeutic strategy.}, }
@article {pmid38676672, year = {2024}, author = {Kutlubaev, MA}, title = {[Promising approaches to the pathogenetic therapy of amyotrophic lateral sclerosis].}, journal = {Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova}, volume = {124}, number = {4}, pages = {13-21}, doi = {10.17116/jnevro202412404113}, pmid = {38676672}, issn = {1997-7298}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/therapy ; Humans ; *Neuroprotective Agents/therapeutic use ; Genetic Therapy ; Antioxidants/therapeutic use ; Stem Cell Transplantation ; Gastrointestinal Microbiome ; Immunologic Factors/therapeutic use ; Immunomodulating Agents/therapeutic use ; }, abstract = {Amyotrophic lateral sclerosis is a severe incurable disease of the nervous system. Currently only methods of palliative care for the patients with this disease are available. Few medications for the pathogenetic therapy are registered in some countries, i.e. riluzole, edaravon, sodium phenylbutyrate/taurursodiol as well as tofersen (conditionally). Their efficacy is relatively low. The main directions in the development of pathogenetic therapy of ALS include gene therapy, use of stem cells, immunomodulators, agents affecting gut microbiota. A search is also underway for low-molecular compounds with neuroprotective and antioxidant properties. Perspective direction is prevention of ALS. This will be possible when biomarkers for identification of patients in pre-manifest/prodromal stage are detected.}, }
@article {pmid38674921, year = {2024}, author = {Wang, W and Pan, D and Liu, Q and Chen, X and Wang, S}, title = {L-Carnitine in the Treatment of Psychiatric and Neurological Manifestations: A Systematic Review.}, journal = {Nutrients}, volume = {16}, number = {8}, pages = {}, pmid = {38674921}, issn = {2072-6643}, mesh = {Humans ; *Carnitine/therapeutic use ; Dietary Supplements ; *Mental Disorders/drug therapy ; *Nervous System Diseases/drug therapy ; }, abstract = {OBJECTIVE: L-carnitine (LC), a vital nutritional supplement, plays a crucial role in myocardial health and exhibits significant cardioprotective effects. LC, being the principal constituent of clinical-grade supplements, finds extensive application in the recovery and treatment of diverse cardiovascular and cerebrovascular disorders. However, controversies persist regarding the utilization of LC in nervous system diseases, with varying effects observed across numerous mental and neurological disorders. This article primarily aims to gather and analyze database information to comprehensively summarize the therapeutic potential of LC in patients suffering from nervous system diseases while providing valuable references for further research.<br><br>METHODS: A comprehensive search was conducted in PubMed, Web Of Science, Embase, Ovid Medline, Cochrane Library and Clinicaltrials.gov databases. The literature pertaining to the impact of LC supplementation on neurological or psychiatric disorders in patients was reviewed up until November 2023. No language or temporal restrictions were imposed on the search.<br><br>RESULTS: A total of 1479 articles were retrieved, and after the removal of duplicates through both automated and manual exclusion processes, 962 articles remained. Subsequently, a meticulous re-screening led to the identification of 60 relevant articles. Among these, there were 12 publications focusing on hepatic encephalopathy (HE), while neurodegenerative diseases (NDs) and peripheral nervous system diseases (PNSDs) were represented by 9 and 6 articles, respectively. Additionally, stroke was addressed in five publications, whereas Raynaud's syndrome (RS) and cognitive disorder (CD) each had three dedicated studies. Furthermore, migraine, depression, and amyotrophic lateral sclerosis (ALS) each accounted for two publications. Lastly, one article was found for other symptoms under investigation.<br><br>CONCLUSION: In summary, LC has demonstrated favorable therapeutic effects in the management of HE, Alzheimer's disease (AD), carpal tunnel syndrome (CTS), CD, migraine, neurofibromatosis (NF), PNSDs, RS, and stroke. However, its efficacy appears to be relatively limited in conditions such as ALS, ataxia, attention deficit hyperactivity disorder (ADHD), depression, chronic fatigue syndrome (CFS), Down syndrome (DS), and sciatica.}, }
@article {pmid38674431, year = {2024}, author = {Shahim, P and Norato, G and Sinaii, N and Zetterberg, H and Blennow, K and Chan, L and Grunseich, C}, title = {Neurofilaments in Sporadic and Familial Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis.}, journal = {Genes}, volume = {15}, number = {4}, pages = {}, pmid = {38674431}, issn = {2073-4425}, mesh = {*Amyotrophic Lateral Sclerosis/genetics/blood/diagnosis/cerebrospinal fluid ; Humans ; *Neurofilament Proteins/blood/cerebrospinal fluid ; Biomarkers/blood/cerebrospinal fluid ; Intermediate Filaments/metabolism/genetics ; Prognosis ; }, abstract = {BACKGROUND: Neurofilament proteins have been implicated to be altered in amyotrophic lateral sclerosis (ALS). The objectives of this study were to assess the diagnostic and prognostic utility of neurofilaments in ALS.<br><br>METHODS: Studies were conducted in electronic databases (PubMed/MEDLINE, Embase, Web of Science, and Cochrane CENTRAL) from inception to 17 August 2023, and investigated neurofilament light (NfL) or phosphorylated neurofilament heavy chain (pNfH) in ALS. The study design, enrolment criteria, neurofilament concentrations, test accuracy, relationship between neurofilaments in cerebrospinal fluid (CSF) and blood, and clinical outcome were recorded. The protocol was registered with PROSPERO, CRD42022376939.<br><br>RESULTS: Sixty studies with 8801 participants were included. Both NfL and pNfH measured in CSF showed high sensitivity and specificity in distinguishing ALS from disease mimics. Both NfL and pNfH measured in CSF correlated with their corresponding levels in blood (plasma or serum); however, there were stronger correlations between CSF NfL and blood NfL. NfL measured in blood exhibited high sensitivity and specificity in distinguishing ALS from controls. Both higher levels of NfL and pNfH either measured in blood or CSF were correlated with more severe symptoms as assessed by the ALS Functional Rating Scale Revised score and with a faster disease progression rate; however, only blood NfL levels were associated with shorter survival.<br><br>DISCUSSION: Both NfL and pNfH measured in CSF or blood show high diagnostic utility and association with ALS functional scores and disease progression, while CSF NfL correlates strongly with blood (either plasma or serum) and is also associated with survival, supporting its use in clinical diagnostics and prognosis. Future work must be conducted in a prospective manner with standardized bio-specimen collection methods and analytical platforms, further improvement in immunoassays for quantification of pNfH in blood, and the identification of cut-offs across the ALS spectrum and controls.}, }
@article {pmid38672416, year = {2024}, author = {Cheslow, L and Snook, AE and Waldman, SA}, title = {Biomarkers for Managing Neurodegenerative Diseases.}, journal = {Biomolecules}, volume = {14}, number = {4}, pages = {}, pmid = {38672416}, issn = {2218-273X}, support = {F30 NS125921/NS/NINDS NIH HHS/United States ; R01 DK138834/DK/NIDDK NIH HHS/United States ; R21 NS130388/NS/NINDS NIH HHS/United States ; 1R01 CA204881, 1R01 CA206026, 1R21 1NS130388, 1R01 DK1388341/NH/NIH HHS/United States ; }, mesh = {Humans ; *Biomarkers/metabolism ; *Neurodegenerative Diseases/metabolism/diagnosis/therapy ; *Alzheimer Disease/metabolism/diagnosis/therapy ; Amyotrophic Lateral Sclerosis/metabolism/therapy/diagnosis ; Parkinson Disease/metabolism/diagnosis/therapy ; Animals ; }, abstract = {Neurological disorders are the leading cause of cognitive and physical disability worldwide, affecting 15% of the global population. Due to the demographics of aging, the prevalence of neurological disorders, including neurodegenerative diseases, will double over the next two decades. Unfortunately, while available therapies provide symptomatic relief for cognitive and motor impairment, there is an urgent unmet need to develop disease-modifying therapies that slow the rate of pathological progression. In that context, biomarkers could identify at-risk and prodromal patients, monitor disease progression, track responses to therapy, and parse the causality of molecular events to identify novel targets for further clinical investigation. Thus, identifying biomarkers that discriminate between diseases and reflect specific stages of pathology would catalyze the discovery and development of therapeutic targets. This review will describe the prevalence, known mechanisms, ongoing or recently concluded therapeutic clinical trials, and biomarkers of three of the most prevalent neurodegenerative diseases, including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD).}, }
@article {pmid38671345, year = {2024}, author = {Kwok, VK and Reid, N and Hubbard, RE and Thavarajah, H and Gordon, EH}, title = {Multicomponent perioperative interventions to improve outcomes for frail patients: a systematic review.}, journal = {BMC geriatrics}, volume = {24}, number = {1}, pages = {376}, pmid = {38671345}, issn = {1471-2318}, mesh = {Humans ; *Perioperative Care/methods ; Aged ; *Frail Elderly ; Postoperative Complications/prevention &amp; control/epidemiology ; Frailty ; Aged, 80 and over ; Treatment Outcome ; }, abstract = {BACKGROUND: Preoperative frailty is associated with increased risk of adverse outcomes. In 2017, McIsaac and colleagues' systematic review found that few interventions improved outcomes in this population and evidence was low-quality. We aimed to systematically review the evidence for multicomponent perioperative interventions in frail patients that has emerged since McIsaac et al.'s review.<br><br>METHODS: PUBMED, EMBASE, Cochrane, and CINAHL databases were searched for English-language studies published since January 1, 2016, that evaluated multicomponent perioperative interventions in patients identified as frail. Quality was assessed using the National Institute of Health Quality Assessment Tool. A narrative synthesis of the extracted data was conducted.<br><br>RESULTS: Of 2835 articles screened, five studies were included, all of which were conducted in elective oncologic gastrointestinal surgical populations. Four hundred and thirteen patients were included across the five studies and the mean/median age ranged from 70.1 to 87.0 years. Multicomponent interventions were all applied in the preoperative period. Two studies also applied interventions postoperatively. All interventions addressed exercise and nutritional domains with variability in timing, delivery, and adherence. Multicomponent interventions were associated with reduced postoperative complications, functional deterioration, length of stay, and mortality. Four studies reported on patient-centred outcomes. The quality of evidence was fair.<br><br>CONCLUSIONS: This systematic review provides evidence that frail surgical patients undergoing elective oncologic gastrointestinal surgery may benefit from targeted multicomponent perioperative interventions. Yet methodological issues and substantial heterogeneity of the interventions precludes drawing clear conclusions regarding the optimal model of care. Larger, low risk of bias studies are needed to evaluate optimal intervention delivery, effectiveness in other populations, implementation in health care settings and ascertain outcomes of importance for frail patients and their carers.}, }
@article {pmid38670433, year = {2024}, author = {Sitruk-Ware, R and Sussman, H and Brinton, R and Schumacher, M and Singer, P and Kumar, N and De Nicola, AF and El-Etr, M and Guennoun, R and V Borlongan, C}, title = {Nestorone (segesterone acetate) effects on neuroregeneration.}, journal = {Frontiers in neuroendocrinology}, volume = {73}, number = {}, pages = {101136}, doi = {10.1016/j.yfrne.2024.101136}, pmid = {38670433}, issn = {1095-6808}, mesh = {Animals ; Humans ; *Norprogesterones/pharmacology ; *Neuroprotective Agents/pharmacology ; Nerve Regeneration/drug effects/physiology ; Female ; }, abstract = {Nestorone® (segesterone acetate) is a progestin with a chemical structure closely related to progesterone with high affinity and selectivity for the progesterone receptor without significant interaction with other steroid receptors. It has been developed for female and male contraception and is FDA-approved in a first long-acting contraceptive vaginal system for female contraception. Its safety has been extensively demonstrated in both preclinical and clinical studies for contraceptive indications. Nestorone was found to display neuroprotective and neuroregenerative activity in animal models of various central nervous system diseases, including multiple sclerosis, stroke, and amyotrophic lateral sclerosis. Reviewed herein are neuroprotective and myelin- regenerating properties of Nestorone in various animal models and its translational potential as a therapeutic agent for debilitating neurological diseases for which limited therapeutic options are available (Table 1).}, }
@article {pmid38667285, year = {2024}, author = {Alzahrani, FA and Riza, YM and Eid, TM and Almotairi, R and Scherschinski, L and Contreras, J and Nadeem, M and Perez, SE and Raikwar, SP and Jha, RM and Preul, MC and Ducruet, AF and Lawton, MT and Bhatia, K and Akhter, N and Ahmad, S}, title = {Exosomes in Vascular/Neurological Disorders and the Road Ahead.}, journal = {Cells}, volume = {13}, number = {8}, pages = {}, pmid = {38667285}, issn = {2073-4409}, mesh = {*Exosomes/metabolism ; Humans ; Animals ; Neurodegenerative Diseases/metabolism/pathology ; Vascular Diseases/metabolism/pathology ; Nervous System Diseases/metabolism/pathology ; }, abstract = {Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), stroke, and aneurysms, are characterized by the abnormal accumulation and aggregation of disease-causing proteins in the brain and spinal cord. Recent research suggests that proteins linked to these conditions can be secreted and transferred among cells using exosomes. The transmission of abnormal protein buildup and the gradual degeneration in the brains of impacted individuals might be supported by these exosomes. Furthermore, it has been reported that neuroprotective functions can also be attributed to exosomes in neurodegenerative diseases. The potential neuroprotective functions may play a role in preventing the formation of aggregates and abnormal accumulation of proteins associated with the disease. The present review summarizes the roles of exosomes in neurodegenerative diseases as well as elucidating their therapeutic potential in AD, PD, ALS, HD, stroke, and aneurysms. By elucidating these two aspects of exosomes, valuable insights into potential therapeutic targets for treating neurodegenerative diseases may be provided.}, }
@article {pmid38666601, year = {2024}, author = {Officer, L and Armon, C and Barkhaus, P and Beauchamp, M and Benatar, M and Bertorini, T and Bowser, R and Bromberg, M and Brown, A and Carbunar, OM and Carter, GT and Crayle, J and Denson, K and Feldman, E and Fullam, T and Heiman-Patterson, T and Jackson, C and Jhooty, S and Levinson, D and Li, X and Linares, A and Mallon, E and Mascias Cadavid, J and Mcdermott, C and Mushannen, T and Ostrow, L and Patel, R and Pattee, G and Ratner, D and Sun, Y and Sladky, J and Wicks, P and Bedlack, R}, title = {ALSUntangled #75: Portable neuromodulation stimulator therapy.}, journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration}, volume = {25}, number = {5-6}, pages = {648-652}, doi = {10.1080/21678421.2024.2346825}, pmid = {38666601}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy ; *Electric Stimulation Therapy/methods/instrumentation ; }, abstract = {Spurred by patient interest, ALSUntangled herein examines the potential of the Portable Neuromodulation Stimulator (PoNS™) in treating amyotrophic lateral sclerosis (ALS). The PoNS™ device, FDA-approved for the treatment of gait deficits in adult patients with multiple sclerosis, utilizes translingual neurostimulation to stimulate trigeminal and facial nerves via the tongue, aiming to induce neuroplastic changes. While there are early, promising data for PoNS treatment to improve gait and balance in multiple sclerosis, stroke, and traumatic brain injury, no pre-clinical or clinical studies have been performed in ALS. Although reasonably safe, high costs and prescription requirements will limit PoNS accessibility. At this time, due to the lack of ALS-relevant data, we cannot endorse the use of PoNS as an ALS treatment.}, }
@article {pmid38664109, year = {2024}, author = {Hastings, RL and Valdez, G}, title = {Origin, identity, and function of terminal Schwann cells.}, journal = {Trends in neurosciences}, volume = {47}, number = {6}, pages = {432-446}, pmid = {38664109}, issn = {1878-108X}, support = {R56 AG077814/AG/NIA NIH HHS/United States ; R01 AG055545/AG/NIA NIH HHS/United States ; T32 AG041688/AG/NIA NIH HHS/United States ; R56 AG051501/AG/NIA NIH HHS/United States ; R21 NS106313/NS/NINDS NIH HHS/United States ; }, mesh = {*Schwann Cells/physiology ; Animals ; Humans ; }, abstract = {The highly specialized nonmyelinating glial cells present at somatic peripheral nerve endings, known collectively as terminal Schwann cells (TSCs), play critical roles in the development, function and repair of their motor and sensory axon terminals and innervating tissue. Over the past decades, research efforts across various vertebrate species have revealed that while TSCs are a diverse group of cells, they share a number of features among them. In this review, we summarize the state-of-knowledge about each TSC type and explore the opportunities that TSCs provide to treat conditions that afflict peripheral axon terminals.}, }
@article {pmid38663088, year = {2024}, author = {Frost, B and Dubnau, J}, title = {The Role of Retrotransposons and Endogenous Retroviruses in Age-Dependent Neurodegenerative Disorders.}, journal = {Annual review of neuroscience}, volume = {47}, number = {1}, pages = {123-143}, doi = {10.1146/annurev-neuro-082823-020615}, pmid = {38663088}, issn = {1545-4126}, support = {RF1 NS112391/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Neurodegenerative Diseases/genetics ; *Retroelements/genetics ; *Endogenous Retroviruses/genetics ; Animals ; *Aging/genetics ; DNA-Binding Proteins/genetics/metabolism ; tau Proteins/genetics/metabolism ; }, abstract = {Over 40% of the human genome is composed of retrotransposons, DNA species that hold the potential to replicate via an RNA intermediate and are evolutionarily related to retroviruses. Retrotransposons are most studied for their ability to jump within a genome, which can cause DNA damage and novel insertional mutations. Retrotransposon-encoded products, including viral-like proteins, double-stranded RNAs, and extrachromosomal circular DNAs, can also be potent activators of the innate immune system. A growing body of evidence suggests that retrotransposons are activated in age-related neurodegenerative disorders and that such activation causally contributes to neurotoxicity. Here we provide an overview of retrotransposon biology and outline evidence of retrotransposon activation in age-related neurodegenerative disorders, with an emphasis on those involving TAR-DNA binding protein-43 (TDP-43) and tau. Studies to date provide the basis for ongoing clinical trials and hold promise for innovative strategies to ameliorate the adverse effects of retrotransposon dysregulation in neurodegenerative disorders.}, }
@article {pmid38661440, year = {2024}, author = {Tate, K and Cummings, G and Jacobsen, F and Halas, G and Van den Bergh, G and Devkota, R and Shrestha, S and Doupe, M}, title = {Strategies to Improve Emergency Transitions From Long-Term Care Facilities: A Scoping Review.}, journal = {The Gerontologist}, volume = {64}, number = {7}, pages = {}, pmid = {38661440}, issn = {1758-5341}, support = {//Norges Forskningsr&#xe5;d/ ; }, mesh = {Humans ; Aged ; *Emergency Service, Hospital ; *Long-Term Care/standards/organization &amp; administration ; *Patient Transfer/standards ; Homes for the Aged/standards/organization &amp; administration ; Aged, 80 and over ; Quality Improvement ; }, abstract = {BACKGROUND AND OBJECTIVES: Older adults residing in residential aged care facilities (RACFs) often experience substandard transitions to emergency departments (EDs) through rationed and delayed ED care. We aimed to identify research describing interventions to improve transitions from RACFs to EDs.<br><br>RESEARCH DESIGN AND METHODS: In our scoping review, we included English language articles that (a) examined an intervention to improve transitions from RACF to EDs; and (b) focused on older adults (&#x2265;65 years). We employed content analysis. Dy et al.'s Care Transitions Framework was used to assess the contextualization of interventions and measurement of implementation success.<br><br>RESULTS: Interventions in 28 studies included geriatric assessment or outreach services (n&#x2005;=&#x2005;7), standardized documentation forms (n&#x2005;=&#x2005;6), models of care to improve transitions from RACFs to EDs (n&#x2005;=&#x2005;6), telehealth services (n&#x2005;=&#x2005;3), nurse-led care coordination programs (n&#x2005;=&#x2005;2), acute-care geriatric departments (n&#x2005;=&#x2005;2), an extended paramedicine program (n&#x2005;=&#x2005;1), and a web-based referral system (n&#x2005;=&#x2005;1). Many studies (n&#x2005;=&#x2005;17) did not define what "improvement" entailed and instead assessed documentation strategies and distal outcomes (e.g., hospital admission rates, length of stay). Few authors reported how they contextualized interventions to align with care environments and/or evaluated implementation success. Few studies included clinician perspectives and no study examined resident- or family/friend caregiver-reported outcomes.<br><br>DISCUSSION AND IMPLICATIONS: Mixed or nonsignificant results prevent us from recommending (or discouraging) any interventions. Given the complexity of these transitions and the need to create sustainable improvement strategies, future research should describe strategies used to embed innovations in care contexts and to measure both implementation and intervention success.}, }
@article {pmid38644578, year = {2024}, author = {Yao, Q and Long, C and Yi, P and Zhang, G and Wan, W and Rao, X and Ying, J and Liang, W and Hua, F}, title = {C/EBPβ: A transcription factor associated with the irreversible progression of Alzheimer's disease.}, journal = {CNS neuroscience &amp; therapeutics}, volume = {30}, number = {4}, pages = {e14721}, pmid = {38644578}, issn = {1755-5949}, support = {jxsq2019201023//Jiangxi Province "Double Thousand Plan"/ ; 82060219//National Natural Science Foundation of China/ ; 82271234//National Natural Science Foundation of China/ ; 20212ACB216009//Natural Science Foundation of Jiangxi Province/ ; 20212BAB216048//Natural Science Foundation of Jiangxi Province/ ; 2019YNTD12003//Youth Team Project of the Second Affiliated Hospital of Nanchang University/ ; }, mesh = {Humans ; *Alzheimer Disease/metabolism/pathology ; *CCAAT-Enhancer-Binding Protein-beta/metabolism/genetics ; *Disease Progression ; Animals ; Amyloid beta-Peptides/metabolism ; }, abstract = {BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder distinguished by a swift cognitive deterioration accompanied by distinctive pathological hallmarks such as extracellular Aβ (β-amyloid) peptides, neuronal neurofibrillary tangles (NFTs), sustained neuroinflammation, and synaptic degeneration. The elevated frequency of AD cases and its proclivity to manifest at a younger age present a pressing challenge in the quest for novel therapeutic interventions. Numerous investigations have substantiated the involvement of C/EBPβ in the progression of AD pathology, thus indicating its potential as a therapeutic target for AD treatment.<br><br>AIMS: Several studies have demonstrated an elevation in the expression level of C/EBP&#x3b2; among individuals afflicted with AD. Consequently, this review predominantly delves into the association between C/EBP&#x3b2; expression and the pathological progression of Alzheimer's disease, elucidating its underlying molecular mechanism, and pointing out the possibility that C/EBP&#x3b2; can be a new therapeutic target for AD.<br><br>METHODS: A systematic literature search was performed across multiple databases, including PubMed, Google Scholar, and so on, utilizing predetermined keywords and MeSH terms, without temporal constraints. The inclusion criteria encompassed diverse study designs, such as experimental, case-control, and cohort studies, restricted to publications in the English language, while conference abstracts and unpublished sources were excluded.<br><br>RESULTS: Overexpression of C/EBP&#x3b2; exacerbates the pathological features of AD, primarily by promoting neuroinflammation and mediating the transcriptional regulation of key molecular pathways, including &#x3b4;-secretase, apolipoprotein E4 (APOE4), acidic leucine-rich nuclear phosphoprotein-32A (ANP32A), transient receptor potential channel 1 (TRPC1), and Forkhead BoxO (FOXO).<br><br>DISCUSSION: The correlation between overexpression of C/EBP&#x3b2; and the pathological development of AD, along with its molecular mechanisms, is evident. Investigating the pathways through which C/EBP&#x3b2; regulates the development of AD reveals numerous multiple vicious cycle pathways exacerbating the pathological progression of the disease. Furthermore, the exacerbation of pathological progression due to C/EBP&#x3b2; overexpression and its molecular mechanism is not limited to AD but also extends to other neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and multiple sclerosis (MS).<br><br>CONCLUSION: The overexpression of C/EBP&#x3b2; accelerates the irreversible progression of AD pathophysiology. Additionally, C/EBP&#x3b2; plays a crucial role in mediating multiple pathways linked to AD pathology, some of which engender vicious cycles, leading to the establishment of feedback mechanisms. To sum up, targeting C/EBP&#x3b2; could hold promise as a therapeutic strategy not only for AD but also for other degenerative diseases.}, }
@article {pmid38635204, year = {2024}, author = {Javalagi, AA and Newman, DA and Li, M}, title = {Personality and leadership: Meta-analytic review of cross-cultural moderation, behavioral mediation, and honesty-humility.}, journal = {The Journal of applied psychology}, volume = {109}, number = {9}, pages = {1489-1511}, doi = {10.1037/apl0001182}, pmid = {38635204}, issn = {1939-1854}, mesh = {Humans ; *Leadership ; *Personality ; *Cross-Cultural Comparison ; Social Behavior ; }, abstract = {We advance the trait approach to leadership by leveraging a large multinational database on leader emergence (k = 120 samples, N = 32,579) and leader effectiveness (k = 116, N = 42,487) to extend Judge et al.'s (2002) classic meta-analysis of Big Five personality and leadership. By testing novel hypotheses rooted in culturally endorsed implicit leadership theory and socioanalytic theory, we offer three unique insights. First, in collectivist societies (cultures that value interdependence with one's group), the five factor model traits-and leader Extraversion and Agreeableness in particular-are stronger predictors of leader effectiveness, consistent with the theorized need for enhanced social coordination in such cultures. Second, a theoretical model is proposed to specify that leader Big Five trait effects are mediated by leader behavior (confirming that Consideration mediates Extraversion and Agreeableness, whereas Initiating Structure mediates Conscientiousness, Extraversion, and Openness). Third, trait Honesty-Humility robustly predicts leader effectiveness beyond the Big Five traits, expanding the trait approach. New implications for understanding when and why personality traits predict leadership are discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).}, }
@article {pmid38631798, year = {2024}, author = {Gerecht, RB and Nable, JV}, title = {Out-of-Hospital Cardiac Arrest.}, journal = {Cardiology clinics}, volume = {42}, number = {2}, pages = {317-331}, doi = {10.1016/j.ccl.2024.02.014}, pmid = {38631798}, issn = {1558-2264}, mesh = {Humans ; *Out-of-Hospital Cardiac Arrest ; *Cardiopulmonary Resuscitation ; *Emergency Medical Services ; }, abstract = {Survival from out-of-hospital cardiac arrest (OHCA) is predicated on a community and system-wide approach that includes rapid recognition of cardiac arrest, capable bystander CPR, effective basic and advanced life support (BLS and ALS) by EMS providers, and coordinated postresuscitation care. Management of these critically ill patients continues to evolve. This article focuses on the management of OHCA by EMS providers.}, }
@article {pmid38630299, year = {2024}, author = {Wolff, A and Demleitner, AF and Feneberg, E and Lingor, P}, title = {[Smell the smoke before one sees the fire-The oligosymptomatic prodromal phase of neurodegenerative diseases].}, journal = {Der Nervenarzt}, volume = {95}, number = {8}, pages = {689-696}, pmid = {38630299}, issn = {1433-0407}, mesh = {*Neurodegenerative Diseases/diagnosis ; *Prodromal Symptoms ; Humans ; *Early Diagnosis ; *Biomarkers/blood ; Disease Progression ; }, abstract = {BACKGROUND: With the increasing development of disease-modifying causative treatment, the importance of early diagnosis and detection of asymptomatic or oligosymptomatic early stages of neurodegenerative diseases is increasing.<br><br>OBJECTIVE: Presentation of early stages of neurodegenerative diseases, diagnostic procedures for the early detection and possible treatment consequences.<br><br>MATERIAL AND METHODS: Selective literature search, discussion of basic research and expert recommendations.<br><br>RESULTS: Many neurodegenerative diseases have a&#xa0;prodromal phase preceding the manifest disease that can be diagnosed with current criteria. In this prodromal phase, those affected are often oligosymptomatic but in some cases can already be identified using biomarkers. These developments are already taken into account in diagnostic criteria for some of these prodromal phases. The prodromal phase, in turn, is preceded by an asymptomatic phase which, however, already shows molecular changes and can be identified by biomarkers in some diseases. The early identification and stratification of patients is particularly important when planning studies for disease-modifying treatment, and biomarkers are already being used in clinical trials for this purpose.<br><br>DISCUSSION: Biomarker-based identification of individuals in the prodromal phase of neurodegenerative diseases is already possible for some entities. People who show the first signs of a&#xa0;neurodegenerative disease can be referred to centers for clinical trials and observational studies.}, }
@article {pmid38628839, year = {2023}, author = {Uzunoglu-Ozyurek, E and Önal, G and Dökmeci, S}, title = {Investigating the Therapeutics Effects of Oral Cavity Derived Stem Cells on Neurodegenerative Diseases: A Systematic Review.}, journal = {Basic and clinical neuroscience}, volume = {14}, number = {5}, pages = {565-584}, pmid = {38628839}, issn = {2008-126X}, abstract = {INTRODUCTION: Published data obtained from in vitro and in vivo studies was reviewed systematically and analyzed critically to evaluate the effect of oral cavity-derived stem cells (OCDSCs) on the recovery or therapy of neurodegenerative diseases (NDs), such as Alzheimer disease (AD), amyotrophic lateral sclerosis (ALS), Huntington (HD) diseases, and Parkinson disease (PD).<br><br>METHODS: An electronic search was accomplished. References of included articles were also manually searched. Studies were critically evaluated for suitability against the inclusion/exclusion criteria and the data was extracted. Bias risk evaluation of the studies and evidence synthesis were conducted.<br><br>RESULTS: A total of 14 in vivo and 10 in vitro studies met the inclusion criteria. PD was induced in 10 in vivo and 7 in vitro studies, while AD was induced in 2 in vivo and 4 in vitro studies. Two studies (1 in vitro and 1 in vivo) evaluated ALS disease and 1 in vivo study evaluated HD. Moderate evidence was found for in vitro studies reporting the positive effect of OCDSCs on PD or AD recovery. Strong evidence was found for in vivo studies in which PD animal models were used; meanwhile, moderate evidence was found for the impact of OCDSCs on AD recovery. Limited evidence was found for in vivo studies evaluating HD and ALS.<br><br>CONCLUSION: Although studies reported favorable data regarding the OCDSCs on NDs, they presented a considerable risk of bias. Because of heterogeneous study characteristics, the current study recommends improving standardized methods to evaluate the therapeutic effects of OCDSCs on the NDs.}, }
@article {pmid38623278, year = {2024}, author = {Inci, OK and Basırlı, H and Can, M and Yanbul, S and Seyrantepe, V}, title = {Gangliosides as Therapeutic Targets for Neurodegenerative Diseases.}, journal = {Journal of lipids}, volume = {2024}, number = {}, pages = {4530255}, pmid = {38623278}, issn = {2090-3030}, abstract = {Gangliosides, sialic acid-containing glycosphingolipids, are abundant in cell membranes and primarily involved in controlling cell signaling and cell communication. The altered ganglioside pattern has been demonstrated in several neurodegenerative diseases, characterized during early-onset or infancy, emphasizing the significance of gangliosides in the brain. Enzymes required for the biosynthesis of gangliosides are linked to several devastating neurological disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), hereditary spastic paraplegia (HSP). In this review, we summarized not only the critical roles of biosynthetic enzymes and their inhibitors in ganglioside metabolism but also the efficacy of treatment strategies of ganglioside to address their significance in those diseases.}, }
@article {pmid38622643, year = {2024}, author = {Filipe, CB and Carreira, NR and Reis-Pina, P}, title = {Optimizing breathlessness management in amyotrophic lateral sclerosis: insights from a comprehensive systematic review.}, journal = {BMC palliative care}, volume = {23}, number = {1}, pages = {100}, pmid = {38622643}, issn = {1472-684X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/therapy ; *Dyspnea/etiology/therapy ; Palliative Care/methods/standards ; Noninvasive Ventilation/methods/standards ; Quality of Life ; Analgesics, Opioid/therapeutic use ; }, abstract = {BACKGROUND: Breathlessness is a prevalent symptom affecting the quality of life (QOL) of Amyotrophic Lateral Sclerosis (ALS) patients. This systematic review explored the interventions for controlling breathlessness in ALS patients, emphasizing palliative care (PALC), non-invasive ventilation (NIV), opioids, and non-pharmacological strategies.<br><br>METHODS: A comprehensive search of PubMed, Cochrane Library, and Web of Science databases was conducted. Eligibility criteria encompassed adults with ALS or motor neuron disease experiencing breathlessness. Outcomes included QOL and symptom control. Study designs comprised qualitative studies, cohort studies, and randomized controlled trials.<br><br>RESULTS: Eight studies were included, most exhibiting low bias risk, comprising one randomized controlled trial, three cohort studies, two comparative retrospective studies, and two qualitative studies (interviews). Most studies originated from Europe, with one from the United States of America. The participants totaled 3423, with ALS patients constituting 95.6%. PALC consultations significantly improved symptom assessment, advance care planning, and discussions about goals of care. NIV demonstrated efficacy in managing breathlessness, with considerations for device limitations. Opioids were effective, though predominantly studied in non-ALS patients. Non-pharmacological strategies varied in efficacy among patients.<br><br>CONCLUSION: The findings underscore the need for individualized approaches in managing breathlessness in ALS. PALC, NIV, opioids, and non-pharmacological strategies each play a role, with unique considerations. Further research, especially ALS-specific self-management studies, is warranted.}, }
@article {pmid38621750, year = {2024}, author = {Kosmachevskaya, OV and Novikova, NN and Yakunin, SN and Topunov, AF}, title = {Formation of Supplementary Metal-Binding Centers in Proteins under Stress Conditions.}, journal = {Biochemistry. Biokhimiia}, volume = {89}, number = {Suppl 1}, pages = {S180-S204}, doi = {10.1134/S0006297924140104}, pmid = {38621750}, issn = {1608-3040}, mesh = {*Metals/chemistry/metabolism ; *Oxidative Stress ; Oxidation-Reduction ; Protein Processing, Post-Translational ; }, abstract = {In many proteins, supplementary metal-binding centers appear under stress conditions. They are known as aberrant or atypical sites. Physico-chemical properties of proteins are significantly changed after such metal binding, and very stable protein aggregates are formed, in which metals act as "cross-linking" agents. Supplementary metal-binding centers in proteins often arise as a result of posttranslational modifications caused by reactive oxygen and nitrogen species and reactive carbonyl compounds. New chemical groups formed as a result of these modifications can act as ligands for binding metal ions. Special attention is paid to the role of cysteine SH-groups in the formation of supplementary metal-binding centers, since these groups are the main target for the action of reactive species. Supplementary metal binding centers may also appear due to unmasking of amino acid residues when protein conformation changing. Appearance of such centers is usually considered as a pathological process. Such unilateral approach does not allow to obtain an integral view of the phenomenon, ignoring cases when formation of metal complexes with altered proteins is a way to adjust protein properties, activity, and stability under the changed redox conditions. The role of metals in protein aggregation is being studied actively, since it leads to formation of non-membranous organelles, liquid condensates, and solid conglomerates. Some proteins found in such aggregates are typical for various diseases, such as Alzheimer's and Huntington's diseases, amyotrophic lateral sclerosis, and some types of cancer.}, }
@article {pmid38621743, year = {2024}, author = {Rezvykh, A and Shteinberg, D and Bronovitsky, E and Ustyugov, A and Funikov, S}, title = {Animal Models of FUS-Proteinopathy: A Systematic Review.}, journal = {Biochemistry. Biokhimiia}, volume = {89}, number = {Suppl 1}, pages = {S34-S56}, doi = {10.1134/S0006297924140037}, pmid = {38621743}, issn = {1608-3040}, mesh = {Animals ; Humans ; *Amyotrophic Lateral Sclerosis/genetics ; RNA-Binding Protein FUS/genetics/metabolism ; Motor Neurons/metabolism/pathology ; Cytoplasm/metabolism ; Mutation ; Disease Models, Animal ; }, abstract = {Mutations that disrupt the function of the DNA/RNA-binding protein FUS could cause amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. One of the key features in ALS pathogenesis is the formation of insoluble protein aggregates containing aberrant isoforms of the FUS protein in the cytoplasm of upper and lower motor neurons. Reproduction of human pathology in animal models is the main tool for studying FUS-associated pathology and searching for potential therapeutic agents for ALS treatment. In this review, we provide a systematic analysis of the role of FUS protein in ALS pathogenesis and an overview of the results of modelling FUS-proteinopathy in animals.}, }
@article {pmid38614367, year = {2024}, author = {Roghani, AK and Garcia, RI and Roghani, A and Reddy, A and Khemka, S and Reddy, RP and Pattoor, V and Jacob, M and Reddy, PH and Sehar, U}, title = {Treating Alzheimer's disease using nanoparticle-mediated drug delivery strategies/systems.}, journal = {Ageing research reviews}, volume = {97}, number = {}, pages = {102291}, doi = {10.1016/j.arr.2024.102291}, pmid = {38614367}, issn = {1872-9649}, support = {R01 AG069333/AG/NIA NIH HHS/United States ; RF1 AG079264/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Alzheimer Disease/drug therapy ; *Drug Delivery Systems/methods ; Animals ; *Blood-Brain Barrier/drug effects/metabolism ; *Nanoparticles/administration &amp; dosage ; Nanoparticle Drug Delivery System ; }, abstract = {The administration of promising medications for the treatment of neurodegenerative disorders (NDDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) is significantly hampered by the blood-brain barrier (BBB). Nanotechnology has recently come to light as a viable strategy for overcoming this obstacle and improving drug delivery to the brain. With a focus on current developments and prospects, this review article examines the use of nanoparticles to overcome the BBB constraints to improve drug therapy for AD The potential for several nanoparticle-based approaches, such as those utilizing lipid-based, polymeric, and inorganic nanoparticles, to enhance drug transport across the BBB are highlighted. To shed insight on their involvement in aiding effective drug transport to the brain, methods of nanoparticle-mediated drug delivery, such as surface modifications, functionalization, and particular targeting ligands, are also investigated. The article also discusses the most recent findings on innovative medication formulations encapsulated within nanoparticles and the therapeutic effects they have shown in both preclinical and clinical testing. This sector has difficulties and restrictions, such as the need for increased safety, scalability, and translation to clinical applications. However, the major emphasis of this review aims to provide insight and contribute to the knowledge of how nanotechnology can potentially revolutionize the worldwide treatment of NDDs, particularly AD, to enhance clinical outcomes.}, }
@article {pmid38612804, year = {2024}, author = {Giri, PM and Banerjee, A and Ghosal, A and Layek, B}, title = {Neuroinflammation in Neurodegenerative Disorders: Current Knowledge and Therapeutic Implications.}, journal = {International journal of molecular sciences}, volume = {25}, number = {7}, pages = {}, pmid = {38612804}, issn = {1422-0067}, support = {P20 GM109024/GM/NIGMS NIH HHS/United States ; 2P20M109024/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; Neuroinflammatory Diseases ; Inflammation/therapy ; *Alzheimer Disease ; *Amyotrophic Lateral Sclerosis ; Central Nervous System ; }, abstract = {Neurodegenerative disorders (NDs) have become increasingly common during the past three decades. Approximately 15% of the total population of the world is affected by some form of NDs, resulting in physical and cognitive disability. The most common NDs include Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease. Although NDs are caused by a complex interaction of genetic, environmental, and lifestyle variables, neuroinflammation is known to be associated with all NDs, often leading to permanent damage to neurons of the central nervous system. Furthermore, numerous emerging pieces of evidence have demonstrated that inflammation not only supports the progression of NDs but can also serve as an initiator. Hence, various medicines capable of preventing or reducing neuroinflammation have been investigated as ND treatments. While anti-inflammatory medicine has shown promising benefits in several preclinical models, clinical outcomes are often questionable. In this review, we discuss various NDs with their current treatment strategies, the role of neuroinflammation in the pathophysiology of NDs, and the use of anti-inflammatory agents as a potential therapeutic option.}, }
@article {pmid38612448, year = {2024}, author = {Homma, H and Tanaka, H and Fujita, K and Okazawa, H}, title = {Necrosis Links Neurodegeneration and Neuroinflammation in Neurodegenerative Disease.}, journal = {International journal of molecular sciences}, volume = {25}, number = {7}, pages = {}, pmid = {38612448}, issn = {1422-0067}, mesh = {Humans ; *HMGB1 Protein ; *Neurodegenerative Diseases ; Neuroinflammatory Diseases ; Necrosis ; Cell Death ; }, abstract = {The mechanisms of neuronal cell death in neurodegenerative disease remain incompletely understood, although recent studies have made significant advances. Apoptosis was previously considered to be the only mechanism of neuronal cell death in neurodegenerative diseases. However, recent findings have challenged this dogma, identifying new subtypes of necrotic neuronal cell death. The present review provides an updated summary of necrosis subtypes and discusses their potential roles in neurodegenerative cell death. Among numerous necrosis subtypes, including necroptosis, paraptosis, ferroptosis, and pyroptosis, transcriptional repression-induced atypical cell death (TRIAD) has been identified as a potential mechanism of neuronal cell death. TRIAD is induced by functional deficiency of TEAD-YAP and self-amplifies via the release of HMGB1. TRIAD is a feasible potential mechanism of neuronal cell death in Alzheimer's disease and other neurodegenerative diseases. In addition to induction of cell death, HMGB1 released during TRIAD activates brain inflammatory responses, which is a potential link between neurodegeneration and neuroinflammation.}, }
@article {pmid38610192, year = {2024}, author = {Papadopoulou, M and Papapostolou, A and Dimakopoulos, R and Salakou, S and Koropouli, E and Fanouraki, S and Bakola, E and Moschovos, C and Tsivgoulis, G}, title = {Non-Pharmacological Interventions on Pain in Amyotrophic Lateral Sclerosis Patients: A Systematic Review and Meta-Analysis.}, journal = {Healthcare (Basel, Switzerland)}, volume = {12}, number = {7}, pages = {}, pmid = {38610192}, issn = {2227-9032}, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting upper and lower motor neurons. Some ALS patients exhibit concomitant nonmotor signs; thus, ALS is considered a multisystemic disorder. Pain is an important nonmotor symptom. Observational and case-control studies report high frequency of pain in ALS patients and it has been correlated with depression and quality of life. There are no specific scales for the assessment of pain and no randomized controlled trials (RCTs) regarding the drug management of pain in ALS.<br><br>AIM: To systematically review the evidence for the nonpharmacological interventions (NPIs) in relieving pain in ALS, on March 2024, we searched the following databases: Pubmed, Scopus, Web of Science, and Cochrane. We also checked the bibliographies of trials identified to include further published or unpublished trials.<br><br>MAIN RESULTS: A total of 1003 records were identified. Finally, five RCTs including 131 patients (64 in the intervention group and 67 in the control group) were included for meta-analysis. The interventions of the included RCTs consisted of muscle exercise, combined aerobics-strength intervention, and osteopathic manual treatment. The meta-analysis did not find a statistically significant difference in favor of NPIs for alleviating pain in ALS patients.<br><br>CONCLUSIONS: ALS has a fulminant course and irreversibly leads to death. Pain in ALS patients, although a common nonmotor symptom, is often unrecognized and undertreated, and this is underlined by the lack of any RCTs on drug therapy for pain. Albeit NPIs are considered safe, as adverse effects are rarely reported, this systematic review did not provide sufficient evidence for a beneficial effect on pain. The scarceness of relevant literature highlights the need for future studies, with larger samples, more homogeneous in terms of interventions and population characteristics (stage of disease), and better choice of measurement scales to further investigate the efficacy, if any, of various pain interventions in ALS patients.}, }
@article {pmid38610012, year = {2024}, author = {Liu, X and Shen, L and Wan, M and Xie, H and Wang, Z}, title = {Peripheral extracellular vesicles in neurodegeneration: pathogenic influencers and therapeutic vehicles.}, journal = {Journal of nanobiotechnology}, volume = {22}, number = {1}, pages = {170}, pmid = {38610012}, issn = {1477-3155}, support = {82301625; 81801395; 82125023; 82072504; 81871822; U22A20300, 81971029//National Natural Science Foundation of China/ ; 82301625; 81801395; 82125023; 82072504; 81871822; U22A20300, 81971029//National Natural Science Foundation of China/ ; 82301625; 81801395; 82125023; 82072504; 81871822; U22A20300, 81971029//National Natural Science Foundation of China/ ; 82301625; 81801395; 82125023; 82072504; 81871822; U22A20300, 81971029//National Natural Science Foundation of China/ ; 2020YFC2008500//National Key R&amp;D Program of China/ ; }, mesh = {Humans ; Prospective Studies ; *Extracellular Vesicles ; *Exosomes ; *Parkinson Disease ; *Alzheimer Disease ; }, abstract = {Neurodegenerative diseases (NDDs) such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis epitomize a class of insidious and relentless neurological conditions that are difficult to cure. Conventional therapeutic regimens often fail due to the late onset of symptoms, which occurs well after irreversible neurodegeneration has begun. The integrity of the blood-brain barrier (BBB) further impedes efficacious drug delivery to the central nervous system, presenting a formidable challenge in the pharmacological treatment of NDDs. Recent scientific inquiries have shifted focus toward the peripheral biological systems, investigating their influence on central neuropathology through the lens of extracellular vesicles (EVs). These vesicles, distinguished by their ability to breach the BBB, are emerging as dual operatives in the context of NDDs, both as conveyors of pathogenic entities and as prospective vectors for therapeutic agents. This review critically summarizes the burgeoning evidence on the role of extracerebral EVs, particularly those originating from bone, adipose tissue, and gut microbiota, in modulating brain pathophysiology. It underscores the duplicity potential of peripheral EVs as modulators of disease progression and suggests their potential as novel vehicles for targeted therapeutic delivery, positing a transformative impact on the future landscape of NDD treatment strategies. Search strategy A comprehensive literature search was conducted using PubMed, Web of Science, and Scopus from January 2000 to December 2023. The search combined the following terms using Boolean operators: "neurodegenerative disease" OR "Alzheimer's disease" OR "Parkinson's disease" OR "Amyotrophic lateral sclerosis" AND "extracellular vesicles" OR "exosomes" OR "outer membrane vesicles" AND "drug delivery systems" AND "blood-brain barrier". MeSH terms were employed when searching PubMed to refine the results. Studies were included if they were published in English, involved human subjects, and focused on the peripheral origins of EVs, specifically from bone, adipose tissue, and gut microbiota, and their association with related diseases such as osteoporosis, metabolic syndrome, and gut dysbiosis. Articles were excluded if they did not address the role of EVs in the context of NDDs or did not discuss therapeutic applications. The titles and abstracts of retrieved articles were screened using a dual-review process to ensure relevance and accuracy. The reference lists of selected articles were also examined to identify additional relevant studies.}, }
@article {pmid38609750, year = {2024}, author = {Sellier, C and Corcia, P and Vourc'h, P and Dupuis, L}, title = {C9ORF72 hexanucleotide repeat expansion: From ALS and FTD to a broader pathogenic role?.}, journal = {Revue neurologique}, volume = {180}, number = {5}, pages = {417-428}, doi = {10.1016/j.neurol.2024.03.008}, pmid = {38609750}, issn = {0035-3787}, mesh = {Humans ; *C9orf72 Protein/genetics ; *Amyotrophic Lateral Sclerosis/genetics ; *Frontotemporal Dementia/genetics ; *DNA Repeat Expansion ; Phenotype ; Genetic Association Studies/methods ; Proteins/genetics ; }, abstract = {The major gene underlying monogenic forms of amyotrophic lateral sclerosis (ALS) and fronto-temporal dementia (FTD) is C9ORF72. The causative mutation in C9ORF72 is an abnormal hexanucleotide (G4C2) repeat expansion (HRE) located in the first intron of the gene. The aim of this review is to propose a comprehensive update on recent developments on clinical, biological and therapeutics aspects related to C9ORF72 in order to highlight the current understanding of genotype-phenotype correlations, and also on biological machinery leading to neuronal death. We will particularly focus on the broad phenotypic presentation of C9ORF72-related diseases, that goes well beyond the classical phenotypes observed in ALS and FTD patients. Last, we will comment the possible therapeutical hopes for patients carrying a C9ORF72 HRE.}, }
@article {pmid38609644, year = {2024}, author = {Khalil, M and Teunissen, CE and Lehmann, S and Otto, M and Piehl, F and Ziemssen, T and Bittner, S and Sormani, MP and Gattringer, T and Abu-Rumeileh, S and Thebault, S and Abdelhak, A and Green, A and Benkert, P and Kappos, L and Comabella, M and Tumani, H and Freedman, MS and Petzold, A and Blennow, K and Zetterberg, H and Leppert, D and Kuhle, J}, title = {Neurofilaments as biomarkers in neurological disorders - towards clinical application.}, journal = {Nature reviews. Neurology}, volume = {20}, number = {5}, pages = {269-287}, pmid = {38609644}, issn = {1759-4766}, mesh = {Humans ; *Biomarkers/metabolism/blood ; *Intermediate Filaments/metabolism ; *Nervous System Diseases/diagnosis/metabolism/blood ; *Neurofilament Proteins/blood/metabolism ; }, abstract = {Neurofilament proteins have been validated as specific body fluid biomarkers of neuro-axonal injury. The advent of highly sensitive analytical platforms that enable reliable quantification of neurofilaments in blood samples and simplify longitudinal follow-up has paved the way for the development of neurofilaments as a biomarker in clinical practice. Potential applications include assessment of disease activity, monitoring of treatment responses, and determining prognosis in many acute and chronic neurological disorders as well as their use as an outcome measure in trials of novel therapies. Progress has now moved the measurement of neurofilaments to the doorstep of routine clinical practice for the evaluation of individuals. In this Review, we first outline current knowledge on the structure and function of neurofilaments. We then discuss analytical and statistical approaches and challenges in determining neurofilament levels in different clinical contexts and assess the implications of neurofilament light chain (NfL) levels in normal ageing and the confounding factors that need to be considered when interpreting NfL measures. In addition, we summarize the current value and potential clinical applications of neurofilaments as a biomarker of neuro-axonal damage in a range of neurological disorders, including multiple sclerosis, Alzheimer disease, frontotemporal dementia, amyotrophic lateral sclerosis, stroke and cerebrovascular disease, traumatic brain injury, and Parkinson disease. We also consider the steps needed to complete the translation of neurofilaments from the laboratory to the management of neurological diseases in clinical practice.}, }
@article {pmid38607083, year = {2024}, author = {Tamberi, L and Belloni, A and Pugnaloni, A and Rippo, MR and Olivieri, F and Procopio, AD and Bronte, G}, title = {The Influence of Myeloid-Derived Suppressor Cell Expansion in Neuroinflammation and Neurodegenerative Diseases.}, journal = {Cells}, volume = {13}, number = {7}, pages = {}, pmid = {38607083}, issn = {2073-4409}, mesh = {Humans ; *Myeloid-Derived Suppressor Cells/pathology ; Neuroinflammatory Diseases ; *Neurodegenerative Diseases/pathology ; Inflammation/pathology ; Cell Proliferation ; }, abstract = {The neuro-immune axis has a crucial function both during physiological and pathological conditions. Among the immune cells, myeloid-derived suppressor cells (MDSCs) exert a pivotal role in regulating the immune response in many pathological conditions, influencing neuroinflammation and neurodegenerative disease progression. In chronic neuroinflammation, MDSCs could lead to exacerbation of the inflammatory state and eventually participate in the impairment of cognitive functions. To have a complete overview of the role of MDSCs in neurodegenerative diseases, research on PubMed for articles using a combination of terms made with Boolean operators was performed. According to the search strategy, 80 papers were retrieved. Among these, 44 papers met the eligibility criteria. The two subtypes of MDSCs, monocytic and polymorphonuclear MDSCs, behave differently in these diseases. The initial MDSC proliferation is fundamental for attenuating inflammation in Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS), but not in amyotrophic lateral sclerosis (ALS), where MDSC expansion leads to exacerbation of the disease. Moreover, the accumulation of MDSC subtypes in distinct organs changes during the disease. The proliferation of MDSC subtypes occurs at different disease stages and can influence the progression of each neurodegenerative disorder differently.}, }
@article {pmid38603949, year = {2024}, author = {Shin-Yi Lin, C and Howells, J and Rutkove, S and Nandedkar, S and Neuwirth, C and Noto, YI and Shahrizaila, N and Whittaker, RG and Bostock, H and Burke, D and Tankisi, H}, title = {Neurophysiological and imaging biomarkers of lower motor neuron dysfunction in motor neuron diseases/amyotrophic lateral sclerosis: IFCN handbook chapter.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {162}, number = {}, pages = {91-120}, doi = {10.1016/j.clinph.2024.03.015}, pmid = {38603949}, issn = {1872-8952}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnostic imaging ; *Motor Neurons/physiology ; *Motor Neuron Disease/physiopathology/diagnostic imaging/diagnosis ; *Biomarkers ; *Electromyography/methods ; *Neural Conduction/physiology ; }, abstract = {This chapter discusses comprehensive neurophysiological biomarkers utilised in motor neuron disease (MND) and, in particular, its commonest form, amyotrophic lateral sclerosis (ALS). These encompass the conventional techniques including nerve conduction studies (NCS), needle and high-density surface electromyography (EMG) and H-reflex studies as well as novel techniques. In the last two decades, new methods of assessing the loss of motor units in a muscle have been developed, that are more convenient than earlier methods of motor unit number estimation (MUNE),and may use either electrical stimulation (e.g. MScanFit MUNE) or voluntary activation (MUNIX). Electrical impedance myography (EIM) is another novel approach for the evaluation that relies upon the application and measurement of high-frequency, low-intensity electrical current. Nerve excitability techniques (NET) also provide insights into the function of an axon and reflect the changes in resting membrane potential, ion channel dysfunction and the structural integrity of the axon and myelin sheath. Furthermore, imaging ultrasound techniques as well as magnetic resonance imaging are capable of detecting the constituents of morphological changes in the nerve and muscle. The chapter provides a critical description of the ability of each technique to provide neurophysiological insight into the complex pathophysiology of MND/ALS. However, it is important to recognise the strengths and limitations of each approach in order to clarify utility. These neurophysiological biomarkers have demonstrated reliability, specificity and provide additional information to validate and assess lower motor neuron dysfunction. Their use has expanded the knowledge about MND/ALS and enhanced our understanding of the relationship between motor units, axons, reflexes and other neural circuits in relation to clinical features of patients with MND/ALS at different stages of the disease. Taken together, the ultimate goal is to aid early diagnosis, distinguish potential disease mimics, monitor and stage disease progression, quantify response to treatment and develop potential therapeutic interventions.}, }
@article {pmid38601118, year = {2024}, author = {Patel, GD and Liu, L and Li, A and Yang, YH and Shen, CC and Brand-Saberi, B and Yang, X}, title = {Mesenchymal stem cell-based therapies for treating well-studied neurological disorders: a systematic review.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1361723}, pmid = {38601118}, issn = {2296-858X}, abstract = {BACKGROUND: Millions of people across the globe are affected by conditions like Amyotrophic Lateral Sclerosis (ALS), Parkinson's Disease (PD), Multiple Sclerosis (MS), Spinal Cord Injury (SCI), and Traumatic Brain Injury (TBI), although most occurrences are common in the elderly population. This systematic review aims to highlight the safety of the procedures, their tolerability, and efficacy of the available therapies conducted over the years using mesenchymal stem cells (MSCs) in treating the neurological conditions mentioned above.<br><br>METHODS: PubMed was used to search for published data from clinical trials performed using mesenchymal stem cells. Studies that provided the necessary information that mentioned the efficacy and adverse effects of the treatment in patients were considered for this review.<br><br>RESULTS: In total, 43 manuscripts were selected after a strategic search, and these studies have been included in this systematic review. Most included studies reported the safety of the procedures used and the treatment's good tolerability, with mild adverse events such as fever, headache, mild pain at the injection site, or nausea being common. A few studies also reported death of some patients, attributed to the progression of the disease to severe stages before the treatment. Other severe events, such as respiratory or urinary infections reported in some studies, were not related to the treatment. Different parameters were used to evaluate the efficacy of the treatment based on the clinical condition of the patient.<br><br>CONCLUSION: Mesenchymal stem cells transplantation has so far proven to be safe and tolerable in select studies and patient types. This systematic review includes the results from the 43 selected studies in terms of safety and tolerability of the procedures, and several adverse events and therapeutic benefits during the follow-up period after administration of MSCs.}, }
@article {pmid38600725, year = {2024}, author = {Madhubala, D and Patra, A and Khan, MR and Mukherjee, AK}, title = {Phytomedicine for neurodegenerative diseases: The road ahead.}, journal = {Phytotherapy research : PTR}, volume = {38}, number = {6}, pages = {2993-3019}, doi = {10.1002/ptr.8192}, pmid = {38600725}, issn = {1099-1573}, support = {//IASST/ ; EMR/2017/001829//Science and Engineering Research Board/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy ; *Catechin/analogs &amp; derivatives/therapeutic use/pharmacology ; *Phytotherapy ; Curcumin/therapeutic use/pharmacology ; Quercetin/pharmacology/therapeutic use ; Animals ; Cannabinoids/therapeutic use/pharmacology ; Apigenin/pharmacology/therapeutic use ; Blood-Brain Barrier/drug effects ; Phytochemicals/pharmacology/therapeutic use ; Plant Extracts/therapeutic use/pharmacology ; }, abstract = {Neurodegenerative disorders (NDs) are among the most common causes of death across the globe. NDs are characterized by progressive damage to CNS neurons, leading to defects in specific brain functions such as memory, cognition, and movement. The most common NDs are Parkinson's, Alzheimer's, Huntington's, and amyotrophic lateral sclerosis (ALS). Despite extensive research, no therapeutics or medications against NDs have been proven to be effective. The current treatment of NDs involving symptom-based targeting of the disease pathogenesis has certain limitations, such as drug resistance, adverse side effects, poor blood-brain barrier permeability, and poor bioavailability of drugs. Some studies have shown that plant-derived natural compounds hold tremendous promise for treating and preventing NDs. Therefore, the primary objective of this review article is to critically analyze the properties and potency of some of the most studied phytomedicines, such as quercetin, curcumin, epigallocatechin gallate (EGCG), apigenin, and cannabinoids, and highlight their advantages and limitations for developing next-generation alternative treatments against NDs. Further extensive research on pre-clinical and clinical studies for developing plant-based drugs against NDs from bench to bedside is warranted.}, }
@article {pmid38599171, year = {2024}, author = {Castro-Gomez, S and Heneka, MT}, title = {Innate immune activation in neurodegenerative diseases.}, journal = {Immunity}, volume = {57}, number = {4}, pages = {790-814}, doi = {10.1016/j.immuni.2024.03.010}, pmid = {38599171}, issn = {1097-4180}, mesh = {Humans ; *Neurodegenerative Diseases ; Receptors, Pattern Recognition ; Immune System ; Inflammation Mediators ; Immunity, Innate ; }, abstract = {Activation of the innate immune system following pattern recognition receptor binding has emerged as one of the major pathogenic mechanisms in neurodegenerative disease. Experimental, epidemiological, pathological, and genetic evidence underscores the meaning of innate immune activation during the prodromal as well as clinical phases of several neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and frontotemporal dementia. Importantly, innate immune activation and the subsequent release of inflammatory mediators contribute mechanistically to other hallmarks of neurodegenerative diseases such as aberrant proteostatis, pathological protein aggregation, cytoskeleton abnormalities, altered energy homeostasis, RNA and DNA defects, and synaptic and network disbalance and ultimately to the induction of neuronal cell death. In this review, we discuss common mechanisms of innate immune activation in neurodegeneration, with particular emphasis on the pattern recognition receptors (PRRs) and other receptors involved in the detection of damage-associated molecular patterns (DAMPs).}, }
@article {pmid38595972, year = {2024}, author = {Zhou, L and Xie, M and Wang, X and Xu, R}, title = {The usage and advantages of several common amyotrophic lateral sclerosis animal models.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1341109}, pmid = {38595972}, issn = {1662-4548}, abstract = {Amyotrophic lateral sclerosis is a fatal, multigenic, multifactorial neurodegenerative disease characterized by upper and lower motor neuron loss. Animal models are essential for investigating pathogenesis and reflecting clinical manifestations, particularly in developing reasonable prevention and therapeutic methods for human diseases. Over the decades, researchers have established a host of different animal models in order to dissect amyotrophic lateral sclerosis (ALS), such as yeast, worms, flies, zebrafish, mice, rats, pigs, dogs, and more recently, non-human primates. Although these models show different peculiarities, they are all useful and complementary to dissect the pathological mechanisms of motor neuron degeneration in ALS, contributing to the development of new promising therapeutics. In this review, we describe several common animal models in ALS, classified by the naturally occurring and experimentally induced, pointing out their features in modeling, the onset and progression of the pathology, and their specific pathological hallmarks. Moreover, we highlight the pros and cons aimed at helping the researcher select the most appropriate among those common experimental animal models when designing a preclinical ALS study.}, }
@article {pmid38592845, year = {2024}, author = {Lerose, V and Ponticelli, M and Benedetto, N and Carlucci, V and Lela, L and Tzvetkov, NT and Milella, L}, title = {Withania somnifera (L.) Dunal, a Potential Source of Phytochemicals for Treating Neurodegenerative Diseases: A Systematic Review.}, journal = {Plants (Basel, Switzerland)}, volume = {13}, number = {6}, pages = {}, pmid = {38592845}, issn = {2223-7747}, support = {CUP: B34I20000320005//Project RESO - REsilienza e SOstenibilit&#xe0; delle filiere ortofrutticole e cerealicole per valorizzare i territori" - cod. identif. ARS01_01224 -/ ; CUP: G49J19001350004//Project SPIA-Valorization of by-products from the agro-food chain/ ; CUP: ECS00000036//Project NODES - Ecosistema dell'Innovazione "Nord Ovest Digitale e Sostenibile"/ ; }, abstract = {Withania somnifera (L.) Dunal is a medicinal plant belonging to the traditional Indian medical system, showing various therapeutic effects such as anti-cancer, anti-inflammatory, anti-microbial, anti-diabetic, and hepatoprotective activity. Of great interest is W. somnifera's potential beneficial effect against neurodegenerative diseases, since the authorized medicinal treatments can only delay disease progression and provide symptomatic relief and are not without side effects. A systematic search of PubMed and Scopus databases was performed to identify preclinical and clinical studies focusing on the applications of W. somnifera in preventing neurodegenerative diseases. Only English articles and those containing the keywords (Withania somnifera AND "neurodegenerative diseases", "neuroprotective effects", "Huntington", "Parkinson", "Alzheimer", "Amyotrophic Lateral Sclerosis", "neurological disorders") in the title or abstract were considered. Reviews, editorials, letters, meta-analyses, conference papers, short surveys, and book chapters were not considered. Selected articles were grouped by pathologies and summarized, considering the mechanism of action. The quality assessment and the risk of bias were performed using the Cochrane Handbook for Systematic Reviews of Interventions checklist. This review uses a systematic approach to summarize the results from 60 investigations to highlight the potential role of W. somnifera and its specialized metabolites in treating or preventing neurodegenerative diseases.}, }
@article {pmid38591201, year = {2024}, author = {Roy, T and Padhi, S and Mazumder, R and Majee, C and Das, S and Monika,  and Mishra, R and Kapoor, B}, title = {Alleviating Neurodegenerative Diseases Associated with Mitochondrial Defects by Therapeutic Biomolecules.}, journal = {Current topics in medicinal chemistry}, volume = {24}, number = {16}, pages = {1377-1407}, pmid = {38591201}, issn = {1873-4294}, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Mitochondria/metabolism/drug effects ; *Antioxidants/pharmacology/chemistry ; Reactive Oxygen Species/metabolism ; Animals ; }, abstract = {Neurodegenerative diseases are emerging as a global health concern in the current scenario, and their association with mitochondrial defects has been a potential area of research. Mitochondria, one of the essential organelles of the cell, serve as the cell's powerhouse, producing energy and ensuring cellular health. Neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis, and Pelizaeus-Merzbacher disease have been found to be primarily triggered by mitochondrial malfunction. One of the key byproducts of mitochondrial respiration, reactive oxygen species, also contributes significantly to mitochondrial DNA mutations that eventually cause mitochondrial breakdown. This review paper comprehensively examines the potential of therapeutic biomolecules, specifically mitochondria-specific antioxidants, in mitigating the impact of mitochondrial defects on neurodegenerative diseases. It provides a detailed analysis of the mechanisms involved in mitochondrial dysfunction, the potential therapeutic targets of these biomolecules, and their structureactivity relationship information are also discussed in this review. Various research articles and publications were used extensively in compiling the data, and the structures of biomolecules were prepared using software such as ChemDraw and ChemSketch. Crucial elements triggering mitochondrial abnormalities were identified and a tabular compilation of bioactive antioxidant compounds along with their therapeutic targets, was presented. Mitochondria-specific antioxidant therapy is an innovative and promising strategy for the management of neurodegenerative diseases associated with mitochondrial defects. This review provides a thorough summary of the current state of research and promising avenues of research and development in this field, emphasizing the importance of further investigations and clinical trials to elucidate their therapeutic benefits.}, }
@article {pmid38588013, year = {2024}, author = {El Hajj, R and Al Sagheer, T and Ballout, N}, title = {Optogenetics in chronic neurodegenerative diseases, controlling the brain with light: A systematic review.}, journal = {Journal of neuroscience research}, volume = {102}, number = {4}, pages = {e25321}, doi = {10.1002/jnr.25321}, pmid = {38588013}, issn = {1097-4547}, mesh = {*Optogenetics/methods ; Animals ; *Neurodegenerative Diseases/therapy/genetics ; Humans ; *Brain/metabolism ; Disease Models, Animal ; Neurons/physiology/metabolism ; Deep Brain Stimulation/methods ; }, abstract = {Neurodegenerative diseases are progressive disorders characterized by synaptic loss and neuronal death. Optogenetics combines optical and genetic methods to control the activity of specific cell types. The efficacy of this approach in neurodegenerative diseases has been investigated in many reviews, however, none of them tackled it systematically. Our study aimed to review systematically the findings of optogenetics and its potential applications in animal models of chronic neurodegenerative diseases and compare it with deep brain stimulation and designer receptors exclusively activated by designer drugs techniques. The search strategy was performed based on the PRISMA guidelines and the risk of bias was assessed following the Systematic Review Centre for Laboratory Animal Experimentation tool. A total of 247 articles were found, of which 53 were suitable for the qualitative analysis. Our data revealed that optogenetic manipulation of distinct neurons in the brain is efficient in rescuing memory impairment, alleviating neuroinflammation, and reducing plaque pathology in Alzheimer's disease. Similarly, this technique shows an advanced understanding of the contribution of various neurons involved in the basal ganglia pathways with Parkinson's disease motor symptoms and pathology. However, the optogenetic application using animal models of Huntington's disease, multiple sclerosis, and amyotrophic lateral sclerosis was limited. Optogenetics is a promising technique that enhanced our knowledge in the research of neurodegenerative diseases and addressed potential therapeutic solutions for managing these diseases' symptoms and delaying their progression. Nevertheless, advanced investigations should be considered to improve optogenetic tools' efficacy and safety to pave the way for their translatability to the clinic.}, }
@article {pmid38586597, year = {2024}, author = {Zhang, T and Bao, L and Chen, H}, title = {Review of Phenotypic Heterogeneity of Neuronal Intranuclear Inclusion Disease and NOTCH2NLC-Related GGC Repeat Expansion Disorders.}, journal = {Neurology. Genetics}, volume = {10}, number = {2}, pages = {e200132}, pmid = {38586597}, issn = {2376-7839}, abstract = {Neuronal intranuclear inclusion disease (NIID) is an underdiagnosed neurodegenerative disorder caused by pathogenic GGC expansions in NOTCH2NLC. However, an increasing number of reports of NOTCH2NLC GGC expansions in patients with Alzheimer disease, essential tremor, Parkinson disease, amyotrophic lateral sclerosis, and oculopharyngodistal myopathy have led to the proposal of a new concept known as NOTCH2NLC-related GGC repeat expansion disorders (NREDs). The majority of studies have mainly focused on screening for NOTCH2NLC GGC repeat variation in populations previously diagnosed with the associated disease, subsequently presenting it as a novel causative gene for the condition. These studies appear to be clinically relevant but do have their limitations because they may incorrectly regard the lack of MRI abnormalities as an exclusion criterion for NIID or overlook concomitant clinical presentations not typically observed in the associated diseases. Besides, in many instances within these reports, patients lack pathologic evidence or undergo long-term follow-up to conclusively rule out NIID. In this review, we will systematically review the research on NOTCH2NLC 5' untranslated region GGC repeat expansions and their association with related neurologic disorders, explaining the limitations of the relevant reports. Furthermore, we will integrate subsequent studies to further demonstrate that these patients actually experienced distinct clinical phenotypes of NIID.}, }
@article {pmid38585631, year = {2024}, author = {Pinilla-González, V and Montecinos-Barrientos, B and Martin-Kommer, C and Chichiarelli, S and Saso, L and Rodrigo, R}, title = {Exploring antioxidant strategies in the pathogenesis of ALS.}, journal = {Open life sciences}, volume = {19}, number = {1}, pages = {20220842}, pmid = {38585631}, issn = {2391-5412}, abstract = {The central nervous system is essential for maintaining homeostasis and controlling the body's physiological functions. However, its biochemical characteristics make it highly vulnerable to oxidative damage, which is a common factor in neurodegenerative diseases like amyotrophic lateral sclerosis (ALS). ALS is a leading cause of motor neuron disease, characterized by a rapidly progressing and incurable condition. ALS often results in death from respiratory failure within 3-5 years from the onset of the first symptoms, underscoring the urgent need to address this medical challenge. The aim of this study is to present available data supporting the role of oxidative stress in the mechanisms underlying ALS and to discuss potential antioxidant therapies currently in development. These therapies aim to improve the quality of life and life expectancy for patients affected by this devastating disease.}, }
@article {pmid38585368, year = {2024}, author = {Jamet, M and Dupuis, L and Gonzalez De Aguilar, JL}, title = {Oligodendrocytes in amyotrophic lateral sclerosis and frontotemporal dementia: the new players on stage.}, journal = {Frontiers in molecular neuroscience}, volume = {17}, number = {}, pages = {1375330}, pmid = {38585368}, issn = {1662-5099}, abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are fatal adult-onset neurodegenerative disorders that share clinical, neuropathological and genetic features, which forms part of a multi-system disease spectrum. The pathological process leading to ALS and FTD is the result of the combination of multiple mechanisms that operate within specific populations of neurons and glial cells. The implication of oligodendrocytes has been the subject of a number of studies conducted on patients and related animal models. In this review we summarize our current knowledge on the alterations specific to myelin and the oligodendrocyte lineage occurring in ALS and FTD. We also consider different ways by which specific oligodendroglial alterations influence neurodegeneration and highlight the important role of oligodendrocytes in these two intrinsically associated neurodegenerative diseases.}, }
@article {pmid38583129, year = {2024}, author = {Thal, DR and Gawor, K and Moonen, S}, title = {Regulated cell death and its role in Alzheimer's disease and amyotrophic lateral sclerosis.}, journal = {Acta neuropathologica}, volume = {147}, number = {1}, pages = {69}, pmid = {38583129}, issn = {1432-0533}, support = {22-AAIIA-963171/ALZ/Alzheimer's Association/United States ; }, mesh = {Humans ; *Alzheimer Disease ; *Amyotrophic Lateral Sclerosis ; *Regulated Cell Death ; Cell Death ; Motor Neurons ; }, abstract = {Despite considerable research efforts, it is still not clear which mechanisms underlie neuronal cell death in neurodegenerative diseases. During the last 20 years, multiple pathways have been identified that can execute regulated cell death (RCD). Among these RCD pathways, apoptosis, necroptosis, pyroptosis, ferroptosis, autophagy-related cell death, and lysosome-dependent cell death have been intensively investigated. Although RCD consists of numerous individual pathways, multiple common proteins have been identified that allow shifting from one cell death pathway to another. Another layer of complexity is added by mechanisms such as the endosomal machinery, able to regulate the activation of some RCD pathways, preventing cell death. In addition, restricted axonal degeneration and synaptic pruning can occur as a result of RCD activation without loss of the cell body. RCD plays a complex role in neurodegenerative processes, varying across different disorders. It has been shown that RCD is differentially involved in Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS), among the most common neurodegenerative diseases. In AD, neuronal loss is associated with the activation of not only necroptosis, but also pyroptosis. In ALS, on the other hand, motor neuron death is not linked to canonical necroptosis, whereas pyroptosis pathway activation is seen in white matter microglia. Despite these differences in the activation of RCD pathways in AD and ALS, the accumulation of protein aggregates immunoreactive for p62/SQSTM1 (sequestosome 1) is a common event in both diseases and many other neurodegenerative disorders. In this review, we describe the major RCD pathways with clear activation in AD and ALS, the main interactions between these pathways, as well as their differential and similar involvement in these disorders. Finally, we will discuss targeting RCD as an innovative therapeutic concept for neurodegenerative diseases, such as AD and ALS. Considering that the execution of RCD or "cellular suicide" represents the final stage in neurodegeneration, it seems crucial to prevent neuronal death in patients by targeting RCD. This would offer valuable time to address upstream events in the pathological cascade by keeping the neurons alive.}, }
@article {pmid38577753, year = {2024}, author = {Yellepeddi, VK and Race, JA and McFarland, MM and Constance, JE and Fanaeian, E and Murphy, NA}, title = {Effectiveness of atropine in managing sialorrhea: A systematic review and meta-analysis.}, journal = {International journal of clinical pharmacology and therapeutics}, volume = {62}, number = {6}, pages = {267-277}, doi = {10.5414/CP204538}, pmid = {38577753}, issn = {0946-1965}, mesh = {*Sialorrhea/drug therapy ; Humans ; *Atropine/therapeutic use ; Treatment Outcome ; Salivation/drug effects ; }, abstract = {OBJECTIVES: To describe the efficacy of atropine in controlling salivary flow in patients with sialorrhea or drooling.<br><br>MATERIALS AND METHODS: We included randomized controlled studies, quasi-randomized trials, case reports, clinical trials, systematic reviews, and meta-analyses assessing the use of atropine in patients with sialorrhea or drooling. The endpoints were reduction in salivary flow rate, amount of saliva secreted, reduction in clinical symptoms of sialorrhea, death rattle intensity, or reduction in drooling intensity as measured by an objective scale such as the drooling intensity scale.<br><br>RESULTS: A total of 56 studies with 2,378 patients were included in the systematic review. The underlying disease states included brain injury, amyotrophic lateral sclerosis, cerebral palsy, clozapine- and perphenazine-induced sialorrhea, Parkinson's disease, and terminal illness. The routes of atropine administration included sublingual, intravenous, subcutaneous, oral tablet or solution, and direct injection of atropine into parotid glands or at the base of the tongue. The generalized estimated equation regression models showed that sublingual administration is superior to oral and subcutaneous routes.<br><br>CONCLUSION: Atropine is efficacious in managing sialorrhea in most disease states. Sublingual administration of atropine is superior to other routes of administration in reducing salivary flow in patients with sialorrhea.}, }
@article {pmid38575486, year = {2024}, author = {Chandran, SK and Doucet, M}, title = {Neurogenic Dysphagia.}, journal = {Otolaryngologic clinics of North America}, volume = {57}, number = {4}, pages = {589-597}, doi = {10.1016/j.otc.2024.02.023}, pmid = {38575486}, issn = {1557-8259}, mesh = {Humans ; *Deglutition Disorders/etiology/therapy/diagnosis ; *Amyotrophic Lateral Sclerosis/complications/therapy ; Multiple Sclerosis/complications ; Parkinson Disease/complications ; Stroke/complications ; }, abstract = {This article provides an overview of neurogenic dysphagia, describing the evaluation and management of swallowing dysfunction in various neurologic diseases. The article will focus on stroke, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis.}, }
@article {pmid38570095, year = {2024}, author = {Wiblin, L}, title = {An introduction to neuropalliative care: A growing need.}, journal = {Clinical medicine (London, England)}, volume = {24}, number = {2}, pages = {100038}, pmid = {38570095}, issn = {1473-4893}, mesh = {Humans ; *Palliative Care/methods ; *Quality of Life ; Motor Neuron Disease/therapy/psychology ; }, abstract = {Palliative care (PC) defined as 'an approach improving the quality of life of patients and their families facing problems associated with life-limiting illness, through the prevention and relief of suffering by means of early identification and impeccable assessment and treatment of pain and other problems, physical, psychosocial and spiritual' aims to enhance the improve the remaining time that patients have, emphasising choice for patients and families.[1] Patients with neurological disease such as Parkinson's (PD) and motor neurone disease (MND) benefit from PC earlier in disease with increasing emphasis over time. Understanding and communicating uncertain trajectories, honest prognostic communication when patients are ready and careful symptom control has been shown to enhance quality of life in patients and caregivers, giving greater autonomy to these patients when supported in decision-making by a palliative approach. Although obstacles to palliative care are frequent, there are strategies which can help overcome them.}, }
@article {pmid38563162, year = {2024}, author = {Pastora, LE and Namburu, NS and Arora, K and Christov, PP and Wilson, JT}, title = {STING-Pathway Inhibiting Nanoparticles (SPINs) as a Platform for Treatment of Inflammatory Diseases.}, journal = {ACS applied bio materials}, volume = {7}, number = {8}, pages = {4867-4878}, pmid = {38563162}, issn = {2576-6422}, support = {T32 DK101003/DK/NIDDK NIH HHS/United States ; P30 DK058404/DK/NIDDK NIH HHS/United States ; }, mesh = {*Membrane Proteins/metabolism/antagonists &amp; inhibitors ; *Nanoparticles/chemistry ; Animals ; Mice ; Inflammation/drug therapy ; Humans ; Biocompatible Materials/chemistry/pharmacology ; Particle Size ; Materials Testing ; Nucleotidyltransferases/antagonists &amp; inhibitors/metabolism ; Signal Transduction/drug effects ; Polylactic Acid-Polyglycolic Acid Copolymer/chemistry ; }, abstract = {Aberrant activation of the cyclic GMP-AMP synthase (cGAS)/Stimulator of Interferon Genes (STING) pathway has been implicated in the development and progression of a myriad of inflammatory diseases including colitis, nonalcoholic steatohepatitis, amyotrophic lateral sclerosis (ALS), and age-related macular degeneration. Thus, STING pathway inhibitors could have therapeutic application in many of these inflammatory conditions. The cGAS inhibitor RU.521 and the STING inhibitor H-151 have shown promise as therapeutics in mouse models of colitis, ALS, and more. However, these agents require frequent high-dose intraperitoneal injections, which may limit translatability. Furthermore, long-term use of systemically administered cGAS/STING inhibitors may leave patients vulnerable to viral infections and cancer. Thus, localized or targeted inhibition of the cGAS/STING pathway may be an attractive, broadly applicable treatment for a variety of STING pathway-driven ailments. Here we describe STING-Pathway Inhibiting Nanoparticles (SPINS)-poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with RU.521 and H-151-as a platform for enhanced and sustained inhibition of cGAS/STING signaling. We demonstrate that SPINs are equally or more effective at inhibiting type-I interferon responses induced by cytosolic DNA than free H-151 or RU.521. Additionally, we describe a SPIN formulation in which PLGA is coemulsified with poly(benzoyloxypropyl methacrylamide) (P(HPMA-Bz)), which significantly improves drug loading and allows for tunable release of H-151 over a period of days to over a week by varying P(HPMA-Bz) content. Finally, we find that all SPIN formulations were as potent or more potent in inhibiting cGAS/STING signaling in primary murine macrophages, resulting in decreased expression of inflammatory M1-like macrophage markers. Therefore, our study provides an in vitro proof-of-concept for nanoparticle delivery of STING pathway inhibitors and positions SPINs as a potential platform for slowing or reversing the onset or progression of cGAS/STING-driven inflammatory conditions.}, }
@article {pmid38563056, year = {2024}, author = {Umar, TP and Jain, N and Papageorgakopoulou, M and Shaheen, RS and Alsamhori, JF and Muzzamil, M and Kostiks, A}, title = {Artificial intelligence for screening and diagnosis of amyotrophic lateral sclerosis: a systematic review and meta-analysis.}, journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration}, volume = {25}, number = {5-6}, pages = {425-436}, doi = {10.1080/21678421.2024.2334836}, pmid = {38563056}, issn = {2167-9223}, mesh = {*Amyotrophic Lateral Sclerosis/diagnosis/epidemiology ; Humans ; *Artificial Intelligence ; }, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a rare and fatal neurological disease that leads to progressive motor function degeneration. Diagnosing ALS is challenging due to the absence of a specific detection test. The use of artificial intelligence (AI) can assist in the investigation and treatment of ALS.<br><br>METHODS: We searched seven databases for literature on the application of AI in the early diagnosis and screening of ALS in humans. The findings were summarized using random-effects summary receiver operating characteristic curve. The risk of bias (RoB) analysis was carried out using QUADAS-2 or QUADAS-C tools.<br><br>RESULTS: In the 34 analyzed studies, a meta-prevalence of 47% for ALS was noted. For ALS detection, the pooled sensitivity of AI models was 94.3% (95% CI - 63.2% to 99.4%) with a pooled specificity of 98.9% (95% CI - 92.4% to 99.9%). For ALS classification, the pooled sensitivity of AI models was 90.9% (95% CI - 86.5% to 93.9%) with a pooled specificity of 92.3% (95% CI - 84.8% to 96.3%). Based on type of input for classification, the pooled sensitivity of AI models for gait, electromyography, and magnetic resonance signals was 91.2%, 92.6%, and 82.2%, respectively. The pooled specificity for gait, electromyography, and magnetic resonance signals was 94.1%, 96.5%, and 77.3%, respectively.<br><br>CONCLUSIONS: Although AI can play a significant role in the screening and diagnosis of ALS due to its high sensitivities and specificities, concerns remain regarding quality of evidence reported in the literature.}, }
@article {pmid38561605, year = {2024}, author = {Singh, K and Gupta, JK and Kumar, S and Soni, U}, title = {A Review of the Common Neurodegenerative Disorders: Current Therapeutic Approaches and the Potential Role of Bioactive Peptides.}, journal = {Current protein &amp; peptide science}, volume = {25}, number = {7}, pages = {507-526}, pmid = {38561605}, issn = {1875-5550}, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/metabolism/pathology ; *Peptides/therapeutic use/chemistry/pharmacology ; Animals ; Alzheimer Disease/drug therapy/metabolism/pathology ; Parkinson Disease/drug therapy/metabolism/pathology ; Neuroprotective Agents/therapeutic use/pharmacology/chemistry ; Oxidative Stress/drug effects ; Huntington Disease/drug therapy/metabolism/pathology ; Amyotrophic Lateral Sclerosis/drug therapy/metabolism/pathology ; Cholinesterase Inhibitors/therapeutic use/pharmacology/chemistry ; }, abstract = {Neurodegenerative disorders, which include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), represent a significant and growing global health challenge. Current therapies predominantly focus on symptom management rather than altering disease progression. In this review, we discuss the major therapeutic strategies in practice for these disorders, highlighting their limitations. For AD, the mainstay treatments are cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists. For PD, dopamine replacement therapies, including levodopa, are commonly used. HD is managed primarily with symptomatic treatments, and reusable extends survival in ALS. However, none of these therapies halts or substantially slows the neurodegenerative process. In contrast, this review highlights emerging research into bioactive peptides as potential therapeutic agents. These naturally occurring or synthetically designed molecules can interact with specific cellular targets, potentially modulating disease processes. Preclinical studies suggest that bioactive peptides may mitigate oxidative stress, inflammation, and protein misfolding, which are common pathological features in neurodegenerative diseases. Clinical trials using bioactive peptides for neurodegeneration are limited but show promising initial results. For instance, hemiacetal, a γ-secretase inhibitor peptide, has shown potential in AD by reducing amyloid-beta production, though its development was discontinued due to side effects. Despite these advancements, many challenges remain, including identifying optimal peptides, confirming their mechanisms of action, and overcoming obstacles related to their delivery to the brain. Future research should prioritize the discovery and development of novel bioactive peptides and improve our understanding of their pharmacokinetics and pharmacodynamics. Ultimately, this approach may lead to more effective therapies for neurodegenerative disorders, moving beyond symptom management to potentially modify the course of these devastating diseases.}, }
@article {pmid38560980, year = {2024}, author = {Xiang, SR and Ma, Q and Dong, J and Ren, YF and Lin, JZ and Zheng, C and Xiao, P and You, FM}, title = {Contrasting Effects of Music Therapy and Aromatherapy on Perioperative Anxiety: A Systematic Review and Meta-Analysis.}, journal = {Complementary medicine research}, volume = {31}, number = {3}, pages = {278-291}, doi = {10.1159/000538425}, pmid = {38560980}, issn = {2504-2106}, mesh = {*Aromatherapy ; *Music Therapy ; Humans ; *Anxiety/therapy ; Heart Rate ; }, abstract = {INTRODUCTION: Music therapy and aromatherapy have been demonstrated effective for perioperative anxiety. However, the available studies have indicated discordant results about which adjunct treatment is better for perioperative anxiety. Therefore, we conducted this meta-analysis to explore the contrasting effects between them.<br><br>METHODS: Six electronic databases were searched for clinical trials evaluating the efficacy of music therapy compared with aromatherapy in alleviating perioperative anxiety. The primary outcome was the postintervention anxiety level. Secondary outcomes included differences in blood pressure and heart rate before and after the intervention as well as pain scores at intraoperative and postoperative time points. The study protocol was registered on PROSPERO (CRD42021249737).<br><br>RESULTS: Twelve studies (894 patients) were included. The anxiety level showed no statistically significant difference (SMD, 0.28; 95% CI: -0.12, 0.68; p = 0.17). The analysis of blood pressure and heart rate also did not identify statistically significant differences. Notably, the pain scores at the intraoperative time point suggested that aromatherapy was superior to music therapy (WMD, 0.29 cm; 95% CI: 0.05, 0.52; p = 0.02), while those at 4 h after surgery indicated the opposite results (WMD, -0.48 cm; 95% CI: -0.60, -0.36; p < 0.001).<br><br>CONCLUSION: Low-to-moderate quality evidence suggests that music therapy and aromatherapy have similar potential to relieve perioperative anxiety. The potential data indicate that the two therapies have different benefits in intervention duration and age distribution. More direct high-quality comparisons are encouraged in the future to verify this point.<br><br>UNLABELLED: <title>Einleitung</title>Musik- und Aromatherapie haben sich bei perioperativen Angstzust&#xe4;nden als wirksam erwiesen. Die verf&#xfc;gbaren Studien zeigten jedoch widerspr&#xfc;chliche Ergebnisse zur Frage, welche adjuvante Therapie bei perioperativen Angstzust&#xe4;nden besser ist. Daher f&#xfc;hrten wir die vorliegende Metaanalyse durch, um die unterschiedlichen Effekte der beiden Therapien zu untersuchen.<title>Methoden</title>Sechs (6) elektronische Datenbanken wurden nach klinischen Studien zur Wirksamkeit von Musiktherapie im Vergleich zur Aromatherapie bei der Linderung perioperativer Angstzust&#xe4;nde durchsucht. Prim&#xe4;res Zielkriterium war das Angstniveau nach der Intervention. Die sekund&#xe4;ren Zielkriterien umfassten die Unterschiede bei Blutdruck und Herzfrequenz vor und nach der Intervention sowie die Schmerz-Scores zu intra- und postoperativen Zeitpunkten. Das Studienprotokoll wurde auf PROSPERO (CRD42021249737) registriert.<title>Ergebnisse</title>Zw&#xf6;lf (12) Studien (894 Patienten) wurden eingeschlossen. Das Angstniveau zeigte keinen statistisch signifikanten Unterschied (SMD, 0,28; 95%-KI: &#x2212;0,12, 0,68, <italic>p</italic>&#xa0;=&#xa0;0,17) und auch die Analyse von Blutdruck und Herzfrequenz ergab keine statistisch signifikanten Unterschiede. Insbesondere die Schmerz-Scores zum intraoperativen Zeitpunkt sprachen daf&#xfc;r, dass die Aromatherapie gegen&#xfc;ber der Musiktherapie &#xfc;berlegen war (WMD, 0,29&#xa0;cm; 95%-KI: 0,05, 0,52; <italic>p&#xa0;</italic>=&#xa0;0,02), w&#xe4;hrend die Werte 4 Stunden nach der Operation gegenteilige Ergebnisse zeigten (WMD, &#x2212;0,48 cm; 95%-KI: &#x2212;0,60, &#x2212;0,36, <italic>p</italic>&#xa0;<&#xa0;0,001).<title>Schlussfolgerung</title>Evidenzen von geringer bis m&#xe4;ssiger Qualit&#xe4;t deuten darauf hin, dass Musik- und Aromatherapie ein vergleichbares Potenzial bei der Linderung perioperativer &#xc4;ngste besitzen. Die potenziellen Daten zeigen, dass die beiden Therapien unterschiedliche Vorteile hinsichtlich Interventionsdauer und Altersverteilung haben. K&#xfc;nftig sollten mehr direkte und qualitativ hochwertige Vergleiche durchgef&#xfc;hrt werden, um diesen Aspekt zu &#xfc;berpr&#xfc;fen.}, }
@article {pmid38560897, year = {2024}, author = {Minatoguchi, S and Fujita, Y and Niizuma, K and Tominaga, T and Yamashita, T and Abe, K and Dezawa, M}, title = {Donor Muse Cell Treatment Without HLA-Matching Tests and Immunosuppressant Treatment.}, journal = {Stem cells translational medicine}, volume = {13}, number = {6}, pages = {532-545}, pmid = {38560897}, issn = {2157-6580}, support = {//New Energy and Industrial Technology Development Organization/ ; //Japan Agency for Medical Research and Development/ ; //Ministry of Education, Culture, Sports, Science and Technology/ ; //Japan Society for the Promotion of Science/ ; //SENSHIN Medical Research Foundation/ ; //Life Science Institute Inc/ ; }, mesh = {Humans ; *Mesenchymal Stem Cells/cytology/metabolism ; Mesenchymal Stem Cell Transplantation/methods ; Immunosuppressive Agents/pharmacology/therapeutic use ; HLA Antigens/metabolism ; Cell Differentiation ; Animals ; Histocompatibility Testing/methods ; }, abstract = {The strength of stem cell therapy is the regeneration of tissues by synergistic pleiotropic effects. Among many stem cell types, mesenchymal stem cells (MSCs) that are comprised of heterogenous population are widely used for clinical applications with the expectation of pleiotropic bystander effects. Muse cells are pluripotent-like/macrophage-like stem cells distributed in the bone marrow, peripheral blood, and organ connective tissues as cells positive for the pluripotent surface marker stage-specific-embryonic antigen -3. Muse cells comprise ~1% to several percent of MSCs. While Muse cells and MSCs share several characteristics, such as mesenchymal surface marker expression and their bystander effects, Muse cells exhibit unique characteristics not observed in MSCs. These unique characteristics of Muse cells include selective homing to damaged tissue after intravenous injection rather than being trapped in the lung like MSCs, replacement of a wide range of damaged/apoptotic cells by differentiation through phagocytosis, and long-lasting immunotolerance for donor cell use. In this review, we focus on the basic properties of Muse cells clarified through preclinical studies and clinical trials conducted by intravenous injection of donor-Muse cells without HLA-matching tests or immunosuppressant treatment. MSCs are considered to differentiate into osteogenic, chondrogenic, and adipogenic cells, whereas the range of their differentiation has long been debated. Muse cells may provide clues to the wide-ranging differentiation potential of MSCs that are observed with low frequency. Furthermore, the utilization of Muse cells may provide a novel strategy for clinical treatment.}, }
@article {pmid38558150, year = {2024}, author = {Pensato, U and Cortelli, P}, title = {Soccer (football) and brain health.}, journal = {Journal of neurology}, volume = {271}, number = {6}, pages = {3019-3029}, pmid = {38558150}, issn = {1432-1459}, mesh = {Humans ; *Soccer/injuries ; *Brain Concussion/complications/epidemiology/etiology ; Athletic Injuries/complications ; Brain/physiopathology ; Chronic Traumatic Encephalopathy/etiology ; }, abstract = {Soccer is one of the most popular sports worldwide, played by over 270 million people and followed by many more. Several brain health benefits are promoted by practising soccer and physical exercise at large, which helps contrast the cognitive decline associated with ageing by enhancing neurogenesis processes. However, sport-related concussions have been increasingly recognised as a pressing public health concern, not only due to their acute impact but also, more importantly, due to mounting evidence indicating an elevated risk for the development of neurological sequelae following recurrent head traumas, especially chronic traumatic encephalopathy (CTE). While soccer players experience less frequent concussions compared with other contact or combat sports, such as American football or boxing, it stands alone in its purposeful use of the head to hit the ball (headings), setting its players apart as the only athletes exposed to intentional, sub-concussive head impacts. Additionally, an association between soccer and amyotrophic lateral sclerosis has been consistently observed, suggesting a potential "soccer-specific" risk factor. In this review, we discuss the neurological sequelae related to soccer playing, the emerging evidence of a detrimental effect related to recurrent headings, and the need for implementation of comprehensive strategies aimed at preventing and managing the burden of head impact in soccer.}, }
@article {pmid38552851, year = {2024}, author = {Yang, L and Guttman, L and Dawson, VL and Dawson, TM}, title = {Parthanatos: Mechanisms, modulation, and therapeutic prospects in neurodegenerative disease and stroke.}, journal = {Biochemical pharmacology}, volume = {228}, number = {}, pages = {116174}, pmid = {38552851}, issn = {1873-2968}, support = {R01 AG085688/AG/NIA NIH HHS/United States ; R01 NS067525/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/metabolism ; Animals ; *Stroke/drug therapy/metabolism/therapy ; *Parthanatos/drug effects/physiology ; Neuroprotective Agents/therapeutic use ; }, abstract = {Parthanatos is a cell death signaling pathway that has emerged as a compelling target for pharmaceutical intervention. It plays a pivotal role in the neuron loss and neuroinflammation that occurs in Parkinson's Disease (PD), Alzheimer's Disease (AD), Huntington's Disease (HD), Amyotrophic Lateral Sclerosis (ALS), and stroke. There are currently no treatments available to humans to prevent cell death in any of these diseases. This review provides an in-depth examination of the current understanding of the Parthanatos mechanism, with a particular focus on its implications in neuroinflammation and various diseases discussed herein. Furthermore, we thoroughly review potential intervention targets within the Parthanatos pathway. We dissect recent progress in inhibitory strategies, complimented by a detailed structural analysis of key Parthanatos executioners, PARP-1, AIF, and MIF, along with an assessment of their established inhibitors. We hope to introduce a new perspective on the feasibility of targeting components within the Parthanatos pathway, emphasizing its potential to bring about transformative outcomes in therapeutic interventions. By delineating therapeutic opportunities and known targets, we seek to emphasize the imperative of blocking Parthanatos as a precursor to developing disease-modifying treatments. This comprehensive exploration aims to catalyze a paradigm shift in our understanding of potential neurodegenerative disease therapeutics, advocating for the pursuit of effective interventions centered around Parthanatos inhibition.}, }
@article {pmid38551974, year = {2024}, author = {Jiménez-García, AM and Bonnel, G and Álvarez-Mota, A and Arias, N}, title = {Current perspectives on neuromodulation in ALS patients: A systematic review and meta-analysis.}, journal = {PloS one}, volume = {19}, number = {3}, pages = {e0300671}, pmid = {38551974}, issn = {1932-6203}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; Quality of Life ; *Neurodegenerative Diseases ; Exercise Therapy/methods ; Muscle Spasticity ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease that affects motor neurons, resulting in muscle weakness, paralysis, and eventually patient mortality. In recent years, neuromodulation techniques have emerged as promising potential therapeutic approaches to slow disease progression and improve the quality of life of ALS patients. A systematic review was conducted until August 8, 2023, to evaluate the neuromodulation methods used and their potential in the treatment of ALS. The search strategy was applied in the Cochrane Central database, incorporating results from other databases such as PubMed, Embase, CTgov, CINAHL, and ICTRP. Following the exclusion of papers that did not fulfil the inclusion criteria, a total of 2090 records were found, leaving a total of 10 studies. R software was used to conduct meta-analyses based on the effect sizes between the experimental and control groups. This revealed differences in muscle stretch measures with manual muscle testing (p = 0.012) and resting motor threshold (p = 0.0457), but not with voluntary isometric contraction (p = 0.1883). The functionality of ALS was also different (p = 0.007), but not the quality of life. Although intracortical facilitation was not seen in motor cortex 1 (M1) (p = 0.1338), short-interval intracortical inhibition of M1 was significant (p = 0.0001). BDNF showed no differences that were statistically significant (p = 0.2297). Neuromodulation-based treatments are proposed as a promising therapeutic approach for ALS that can produce effects on muscle function, spasticity, and intracortical connections through electrical, magnetic, and photonic stimulation. Photobiomodulation stands out as an innovative approach that uses specific wavelengths to influence mitochondria, with the aim of improving mitochondrial function and reducing excitotoxicity. The lack of reliable placebo controls and the variation in stimulation frequency are some of the drawbacks of neuromodulation.}, }
@article {pmid38550565, year = {2024}, author = {Di Nardo, AA and Prochiantz, A}, title = {Therapeutic value of homeoprotein signaling pathways.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1359523}, pmid = {38550565}, issn = {1662-4548}, abstract = {Cell signaling based on homeoprotein transfer is a pathway with developmental and physiological functions. For a few transcription factors of this family, primarily ENGRAILED1, ENGRAILED2 and OTX2, their physiological functions have led to therapeutic strategies in animal models of human diseases, including Parkinson's disease, amyotrophic lateral sclerosis, amblyopia and anxiety-related disorders. In mesencephalic dopaminergic neurons which degenerate in Parkinson's disease, ENGRAILED1/2 have cell autonomous activities, but their transducing properties enables their use as therapeutic proteins. In contrast, in spinal alpha-motoneurons, which are lost in amyotrophic lateral sclerosis, ENGRAILED1 is supplied by V1 interneurons. Thus, its use as a therapeutic protein to protect alpha-motoneurons against degeneration mimics its normal non-cell autonomous neurotrophic activity. OTX2, synthesized and secreted by the choroid plexus, is transferred to parvalbumin interneurons and exerts regulatory functions controlling cerebral cortex plasticity. Understanding the latter OTX2 function has led to strategies for manipulating visual acuity and anxiety-like behavior in adult mice. In this review, we describe these cases and what is known about the involved molecular mechanisms. Because the transduction sequences are conserved in most of the few hundred homeoproteins, we argue how this family of molecules constitutes an important reservoir of physiological knowledge, with potential consequences in the search for new therapeutic strategies.}, }
@article {pmid38548126, year = {2024}, author = {Krut', VG and Kalinichenko, AL and Maltsev, DI and Jappy, D and Shevchenko, EK and Podgorny, OV and Belousov, VV}, title = {Optogenetic and chemogenetic approaches for modeling neurological disorders in vivo.}, journal = {Progress in neurobiology}, volume = {235}, number = {}, pages = {102600}, doi = {10.1016/j.pneurobio.2024.102600}, pmid = {38548126}, issn = {1873-5118}, mesh = {Animals ; Humans ; Optogenetics/methods ; *Epilepsy ; Models, Animal ; *Parkinson Disease ; Neuropathology ; }, abstract = {Animal models of human neurological disorders provide valuable experimental tools which enable us to study various aspects of disorder pathogeneses, ranging from structural abnormalities and disrupted metabolism and signaling to motor and mental deficits, and allow us to test novel therapies in preclinical studies. To be valid, these animal models should recapitulate complex pathological features at the molecular, cellular, tissue, and behavioral levels as closely as possible to those observed in human subjects. Pathological states resembling known human neurological disorders can be induced in animal species by toxins, genetic factors, lesioning, or exposure to extreme conditions. In recent years, novel animal models recapitulating neuropathologies in humans have been introduced. These animal models are based on synthetic biology approaches: opto- and chemogenetics. In this paper, we review recent opto- and chemogenetics-based animal models of human neurological disorders. These models allow for the creation of pathological states by disrupting specific processes at the cellular level. The artificial pathological states mimic a range of human neurological disorders, such as aging-related dementia, Alzheimer's and Parkinson's diseases, amyotrophic lateral sclerosis, epilepsy, and ataxias. Opto- and chemogenetics provide new opportunities unavailable with other animal models of human neurological disorders. These techniques enable researchers to induce neuropathological states varying in severity and ranging from acute to chronic. We also discuss future directions for the development and application of synthetic biology approaches for modeling neurological disorders.}, }
@article {pmid38542497, year = {2024}, author = {Nemeth, C and Banik, NL and Haque, A}, title = {Disruption of Neuromuscular Junction Following Spinal Cord Injury and Motor Neuron Diseases.}, journal = {International journal of molecular sciences}, volume = {25}, number = {6}, pages = {}, pmid = {38542497}, issn = {1422-0067}, support = {R21 NS118393/NS/NINDS NIH HHS/United States ; I01 BX001262/BX/BLRD VA/United States ; 1R21NS118393-01/NH/NIH HHS/United States ; I01 BX004269/BX/BLRD VA/United States ; I01 BX006101/BX/BLRD VA/United States ; IK6 BX005964/BX/BLRD VA/United States ; }, mesh = {Humans ; Neuromuscular Junction/metabolism ; Motor Neurons/metabolism ; Muscle Fibers, Skeletal/metabolism ; Spinal Cord/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism ; *Spinal Cord Injuries/metabolism ; }, abstract = {The neuromuscular junction (NMJ) is a crucial structure that connects the cholinergic motor neurons to the muscle fibers and allows for muscle contraction and movement. Despite the interruption of the supraspinal pathways that occurs in spinal cord injury (SCI), the NMJ, innervated by motor neurons below the injury site, has been found to remain intact. This highlights the importance of studying the NMJ in rodent models of various nervous system disorders, such as amyotrophic lateral sclerosis (ALS), Charcot-Marie-Tooth disease (CMT), spinal muscular atrophy (SMA), and spinal and bulbar muscular atrophy (SBMA). The NMJ is also involved in myasthenic disorders, such as myasthenia gravis (MG), and is vulnerable to neurotoxin damage. Thus, it is important to analyze the integrity of the NMJ in rodent models during the early stages of the disease, as this may allow for a better understanding of the condition and potential treatment options. The spinal cord also plays a crucial role in the functioning of the NMJ, as the junction relays information from the spinal cord to the muscle fibers, and the integrity of the NMJ could be disrupted by SCI. Therefore, it is vital to study SCI and muscle function when studying NMJ disorders. This review discusses the formation and function of the NMJ after SCI and potential interventions that may reverse or improve NMJ dysfunction, such as exercise, nutrition, and trophic factors.}, }
@article {pmid38542306, year = {2024}, author = {Marshall Moscon, SL and Connor, JR}, title = {HFE Mutations in Neurodegenerative Disease as a Model of Hormesis.}, journal = {International journal of molecular sciences}, volume = {25}, number = {6}, pages = {}, pmid = {38542306}, issn = {1422-0067}, mesh = {Mice ; Animals ; *Neurodegenerative Diseases/genetics ; Hemochromatosis Protein/genetics ; Histocompatibility Antigens Class I/genetics ; Hormesis ; Mutation ; Iron/metabolism ; }, abstract = {Common variants in the iron regulatory protein HFE contribute to systematically increased iron levels, yet the effects in the brain are not fully characterized. It is commonly believed that iron dysregulation is a key contributor to neurodegenerative disease due to iron's ability to catalyze reactive oxygen species production. However, whether HFE variants exacerbate or protect against neurodegeneration has been heavily debated. Some claim that mutated HFE exacerbates oxidative stress and neuroinflammation, thus predisposing carriers to neurodegeneration-linked pathologies. However, H63D HFE has also been shown to slow the progression of multiple neurodegenerative diseases and to protect against environmental toxins that cause neurodegeneration. These conflicting results showcase the need to further understand the contribution of HFE variants to neurodegenerative disease heterogeneity. Data from mouse models consistently demonstrate robust neuroprotection against toxins known to increase the risk of neurodegenerative disease. This may represent an adaptive, or hormetic, response to increased iron, which leaves cells better protected against future stressors. This review describes the current research regarding the contribution of HFE variants to neurodegenerative disease prognosis in the context of a hormetic model. To our knowledge, this is the first time that a hormetic model for neurodegenerative disease has been presented.}, }
@article {pmid38540795, year = {2024}, author = {Gascón, E and Zaragoza, P and Calvo, AC and Osta, R}, title = {Sporadic Amyotrophic Lateral Sclerosis Skeletal Muscle Transcriptome Analysis: A Comprehensive Examination of Differentially Expressed Genes.}, journal = {Biomolecules}, volume = {14}, number = {3}, pages = {}, pmid = {38540795}, issn = {2218-273X}, support = {PI17/00949//Instituto de Salud Carlos III/ ; A19_23R//"LAGENBIO GRUPO INVESTIGACION"/ ; CIBER-358 NED-612-CB18/05/00037//Centro de Investigaci&#xf3;n Biom&#xe9;dica en Red sobre Enfermedades Neurodegenerativas/ ; }, mesh = {Humans ; Transcriptome/genetics ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; *MicroRNAs/genetics/metabolism ; Muscle, Skeletal/metabolism ; Biomarkers ; }, abstract = {Amyotrophic lateral sclerosis (ALS) that comprises sporadic (sALS) and familial (fALS) cases, is a devastating neurodegenerative disorder characterized by progressive degeneration of motor neurons, leading to muscle atrophy and various clinical manifestations. However, the complex underlying mechanisms affecting this disease are not yet known. On the other hand, there is also no good prognosis of the disease due to the lack of biomarkers and therapeutic targets. Therefore, in this study, by means of bioinformatics analysis, sALS-affected muscle tissue was analyzed using the GEO GSE41414 dataset, identifying 397 differentially expressed genes (DEGs). Functional analysis revealed 320 up-regulated DEGs associated with muscle development and 77 down-regulated DEGs linked to energy metabolism. Protein-protein interaction network analysis identified 20 hub genes, including EIF4A1, HNRNPR and NDUFA4. Furthermore, miRNA target gene networks revealed 17 miRNAs linked to hub genes, with hsa-mir-206, hsa-mir-133b and hsa-mir-100-5p having been previously implicated in ALS. This study presents new potential biomarkers and therapeutic targets for ALS by correlating the information obtained with a comprehensive literature review, providing new potential targets to study their role in ALS.}, }
@article {pmid38540709, year = {2024}, author = {Stoklund Dittlau, K and Freude, K}, title = {Astrocytes: The Stars in Neurodegeneration?.}, journal = {Biomolecules}, volume = {14}, number = {3}, pages = {}, pmid = {38540709}, issn = {2218-273X}, support = {R434-2023-242//Lundbeck Foundation/ ; 2078-00002B//Innovation Fund Denmark/ ; NNF21OC0071571//Novo Nordisk Foundation/ ; N/A//Alzheimer Foundation Denmark/ ; }, mesh = {Humans ; Astrocytes/physiology ; *Neurodegenerative Diseases ; *Alzheimer Disease ; *Parkinson Disease ; *Amyotrophic Lateral Sclerosis/therapy ; }, abstract = {Today, neurodegenerative disorders like Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) affect millions of people worldwide, and as the average human lifespan increases, similarly grows the number of patients. For many decades, cognitive and motoric decline has been explained by the very apparent deterioration of neurons in various regions of the brain and spinal cord. However, more recent studies show that disease progression is greatly influenced by the vast population of glial cells. Astrocytes are traditionally considered star-shaped cells on which neurons rely heavily for their optimal homeostasis and survival. Increasing amounts of evidence depict how astrocytes lose their supportive functions while simultaneously gaining toxic properties during neurodegeneration. Many of these changes are similar across various neurodegenerative diseases, and in this review, we highlight these commonalities. We discuss how astrocyte dysfunction drives neuronal demise across a wide range of neurodegenerative diseases, but rather than categorizing based on disease, we aim to provide an overview based on currently known mechanisms. As such, this review delivers a different perspective on the disease causes of neurodegeneration in the hope to encourage further cross-disease studies into shared disease mechanisms, which might ultimately disclose potentially common therapeutic entry points across a wide panel of neurodegenerative diseases.}, }
@article {pmid38540369, year = {2024}, author = {Souza, PVS and Serrano, PL and Farias, IB and Machado, RIL and Badia, BML and Oliveira, HB and Barbosa, AS and Pereira, CA and Moreira, VF and Chieia, MAT and Barbosa, AR and Braga, VL and Pinto, WBVR and Oliveira, ASB}, title = {Clinical and Genetic Aspects of Juvenile Amyotrophic Lateral Sclerosis: A Promising Era Emerges.}, journal = {Genes}, volume = {15}, number = {3}, pages = {}, pmid = {38540369}, issn = {2073-4425}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics ; Motor Neurons ; Neuroimaging ; }, abstract = {Juvenile Amyotrophic Lateral Sclerosis is a genetically heterogeneous neurodegenerative disorder, which is frequently misdiagnosed due to low clinical suspicion and little knowledge about disease characteristics. More than 20 different genetic loci have been associated with both sporadic and familial juvenile Amyotrophic Lateral Sclerosis. Currently, almost 40% of cases have an identifiable monogenic basis; type 6, associated with FUS gene variants, is the most prevalent globally. Despite several upper motor neuron-dominant forms being generally associated with long-standing motor symptoms and slowly progressive course, certain subtypes with lower motor neuron-dominant features and early bulbar compromise lead to rapidly progressive motor handicap. For some monogenic forms, there is a well-established genotypic-phenotypic correlation. There are no specific biochemical and neuroimaging biomarkers for the diagnosis of juvenile Amyotrophic Lateral Sclerosis. There are several inherited neurodegenerative and neurometabolic disorders which can lead to the signs of motor neuron impairment. This review emphasizes the importance of high clinical suspicion, assessment, and proper diagnostic work-up for juvenile Amyotrophic Lateral Sclerosis.}, }
@article {pmid38538275, year = {2024}, author = {Ceccarelli, L and Verriello, L and Pauletto, G and Valente, M and Spadea, L and Salati, C and Zeppieri, M and Ius, T}, title = {The Role of Human Pluripotent Stem Cells in Amyotrophic Lateral Sclerosis: From Biological Mechanism to Practical Implications.}, journal = {Frontiers in bioscience (Landmark edition)}, volume = {29}, number = {3}, pages = {114}, doi = {10.31083/j.fbl2903114}, pmid = {38538275}, issn = {2768-6698}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/therapy/metabolism ; Motor Neurons/metabolism ; *Pluripotent Stem Cells/metabolism/pathology ; *Induced Pluripotent Stem Cells/metabolism/pathology ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder, characterized by progressive loss of both upper and lower motor neurons, resulting in clinical features such as muscle weakness, paralysis, and ultimately, respiratory failure. Nowadays, there is not effective treatment to reverse the progression of the disease, that leads to death within 3-5 years after the onset. Nevertheless, the induced pluripotent stem cells (iPS) technology could be the answer, providing disease modelling, drug testing, and cell-based therapies for this pathology. The aim of this work was to conduct a literature review of the past 5 years about the role of iPS in ALS, to better define the neurobiological mechanisms involved in the pathogenesis and the potential future therapies. The review also deals with advanced and currently available technologies used to reprogram cell lines and generate human motor neurons in vitro, which represent the source to study the pathological processes, the relationship between phenotype and genotype, the disease progression and the potential therapeutic targets of these group of disorders. Specific treatment options with stem cells involve Advance Gene Editing Technology, neuroprotective agents, and cells or exosomes transplantation, aimed to replace dead or damaged nerve cells. In summary, this review comprehensively addresses the role of human pluripotent stem cells (hPSCs) in motor neuron diseases (MND), with a focus on physiopathology, diagnostic and prognostic implications, specific and potential future treatment options. Understanding the biological mechanisms and practical implications of hPSCs in MND is crucial for advancing therapeutic strategies and improving outcomes for patients affected by these devastating diseases.}, }
@article {pmid38535081, year = {2024}, author = {Liampas, I and Danga, F and Kyriakoulopoulou, P and Siokas, V and Stamati, P and Messinis, L and Dardiotis, E and Nasios, G}, title = {The Contribution of Functional Near-Infrared Spectroscopy (fNIRS) to the Study of Neurodegenerative Disorders: A Narrative Review.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {14}, number = {6}, pages = {}, pmid = {38535081}, issn = {2075-4418}, abstract = {Functional near-infrared spectroscopy (fNIRS) is an innovative neuroimaging method that offers several advantages over other commonly used modalities. This narrative review investigated the potential contribution of this method to the study of neurodegenerative disorders. Thirty-four studies involving patients with Alzheimer's disease (AD), mild cognitive impairment (MCI), frontotemporal dementia (FTD), Parkinson's disease (PD), or amyotrophic lateral sclerosis (ALS) and healthy controls were reviewed. Overall, it was revealed that the prefrontal cortex of individuals with MCI may engage compensatory mechanisms to support declining brain functions. A rightward shift was suggested to compensate for the loss of the left prefrontal capacity in the course of cognitive decline. In parallel, some studies reported the failure of compensatory mechanisms in MCI and early AD; this lack of appropriate hemodynamic responses may serve as an early biomarker of neurodegeneration. One article assessing FTD demonstrated a heterogeneous cortical activation pattern compared to AD, indicating that fNIRS may contribute to the challenging distinction of these conditions. Regarding PD, there was evidence that cognitive resources (especially executive function) were recruited to compensate for locomotor impairments. As for ALS, fNIRS data support the involvement of extra-motor networks in ALS, even in the absence of measurable cognitive impairment.}, }
@article {pmid38534355, year = {2024}, author = {Cohen, J and Mathew, A and Dourvetakis, KD and Sanchez-Guerrero, E and Pangeni, RP and Gurusamy, N and Aenlle, KK and Ravindran, G and Twahir, A and Isler, D and Sosa-Garcia, SR and Llizo, A and Bested, AC and Theoharides, TC and Klimas, NG and Kempuraj, D}, title = {Recent Research Trends in Neuroinflammatory and Neurodegenerative Disorders.}, journal = {Cells}, volume = {13}, number = {6}, pages = {}, pmid = {38534355}, issn = {2073-4409}, mesh = {Humans ; Neuroinflammatory Diseases ; Endothelial Cells ; *Induced Pluripotent Stem Cells ; *Neurodegenerative Diseases ; Inflammation ; }, abstract = {Neuroinflammatory and neurodegenerative disorders including Alzheimer's disease (AD), Parkinson's disease (PD), traumatic brain injury (TBI) and Amyotrophic lateral sclerosis (ALS) are chronic major health disorders. The exact mechanism of the neuroimmune dysfunctions of these disease pathogeneses is currently not clearly understood. These disorders show dysregulated neuroimmune and inflammatory responses, including activation of neurons, glial cells, and neurovascular unit damage associated with excessive release of proinflammatory cytokines, chemokines, neurotoxic mediators, and infiltration of peripheral immune cells into the brain, as well as entry of inflammatory mediators through damaged neurovascular endothelial cells, blood-brain barrier and tight junction proteins. Activation of glial cells and immune cells leads to the release of many inflammatory and neurotoxic molecules that cause neuroinflammation and neurodegeneration. Gulf War Illness (GWI) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are chronic disorders that are also associated with neuroimmune dysfunctions. Currently, there are no effective disease-modifying therapeutic options available for these diseases. Human induced pluripotent stem cell (iPSC)-derived neurons, astrocytes, microglia, endothelial cells and pericytes are currently used for many disease models for drug discovery. This review highlights certain recent trends in neuroinflammatory responses and iPSC-derived brain cell applications in neuroinflammatory disorders.}, }
@article {pmid38533300, year = {2024}, author = {Moskvin, SV}, title = {A brief literature review of low-level laser therapy for treating amyotrophic lateral sclerosis and confirmation of its effectiveness.}, journal = {BioMedicine}, volume = {14}, number = {1}, pages = {1-9}, pmid = {38533300}, issn = {2211-8020}, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a steadily progressive course due to the death of central and peripheral motor neurons responsible for voluntary movements. Low-level laser therapy (LLLT) is a treatment method unique in its universality and efficacy, particularly for neurodegenerative diseases.<br><br>METHODS: In this review, we discuss the effect and application of LLLT in the treatment of ALS. A literature search for English and Russian publications for the keywords "Amyotrophic Lateral Sclerosis", "Low-Level Laser Therapy" was performed using PubMed, Scopus, Google Scholar, Web of Science and Russian Science Citation Index (RSCI) databases.<br><br>RESULTS: The article provided a brief literature review, substantiated the potential use of low-level laser therapy for ALS. The particular techniques of LLLT were developed.<br><br>CONCLUSION: Based on the results of several studies and many years of successful experience with low-level laser therapy in Russia we conclude that a LLLT technique, including intravenous laser blood illumination (ILBI), noninvasive laser blood illumination (NLBI), and local exposure, is a promising treatment method for ALS.}, }
@article {pmid38531340, year = {2024}, author = {Lee, KH and Kim, MH and Kim, J and Nam, HJ}, title = {Acupuncture for Tinnitus: A Scoping Review of Clinical Studies.}, journal = {Complementary medicine research}, volume = {31}, number = {3}, pages = {292-301}, pmid = {38531340}, issn = {2504-2106}, mesh = {Humans ; *Acupuncture Therapy/methods ; *Tinnitus/therapy ; Randomized Controlled Trials as Topic ; Acupuncture Points ; }, abstract = {BACKGROUND: Acupuncture treatment for tinnitus has received attention owing to its potential as an alternative to conventional treatment modalities. We conducted a scoping review to identify detailed information on acupuncture treatment methods used in clinical studies and to provide useful information for practitioners, patients, and researchers.<br><br>METHODS: MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, Oriental Medicine Advanced Searching Integrated System (OASIS), Korean Research Information Sharing Service (RISS), DataBase Periodical Information Academic (DBPIA), and the China National Knowledge Infrastructure (CNKI) were searched from their inception to December 2023. This review included single-arm trials, open-label randomized controlled trials (RCTs), and double-blind RCTs using needle-type acupuncture to treat tinnitus in English, Chinese, and Korean. We investigated basic and detailed information on the acupuncture treatment methods, assessment methods, and study outcomes. Network analysis was also conducted to evaluate the centrality between acupoints in the double-blind RCTs.<br><br>RESULTS: We included 106 articles. There were 11 single-arm trials, 90 open-label RCTs, and 5 double-blind RCTs. Most (89.6%) of these studies were conducted in China. Manual acupuncture was the most common type of acupuncture in treatment group. A total of 119 acupuncture points were used 1,138 times. The most frequently used acupoints were local points around the ear (TE17, GB2, SI19, and TE21). Both local and distant acupoints were used simultaneously in these studies. The treatment duration of 20-39 days, 10 to 19 sessions of treatment, the mean acupuncture duration of 30 min, needle diameter of 0.30 mm &#xd7; 40 mm, and needling depth over 30 mm and less than 50 mm were confirmed as the most common.<br><br>CONCLUSION: These study outcomes will enable future acupuncture studies on tinnitus to perform more effective and standardized acupuncture treatments in selecting acupoints and procedures. Furthermore, the study has implications for informing clinicians and students about more impactful acupuncture strategies for addressing tinnitus.<br><br>UNLABELLED: <title>Hintergrund</title>Die Anwendung von Akupunktur bei Tinnitus erh&#xe4;lt seit einiger Zeit Aufmerksamkeit als potenzielle Alternative zu konventionellen Behandlungsmodalit&#xe4;ten. Wir f&#xfc;hrten einen Scoping-Review durch, um detaillierte Informationen zu den in klinischen Studien angewandten Akupunktur-Behandlungsmethoden zu sammeln und n&#xfc;tzliche Informationen f&#xfc;r Praktiker, Patienten und Forscher bereitzustellen.<title>Methoden</title>MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, Oriental Medicine Advanced Searching Integrated System (OASIS), Korean Research Information Sharing Service (RISS), DataBase Periodical Information Academic (DBPIA) und die China National Knowledge Infrastructure (CNKI) wurden von ihrem jeweiligen Beginn bis Dezember 2023 durchsucht. In diese &#xdc;bersichtsarbeit wurden einarmige Studien, offene, randomisierte, kontrollierte Studien (RCTs) sowie doppelt verblindete RCTs zu Nadel-Akupunktur zur Behandlung von Tinnitus in englischer, chinesischer und koreanischer Sprache einbezogen. Wir untersuchten grundlegende und detaillierte Informationen zu den Akupunktur-Behandlungsmethoden, Untersuchungsmethoden und Studienergebnissen. Au&#xdf;erdem wurden Netzwerkanalysen zur Beurteilung der Zentralit&#xe4;t zwischen Akupunkten in den doppelt verblindeten RCTs durchgef&#xfc;hrt.<title>Ergebnisse</title>106 Artikel wurden eingeschlossen. Sie behandelten 11 einarmige Studien, 90 offene RCTs und 5 doppelt verblindete RCTs. Die meisten (89,6%) dieser Studien waren in China durchgef&#xfc;hrt worden. Manuelle Akupunktur war die h&#xe4;ufigste Form der Akupunktur in den Behandlungsgruppen. 119 Akupunkturpunkte wurden insgesamt 1&#x2019;138 Mal verwendet. Die am h&#xe4;ufigsten verwendeten Akupunkte waren lokale Punkte im Bereich des Ohrs (TE17, GB2, SI19 und TE21). Jedoch wurden in den Studien lokale und entfernte Akupunkte gleichzeitig angewendet. Au&#xdf;erdem wurde festgestellt, dass die Behandlungsdauer am h&#xe4;ufigsten 20 bis 39 Tage betrug, die Zahl der Sitzungen 10 bis 19, die mittlere Akupunkturdauer 30 Minuten, die Nadelgr&#xf6;&#xdf;e 0.30 mm &#xd7; 40 mm und die Einstichtiefe zwischen 30 mm und weniger als 50 mm.<title>Schlussfolgerung</title>Diese Studienergebnisse bieten eine Grundlage f&#xfc;r k&#xfc;nftige Studien zu Akupunktur bei Tinnitus, um durch die Auswahl der Akupunkte und Verfahren wirksamere und standardisierte Akupunkturbehandlungen durchzuf&#xfc;hren. Dar&#xfc;ber hinaus hat die Studie Implikationen f&#xfc;r die Aufkl&#xe4;rung von Praktikern und Sch&#xfc;lern &#xfc;ber wirkungsvollere Akupunkturstrategien zur Behandlung von Tinnitus.}, }
@article {pmid38525704, year = {2024}, author = {Shirai, R and Yamauchi, J}, title = {Emerging Evidence of Golgi Stress Signaling for Neuropathies.}, journal = {Neurology international}, volume = {16}, number = {2}, pages = {334-348}, pmid = {38525704}, issn = {2035-8385}, abstract = {The Golgi apparatus is an intracellular organelle that modifies cargo, which is transported extracellularly through the nucleus, endoplasmic reticulum, and plasma membrane in order. First, the general function of the Golgi is reviewed and, then, Golgi stress signaling is discussed. In addition to the six main Golgi signaling pathways, two pathways that have been increasingly reported in recent years are described in this review. The focus then shifts to neurological disorders, examining Golgi stress reported in major neurological disorders, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease. The review also encompasses findings related to other diseases, including hypomyelinating leukodystrophy, frontotemporal spectrum disorder/amyotrophic lateral sclerosis, microcephaly, Wilson's disease, and prion disease. Most of these neurological disorders cause Golgi fragmentation and Golgi stress. As a result, strong signals may act to induce apoptosis.}, }
@article {pmid38524401, year = {2024}, author = {Pota, V and Sansone, P and De Sarno, S and Aurilio, C and Coppolino, F and Barbarisi, M and Barbato, F and Fiore, M and Cosenza, G and Passavanti, MB and Pace, MC}, title = {Amyotrophic Lateral Sclerosis and Pain: A Narrative Review from Pain Assessment to Therapy.}, journal = {Behavioural neurology}, volume = {2024}, number = {}, pages = {1228194}, pmid = {38524401}, issn = {1875-8584}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications ; Pain Measurement ; Quality of Life ; *Neurodegenerative Diseases/complications ; Pain/drug therapy ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is the most frequent neurodegenerative disease of the motor system that affects upper and lower motor neurons, leading to progressive muscle weakness, spasticity, atrophy, and respiratory failure, with a life expectancy of 2-5 years after symptom onset. In addition to motor symptoms, patients with ALS have a multitude of nonmotor symptoms; in fact, it is currently considered a multisystem disease. The purpose of our narrative review is to evaluate the different types of pain, the correlation between pain and the disease's stages, the pain assessment tools in ALS patients, and the available therapies focusing above all on the benefits of cannabis use. Pain is an underestimated and undertreated symptom that, in the last few years, has received more attention from research because it has a strong impact on the quality of life of these patients. The prevalence of pain is between 15% and 85% of ALS patients, and the studies on the type and intensity of pain are controversial. The absence of pain assessment tools validated in the ALS population and the dissimilar study designs influence the knowledge of ALS pain and consequently the pharmacological therapy. Several studies suggest that ALS is associated with changes in the endocannabinoid system, and the use of cannabis could slow the disease progression due to its neuroprotective action and act on pain, spasticity, cramps, sialorrhea, and depression. Our research has shown high patients' satisfaction with the use of cannabis for the treatment of spasticity and related pain. However, especially due to the ethical problems and the lack of interest of pharmaceutical companies, further studies are needed to ensure the most appropriate care for ALS patients.}, }
@article {pmid38522247, year = {2024}, author = {Flodgren, GM and Bezuidenhoudt, JE and Alkanhal, N and Brinkwirth, S and Lee, ACK}, title = {Conceptualisation and implementation of integrated disease surveillance globally: a scoping review.}, journal = {Public health}, volume = {230}, number = {}, pages = {105-112}, doi = {10.1016/j.puhe.2024.02.018}, pmid = {38522247}, issn = {1476-5616}, mesh = {Humans ; *Pandemics ; Concept Formation ; *COVID-19/epidemiology ; Africa/epidemiology ; }, abstract = {OBJECTIVES: The objective of this study was to examine the conceptualisation and operationalisation of Integrated Disease Surveillance (IDS) systems globally and the evidence for their effectiveness. Furthermore, to determine whether the recommendations made by Morgan et al. are supported by the evidence and what the evidence is to inform country development of IDS.<br><br>STUDY DESIGN: The study incorporated a scoping review.<br><br>METHODS: This review summarised evidence meeting the following inclusion criteria: Participants: any health sector; Concept: IDS; and Context: global. We searched Medline, Embase, and Epistemonikos for English publications between 1998 and 2022. Standard review methods were applied. A bespoke conceptual framework guided the narrative analysis. This scoping review is part of a research programme with three key elements, with the other studies being a survey of the International Association of National Public Health Institutes members on the current status of their disease surveillance systems and a deeper analysis and case studies of the surveillance systems in seven countries, to highlight the opportunities and challenges of integration.<br><br>RESULTS: Eight reviews and five primary studies, which were assessed as being of low quality, were included, mostly examining IDS in Africa, the human sector, and communicable diseases. None reported on the effects on disease control or on the evolution of IDS during the COVID-19 pandemic. Descriptions of IDS and of integration varied. Prerequisites of effective IDS systems mostly related to the adequacy of core functions and resourcing requirements. Laws or regulations supporting system integration and data sharing were not addressed. The provision of core functions and resourcing requirements were described as inadequate, financing as non-sustainable, and governance as poor. Enablers included active data sharing, close cooperation between agencies, clear reporting channels, integration of vertical programs, increased staff training, and adopting mobile reporting. Whilst the conceptual framework for IDS and Morgan et&#xa0;al.'s proposed principles were to some extent reflected in the highlighted priorities for IDS in the literature, the evidence base remains weak.<br><br>CONCLUSIONS: Available evidence is fragmented, incomplete, and of poor quality. The review found a lack of robust evaluation studies on the impact of IDS on disease control. Whilst a lack of evidence does not imply a lack of benefit or effect, it should signal the need to evaluate the process and impact of integration in the future development of surveillance systems. A common IDS definition and articulation of the parts that constitute an IDS system are needed. Further robust impact evaluations, as well as country reviews and evaluations of their IDS systems, are required to improve the evidence base.}, }
@article {pmid38520811, year = {2024}, author = {Li, J and Hodson, ME and Brown, CD and Bottoms, MJ and Ashauer, R and Alvarez, T}, title = {Evaluation of models to estimate the bioaccumulation of organic chemicals in earthworms.}, journal = {Ecotoxicology and environmental safety}, volume = {275}, number = {}, pages = {116240}, doi = {10.1016/j.ecoenv.2024.116240}, pmid = {38520811}, issn = {1090-2414}, mesh = {Animals ; *Oligochaeta ; *Soil Pollutants/analysis ; Bioaccumulation ; *Pesticides ; Organic Chemicals ; Soil/chemistry ; }, abstract = {Modelling approaches to estimate the bioaccumulation of organic chemicals by earthworms are important for improving the realism in risk assessment of chemicals. However, the applicability of existing models is uncertain, partly due to the lack of independent datasets to test them. This study therefore conducted a comprehensive literature review on existing empirical and kinetic models that estimate the bioaccumulation of organic chemicals in earthworms and gathered two independent datasets from published literature to evaluate the predictive performance of these models. The Belfroid et al. (1995a) model is the best-performing empirical model, with 91.2% of earthworm body residue simulations within an order of magnitude of observation. However, this model is limited to the more hydrophobic pesticides and to the earthworm species Eisenia fetida or Eisenia andrei. The kinetic model proposed by Jager et al. (2003b) which out-performs that of Armitage and Gobas (2007), predicted uptake of PCB 153 in the earthworm E. andrei to within a factor of 10. However, the applicability of Jager et al.'s model to other organic compounds and other earthworm species is unknown due to the limited evaluation dataset. The model needs to be parameterised for different chemical, soil, and species types prior to use, which restricts its applicability to risk assessment on a broad scale. Both the empirical and kinetic models leave room for improvement in their ability to reliably predict bioaccumulation in earthworms. Whether they are fit for purpose in environmental risk assessment needs careful consideration on a case by case basis.}, }
@article {pmid38517530, year = {2024}, author = {Kotsia, E and Chroni, E and Alexandropoulou, A and Mills, C and Veltsista, D and Kefalopoulou, ZM and Michou, E}, title = {Dysphagia Assessments as Criteria in the 'Decision-Making Process' for Percutaneous Endoscopic Gastrostomy Placement in People with Amyotrophic Lateral Sclerosis: A Systematic Review.}, journal = {Dysphagia}, volume = {39}, number = {6}, pages = {977-988}, pmid = {38517530}, issn = {1432-0460}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications ; *Deglutition Disorders/etiology ; *Gastrostomy/methods ; *Clinical Decision-Making/methods ; Male ; Female ; }, abstract = {To review the assessment methods of dysphagia as a criterion for the decision-making process for Percutaneous Endoscopic Gastrostomy (PEG) placement in patients with Amyotrophic Lateral Sclerosis (ALS). Systematic review. A search was conducted in three databases (EMBASE, CINAHL, PUBMED) in December 2022 and updated in July 2023. Two reviewers independently screened, selected, and extracted data. Study quality was appraised using the Joanna Briggs Institute Critical Appraisal Tools. Systematic review registration number in the International Prospective Register of Systematic Reviews (PROSPERO): CRD42022385461. The searches identified 240 records. The 10 eligible studies included 2 case reports, 4 retrospective studies, 3 prospective studies, and 1 cohort observational study. Study quality was low, with most studies having moderate to high risk of bias. Dysphagia is a common criterion for decision-making. Dysphagia assessment is usually in the form of either self-reports, objective instrumental assessments, or both. Dysphagia is a common criterion for the decision-making process, yet is missing in clinical guidelines. Establishing the optimal means of dysphagia assessment is important for timely decision-making procedures, so that life-threatening consequences of dysphagia are minimized.}, }
@article {pmid38516735, year = {2024}, author = {Li, X and Bedlack, R}, title = {Evaluating emerging drugs in phase II &amp; III for the treatment of amyotrophic lateral sclerosis.}, journal = {Expert opinion on emerging drugs}, volume = {29}, number = {2}, pages = {93-102}, doi = {10.1080/14728214.2024.2333420}, pmid = {38516735}, issn = {1744-7623}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/physiopathology ; Humans ; *Drug Development ; *Drugs, Investigational/pharmacology ; Animals ; *Clinical Trials, Phase II as Topic ; Clinical Trials, Phase III as Topic ; Drug Design ; Molecular Targeted Therapy ; Research Design ; }, abstract = {INTRODUCTION: Amyotrophic Lateral Sclerosis is a rapidly progressive motor neuron disorder causing severe disability and premature death. Owing to the advances in uncovering ALS pathophysiology, efficient clinical trial design and research advocacy program, several disease-modifying drugs have been approved for treating ALS. Despite this progress, ALS remains a rapidly disabling and life shortening condition. There is a critical need for more effective therapies.<br><br>AREAS COVERED: Here, we reviewed the emerging ALS therapeutics undergoing phase II &amp; III clinical trials. To identify the investigational drugs, we searched ALS and phase II/III trials that are active and recruiting or not yet recruiting on clinicaltrials.gov and Pharmaprojects database.<br><br>EXPERT OPINION: The current pipeline is larger and more diverse than ever, with drugs targeting potential genetic and retroviral causes of ALS and drugs targeting a wide array of downstream pathways, including RNA metabolism, protein aggregation, integrated stress response and neuroinflammation.We remain most excited about those that target direct causes of ALS, e.g. antisense oligonucleotides targeting causative genes. Drugs that eliminate abnormal protein aggregates are also up-and-coming. Eventually, because of the heterogeneity of ALS pathophysiology, biomarkers that determine which biological events are most important for an individual ALS patient are needed.}, }
@article {pmid38515787, year = {2024}, author = {Wang, L and Fang, X and Ling, B and Wang, F and Xia, Y and Zhang, W and Zhong, T and Wang, X}, title = {Research progress on ferroptosis in the pathogenesis and treatment of neurodegenerative diseases.}, journal = {Frontiers in cellular neuroscience}, volume = {18}, number = {}, pages = {1359453}, pmid = {38515787}, issn = {1662-5102}, abstract = {Globally, millions of individuals are impacted by neurodegenerative disorders including Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and Alzheimer's disease (AD). Although a great deal of energy and financial resources have been invested in disease-related research, breakthroughs in therapeutic approaches remain elusive. The breakdown of cells usually happens together with the onset of neurodegenerative diseases. However, the mechanism that triggers neuronal loss is unknown. Lipid peroxidation, which is iron-dependent, causes a specific type of cell death called ferroptosis, and there is evidence its involvement in the pathogenic cascade of neurodegenerative diseases. However, the specific mechanisms are still not well known. The present article highlights the basic processes that underlie ferroptosis and the corresponding signaling networks. Furthermore, it provides an overview and discussion of current research on the role of ferroptosis across a variety of neurodegenerative conditions.}, }
@article {pmid38514815, year = {2024}, author = {Baxter, RC}, title = {Endocrine and cellular physiology and pathology of the insulin-like growth factor acid-labile subunit.}, journal = {Nature reviews. Endocrinology}, volume = {20}, number = {7}, pages = {414-425}, pmid = {38514815}, issn = {1759-5037}, mesh = {Humans ; Animals ; *Glycoproteins/metabolism ; Carrier Proteins/metabolism ; Insulin-Like Growth Factor I/metabolism ; Mice ; Insulin-Like Growth Factor Binding Proteins/metabolism/physiology ; Insulin-Like Growth Factor II/metabolism ; Endocrine System/metabolism ; Insulin-Like Peptides ; }, abstract = {The acid-labile subunit (ALS) of the insulin-like growth factor (IGF) binding protein (IGFBP) complex, encoded in humans by IGFALS, has a vital role in regulating the endocrine transport and bioavailability of IGF-1 and IGF-2. Accordingly, ALS has a considerable influence on postnatal growth and metabolism. ALS is a leucine-rich glycoprotein that forms high-affinity ternary complexes with IGFBP-3 or IGFBP-5 when they are occupied by either IGF-1 or IGF-2. These complexes constitute a stable reservoir of circulating IGFs, blocking the potentially hypoglycaemic activity of unbound IGFs. ALS is primarily synthesized by hepatocytes and its expression is lower in non-hepatic tissues. ALS synthesis is strongly induced by growth hormone and suppressed by IL-1β, thus potentially serving as a marker of growth hormone secretion and/or activity and of inflammation. IGFALS mutations in humans and Igfals deletion in mice cause modest growth retardation and pubertal delay, accompanied by decreased osteogenesis and enhanced adipogenesis. In hepatocellular carcinoma, IGFALS is described as a tumour suppressor; however, its contribution to other cancers is not well delineated. This Review addresses the endocrine physiology and pathology of ALS, discusses the latest cell and proteomic studies that suggest emerging cellular roles for ALS and outlines its involvement in other disease states.}, }
@article {pmid38512820, year = {2024}, author = {Bartolomé-Nafría, A and García-Pardo, J and Ventura, S}, title = {Mutations in human prion-like domains: pathogenic but not always amyloidogenic.}, journal = {Prion}, volume = {18}, number = {1}, pages = {28-39}, pmid = {38512820}, issn = {1933-690X}, mesh = {Humans ; *Prions/metabolism ; *Heterogeneous-Nuclear Ribonucleoprotein Group A-B/genetics/metabolism ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *Frontotemporal Dementia/genetics/metabolism/pathology ; Mutation ; }, abstract = {Heterogeneous nuclear ribonucleoproteins (hnRNPs) are multifunctional proteins with integral roles in RNA metabolism and the regulation of alternative splicing. These proteins typically contain prion-like domains of low complexity (PrLDs or LCDs) that govern their assembly into either functional or pathological amyloid fibrils. To date, over 60 mutations targeting the LCDs of hnRNPs have been identified and associated with a spectrum of neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimer's disease (AD). The cryo-EM structures of pathological and functional fibrils formed by different hnRNPs have been recently elucidated, including those of hnRNPA1, hnRNPA2, hnRNPDL-2, TDP-43, and FUS. In this review, we discuss the structural features of these amyloid assemblies, placing particular emphasis on scrutinizing the impact of prevalent disease-associated mutations mapping within their LCDs. By performing systematic energy calculations, we reveal a prevailing trend of destabilizing effects induced by these mutations in the amyloid structure, challenging the traditionally assumed correlation between pathogenicity and amyloidogenic propensity. Understanding the molecular basis of this discrepancy might provide insights for developing targeted therapeutic strategies to combat hnRNP-associated diseases.}, }
@article {pmid38510000, year = {2024}, author = {Ditan, ID and Turalde, CWR}, title = {Treatment gaps in the care of amyotrophic lateral sclerosis in the Philippines: A scoping review.}, journal = {Heliyon}, volume = {10}, number = {6}, pages = {e27944}, pmid = {38510000}, issn = {2405-8440}, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive disease affecting both the upper and lower motor neurons. Much of the management of ALS is supportive with the goal of maximizing patient quality of life. While the Philippines was participative in the "Ice Bucket Challenge" in 2014, it is up for investigation whether substantial changes occurred to improve healthcare for ALS patients. This study aims to evaluate the treatment gaps in the management of ALS in the Philippines through a scoping review. Data on epidemiology, health systems, and pharmacotherapy available regarding ALS in the local setting were synthesized. Nine articles were included. As of July 2023, there were only four indexed studies on ALS from the Philippines. Five of the included articles investigated ALS in Filipino populations but were not authored by Filipinos nor affiliated with Philippine institutions. The available literature showed a distinct lack of local ALS epidemiologic data, as well as limited availability in diagnostic centers, medications, health financing options, and digestible information for Filipinos. The limitations in managing ALS in the country are multifactorial - from political, medical, and social. It is imperative to establish a national database, financing systems, support groups, and accessible diagnostic centers for ALS patients.}, }
@article {pmid38504632, year = {2024}, author = {Higashihara, M and Pavey, N and Menon, P and van den Bos, M and Shibuya, K and Kuwabara, S and Kiernan, MC and Koinuma, M and Vucic, S}, title = {Reduction in short interval intracortical inhibition from the early stage reflects the pathophysiology in amyotrophic lateral sclerosis: A meta-analysis study.}, journal = {European journal of neurology}, volume = {31}, number = {7}, pages = {e16281}, pmid = {38504632}, issn = {1468-1331}, mesh = {*Amyotrophic Lateral Sclerosis/physiopathology ; Humans ; *Transcranial Magnetic Stimulation ; *Neural Inhibition/physiology ; *Motor Cortex/physiopathology ; Evoked Potentials, Motor/physiology ; }, abstract = {BACKGROUND AND PURPOSE: Cortical hyperexcitability has been identified as a diagnostic and pathogenic biomarker of amyotrophic lateral sclerosis (ALS). Cortical excitability is assessed by transcranial magnetic stimulation (TMS), a non-invasive neurophysiological technique. The TMS biomarkers exhibiting highest sensitivity for cortical hyperexcitability in ALS remain to be elucidated. A meta-analysis was performed to determine the TMS biomarkers exhibiting the highest sensitivity for cortical hyperexcitability in ALS.<br><br>METHODS: A systematic literature review was conducted of all relevant studies published in the English language by searching PubMed, MEDLINE, Embase and Scopus electronic databases from 1 January 2006 to 28 February 2023. Inclusion criteria included studies reporting the utility of threshold tracking TMS (serial ascending method) in ALS and controls.<br><br>RESULTS: In total, more than 2500 participants, incorporating 1530 ALS patients and 1102 controls (healthy, 907; neuromuscular, 195) were assessed with threshold tracking TMS across 25 studies. Significant reduction of mean short interval intracortical inhibition (interstimulus interval 1-7&#x2009;ms) exhibited the highest standardized mean difference with moderate heterogeneity (-0.994, 95% confidence interval -1.12 to -0.873, p&#x2009;<&#x2009;0.001; Q&#x2009;=&#x2009;38.61, p&#x2009;<&#x2009;0.05; I[2]&#x2009;=&#x2009;40%). The reduction of cortical silent period duration along with an increase in motor evoked potential amplitude and intracortical facilitation also exhibited significant, albeit smaller, standardized mean differences.<br><br>CONCLUSION: This large meta-analysis study disclosed that mean short interval intracortical inhibition reduction exhibited the highest sensitivity for cortical hyperexcitability in ALS. Combined findings from this meta-analysis suggest that research strategies aimed at understanding the cause of inhibitory interneuronal circuit dysfunction could enhance understanding of ALS pathogenesis.}, }
@article {pmid38502230, year = {2024}, author = {Monsma, E and Seiler, BD}, title = {Picture this! Suggested instructions for guiding the Neuroscience of action imagery: A commentary on Krüger et al. (2022).}, journal = {Psychological research}, volume = {88}, number = {6}, pages = {1885-1887}, pmid = {38502230}, issn = {1430-2772}, mesh = {Humans ; *Imagination/physiology ; Neurosciences ; Movement/physiology ; }, abstract = {Our commentary expands the multisensory and modulating factors proposed by Kruger et al.'s (2023) internal models of action imagery and sensory crossovers. We will discuss the essence of imagery experiences as conceptual intersections among sensory, movement and affective properties that require further neuro-anatomical-contextual mapping to better understand the practical application of imagery. Accordingly, we will propose alternative ideas of daisy-chaining and motor imagery systems. The role of imagery speed, and other properties of movement for refining movement and self-regulation will be considered along with sex as a modulating factor in intra-individual abilities to image movement.}, }
@article {pmid38500677, year = {2024}, author = {Zhou, L and Xu, R}, title = {Invertebrate genetic models of amyotrophic lateral sclerosis.}, journal = {Frontiers in molecular neuroscience}, volume = {17}, number = {}, pages = {1328578}, pmid = {38500677}, issn = {1662-5099}, abstract = {Amyotrophic lateral sclerosis (ALS) is a common adult-onset neurodegenerative disease characterized by the progressive death of motor neurons in the cerebral cortex, brain stem, and spinal cord. The exact mechanisms underlying the pathogenesis of ALS remain unclear. The current consensus regarding the pathogenesis of ALS suggests that the interaction between genetic susceptibility and harmful environmental factors is a promising cause of ALS onset. The investigation of putative harmful environmental factors has been the subject of several ongoing studies, but the use of transgenic animal models to study ALS has provided valuable information on the onset of ALS. Here, we review the current common invertebrate genetic models used to study the pathology, pathophysiology, and pathogenesis of ALS. The considerations of the usage, advantages, disadvantages, costs, and availability of each invertebrate model will also be discussed.}, }
@article {pmid38499161, year = {2024}, author = {Bashir, S and Aiman, A and Shahid, M and Chaudhary, AA and Sami, N and Basir, SF and Hassan, I and Islam, A}, title = {Amyloid-induced neurodegeneration: A comprehensive review through aggregomics perception of proteins in health and pathology.}, journal = {Ageing research reviews}, volume = {96}, number = {}, pages = {102276}, doi = {10.1016/j.arr.2024.102276}, pmid = {38499161}, issn = {1872-9649}, mesh = {Humans ; Amyloid/metabolism ; *Amyloidosis/metabolism ; *Neurodegenerative Diseases/metabolism ; *Parkinson Disease/metabolism ; Amyloidogenic Proteins ; Perception ; }, abstract = {Amyloidosis of protein caused by fibrillation and aggregation are some of the most exciting new edges not only in protein sciences but also in molecular medicines. The present review discusses recent advancements in the field of neurodegenerative diseases and therapeutic applications with ongoing clinical trials, featuring new areas of protein misfolding resulting in aggregation. The endogenous accretion of protein fibrils having fibrillar morphology symbolizes the beginning of neuro-disorders. Prognostic amyloidosis is prominent in numerous degenerative infections such as Alzheimer's and Parkinson's disease, Amyotrophic lateral sclerosis (ALS), etc. However, the molecular basis determining the intracellular or extracellular evidence of aggregates, playing a significant role as a causative factor in neurodegeneration is still unclear. Structural conversions and protein self-assembly resulting in the formation of amyloid oligomers and fibrils are important events in the pathophysiology of the disease. This comprehensive review sheds light on the evolving landscape of potential treatment modalities, highlighting the ongoing clinical trials and the potential socio-economic impact of novel therapeutic interventions in the realm of neurodegenerative diseases. Furthermore, many drugs are undergoing different levels of clinical trials that would certainly help in treating these disorders and will surely improve the socio-impact of human life.}, }
@article {pmid38498721, year = {2024}, author = {Kertesz, A and Finger, E and Munoz, DG}, title = {Progress in Primary Progressive Aphasia: A Review.}, journal = {Cognitive and behavioral neurology : official journal of the Society for Behavioral and Cognitive Neurology}, volume = {37}, number = {1}, pages = {3-12}, pmid = {38498721}, issn = {1543-3641}, mesh = {Humans ; *Frontotemporal Dementia/diagnosis/genetics ; *Supranuclear Palsy, Progressive/genetics/pathology ; Syndrome ; *Aphasia, Primary Progressive ; }, abstract = {We present a review of the definition, classification, and epidemiology of primary progressive aphasia (PPA); an update of the taxonomy of the clinical syndrome of PPA; and recent advances in the neuroanatomy, pathology, and genetics of PPA, as well as the search for biomarkers and treatment. PPA studies that have contributed to concepts of language organization and disease propagation in neurodegeneration are also reviewed. In addition, the issues of heterogeneity versus the relationships of the clinical phenotypes and their relationship to biological, pathological, and genetic advances are discussed, as is PPA's relationship to other conditions such as frontotemporal dementia, corticobasal degeneration, progressive supranuclear palsy, Pick disease, and amyotrophic lateral sclerosis. Arguments are presented in favor of considering these conditions as one entity versus many.}, }
@article {pmid38490348, year = {2024}, author = {Chatterjee, A and Kumar, S and Roy Sarkar, S and Halder, R and Kumari, R and Banerjee, S and Sarkar, B}, title = {Dietary polyphenols represent a phytotherapeutic alternative for gut dysbiosis associated neurodegeneration: A systematic review.}, journal = {The Journal of nutritional biochemistry}, volume = {129}, number = {}, pages = {109622}, doi = {10.1016/j.jnutbio.2024.109622}, pmid = {38490348}, issn = {1873-4847}, mesh = {*Polyphenols/pharmacology ; *Dysbiosis/drug therapy ; *Gastrointestinal Microbiome/drug effects ; Humans ; *Neurodegenerative Diseases/drug therapy ; Animals ; Oxidative Stress/drug effects ; Phytotherapy ; Prebiotics ; Diet ; }, abstract = {Globally, neurodegeneration and cerebrovascular disease are common and growing causes of morbidity and mortality. Pathophysiology of this group of diseases encompasses various factors from oxidative stress to gut microbial dysbiosis. The study of the etiology and mechanisms of oxidative stress as well as gut dysbiosis-induced neurodegeneration in Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, autism spectrum disorder, and Huntington's disease has recently received a lot of attention. Numerous studies lend credence to the notion that changes in the intestinal microbiota and enteric neuroimmune system have an impact on the initiation and severity of these diseases. The prebiotic role of polyphenols can influence the makeup of the gut microbiota in neurodegenerative disorders by modulating intracellular signalling pathways. Metabolites of polyphenols function directly as neurotransmitters by crossing the blood-brain barrier or indirectly via influencing the cerebrovascular system. This assessment aims to bring forth an interlink between the consumption of polyphenols biotransformed by gut microbiota which in turn modulate the gut microbial diversity and biochemical changes in the brain. This systematic review will further augment research towards the association of dietary polyphenols in the management of gut dysbiosis-associated neurodegenerative diseases.}, }
@article {pmid38489867, year = {2024}, author = {Tausendfreund, O and Bidlingmaier, M and Martini, S and Müller, K and Rippl, M and Schilbach, K and Schmidmaier, R and Drey, M}, title = {Growth hormone treatment in aged patients with comorbidities: A systematic review.}, journal = {Growth hormone &amp; IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society}, volume = {75}, number = {}, pages = {101584}, doi = {10.1016/j.ghir.2024.101584}, pmid = {38489867}, issn = {1532-2238}, mesh = {Aged ; Humans ; Comorbidity ; Growth Hormone ; *Human Growth Hormone/adverse effects/therapeutic use ; Insulin-Like Growth Factor I ; Quality of Life ; Randomized Controlled Trials as Topic ; *Aging/pathology ; }, abstract = {OBJECTIVE: Hormonal substitution with growth hormone in aged patients remains a debated research topic and is rarely initiated in clinical practice. This reluctance may originate from concerns about adverse effects and the uncritical use as an anti-aging agent. Nevertheless, beneficial effects for selected patients suffering from certain acute and chronic illnesses could justify its use at an advanced age. This systematic review analyzes randomized controlled studies of GH interventions in older patients with different comorbidities to assess both, beneficial and harmful effects.<br><br>DESIGN: A systematic search strategy was implemented to identify relevant studies from PubMed, MEDLINE, and The Cochrane Library.<br><br>INCLUSION CRITERIA: participants aged over 65&#xa0;years, randomized controlled trials involving human growth hormone (GH) and presence of at least one additional comorbidity independent of a flawed somatotropic axis.<br><br>RESULTS: The eight eligible studies encompassed various comorbidities including osteoporosis, frailty, chronic heart failure, hip fracture, amyotrophic lateral sclerosis and hemodialysis. Outcomes varied, including changes in body composition, physical performance, strength, bone mineral density, cardiovascular parameters, quality of life and housing situation. Study protocols differed greatly in GH application frequency (daily, 2nd day or 3&#xd7;/week), doses (0.41&#xa0;mg-2.6&#xa0;mg; mean 1.3&#xa0;mg per 60&#xa0;kg patient) and duration (1-12&#xa0;months; mean 7&#xa0;months). Mild dose-related side effects were reported, alongside noticeable positive impacts particularly on body composition, functionality, and quality of life.<br><br>CONCLUSION: Despite limited evidence, GH treatment might offer diverse benefits with few adverse effects. Further research with IGF-I dependent indication and clear outcomes, incorporating IGF-I dependent GH titration in older adults is warranted.}, }
@article {pmid38483631, year = {2024}, author = {Perera, A and Brock, O and Ahmed, A and Shaw, C and Ashkan, K}, title = {Taking the knife to neurodegeneration: a review of surgical gene therapy delivery to the CNS.}, journal = {Acta neurochirurgica}, volume = {166}, number = {1}, pages = {136}, pmid = {38483631}, issn = {0942-0940}, mesh = {Humans ; *Central Nervous System ; Genetic Therapy/methods ; Genetic Vectors ; *Neurodegenerative Diseases/genetics/therapy ; }, abstract = {Gene supplementation and editing for neurodegenerative disorders has emerged in recent years as the understanding of the genetic mechanisms underlying several neurodegenerative disorders increases. The most common medium to deliver genetic material to cells is via viral vectors; and with respect to the central nervous system, adeno-associated viral (AAV) vectors are a popular choice. The most successful example of AAV-based gene therapy for neurodegenerative disorders is Zolgensma© which is a transformative intravenous therapy given to babies with spinal muscular atrophy. However, the field has stalled in achieving safe drug delivery to the central nervous system in adults for which treatments for disorders such as amyotrophic lateral sclerosis are desperately needed. Surgical gene therapy delivery has been proposed as a potential solution to this problem. While the field of the so-called regenerative neurosurgery has yielded pre-clinical optimism, several challenges have emerged. This review seeks to explore the field of regenerative neurosurgery with respect to AAV-based gene therapy for neurodegenerative diseases, its progress so far and the challenges that need to be overcome.}, }
@article {pmid38477419, year = {2024}, author = {de Fátima Dos Santos Sampaio, M and de Paiva, YB and Sampaio, TB and Pereira, MG and Coimbra, NC}, title = {Therapeutic applicability of cannabidiol and other phytocannabinoids in epilepsy, multiple sclerosis and Parkinson's disease and in comorbidity with psychiatric disorders.}, journal = {Basic &amp; clinical pharmacology &amp; toxicology}, volume = {134}, number = {5}, pages = {574-601}, doi = {10.1111/bcpt.13997}, pmid = {38477419}, issn = {1742-7843}, support = {2014/11869-0//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado de S&#xe3;o Paulo/ ; 2020/15050-7//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado de S&#xe3;o Paulo/ ; PDJ grant 155489/2018-6//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; Research Grant (NAP-USP-NuPNE; process IaPq2012-15//Universidade de S&#xe3;o Paulo/ ; 374/2022//Funda&#xe7;&#xe3;o de Apoio ao Ensino, Pesquisa e Assist&#xea;ncia do Hospital das Cl&#xed;nicas da Faculdade de Medicina de Ribeir&#xe3;o Preto da Universidade de S&#xe3;o Paulo/ ; 302605/2021-5//CNPq/ ; 301341/2015-0//CNPq/ ; 301905/2010-0//CNPq/ ; 155489/2018-6//CNPq/ ; }, mesh = {Humans ; *Cannabidiol/pharmacology/therapeutic use ; *Parkinson Disease/drug therapy ; *Multiple Sclerosis/drug therapy ; Receptor, Serotonin, 5-HT1A/therapeutic use ; *Cannabinoids/pharmacology/therapeutic use ; *Epilepsy/drug therapy ; *Mental Disorders/drug therapy ; Comorbidity ; }, abstract = {Studies have demonstrated the neuroprotective effect of cannabidiol (CBD) and other Cannabis sativa L. derivatives on diseases of the central nervous system caused by their direct or indirect interaction with endocannabinoid system-related receptors and other molecular targets, such as the 5-HT1A receptor, which is a potential pharmacological target of CBD. Interestingly, CBD binding with the 5-HT1A receptor may be suitable for the treatment of epilepsies, parkinsonian syndromes and amyotrophic lateral sclerosis, in which the 5-HT1A serotonergic receptor plays a key role. The aim of this review was to provide an overview of cannabinoid effects on neurological disorders, such as epilepsy, multiple sclerosis and Parkinson's diseases, and discuss their possible mechanism of action, highlighting interactions with molecular targets and the potential neuroprotective effects of phytocannabinoids. CBD has been shown to have significant therapeutic effects on epilepsy and Parkinson's disease, while nabiximols contribute to a reduction in spasticity and are a frequent option for the treatment of multiple sclerosis. Although there are multiple theories on the therapeutic potential of cannabinoids for neurological disorders, substantially greater progress in the search for strong scientific evidence of their pharmacological effectiveness is needed.}, }
@article {pmid38474719, year = {2024}, author = {Noor Eddin, A and Alfuwais, M and Noor Eddin, R and Alkattan, K and Yaqinuddin, A}, title = {Gut-Modulating Agents and Amyotrophic Lateral Sclerosis: Current Evidence and Future Perspectives.}, journal = {Nutrients}, volume = {16}, number = {5}, pages = {}, pmid = {38474719}, issn = {2072-6643}, mesh = {Animals ; Humans ; *Amyotrophic Lateral Sclerosis/pathology ; Dysbiosis/etiology ; *Gastrointestinal Microbiome/physiology ; *Microbiota ; Disease Progression ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a highly fatal neurodegenerative disorder characterized by the progressive wasting and paralysis of voluntary muscle. Despite extensive research, the etiology of ALS remains elusive, and effective treatment options are limited. However, recent evidence implicates gut dysbiosis and gut-brain axis (GBA) dysfunction in ALS pathogenesis. Alterations to the composition and diversity of microbial communities within the gut flora have been consistently observed in ALS patients. These changes are often correlated with disease progression and patient outcome, suggesting that GBA modulation may have therapeutic potential. Indeed, targeting the gut microbiota has been shown to be neuroprotective in several animal models, alleviating motor symptoms and mitigating disease progression. However, the translation of these findings to human patients is challenging due to the complexity of ALS pathology and the varying diversity of gut microbiota. This review comprehensively summarizes the current literature on ALS-related gut dysbiosis, focusing on the implications of GBA dysfunction. It delineates three main mechanisms by which dysbiosis contributes to ALS pathology: compromised intestinal barrier integrity, metabolic dysfunction, and immune dysregulation. It also examines preclinical evidence on the therapeutic potential of gut-microbiota-modulating agents (categorized as prebiotics, probiotics, and postbiotics) in ALS.}, }
@article {pmid38474416, year = {2024}, author = {Tzeplaeff, L and Jürs, AV and Wohnrade, C and Demleitner, AF}, title = {Unraveling the Heterogeneity of ALS-A Call to Redefine Patient Stratification for Better Outcomes in Clinical Trials.}, journal = {Cells}, volume = {13}, number = {5}, pages = {}, pmid = {38474416}, issn = {2073-4409}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology ; Treatment Outcome ; Clinical Trials as Topic ; }, abstract = {Despite tremendous efforts in basic research and a growing number of clinical trials aiming to find effective treatments, amyotrophic lateral sclerosis (ALS) remains an incurable disease. One possible reason for the lack of effective causative treatment options is that ALS may not be a single disease entity but rather may represent a clinical syndrome, with diverse genetic and molecular causes, histopathological alterations, and subsequent clinical presentations contributing to its complexity and variability among individuals. Defining a way to subcluster ALS patients is becoming a central endeavor in the field. Identifying specific clusters and applying them in clinical trials could enable the development of more effective treatments. This review aims to summarize the available data on heterogeneity in ALS with regard to various aspects, e.g., clinical, genetic, and molecular.}, }
@article {pmid38474399, year = {2024}, author = {Manora, L and Borlongan, CV and Garbuzova-Davis, S}, title = {Cellular and Noncellular Approaches for Repairing the Damaged Blood-CNS-Barrier in Amyotrophic Lateral Sclerosis.}, journal = {Cells}, volume = {13}, number = {5}, pages = {}, pmid = {38474399}, issn = {2073-4409}, support = {R01 NS090962/NS/NINDS NIH HHS/United States ; R21 NS132576/NS/NINDS NIH HHS/United States ; 1R21NS132576-01/NS/NINDS NIH HHS/United States ; 1R01NS090962/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; Endothelial Cells/metabolism ; *Neurodegenerative Diseases/metabolism ; Motor Neurons/metabolism ; Stem Cells/metabolism ; }, abstract = {Numerous reports have demonstrated the breakdown of the blood-CNS barrier (B-CNS-B) in amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease. Re-establishing barrier integrity in the CNS is critical to prevent further motor neuron degeneration from harmful components in systemic circulation. Potential therapeutic strategies for repairing the B-CNS-B may be achieved by the replacement of damaged endothelial cells (ECs) via stem cell administration or enhancement of endogenous EC survival through the delivery of bioactive particles secreted by stem cells. These cellular and noncellular approaches are thoroughly discussed in the present review. Specific attention is given to certain stem cell types for EC replacement. Also, various nanoparticles secreted by stem cells as well as other biomolecules are elucidated as promising agents for endogenous EC repair. Although the noted in vitro and in vivo studies show the feasibility of the proposed therapeutic approaches to the repair of the B-CNS-B in ALS, further investigation is needed prior to clinical transition.}, }
@article {pmid38474192, year = {2024}, author = {Yamashita, T and Abe, K}, title = {Update on Antioxidant Therapy with Edaravone: Expanding Applications in Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {25}, number = {5}, pages = {}, pmid = {38474192}, issn = {1422-0067}, support = {23K08543, 21K19572//Grant-in-Aid for Scientific Research/ ; }, mesh = {Animals ; Female ; Pregnancy ; *Amyotrophic Lateral Sclerosis/drug therapy ; Antioxidants/therapeutic use ; Antipyrine ; Edaravone/pharmacology/therapeutic use ; Free Radical Scavengers/pharmacology ; *Neurodegenerative Diseases/drug therapy ; *Neuroprotective Agents/pharmacology ; Placenta ; }, abstract = {The brain is susceptible to oxidative stress, which is associated with various neurological diseases. Edaravone (MCI-186, 3-methyl-1 pheny-2-pyrazolin-5-one), a free radical scavenger, has promising effects by quenching hydroxyl radicals (∙OH) and inhibiting both ∙OH-dependent and ∙OH-independent lipid peroxidation. Edaravone was initially developed in Japan as a neuroprotective agent for acute cerebral infarction and was later applied clinically to treat amyotrophic lateral sclerosis (ALS), a neurodegenerative disease. There is accumulating evidence for the therapeutic effects of edaravone in a wide range of diseases related to oxidative stress, including ischemic stroke, ALS, Alzheimer's disease, and placental ischemia. These neuroprotective effects have expanded the potential applications of edaravone. Data from experimental animal models support its safety for long-term use, implying broader applications in various neurodegenerative diseases. In this review, we explain the unique characteristics of edaravone, summarize recent findings for specific diseases, and discuss its prospects for future therapeutic applications.}, }
@article {pmid38473944, year = {2024}, author = {Scarian, E and Viola, C and Dragoni, F and Di Gerlando, R and Rizzo, B and Diamanti, L and Gagliardi, S and Bordoni, M and Pansarasa, O}, title = {New Insights into Oxidative Stress and Inflammatory Response in Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {25}, number = {5}, pages = {}, pmid = {38473944}, issn = {1422-0067}, support = {Ricerca Corrente 2022-2024//Ministero della Salute/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/metabolism ; Oxidative Stress/physiology ; Antioxidants/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism ; Inflammation/drug therapy ; }, abstract = {Oxidative stress (OS) and inflammation are two important and well-studied pathological hallmarks of neurodegenerative diseases (NDDs). Due to elevated oxygen consumption, the high presence of easily oxidizable polyunsaturated fatty acids and the weak antioxidant defenses, the brain is particularly vulnerable to oxidative injury. Uncertainty exists over whether these deficits contribute to the development of NDDs or are solely a consequence of neuronal degeneration. Furthermore, these two pathological hallmarks are linked, and it is known that OS can affect the inflammatory response. In this review, we will overview the last findings about these two pathways in the principal NDDs. Moreover, we will focus more in depth on amyotrophic lateral sclerosis (ALS) to understand how anti-inflammatory and antioxidants drugs have been used for the treatment of this still incurable motor neuron (MN) disease. Finally, we will analyze the principal past and actual clinical trials and the future perspectives in the study of these two pathological mechanisms.}, }
@article {pmid38471489, year = {2024}, author = {D'Souza, A and Zink, K and Langhorst, J and Wildner, M and Stupp, C and Keil, T}, title = {How Effective Is Drinking Natural Mineral Water against Heartburn from Functional Dyspepsia, Gastroesophageal Reflux Disease, or Other Causes? A Systematic Review of Clinical Intervention Studies.}, journal = {Complementary medicine research}, volume = {31}, number = {3}, pages = {253-265}, pmid = {38471489}, issn = {2504-2106}, mesh = {Humans ; *Mineral Waters/therapeutic use ; *Gastroesophageal Reflux/therapy/drug therapy ; *Heartburn/drug therapy ; *Dyspepsia/drug therapy ; Randomized Controlled Trials as Topic ; }, abstract = {BACKGROUND: For centuries, spring and other natural waters have been recommended as external or internal remedies for numerous diseases. For studies that examined the effects of drinking mineral waters against heartburn, gastroesophageal reflux disease (GERD), or functional dyspepsia, a systematic review is lacking.<br><br>OBJECTIVES: The main aim of this systematic review was to examine the effects of drinking natural mineral waters on heartburn from various causes by identifying all published intervention studies and critically appraising their methods as well as summarizing their results.<br><br>METHODS: We systematically searched the largest medical literature database MEDLINE, further relevant web sources, and gray literature for randomized and nonrandomized trials, with or without control groups, up to September 2021 and no language restrictions. Further inclusion criteria were adult patients with heartburn, drinking cure with natural mineral water as the intervention, compared to no or other interventions (care-as-usual, waiting list). We defined the reduction of heartburn symptoms and duration of disease episodes as primary and quality of life as secondary outcomes. Two reviewers independently carried out the study quality assessments (risk of bias) using the National Institutes of Health-Study Quality Assessment Tools.<br><br>RESULTS: Nine trials comprising 393 patients from Italy, Russia, Ukraine, and Germany fulfilled all inclusion criteria. We identified three randomized controlled trials (all with poor methodological quality), plus six before-after (pre/post) intervention studies without a control group. The intervention groups of the three comparative trials seemed to show a stronger reduction of self-reported heartburn symptoms, and duration of heartburn episodes than the respective control groups; however, they all had poor methodological quality.<br><br>CONCLUSION: Based on the best available evidence of clinical studies, we cannot recommend or advise against drinking natural mineral waters as a treatment for heartburn. The potential benefits of natural mineral waters that were reported in some studies with a lower evidence level (e.g., lacking a control group) should be verified by good quality randomized clinical trials with adequate comparison groups and longer follow-up periods.<br><br>UNLABELLED: <title>Hintergrund</title>Seit Jahrhunderten werden Quell- und andere nat&#xfc;rliche W&#xe4;sser als &#xe4;u&#xdf;erliche oder innerliche Heilmittel f&#xfc;r zahlreiche Krankheiten empfohlen. F&#xfc;r Studien, die die Wirkung des Trinkens von Mineralwasser gegen Sodbrennen, gastro&#xf6;sophageale Refluxkrankheit (GERD) oder funktionelle Dyspepsie untersuchten, fehlt eine systematische &#xdc;bersicht.<title>Zielsetzung</title>Das Hauptziel dieser systematischen &#xdc;bersichtsarbeit war es, die Auswirkungen von Trinkkuren mit nat&#xfc;rlichen Mineralw&#xe4;ssern auf Sodbrennen verschiedener Ursachen zu untersuchen, indem alle ver&#xf6;ffentlichten Interventionsstudien identifiziert und ihre Methoden kritisch bewertet sowie ihre Ergebnisse zusammengefasst wurden.<title>Methoden</title>Wir durchsuchten systematisch die gr&#xf6;&#xdf;te medizinische Literaturdatenbank MEDLINE, weitere relevante Internetquellen und graue Literatur nach randomisierten und nicht-randomisierten Studien, mit oder ohne Kontrollgruppen, bis September 2021 und ohne sprachliche Einschr&#xe4;nkungen. Weitere Einschlusskriterien waren erwachsene Patienten mit Sodbrennen, Trinkkur mit nat&#xfc;rlichem Mineralwasser als Intervention, im Vergleich zu keiner oder anderen Interventionen (care-as-usual, Warteliste). Wir definierten die Abnahme der Symptome des Sodbrennens und die Dauer der Krankheitsepisoden als prim&#xe4;re und die Lebensqualit&#xe4;t als sekund&#xe4;re Endpunkte. Zwei Gutachter bewerteten unabh&#xe4;ngig voneinander die Qualit&#xe4;t der Studien (Verzerrungsrisiko) anhand der National Institutes of Health-Study Quality Assessment Tools.<title>Ergebnisse</title>Neun Studien mit 393 Patienten aus Italien, Russland, der Ukraine und Deutschland erf&#xfc;llten alle Einschlusskriterien. Wir identifizierten drei randomisierte kontrollierte Studien (alle mit schlechter methodischer Qualit&#xe4;t) sowie sechs Vorher-Nachher-Studien (Pr&#xe4;-/Post-Studien) ohne Kontrollgruppe. Die Interventionsgruppen der drei randomisierten Vergleichsstudien schienen eine st&#xe4;rkere Verringerung der selbstberichteten Symptome und der Dauer der Episoden des Sodbrennens zu zeigen als die jeweiligen Kontrollgruppen, allerdings waren sie alle von schlechter methodischer Qualit&#xe4;t.<title>Schlussfolgerung</title>Auf der Grundlage der besten verf&#xfc;gbaren Belege aus klinischen Studien k&#xf6;nnen wir das Trinken nat&#xfc;rlicher Mineralw&#xe4;sser zur Behandlung von Sodbrennen weder empfehlen noch davon abraten. Die potenziellen Vorteile nat&#xfc;rlicher Mineralw&#xe4;sser, die in einigen Studien mit geringerer Evidenz (z. B. ohne Kontrollgruppe) berichtet wurden, sollten durch qualitativ hochwertige randomisierte klinische Studien mit angemessenen Vergleichsgruppen und l&#xe4;ngeren Nachbeobachtungszeitr&#xe4;umen &#xfc;berpr&#xfc;ft werden.}, }
@article {pmid38471312, year = {2024}, author = {Lorenc, T and Stokes, G and Fulbright, H and Sutcliffe, K and Sowden, A}, title = {Communicating cardiovascular risk: Systematic review of qualitative evidence.}, journal = {Patient education and counseling}, volume = {123}, number = {}, pages = {108231}, doi = {10.1016/j.pec.2024.108231}, pmid = {38471312}, issn = {1873-5134}, mesh = {Humans ; *Communication ; *Qualitative Research ; *Cardiovascular Diseases/prevention &amp; control ; Risk Assessment ; Decision Making ; Physician-Patient Relations ; Heart Disease Risk Factors ; Risk Factors ; }, abstract = {INTRODUCTION: Cardiovascular risk prediction models are widely used to help individuals understand risk and make decisions.<br><br>METHODS: Systematic review of qualitative evidence. We searched MEDLINE, Embase, PsycINFO and CINAHL. We included English-language qualitative studies on the communication of cardiovascular risk. We assessed study quality using Hawker et al.'s tool and synthesised data thematically.<br><br>RESULTS: Thirty-seven studies were included. Many patients think that risk scores are of limited practical value. Other sources of information feed into informal estimates of risk, which may lead patients to reject the results of clinical risk assessment when the two conflict. Clinicians identify a number of barriers to risk communication, including patients' limited understanding of risk and excessive anxiety. They use a range of strategies for adapting risk communication. Both clinicians and individuals express specific preferences for risk communication formats.<br><br>DISCUSSION: Ways of communicating risk that provide some comparison or reference point seem more promising. The broader context of communication around risk may be more important than the risk scoring instrument. Risk communication interventions, in practice, may be more about appeals to emotion than a rationalistic model of decision-making.}, }
@article {pmid38463392, year = {2024}, author = {Chen, Y and Mateski, J and Gerace, L and Wheeler, J and Burl, J and Prakash, B and Svedin, C and Amrick, R and Adams, BD}, title = {Non-coding RNAs and neuroinflammation: implications for neurological disorders.}, journal = {Experimental biology and medicine (Maywood, N.J.)}, volume = {249}, number = {}, pages = {10120}, pmid = {38463392}, issn = {1535-3699}, mesh = {Humans ; Neuroinflammatory Diseases ; *Nervous System Diseases/genetics ; Microglia/metabolism ; *MicroRNAs/genetics/metabolism ; Cytokines/metabolism ; Chemokines/metabolism ; }, abstract = {Neuroinflammation is considered a balanced inflammatory response important in the intrinsic repair process after injury or infection. Under chronic states of disease, injury, or infection, persistent neuroinflammation results in a heightened presence of cytokines, chemokines, and reactive oxygen species that result in tissue damage. In the CNS, the surrounding microglia normally contain macrophages and other innate immune cells that perform active immune surveillance. The resulting cytokines produced by these macrophages affect the growth, development, and responsiveness of the microglia present in both white and gray matter regions of the CNS. Controlling the levels of these cytokines ultimately improves neurocognitive function and results in the repair of lesions associated with neurologic disease. MicroRNAs (miRNAs) are master regulators of the genome and subsequently control the activity of inflammatory responses crucial in sustaining a robust and acute immunological response towards an acute infection while dampening pathways that result in heightened levels of cytokines and chemokines associated with chronic neuroinflammation. Numerous reports have directly implicated miRNAs in controlling the abundance and activity of interleukins, TGF-B, NF-kB, and toll-like receptor-signaling intrinsically linked with the development of neurological disorders such as Parkinson's, ALS, epilepsy, Alzheimer's, and neuromuscular degeneration. This review is focused on discussing the role miRNAs play in regulating or initiating these chronic neurological states, many of which maintain the level and/or activity of neuron-specific secondary messengers. Dysregulated miRNAs present in the microglia, astrocytes, oligodendrocytes, and epididymal cells, contribute to an overall glial-specific inflammatory niche that impacts the activity of neuronal conductivity, signaling action potentials, neurotransmitter robustness, neuron-neuron specific communication, and neuron-muscular connections. Understanding which miRNAs regulate microglial activation is a crucial step forward in developing non-coding RNA-based therapeutics to treat and potentially correct the behavioral and cognitive deficits typically found in patients suffering from chronic neuroinflammation.}, }
@article {pmid38459794, year = {2024}, author = {Campagne, S}, title = {U1 snRNP Biogenesis Defects in Neurodegenerative Diseases.}, journal = {Chembiochem : a European journal of chemical biology}, volume = {25}, number = {9}, pages = {e202300864}, doi = {10.1002/cbic.202300864}, pmid = {38459794}, issn = {1439-7633}, mesh = {Animals ; Humans ; *Neurodegenerative Diseases/metabolism/pathology ; *Ribonucleoprotein, U1 Small Nuclear/metabolism/chemistry ; }, abstract = {The U1 small ribonucleoprotein (U1 snRNP) plays a pivotal role in the intricate process of gene expression, specifically within nuclear RNA processing. By initiating the splicing reaction and modulating 3'-end processing, U1 snRNP exerts precise control over RNA metabolism and gene expression. This ribonucleoparticle is abundantly present, and its complex biogenesis necessitates shuttling between the nuclear and cytoplasmic compartments. Over the past three decades, extensive research has illuminated the crucial connection between disrupted U snRNP biogenesis and several prominent human diseases, notably various neurodegenerative conditions. The perturbation of U1 snRNP homeostasis has been firmly established in diseases such as Spinal Muscular Atrophy, Pontocerebellar hypoplasia, and FUS-mediated Amyotrophic Lateral Sclerosis. Intriguingly, compelling evidence suggests a potential correlation in Fronto-temporal dementia and Alzheimer's disease as well. Although the U snRNP biogenesis pathway is conserved across all eukaryotic cells, neurons, in particular, appear to be highly susceptible to alterations in spliceosome homeostasis. In contrast, other cell types exhibit a greater resilience to such disturbances. This vulnerability underscores the intricate relationship between U1 snRNP dynamics and the health of neuronal cells, shedding light on potential avenues for understanding and addressing neurodegenerative disorders.}, }
@article {pmid38452377, year = {2024}, author = {Rajabi, D and Khanmohammadi, S and Rezaei, N}, title = {The role of long noncoding RNAs in amyotrophic lateral sclerosis.}, journal = {Reviews in the neurosciences}, volume = {35}, number = {5}, pages = {533-547}, pmid = {38452377}, issn = {2191-0200}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *RNA, Long Noncoding/genetics/metabolism ; Animals ; RNA-Binding Protein FUS/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with a poor prognosis leading to death. The diagnosis and treatment of ALS are inherently challenging due to its complex pathomechanism. Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nucleotides involved in different cellular processes, incisively gene expression. In recent years, more studies have been conducted on lncRNA classes and interference in different disease pathologies, showing their promising contribution to diagnosing and treating neurodegenerative diseases. In this review, we discussed the role of lncRNAs like NEAT1 and C9orf72-as in ALS pathogenesis mechanisms caused by mutations in different genes, including TAR DNA-binding protein-43 (TDP-43), fused in sarcoma (FUS), superoxide dismutase type 1 (SOD1). NEAT1 is a well-established lncRNA in ALS pathogenesis; hence, we elaborate on its involvement in forming paraspeckles, stress response, inflammatory response, and apoptosis. Furthermore, antisense lncRNAs (as-lncRNAs), a key group of transcripts from the opposite strand of genes, including ZEB1-AS1 and ATXN2-AS, are discussed as newly identified components in the pathology of ALS. Ultimately, we review the current standing of using lncRNAs as biomarkers and therapeutic agents and the future vision of further studies on lncRNA applications.}, }
@article {pmid38451707, year = {2024}, author = {Clayton, EL and Huggon, L and Cousin, MA and Mizielinska, S}, title = {Synaptopathy: presynaptic convergence in frontotemporal dementia and amyotrophic lateral sclerosis.}, journal = {Brain : a journal of neurology}, volume = {147}, number = {7}, pages = {2289-2307}, pmid = {38451707}, issn = {1460-2156}, support = {P2003//Epilepsy Research UK/ ; /ALZS_/Alzheimer's Society/United Kingdom ; //UK Dementia Research Institute/ ; //UK Medical Research Council/ ; 529508//Simons Foundation/ ; 204954/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; //Alzheimer's Research UK/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology/physiopathology ; *Frontotemporal Dementia/genetics/pathology/physiopathology ; *Synapses/pathology ; *Presynaptic Terminals/pathology/metabolism ; Animals ; Mutation ; }, abstract = {Frontotemporal dementia and amyotrophic lateral sclerosis are common forms of neurodegenerative disease that share overlapping genetics and pathologies. Crucially, no significantly disease-modifying treatments are available for either disease. Identifying the earliest changes that initiate neuronal dysfunction is important for designing effective intervention therapeutics. The genes mutated in genetic forms of frontotemporal dementia and amyotrophic lateral sclerosis have diverse cellular functions, and multiple disease mechanisms have been proposed for both. Identification of a convergent disease mechanism in frontotemporal dementia and amyotrophic lateral sclerosis would focus research for a targetable pathway, which could potentially effectively treat all forms of frontotemporal dementia and amyotrophic lateral sclerosis (both familial and sporadic). Synaptopathies are diseases resulting from physiological dysfunction of synapses, and define the earliest stages in multiple neuronal diseases, with synapse loss a key feature in dementia. At the presynapse, the process of synaptic vesicle recruitment, fusion and recycling is necessary for activity-dependent neurotransmitter release. The unique distal location of the presynaptic terminal means the tight spatio-temporal control of presynaptic homeostasis is dependent on efficient local protein translation and degradation. Recently, numerous publications have shown that mutations associated with frontotemporal dementia and amyotrophic lateral sclerosis present with synaptopathy characterized by presynaptic dysfunction. This review will describe the complex local signalling and membrane trafficking events that occur at the presynapse to facilitate neurotransmission and will summarize recent publications linking frontotemporal dementia/amyotrophic lateral sclerosis genetic mutations to presynaptic function. This evidence indicates that presynaptic synaptopathy is an early and convergent event in frontotemporal dementia and amyotrophic lateral sclerosis and illustrates the need for further research in this area, to identify potential therapeutic targets with the ability to impact this convergent pathomechanism.}, }
@article {pmid38447803, year = {2024}, author = {Porter, L and Sultan, O and Mitchell, BG and Jenney, A and Kiernan, M and Brewster, DJ and Russo, PL}, title = {How long do nosocomial pathogens persist on inanimate surfaces? A scoping review.}, journal = {The Journal of hospital infection}, volume = {147}, number = {}, pages = {25-31}, doi = {10.1016/j.jhin.2024.01.023}, pmid = {38447803}, issn = {1532-2939}, mesh = {Humans ; *Bacteria/classification/isolation &amp; purification ; *Cross Infection/prevention &amp; control/microbiology ; Environmental Microbiology ; *Fungi/isolation &amp; purification/classification ; Time Factors ; Viruses/classification/isolation &amp; purification/pathogenicity ; }, abstract = {Healthcare hygiene plays a crucial role in the prevention of healthcare-associated infections. Patients admitted to a room where the previous occupant had a multi-drug-resistant bacterial infection are at an increased risk of colonization and infection with the same organism. A 2006 systematic review by Kramer et al. found that certain pathogens can survive for months on dry surfaces. The aim of this review is to update Kramer et al.'s previous review and provide contemporary data on the survival of pathogens relevant to the healthcare environment. We systematically searched Ovid MEDLINE, CINAHL and Scopus databases for studies that described the survival time of common nosocomial pathogens in the environment. Pathogens included in the review were bacterial, viral, and fungal. Studies were independently screened against predetermined inclusion/exclusion criteria by two researchers. Conflicts were resolved by one of two senior researchers. A spreadsheet was developed for the data extraction. The search identified 1736 studies. Following removal of duplicates and application of the search criteria, the synthesis of results from 62 included studies were included. 117 organisms were reported. The longest surviving organism reported was Klebsiella pneumoniae which was found to have persisted for 600 days. Common pathogens of concern to infection prevention and control, can survive or persist on inanimate surfaces for months. This data supports the need for a risk-based approach to cleaning and disinfection practices, accompanied by appropriate training, audit and feedback which are proven to be effective when adopted in a 'bundle' approach.}, }
@article {pmid38433528, year = {2024}, author = {Reichenberger, V and Corona, AP and Ramos, VD and Shakespeare, T and Hameed, S and Penn-Kekana, L and Kuper, H}, title = {Access to primary healthcare services for adults with disabilities in Latin America and the Caribbean: a review and meta-synthesis of qualitative studies.}, journal = {Disability and rehabilitation}, volume = {46}, number = {25}, pages = {6011-6020}, pmid = {38433528}, issn = {1464-5165}, support = {MR/R022755/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adult ; Humans ; Caribbean Region ; *Persons with Disabilities/statistics &amp; numerical data ; *Health Services Accessibility/standards/statistics &amp; numerical data ; Latin America ; *Primary Health Care ; Qualitative Research ; }, abstract = {PURPOSE: This review and meta-synthesis of qualitative studies aims to provide an overview of qualitative evidence on primary healthcare access of people with disability in Latin America and the Caribbean, as well as to identify barriers that exist in this region.<br><br>METHODS: Six databases were searched for studies from 2000 to 2022. 34 qualitative studies were identified.<br><br>RESULTS: Barriers exist on both demand and supply sides. The thematic synthesis process generated three broad overarching analytical themes, which authors have related to Levesque et&#xa0;al.'s aspects of "ability to perceive," "availability, accommodation and ability to reach" and "appropriateness and ability to engage." Access to information and health literacy are compromised due to a lack of tailored health education materials. Barriers in the urban environment, including inadequate transportation, and insufficient healthcare facility accessibility create challenges for people with disabilities to reach healthcare facilities independently. Attitudinal barriers contribute to suboptimal care experiences.<br><br>CONCLUSION: People with disabilities face several barriers in accessing healthcare. Lack of healthcare provider training, inappropriate urban infrastructure, lack of accessible transport and inaccessibility in healthcare centers are barriers that need to be addressed. With these actions, people with disabilities will be closer to having their rights met.}, }
@article {pmid38430933, year = {2024}, author = {Li, D and Zhou, L and Cao, Z and Wang, J and Yang, H and Lyu, M and Zhang, Y and Yang, R and Wang, J and Bian, Y and Xu, W and Wang, Y}, title = {Associations of environmental factors with neurodegeneration: An exposome-wide Mendelian randomization investigation.}, journal = {Ageing research reviews}, volume = {95}, number = {}, pages = {102254}, doi = {10.1016/j.arr.2024.102254}, pmid = {38430933}, issn = {1872-9649}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *Exposome ; Genome-Wide Association Study ; Mendelian Randomization Analysis ; *Alzheimer Disease/genetics ; *Parkinson Disease ; *Multiple Sclerosis/genetics ; }, abstract = {Neurodegenerative diseases (NDDs) remain a global health challenge. Previous studies have reported potential links between environmental factors and NDDs, however, findings remain controversial across studies and elusive to be interpreted as evidence of robust causal associations. In this study, we comprehensively explored the causal associations of the common environmental factors with major NDDs including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS), based on updated large-scale genome-wide association study data through two-sample Mendelian randomization (MR) approach. Our results indicated that, overall, 28 significant sets of exposure-outcome causal association evidence were detected, 12 of which were previously underestimated and newly identified, including average weekly beer plus cider intake, strenuous sports or other exercises, diastolic blood pressure, and body fat percentage with AD, alcohol intake frequency with PD, apolipoprotein B, systolic blood pressure, and forced expiratory volume in 1 s (FEV1) with ALS, and alcohol intake frequency, hip circumference, forced vital capacity, and FEV1 with MS. Moreover, the causal effects of several environmental factors on NDDs were found to overlap. From a triangulation perspective, our investigation provided insights into understanding the associations of environmental factors with NDDs, providing causality-oriented evidence to establish the risk profile of NDDs.}, }
@article {pmid38430277, year = {2024}, author = {Jagaraj, CJ and Shadfar, S and Kashani, SA and Saravanabavan, S and Farzana, F and Atkin, JD}, title = {Molecular hallmarks of ageing in amyotrophic lateral sclerosis.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {81}, number = {1}, pages = {111}, pmid = {38430277}, issn = {1420-9071}, support = {1095215//National Institute for Dementia Research/ ; Peter Stearne Familial MND Research Grant//Motor Neurone Disease Australia/ ; Linda Rynalski Bridge Funding Grant//Motor Neurone Disease Australia/ ; 51909/00//FightMND/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Longevity ; Autophagy/genetics ; Brain ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal, severely debilitating and rapidly progressing disorder affecting motor neurons in the brain, brainstem, and spinal cord. Unfortunately, there are few effective treatments, thus there remains a critical need to find novel interventions that can mitigate against its effects. Whilst the aetiology of ALS remains unclear, ageing is the major risk factor. Ageing is a slowly progressive process marked by functional decline of an organism over its lifespan. However, it remains unclear how ageing promotes the risk of ALS. At the molecular and cellular level there are specific hallmarks characteristic of normal ageing. These hallmarks are highly inter-related and overlap significantly with each other. Moreover, whilst ageing is a normal process, there are striking similarities at the molecular level between these factors and neurodegeneration in ALS. Nine ageing hallmarks were originally proposed: genomic instability, loss of telomeres, senescence, epigenetic modifications, dysregulated nutrient sensing, loss of proteostasis, mitochondrial dysfunction, stem cell exhaustion, and altered inter-cellular communication. However, these were recently (2023) expanded to include dysregulation of autophagy, inflammation and dysbiosis. Hence, given the latest updates to these hallmarks, and their close association to disease processes in ALS, a new examination of their relationship to pathophysiology is warranted. In this review, we describe possible mechanisms by which normal ageing impacts on neurodegenerative mechanisms implicated in ALS, and new therapeutic interventions that may arise from this.}, }
@article {pmid38430252, year = {2024}, author = {Carson, HJ and Bobrownicki, R}, title = {Advancing mental imagery research from an interdisciplinary sport science perspective: a commentary on Frank et al. (2023).}, journal = {Psychological research}, volume = {88}, number = {6}, pages = {1833-1836}, pmid = {38430252}, issn = {1430-2772}, mesh = {Humans ; *Imagination/physiology ; Sports/psychology ; Interdisciplinary Research ; Athletes/psychology ; Psychology, Sports ; }, abstract = {Frank et al.'s (2023) perceptual-cognitive scaffold meaningfully extends the cognitive action architecture approach and we support this interdisciplinary advancement. However, there are theoretical and applied aspects that could be further developed within this research to maximise practical impact across domains such as sport. In particular, there is a need to consider how these mechanisms (1) might critically inform or relate to other prominent theories within sport (e.g., constrained action hypothesis and ecological approaches) and, (2) reflect the real-world challenges experienced by athletes. With these ideas in mind, this commentary aims to stimulate discussion and enhance the translational application of Frank et al.'s research.}, }
@article {pmid38429818, year = {2024}, author = {Darabi, S and Ariaei, A and Rustamzadeh, A and Afshari, D and Charkhat Gorgich, EA and Darabi, L}, title = {Cerebrospinal fluid and blood exosomes as biomarkers for amyotrophic lateral sclerosis; a systematic review.}, journal = {Diagnostic pathology}, volume = {19}, number = {1}, pages = {47}, pmid = {38429818}, issn = {1746-1596}, mesh = {Humans ; *Exosomes ; *Amyotrophic Lateral Sclerosis/diagnosis ; Superoxide Dismutase-1 ; Biomarkers ; DNA-Binding Proteins ; Disease Progression ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal motor neuron disease. Due to the limited knowledge about potential biomarkers that help in early diagnosis and monitoring disease progression, today's diagnoses are based on ruling out other diseases, neurography, and electromyography examination, which takes a time-consuming procedure.<br><br>METHODS: PubMed, ScienceDirect, and Web of Science were explored to extract articles published from January 2015 to June 2023. In the searching strategy following keywords were included; amyotrophic lateral sclerosis, biomarkers, cerebrospinal fluid, serum, and plama.<br><br>RESULTS: A total number of 6 studies describing fluid-based exosomal biomarkers were included in this study. Aggregated proteins including SOD1, TDP-43, pTDP-43, and FUS could be detected in the microvesicles (MVs). Moreover, TDP-43 and NFL extracted from plasma exosomes could be used as prognostic biomarkers. Also, downregulated miR-27a-3p detected through exoEasy Maxi and exoQuick Kit in the plasma could be measured as a diagnostic biomarker. Eventually, the upregulated level of CORO1A could be used to monitor disease progression.<br><br>CONCLUSION: Based on the results, each biomarker alone is insufficient to evaluate ALS. CNS-derived exosomes contain multiple ALS-related biomarkers (SOD1, TDP-43, pTDP-43, FUS, and miRNAs) that are detectable in cerebrospinal fluid and blood is a proper alternation. Exosome detecting kits listed as exoEasy, ExoQuick, Exo-spin, ME kit, ExoQuick Plus, and Exo-Flow, are helpful to reach this purpose.}, }
@article {pmid38429379, year = {2024}, author = {de Luzy, IR and Lee, MK and Mobley, WC and Studer, L}, title = {Lessons from inducible pluripotent stem cell models on neuronal senescence in aging and neurodegeneration.}, journal = {Nature aging}, volume = {4}, number = {3}, pages = {309-318}, pmid = {38429379}, issn = {2662-8465}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; R01 AG054720/AG/NIA NIH HHS/United States ; R01 AG070154/AG/NIA NIH HHS/United States ; ASAP-020370//Michael J. Fox Foundation for Parkinson's Research (Michael J. Fox Foundation)/ ; }, mesh = {Humans ; *Neurodegenerative Diseases ; Aging ; Cellular Senescence/physiology ; Neurons ; *Pluripotent Stem Cells ; }, abstract = {Age remains the central risk factor for many neurodegenerative diseases including Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis. Although the mechanisms of aging are complex, the age-related accumulation of senescent cells in neurodegeneration is well documented and their clearance can alleviate disease-related features in preclinical models. Senescence-like characteristics are observed in both neuronal and glial lineages, but their relative contribution to aging and neurodegeneration remains unclear. Human pluripotent stem cell-derived neurons provide an experimental model system to induce neuronal senescence. However, the extensive heterogeneity in the profile of senescent neurons and the methods to assess senescence remain major challenges. Here, we review the evidence of cellular senescence in neuronal aging and disease, discuss human pluripotent stem cell-based model systems used to investigate neuronal senescence and propose a panel of cellular and molecular hallmarks to characterize senescent neurons. Understanding the role of neuronal senescence may yield novel therapeutic opportunities in neurodegenerative disease.}, }
@article {pmid38428126, year = {2024}, author = {Wahbeh, F and Restifo, D and Laws, S and Pawar, A and Parikh, NS}, title = {Impact of tobacco smoking on disease-specific outcomes in common neurological disorders: A scoping review.}, journal = {Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia}, volume = {122}, number = {}, pages = {10-18}, pmid = {38428126}, issn = {1532-2653}, support = {K23 AG073524/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Smoking Cessation ; Smoking/adverse effects/epidemiology ; Tobacco Smoking ; *Stroke/epidemiology/etiology/therapy ; *Multiple Sclerosis ; }, abstract = {Although the association of smoking with the risk of incident neurological disorders is well established, less is known about the impact of smoking and smoking cessation on outcomes of these conditions. The objective of this scoping review was to synthesize what is known about the impact of smoking and smoking cessation on disease-specific outcomes for seven common neurological disorders. We included 67 studies on the association of smoking and smoking cessation on disease-specific outcomes. For multiple sclerosis, smoking was associated with greater clinical and radiological disease progression, relapses, risk for disease-related death, cognitive decline, and mood symptoms, in addition to reduced treatment effectiveness. For stroke and transient ischemic attack, smoking was associated with greater rates of stroke recurrence, post-stroke cardiovascular outcomes, post-stroke mortality, post-stroke cognitive impairment, and functional impairment. In patients with cognitive impairment and dementia, smoking was associated with faster cognitive decline, and smoking was also associated with greater cognitive decline in Parkinson's disease, but not motor symptom worsening. Patients with amyotrophic lateral sclerosis who smoked faced increased mortality. Last, in patients with cluster headache, smoking was associated with more frequent and longer cluster attack periods. Conversely, for multiple sclerosis and stroke, smoking cessation was associated with improved disease-specific outcomes. In summary, whereas smoking is detrimentally associated with disease-specific outcomes in common neurological conditions, there is growing evidence that smoking cessation may improve outcomes. Effective smoking cessation interventions should be leveraged in the management of common neurological disorders to improve patient outcomes.}, }
@article {pmid38417517, year = {2024}, author = {Li, M and Qiu, J and Yan, G and Zheng, X and Li, A}, title = {How does the neurotoxin β-N-methylamino-L-alanine exist in biological matrices and cause toxicity?.}, journal = {The Science of the total environment}, volume = {922}, number = {}, pages = {171255}, doi = {10.1016/j.scitotenv.2024.171255}, pmid = {38417517}, issn = {1879-1026}, mesh = {Animals ; Humans ; *Neurotoxins/chemistry ; *Amino Acids, Diamino/toxicity/chemistry ; Cyanobacteria Toxins ; Oxidative Stress ; }, abstract = {The neurotoxin β-N-methylamino-L-alanine (BMAA) has been deemed as a risk factor for some neurodegenerative diseases such as amyotrophic lateral sclerosis/parkinsonism dementia complex (ALS/PDC). This possible link has been proved in some primate models and cell cultures with the appearance that BMAA exposure can cause excitotoxicity, formation of protein aggregates, and/or oxidative stress. The neurotoxin BMAA extensively exists in the environment and can be transferred through the food web to human beings. In this review, the occurrence, toxicological mechanisms, and characteristics of BMAA were comprehensively summarized, and proteins and peptides were speculated as its possible binding substances in biological matrices. It is difficult to compare the published data from previous studies due to the inconsistent analytical methods and components of BMAA. The binding characteristics of BMAA should be focused on to improve our understanding of its health risk to human health in the future.}, }
@article {pmid38417402, year = {2024}, author = {Hu, N and Soh, KL and Japar, S and Li, T}, title = {Ear-Marking Relief: A Meta-Analysis on the Efficacy of Auricular Acupressure in Alleviating Anxiety Disorders.}, journal = {Complementary medicine research}, volume = {31}, number = {3}, pages = {266-277}, doi = {10.1159/000537734}, pmid = {38417402}, issn = {2504-2106}, mesh = {Humans ; *Acupressure ; *Anxiety Disorders/therapy ; Randomized Controlled Trials as Topic ; Auriculotherapy/methods ; }, abstract = {BACKGROUND: The increasing worldwide mental health crisis, notably anxiety, emphasizes the urgency for available and effective interventions. Traditional therapies, although beneficial, pose limitations due to their considerable costs and possible adverse effects, thereby inviting alternative treatments such as auricular acupressure (AA). This non-pharmacological, integrative method, underpinned by Eastern and Western medical principles, presents a significant prospect for managing anxiety.<br><br>OBJECTIVE: This study aims to evaluate the existing evidence on the efficacy of AA in reducing anxiety, as elucidated through a systematic review.<br><br>METHODS: A comprehensive search of randomized controlled trials was conducted across various databases: the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, Web of Science, Chinese National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), Wan Fang, and Database for Chinese Technical Periodicals (VIP). Two reviewers retrieved the pertinent studies and assessed their methodological quality. A meta-analysis was then conducted, incorporating data from all relevant time points.<br><br>RESULTS: Upon examining 25 studies encompassing 1,909 participants, it was discerned that AA significantly diminished anxiety (SMD = -1.1074; 95% confidence interval, -1.348 to -0.801; z = 7.70, p < 0.01). Subgroup analyses indicated that neither an increased number of auricular points nor extended intervention augmented effects. Larger effect sizes were associated with probing and avoidance of sham acupressure. Notably, 23 of the 25 studies exhibited some bias, suggesting further research is necessary.<br><br>CONCLUSIONS: The extant evidence advocates for AA as an effective supplementary intervention that reduces patient anxiety. The results hint at a potential placebo effect elicited by sham acupressure, necessitating rigorous control group definitions in future inquiries. The study findings suggest that fewer acupressure points and shorter intervention durations could effectively alleviate anxiety symptoms. Nonetheless, the significant heterogeneity across the studies underscores the requirement for more stringent research methodologies to substantiate these conclusions.<br><br>UNLABELLED: <title>Hintergrund</title>Die weltweit zunehmende Krise der psychischen Gesundheit, vor allem von Angstzust&#xe4;nden, zeigt, dass dringend verf&#xfc;gbare und wirksame Interventionen erforderlich sind. Herk&#xf6;mmliche Therapien sind zwar hilfreich, werden aber durch ihre hohen Kosten und m&#xf6;glichen unerw&#xfc;nschten Wirkungen eingeschr&#xe4;nkt, so dass alternative Behandlungen wie die Ohrakupressur gefragt sind. Diese nicht-pharmakologische, integrative Methode, die sich auf &#xf6;stliche und westliche medizinische Prinzipien st&#xfc;tzt, stellt eine bedeutsame Perspektive f&#xfc;r die Behandlung von Angstzust&#xe4;nden dar.<title>Ziel</title>Ziel dieser Studie ist es, die vorhandenen Evidenzen f&#xfc;r die Wirksamkeit der Ohrakupressur (auricular acupressure, AA) zur Verringerung von Angstzust&#xe4;nden, die in einer systematischen &#xdc;bersichtsarbeit ermittelt wurden, zu bewerten.<title>Methoden</title>Es wurde eine umfassende Suche nach randomisierten kontrollierten Studien in verschiedenen Datenbanken durchgef&#xfc;hrt: Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, Web of Science, Chinese National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), Wan Fang und Database for Chinese Technical Periodicals (VIP). Zwei Gutachter suchten die einschl&#xe4;gigen Studien heraus und bewerteten ihre methodische Qualit&#xe4;t. Anschliessend erfolgte eine Metaanalyse, bei der Daten aller relevanten Zeitpunkte ber&#xfc;cksichtigt wurden.<title>Ergebnisse:</title>Die Untersuchung von 25 Studien mit 1&#x2019;909 Teilnehmern ergab, dass die Ohrakupressur (AA) Angstzust&#xe4;nde signifikant verringerte (SMD = &#x2212;1,1074; 95%-KI: &#x2212;1,348 bis &#x2212;0,801; <italic>z</italic> = 7,70, <italic>p</italic> < 0,01). Subgruppenanalysen zeigten, dass die Effekte weder durch eine h&#xf6;here Anzahl von Ohrpunkten noch durch eine l&#xe4;ngere Intervention verst&#xe4;rkt wurden. Gr&#xf6;ssere Effektst&#xe4;rken waren mit Sondenverwendung und Vermeidung von Scheinakupressur assoziiert. Hervorzuheben ist, dass 23 der 25 Studien eine gewisse Verzerrung aufwiesen, weshalb weitere Untersuchungen erforderlich sind.<title>Schlussfolgerungen</title>Die vorhandene Evidenzlage st&#xfc;tzt die Ohrakupressur (AA) als wirksame unterst&#xfc;tzende Intervention, die die Angst der Patienten verringert. Die Ergebnisse deuten auf einen potenziellen Placeboeffekt durch Scheinakupressur hin, so dass in k&#xfc;nftigen Untersuchungen strenge Kontrollgruppendefinitionen erforderlich sind. Die Studienergebnisse sprechen daf&#xfc;r, dass eine geringere Anzahl von Akupressurpunkten und k&#xfc;rzere Interventionszeiten die Angstsymptome wirksam lindern k&#xf6;nnen. Die starke Heterogenit&#xe4;t der Studien zeigt allerdings, dass strengere wissenschaftliche Methoden erforderlich sind, um diese Schlussfolgerungen zu untermauern.}, }
@article {pmid38415696, year = {2024}, author = {Didcote, L and Vitoratou, S and Al-Chalabi, A and Goldstein, LH}, title = {What is the extent of reliability and validity evidence for screening tools for cognitive and behavioral change in people with ALS? A systematic review.}, journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration}, volume = {25}, number = {5-6}, pages = {437-451}, pmid = {38415696}, issn = {2167-9223}, support = {MR/L501529/1/MRC_/Medical Research Council/United Kingdom ; MR/R024804/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology/diagnosis/complications ; Reproducibility of Results ; Neuropsychological Tests/standards ; Cognitive Dysfunction/diagnosis/etiology ; }, abstract = {OBJECTIVE: This systematic review provides an updated summary of the existing literature on the validity of screening tools for cognitive and behavioral impairment in people with Amyotrophic Lateral Sclerosis (pwALS), and also focuses on their reliability.<br><br>METHOD: The following cognitive and behavioral screening tools were assessed in this review: the Edinburgh Cognitive and Behavioral ALS Screen (ECAS); the ALS Cognitive Behavioral Screen (ALS-CBS), the Mini Addenbrooke's Cognitive Examination (Mini-ACE), the Beaumont Behavioral Interview (BBI); the MND Behavior Scale (MiND-B); and the ALS-FTD Questionnaire (ALS-FTD-Q). A search, using Medline, PsychINFO and Embase (21/09/2023), generated 37 results after exclusion criteria were applied. Evidence of internal consistency, item-total correlations, inter-rater reliability, clinical validity, convergent validity, and structural validity were extracted and assessed and risk of bias was evaluated.<br><br>RESULTS: The cognitive component of the ECAS was the tool with most evidence of reliability and validity for the assessment of cognitive impairment in ALS. It is well-suited to accommodate physical symptoms of ALS. For behavioral assessment, the BBI or ALS-FTD-Q had the most evidence of reliability and validity. The BBI is more thorough, but the ALS-FTD-Q is briefer.<br><br>CONCLUSIONS: There is good but limited evidence for the reliability and validity of cognitive and behavioral screens. Further evidence of clinical and convergent validity would increase confidence in their clinical and research use.}, }
@article {pmid38414054, year = {2024}, author = {Ma, YY and Li, X and Yu, JT and Wang, YJ}, title = {Therapeutics for neurodegenerative diseases by targeting the gut microbiome: from bench to bedside.}, journal = {Translational neurodegeneration}, volume = {13}, number = {1}, pages = {12}, pmid = {38414054}, issn = {2047-9158}, support = {92249305//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/therapy ; *Gastrointestinal Microbiome ; *Amyotrophic Lateral Sclerosis ; *Alzheimer Disease ; *Parkinson Disease/therapy ; }, abstract = {The aetiologies and origins of neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD), are complex and multifaceted. A growing body of evidence suggests that the gut microbiome plays crucial roles in the development and progression of neurodegenerative diseases. Clinicians have come to realize that therapeutics targeting the gut microbiome have the potential to halt the progression of neurodegenerative diseases. This narrative review examines the alterations in the gut microbiome in AD, PD, ALS and HD, highlighting the close relationship between the gut microbiome and the brain in neurodegenerative diseases. Processes that mediate the gut microbiome-brain communication in neurodegenerative diseases, including the immunological, vagus nerve and circulatory pathways, are evaluated. Furthermore, we summarize potential therapeutics for neurodegenerative diseases that modify the gut microbiome and its metabolites, including diets, probiotics and prebiotics, microbial metabolites, antibacterials and faecal microbiome transplantation. Finally, current challenges and future directions are discussed.}, }
@article {pmid38411425, year = {2024}, author = {D'Urso, B and Weil, R and Génin, P}, title = {[Optineurin and mitochondrial dysfunction in neurodegeneration].}, journal = {Medecine sciences : M/S}, volume = {40}, number = {2}, pages = {167-175}, doi = {10.1051/medsci/2023220}, pmid = {38411425}, issn = {1958-5381}, mesh = {Humans ; Ubiquitin ; *Amyotrophic Lateral Sclerosis/genetics ; Cytosol ; Mitochondria/genetics ; *Mitochondrial Diseases ; }, abstract = {Optineurin (OPTN) is a multifunctional protein playing a crucial role as a receptor in selective autophagy. OPTN gene mutations are linked to diseases such as normal-tension glaucoma and amyotrophic lateral sclerosis. Recognized as a critical receptor for mitophagy, OPTN is pivotal in selectively degrading damaged mitochondria. This process is essential to prevent their accumulation, the generation of reactive oxygen species, and the release of pro-apoptotic factors. Mitophagy's quality control is governed by the PINK1 kinase and the cytosolic ubiquitin ligase Parkin, whose mutations are associated with Parkinson's disease. This review highlights recent insights emphasizing OPTN's role in mitophagy and its potential involvement in neurodegenerative diseases.}, }
@article {pmid38411261, year = {2024}, author = {Sakowski, SA and Koubek, EJ and Chen, KS and Goutman, SA and Feldman, EL}, title = {Role of the Exposome in Neurodegenerative Disease: Recent Insights and Future Directions.}, journal = {Annals of neurology}, volume = {95}, number = {4}, pages = {635-652}, pmid = {38411261}, issn = {1531-8249}, support = {R01TS000327/CC/CDC HHS/United States ; R01 TS000327/TS/ATSDR CDC HHS/United States ; K23 ES027221/ES/NIEHS NIH HHS/United States ; R01 ES030049/ES/NIEHS NIH HHS/United States ; R01TS000289/CC/CDC HHS/United States ; R01 NS127188/NS/NINDS NIH HHS/United States ; R01 TS000289/TS/ATSDR CDC HHS/United States ; R01TS000289/ACL/ACL HHS/United States ; R01NS127188/NH/NIH HHS/United States ; R01ES030049/NH/NIH HHS/United States ; P30 DK020572/DK/NIDDK NIH HHS/United States ; K23ES027221/NH/NIH HHS/United States ; }, mesh = {Humans ; *Neurodegenerative Diseases/genetics ; *Exposome ; *Alzheimer Disease/genetics ; *Parkinson Disease/genetics ; }, abstract = {Neurodegenerative diseases are increasing in prevalence and place a significant burden on society. The causes are multifactorial and complex, and increasing evidence suggests a dynamic interplay between genes and the environment, emphasizing the importance of identifying and understanding the role of lifelong exposures, known as the exposome, on the nervous system. This review provides an overview of recent advances toward defining neurodegenerative disease exposomes, focusing on Parkinson's disease, amyotrophic lateral sclerosis, and Alzheimer's disease. We present the current state of the field based on emerging data, elaborate on key themes and potential mechanisms, and conclude with limitations and future directions. ANN NEUROL 2024;95:635-652.}, }
@article {pmid38408864, year = {2024}, author = {Odierna, GL and Vucic, S and Dyer, M and Dickson, T and Woodhouse, A and Blizzard, C}, title = {How do we get from hyperexcitability to excitotoxicity in amyotrophic lateral sclerosis?.}, journal = {Brain : a journal of neurology}, volume = {147}, number = {5}, pages = {1610-1621}, pmid = {38408864}, issn = {1460-2156}, support = {//Motor Neuron Disease Research Australia/ ; //National Health and Medical Research Council of Australia/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/physiopathology ; Humans ; *Motor Neurons/physiology ; *Glutamic Acid/metabolism ; Animals ; Motor Cortex/physiopathology ; }, abstract = {Amyotrophic lateral sclerosis is a devastating neurodegenerative disease that, at present, has no effective cure. Evidence of increased circulating glutamate and hyperexcitability of the motor cortex in patients with amyotrophic lateral sclerosis have provided an empirical support base for the 'dying forward' excitotoxicity hypothesis. The hypothesis postulates that increased activation of upper motor neurons spreads pathology to lower motor neurons in the spinal cord in the form of excessive glutamate release, which triggers excitotoxic processes. Many clinical trials have focused on therapies that target excitotoxicity via dampening neuronal activation, but not all are effective. As such, there is a growing tension between the rising tide of evidence for the 'dying forward' excitotoxicity hypothesis and the failure of therapies that target neuronal activation. One possible solution to these contradictory outcomes is that our interpretation of the current evidence requires revision in the context of appreciating the complexity of the nervous system and the limitations of the neurobiological assays we use to study it. In this review we provide an evaluation of evidence relevant to the 'dying forward' excitotoxicity hypothesis and by doing so, identify key gaps in our knowledge that need to be addressed. We hope to provide a road map from hyperexcitability to excitotoxicity so that we can better develop therapies for patients suffering from amyotrophic lateral sclerosis. We conclude that studies of upper motor neuron activity and their synaptic output will play a decisive role in the future of amyotrophic lateral sclerosis therapy.}, }
@article {pmid38401571, year = {2024}, author = {Cheng, F and Chapman, T and Zhang, S and Morsch, M and Chung, R and Lee, A and Rayner, SL}, title = {Understanding age-related pathologic changes in TDP-43 functions and the consequence on RNA splicing and signalling in health and disease.}, journal = {Ageing research reviews}, volume = {96}, number = {}, pages = {102246}, doi = {10.1016/j.arr.2024.102246}, pmid = {38401571}, issn = {1872-9649}, mesh = {Humans ; RNA Splicing ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; *Frontotemporal Dementia/genetics ; DNA-Binding Proteins/genetics/metabolism ; Neurons/metabolism ; }, abstract = {TAR DNA binding protein-43 (TDP-43) is a key component in RNA splicing which plays a crucial role in the aging process. In neurodegenerative diseases such as amyotrophic lateral sclerosis, frontotemporal dementia and limbic-predominant age-related TDP-43 encephalopathy, TDP-43 can be mutated, mislocalised out of the nucleus of neurons and glial cells and form cytoplasmic inclusions. These TDP-43 alterations can lead to its RNA splicing dysregulation and contribute to mis-splicing of various types of RNA, such as mRNA, microRNA, and circular RNA. These changes can result in the generation of an altered transcriptome and proteome within cells, ultimately changing the diversity and quantity of gene products. In this review, we summarise the findings of novel atypical RNAs resulting from TDP-43 dysfunction and their potential as biomarkers or targets for therapeutic development.}, }
@article {pmid38401191, year = {2024}, author = {Lemon, R}, title = {The Corticospinal System and Amyotrophic Lateral Sclerosis: IFCN handbook chapter.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {160}, number = {}, pages = {56-67}, doi = {10.1016/j.clinph.2024.02.001}, pmid = {38401191}, issn = {1872-8952}, mesh = {Animals ; Humans ; *Pyramidal Tracts/physiology ; *Amyotrophic Lateral Sclerosis ; Motor Neurons/physiology ; Primates ; Axons ; }, abstract = {Corticospinal neurons located in motor areas of the cerebral neocortex project corticospinal axons which synapse with the spinal network; a parallel corticobulbar system projects to the cranial motor network and to brainstem motor pathways. The primate corticospinal system has a widespread cortical origin and an extensive range of different fibre diameters, including thick, fast-conducting axons. Direct cortico-motoneuronal (CM) projections from the motor cortex to arm and hand alpha motoneurons are a recent evolutionary feature, that is well developed in dexterous primates and particularly in humans. Many of these projections originate from the caudal subdivision of area 4 ('new' M1: primary motor cortex). They arise from corticospinal neurons of varied soma size, including those with fast- and relatively slow-conducting axons. This CM system has been shown to be involved in the control of skilled movements, carried out with fractionation of the distal extremities and at low force levels. During movement, corticospinal neurons are activated quite differently from 'lower' motoneurons, and there is no simple or fixed functional relationship between a so-called 'upper' motoneuron and its target lower motoneuron. There are key differences in the organisation and function of the corticospinal and CM system in primates versus non-primates, such as rodents. These differences need to be recognized when making the choice of animal model for understanding disorders such as amyotrophic lateral sclerosis (ALS). In this neurodegenerative brain disease there is a selective loss of fast-conducting corticospinal axons, and their synaptic connections, and this is reflected in responses to non-invasive cortical stimuli and measures of cortico-muscular coherence. The loss of CM connections influencing distal limb muscles results in a differential loss of muscle strength or 'split-hand' phenotype. Importantly, there is also a unique impairment in the coordination of skilled hand tasks that require fractionation of digit movement. Scores on validated tests of skilled hand function could be used to assess disease progression.}, }
@article {pmid38400897, year = {2024}, author = {Pirasteh, A and Shamseini Ghiyasvand, M and Pouladian, M}, title = {EEG-based brain-computer interface methods with the aim of rehabilitating advanced stage ALS patients.}, journal = {Disability and rehabilitation. Assistive technology}, volume = {19}, number = {8}, pages = {3183-3193}, doi = {10.1080/17483107.2024.2316312}, pmid = {38400897}, issn = {1748-3115}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/rehabilitation/physiopathology ; *Brain-Computer Interfaces ; *Electroencephalography ; Support Vector Machine ; Neural Networks, Computer ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease that leads to progressive muscle weakness and paralysis, ultimately resulting in the loss of ability to communicate and control the environment. EEG-based Brain-Computer Interface (BCI) methods have shown promise in providing communication and control with the aim of rehabilitating ALS patients. In particular, P300-based BCI has been widely studied and used for ALS rehabilitation. Other EEG-based BCI methods, such as Motor Imagery (MI) based BCI and Hybrid BCI, have also shown promise in ALS rehabilitation. Nonetheless, EEG-based BCI methods hold great potential for improvement. This review article introduces and reviews FFT, WPD, CSP, CSSP, CSP, and GC feature extraction methods. The Common Spatial Pattern (CSP) is an efficient and common technique for extracting data properties used in BCI systems. In addition, Linear Discriminant Analysis (LDA), Support Vector Machine (SVM), Neural Networks (NN), and Deep Learning (DL) classification methods were introduced and reviewed. SVM is the most appropriate classifier due to its insensitivity to the curse of dimensionality. Also, DL is used in the design of BCI systems and is a good choice for BCI systems based on motor imagery with big datasets. Despite the progress made in the field, there are still challenges to overcome, such as improving the accuracy and reliability of EEG signal detection and developing more intuitive and user-friendly interfaces By using BCI, disabled patients can communicate with their caregivers and control their environment using various devices, including wheelchairs, and robotic arms.}, }
@article {pmid38399458, year = {2024}, author = {Al Shaer, D and Al Musaimi, O and Albericio, F and de la Torre, BG}, title = {2023 FDA TIDES (Peptides and Oligonucleotides) Harvest.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {17}, number = {2}, pages = {}, pmid = {38399458}, issn = {1424-8247}, abstract = {A total of nine TIDES (pepTIDES and oligonucleoTIDES) were approved by the FDA during 2023. The four approved oligonucleotides are indicated for various types of disorders, including amyotrophic lateral sclerosis, geographic atrophy, primary hyperoxaluria type 1, and polyneuropathy of hereditary transthyretin-mediated amyloidosis. All oligonucleotides show chemically modified structures to enhance their stability and therapeutic effectiveness as antisense or aptamer oligomers. Some of them demonstrate various types of conjugation to driving ligands. The approved peptides comprise various structures, including linear, cyclic, and lipopeptides, and have diverse applications. Interestingly, the FDA has granted its first orphan drug designation for a peptide-based drug as a highly selective chemokine antagonist. Furthermore, Rett syndrome has found its first-ever core symptoms treatment, which is also peptide-based. Here, we analyze the TIDES approved in 2023 on the basis of their chemical structure, medical target, mode of action, administration route, and common adverse effects.}, }
@article {pmid38399373, year = {2024}, author = {Cha, Y and Kagalwala, MN and Ross, J}, title = {Navigating the Frontiers of Machine Learning in Neurodegenerative Disease Therapeutics.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {17}, number = {2}, pages = {}, pmid = {38399373}, issn = {1424-8247}, abstract = {Recent advances in machine learning hold tremendous potential for enhancing the way we develop new medicines. Over the years, machine learning has been adopted in nearly all facets of drug discovery, including patient stratification, lead discovery, biomarker development, and clinical trial design. In this review, we will discuss the latest developments linking machine learning and CNS drug discovery. While machine learning has aided our understanding of chronic diseases like Alzheimer's disease and Parkinson's disease, only modest effective therapies currently exist. We highlight promising new efforts led by academia and emerging biotech companies to leverage machine learning for exploring new therapies. These approaches aim to not only accelerate drug development but to improve the detection and treatment of neurodegenerative diseases.}, }
@article {pmid38397838, year = {2024}, author = {Peggion, C and Calì, T and Brini, M}, title = {Mitochondria Dysfunction and Neuroinflammation in Neurodegeneration: Who Comes First?.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {13}, number = {2}, pages = {}, pmid = {38397838}, issn = {2076-3921}, abstract = {Neurodegenerative diseases (NDs) encompass an assorted array of disorders such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, each characterised by distinct clinical manifestations and underlying pathological mechanisms. While some cases have a genetic basis, many NDs occur sporadically. Despite their differences, these diseases commonly feature chronic neuroinflammation as a hallmark. Consensus has recently been reached on the possibility that mitochondria dysfunction and protein aggregation can mutually contribute to the activation of neuroinflammatory response and thus to the onset and progression of these disorders. In the present review, we discuss the contribution of mitochondria dysfunction and neuroinflammation to the aetiology and progression of NDs, highlighting the possibility that new potential therapeutic targets can be identified to tackle neurodegenerative processes and alleviate the progression of these pathologies.}, }
@article {pmid38396996, year = {2024}, author = {Firdaus, Z and Li, X}, title = {Unraveling the Genetic Landscape of Neurological Disorders: Insights into Pathogenesis, Techniques for Variant Identification, and Therapeutic Approaches.}, journal = {International journal of molecular sciences}, volume = {25}, number = {4}, pages = {}, pmid = {38396996}, issn = {1422-0067}, support = {R01 DK126662/DK/NIDDK NIH HHS/United States ; R01 DK129241/DK/NIDDK NIH HHS/United States ; R01 DK129241 and DK126662/NH/NIH HHS/United States ; }, mesh = {Humans ; *Neurodegenerative Diseases/genetics/therapy/pathology ; *Parkinson Disease/genetics/therapy/pathology ; *Alzheimer Disease/pathology ; *Amyotrophic Lateral Sclerosis/genetics ; }, abstract = {Genetic abnormalities play a crucial role in the development of neurodegenerative disorders (NDDs). Genetic exploration has indeed contributed to unraveling the molecular complexities responsible for the etiology and progression of various NDDs. The intricate nature of rare and common variants in NDDs contributes to a limited understanding of the genetic risk factors associated with them. Advancements in next-generation sequencing have made whole-genome sequencing and whole-exome sequencing possible, allowing the identification of rare variants with substantial effects, and improving the understanding of both Mendelian and complex neurological conditions. The resurgence of gene therapy holds the promise of targeting the etiology of diseases and ensuring a sustained correction. This approach is particularly enticing for neurodegenerative diseases, where traditional pharmacological methods have fallen short. In the context of our exploration of the genetic epidemiology of the three most prevalent NDDs-amyotrophic lateral sclerosis, Alzheimer's disease, and Parkinson's disease, our primary goal is to underscore the progress made in the development of next-generation sequencing. This progress aims to enhance our understanding of the disease mechanisms and explore gene-based therapies for NDDs. Throughout this review, we focus on genetic variations, methodologies for their identification, the associated pathophysiology, and the promising potential of gene therapy. Ultimately, our objective is to provide a comprehensive and forward-looking perspective on the emerging research arena of NDDs.}, }
@article {pmid38396946, year = {2024}, author = {Anilkumar, AK and Vij, P and Lopez, S and Leslie, SM and Doxtater, K and Khan, MM and Yallapu, MM and Chauhan, SC and Maestre, GE and Tripathi, MK}, title = {Long Non-Coding RNAs: New Insights in Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {25}, number = {4}, pages = {}, pmid = {38396946}, issn = {1422-0067}, support = {DP1 AG069870/AG/NIA NIH HHS/United States ; P30 AG066546/AG/NIA NIH HHS/United States ; R16 GM146696/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Neurodegenerative Diseases/genetics/pathology ; *RNA, Long Noncoding/genetics ; *Alzheimer Disease ; *Parkinson Disease/genetics ; *Amyotrophic Lateral Sclerosis/genetics ; }, abstract = {Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), are gradually becoming a burden to society. The adverse effects and mortality/morbidity rates associated with these NDDs are a cause of many healthcare concerns. The pathologic alterations of NDDs are related to mitochondrial dysfunction, oxidative stress, and inflammation, which further stimulate the progression of NDDs. Recently, long non-coding RNAs (lncRNAs) have attracted ample attention as critical mediators in the pathology of NDDs. However, there is a significant gap in understanding the biological function, molecular mechanisms, and potential importance of lncRNAs in NDDs. This review documents the current research on lncRNAs and their implications in NDDs. We further summarize the potential implication of lncRNAs to serve as novel therapeutic targets and biomarkers for patients with NDDs.}, }
@article {pmid38393299, year = {2024}, author = {García-Parra, B and Guiu, JM and Povedano, M and Mariño, EL and Modamio, P}, title = {Geographical distribution of clinical trials in amyotrophic lateral sclerosis: a scoping review.}, journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration}, volume = {25}, number = {3-4}, pages = {376-381}, doi = {10.1080/21678421.2024.2320881}, pmid = {38393299}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology/genetics/therapy ; Belgium ; France ; Germany ; United Kingdom ; }, abstract = {Introduction: Clinical trials location is determined by many factors, including the availability of patient populations, regulatory environment, scientific expertise, and cost considerations. In clinical drug development of amyotrophic lateral sclerosis (ALS), where genetic differences have been described and may be related to geographic setting, this could have implications for the clinical interpretation of results in underrepresented geographic settings. Objective: The aim of this study was to review country participation in ALS clinical research based on available data from clinical trial registries and databases. Methods: We performed a scoping review with available information about clinical trials on ALS in ClinicalTrials.gov (CT), EU clinical trials register (EudraCT), WHO International Clinical Trials Registry Platform (ICTRP) and Web of Science (WOS). Inclusion criteria were clinical trials in phase 2 and 3 to treat ALS, recruiting or active not recruiting, from 23/06/2018 to 23/06/2023. Results: The total number of clinical trials identified were 188; 54 studies in CT, 38 in EudraCT, 47 in ICTRP and 49 in WOS. We identified 77 clinical trials after deleting duplicates and applying exclusion criteria. The countries with most studies conducted were the US with 35 studies (10.9%), followed by the United Kingdom, Belgium, France and Germany with 21 studies each one of them (6.5%). Conclusion: The data obtained in our review showed a non-homogeneous distribution in clinical trials at the international level, which may influence the interpretation of the results obtained.}, }
@article {pmid38392286, year = {2024}, author = {Jackson, WS and Bauer, S and Kaczmarczyk, L and Magadi, SS}, title = {Selective Vulnerability to Neurodegenerative Disease: Insights from Cell Type-Specific Translatome Studies.}, journal = {Biology}, volume = {13}, number = {2}, pages = {}, pmid = {38392286}, issn = {2079-7737}, support = {grant # 990868//the Konung Gustaf V:s och Drottning Victorias Stiftelse; the Wallenberg Center for Molecular Medicine;the Hereditary Disease Foundation/ ; }, abstract = {Neurodegenerative diseases (NDs) manifest a wide variety of clinical symptoms depending on the affected brain regions. Gaining insights into why certain regions are resistant while others are susceptible is vital for advancing therapeutic strategies. While gene expression changes offer clues about disease responses across brain regions, the mixture of cell types therein obscures experimental results. In recent years, methods that analyze the transcriptomes of individual cells (e.g., single-cell RNA sequencing or scRNAseq) have been widely used and have provided invaluable insights into specific cell types. Concurrently, transgene-based techniques that dissect cell type-specific translatomes (CSTs) in model systems, like RiboTag and bacTRAP, offer unique advantages but have received less attention. This review juxtaposes the merits and drawbacks of both methodologies, focusing on the use of CSTs in understanding conditions like amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), Alzheimer's disease (AD), and specific prion diseases like fatal familial insomnia (FFI), genetic Creutzfeldt-Jakob disease (gCJD), and acquired prion disease. We conclude by discussing the emerging trends observed across multiple diseases and emerging methods.}, }
@article {pmid38391754, year = {2024}, author = {Leão Batista Simões, J and Webler Eichler, S and Raitz Siqueira, ML and de Carvalho Braga, G and Bagatini, MD}, title = {Amyotrophic Lateral Sclerosis in Long-COVID Scenario and the Therapeutic Potential of the Purinergic System in Neuromodulation.}, journal = {Brain sciences}, volume = {14}, number = {2}, pages = {}, pmid = {38391754}, issn = {2076-3425}, support = {Proj. No 404256/2021-0 and 310606/2021-7).//National Council for Scientific and Technological Development/ ; }, abstract = {Amyotrophic lateral sclerosis (ALS) involves the degeneration of motor neurons and debilitating and possibly fatal symptoms. The COVID-19 pandemic directly affected the quality of life of this group, and the SARS-CoV-2 infection accelerated the present neuroinflammatory process. Furthermore, studies indicate that the infection may have led to the development of the pathology. Thus, the scenario after this pandemic presents "long-lasting COVID" as a disease that affects people who have been infected. From this perspective, studying the pathophysiology behind ALS associated with SARS-CoV-2 infection and possible supporting therapies becomes necessary when we understand the impact on the quality of life of these patients. Thus, the purinergic system was trained to demonstrate how its modulation can add to the treatment, reduce disease progression, and result in better prognoses. From our studies, we highlight the P2X7, P2X4, and A2AR receptors and how their activity can directly influence the ALS pathway.}, }
@article {pmid38391732, year = {2024}, author = {Yang, K and Liu, Y and Zhang, M}, title = {The Diverse Roles of Reactive Astrocytes in the Pathogenesis of Amyotrophic Lateral Sclerosis.}, journal = {Brain sciences}, volume = {14}, number = {2}, pages = {}, pmid = {38391732}, issn = {2076-3425}, support = {82271478//National Natural Science Foundation of China/ ; }, abstract = {Astrocytes displaying reactive phenotypes are characterized by their ability to remodel morphologically, molecularly, and functionally in response to pathological stimuli. This process results in the loss of their typical astrocyte functions and the acquisition of neurotoxic or neuroprotective roles. A growing body of research indicates that these reactive astrocytes play a pivotal role in the pathogenesis of amyotrophic lateral sclerosis (ALS), involving calcium homeostasis imbalance, mitochondrial dysfunction, abnormal lipid and lactate metabolism, glutamate excitotoxicity, etc. This review summarizes the characteristics of reactive astrocytes, their role in the pathogenesis of ALS, and recent advancements in astrocyte-targeting strategies.}, }
@article {pmid38390994, year = {2024}, author = {Nájera-Maldonado, JM and Salazar, R and Alvarez-Fitz, P and Acevedo-Quiroz, M and Flores-Alfaro, E and Hernández-Sotelo, D and Espinoza-Rojo, M and Ramírez, M}, title = {Phenolic Compounds of Therapeutic Interest in Neuroprotection.}, journal = {Journal of xenobiotics}, volume = {14}, number = {1}, pages = {227-246}, pmid = {38390994}, issn = {2039-4713}, support = {A1-S-34290 to Monica Ramirez//Consejo Nacional de Humanidades, Ciencias y Tecnolog&#xed;as/ ; }, abstract = {The number of elderly people is projected to double in the next 50 years worldwide, resulting in an increased prevalence of neurodegenerative diseases. Aging causes changes in brain tissue homeostasis, thus contributing to the development of neurodegenerative disorders. Current treatments are not entirely effective, so alternative treatments or adjuvant agents are being actively sought. Antioxidant properties of phenolic compounds are of particular interest for neurodegenerative diseases whose psychopathological mechanisms strongly rely on oxidative stress at the brain level. Moreover, phenolic compounds display other advantages such as the permeability of the blood-brain barrier (BBB) and the interesting molecular mechanisms that we reviewed in this work. We began by briefly outlining the physiopathology of neurodegenerative diseases to understand the mechanisms that result in irreversible brain damage, then we provided an overall classification of the phenolic compounds that would be addressed later. We reviewed in vitro and in vivo studies, as well as some clinical trials in which neuroprotective mechanisms were demonstrated in models of different neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), ischemia, and traumatic brain injury (TBI).}, }
@article {pmid38382884, year = {2024}, author = {Jiao, LL and Dong, HL and Liu, MM and Wu, PL and Cao, Y and Zhang, Y and Gao, FG and Zhu, HY}, title = {The potential roles of salivary biomarkers in neurodegenerative diseases.}, journal = {Neurobiology of disease}, volume = {193}, number = {}, pages = {106442}, doi = {10.1016/j.nbd.2024.106442}, pmid = {38382884}, issn = {1095-953X}, mesh = {Humans ; *Neurodegenerative Diseases/diagnosis ; Reproducibility of Results ; *Parkinson Disease/metabolism ; *Alzheimer Disease ; *Huntington Disease/diagnosis ; Biomarkers ; }, abstract = {Current research efforts on neurodegenerative diseases are focused on identifying novel and reliable biomarkers for early diagnosis and insight into disease progression. Salivary analysis is gaining increasing interest as a promising source of biomarkers and matrices for measuring neurodegenerative diseases. Saliva collection offers multiple advantages over the currently detected biofluids as it is easily accessible, non-invasive, and repeatable, allowing early diagnosis and timely treatment of the diseases. Here, we review the existing findings on salivary biomarkers and address the potential value in diagnosing neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease and Amyotrophic lateral sclerosis. Based on the available research, β-amyloid, tau protein, α-synuclein, DJ-1, Huntington protein in saliva profiles display reliability and validity as the biomarkers of neurodegenerative diseases.}, }
@article {pmid38381656, year = {2024}, author = {Wang, XX and Chen, WZ and Li, C and Xu, RS}, title = {Current potential pathogenic mechanisms of copper-zinc superoxide dismutase 1 (SOD1) in amyotrophic lateral sclerosis.}, journal = {Reviews in the neurosciences}, volume = {35}, number = {5}, pages = {549-563}, pmid = {38381656}, issn = {2191-0200}, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; Humans ; *Superoxide Dismutase-1/metabolism/genetics ; Animals ; Motor Neurons/metabolism/pathology ; Oxidative Stress/physiology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease which damages upper and lower motor neurons (UMN and LMN) innervating the muscles of the trunk, extremities, head, neck and face in cerebrum, brain stem and spinal cord, which results in the progressive weakness, atrophy and fasciculation of muscle innervated by the related UMN and LMN, accompanying with the pathological signs leaded by the cortical spinal lateral tract lesion. The pathogenesis about ALS is not fully understood, and no specific drugs are available to cure and prevent the progression of this disease at present. In this review, we reviewed the structure and associated functions of copper-zinc superoxide dismutase 1 (SOD1), discuss why SOD1 is crucial to the pathogenesis of ALS, and outline the pathogenic mechanisms of SOD1 in ALS that have been identified at recent years, including glutamate-related excitotoxicity, mitochondrial dysfunction, endoplasmic reticulum stress, oxidative stress, axonal transport disruption, prion-like propagation, and the non-cytologic toxicity of glial cells. This review will help us to deeply understand the current progression in this field of SOD1 pathogenic mechanisms in ALS.}, }
@article {pmid38381447, year = {2024}, author = {Bahr, T and Vu, TA and Tuttle, JJ and Iezzi, R}, title = {Deep Learning and Machine Learning Algorithms for Retinal Image Analysis in Neurodegenerative Disease: Systematic Review of Datasets and Models.}, journal = {Translational vision science &amp; technology}, volume = {13}, number = {2}, pages = {16}, pmid = {38381447}, issn = {2164-2591}, mesh = {Humans ; Algorithms ; *Alzheimer Disease/diagnostic imaging ; *Deep Learning ; Machine Learning ; *Neurodegenerative Diseases/diagnostic imaging ; Datasets as Topic ; *Retina/diagnostic imaging ; }, abstract = {PURPOSE: Retinal images contain rich biomarker information for neurodegenerative disease. Recently, deep learning models have been used for automated neurodegenerative disease diagnosis and risk prediction using retinal images with good results.<br><br>METHODS: In this review, we systematically report studies with datasets of retinal images from patients with neurodegenerative diseases, including Alzheimer's disease, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, and others. We also review and characterize the models in the current literature which have been used for classification, regression, or segmentation problems using retinal images in patients with neurodegenerative diseases.<br><br>RESULTS: Our review found several existing datasets and models with various imaging modalities primarily in patients with Alzheimer's disease, with most datasets on the order of tens to a few hundred images. We found limited data available for the other neurodegenerative diseases. Although cross-sectional imaging data for Alzheimer's disease is becoming more abundant, datasets with longitudinal imaging of any disease are lacking.<br><br>CONCLUSIONS: The use of bilateral and multimodal imaging together with metadata seems to improve model performance, thus multimodal bilateral image datasets with patient metadata are needed. We identified several deep learning tools that have been useful in this context including feature extraction algorithms specifically for retinal images, retinal image preprocessing techniques, transfer learning, feature fusion, and attention mapping. Importantly, we also consider the limitations common to these models in real-world clinical applications.<br><br>TRANSLATIONAL RELEVANCE: This systematic review evaluates the deep learning models and retinal features relevant in the evaluation of retinal images of patients with neurodegenerative disease.}, }
@article {pmid38380436, year = {2024}, author = {Nakaso, K}, title = {Roles of Microglia in Neurodegenerative Diseases.}, journal = {Yonago acta medica}, volume = {67}, number = {1}, pages = {1-8}, pmid = {38380436}, issn = {0513-5710}, abstract = {In recent years, microglia have attracted attention owing to their roles in various neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Microglia, which are brain-resident macrophages, not only act as immune cells but also perform other functions in the body. Interestingly, they exert contrasting effects on different neurodegenerative diseases. In addition to the previously reported M1 (toxic) and M2 (protective) types, microglia now also include disease-associated microglia owing to a more elaborate classification. Understanding this detailed classification is necessary to elucidate the association between microglia and neurodegenerative diseases. In this review, we discuss the diverse roles of microglia in neurodegenerative diseases and highlight their potential as therapeutic targets.}, }
@article {pmid38378992, year = {2024}, author = {Song, M and Qiang, Y and Zhao, X and Song, F}, title = {Cyclin-dependent Kinase 5 and Neurodegenerative Diseases.}, journal = {Molecular neurobiology}, volume = {61}, number = {10}, pages = {7287-7302}, pmid = {38378992}, issn = {1559-1182}, mesh = {Humans ; *Neurodegenerative Diseases/enzymology/metabolism ; *Cyclin-Dependent Kinase 5/metabolism ; Animals ; Oxidative Stress/physiology ; Mitochondria/metabolism ; }, abstract = {Neurodegenerative diseases are a group of diseases characterized by the progressive loss of neurons, including Alzheimer's disease, Parkinson's disease, and Amyotrophic lateral sclerosis. These diseases have a high incidence and mortality rate globally, placing a heavy burden on patients and their families. The pathogenesis of neurodegenerative diseases is complex, and there are no effective treatments at present. Cyclin-dependent kinase 5 is a proline-directed serine/threonine protein kinase that is closely related to the development and function of the nervous system. Under physiological conditions, it is involved in regulating the process of neuronal proliferation, differentiation, migration, and synaptic plasticity. Moreover, there is increasing evidence that cyclin-dependent kinase 5 also plays an important role in the pathogenesis of neurodegenerative diseases. In this review, we address the biological characteristics of cyclin-dependent kinase 5 and its role in neurodegenerative diseases. In particular, this review highlights the underlying mechanistic linkages between cyclin-dependent kinase 5 and mitochondrial dysfunction, oxidative stress and neuroinflammation in the context of neurodegeneration. Finally, we also summarize the currently available cyclin-dependent kinase 5 inhibitors and their prospects for the treatment of neurodegenerative diseases. Taken together, a better understanding of the molecular mechanisms of cyclin-dependent kinase 5 involved in neurodegenerative diseases can lead to the development of new strategies for the prevention and treatment of these devastating diseases.}, }
@article {pmid38378788, year = {2024}, author = {Rim, C and You, MJ and Nahm, M and Kwon, MS}, title = {Emerging role of senescent microglia in brain aging-related neurodegenerative diseases.}, journal = {Translational neurodegeneration}, volume = {13}, number = {1}, pages = {10}, pmid = {38378788}, issn = {2047-9158}, support = {2023R1A2C1006622//National Research Foundation (NRF)/ ; RS-2023-00265515//National Research Foundation (NRF)/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/pathology ; Microglia/pathology ; Brain/pathology ; Cellular Senescence ; *Amyotrophic Lateral Sclerosis/pathology ; }, abstract = {Brain aging is a recognized risk factor for neurodegenerative diseases like Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease), but the intricate interplay between brain aging and the pathogenesis of these conditions remains inadequately understood. Cellular senescence is considered to contribute to cellular dysfunction and inflammaging. According to the threshold theory of senescent cell accumulation, the vulnerability to neurodegenerative diseases is associated with the rates of senescent cell generation and clearance within the brain. Given the role of microglia in eliminating senescent cells, the accumulation of senescent microglia may lead to the acceleration of brain aging, contributing to inflammaging and increased vulnerability to neurodegenerative diseases. In this review, we propose the idea that the senescence of microglia, which is notably vulnerable to aging, could potentially serve as a central catalyst in the progression of neurodegenerative diseases. The senescent microglia are emerging as a promising target for mitigating neurodegenerative diseases.}, }
@article {pmid38370434, year = {2024}, author = {Chen, C and Qi, J and Li, Y and Li, D and Wu, L and Li, R and Chen, Q and Sun, N}, title = {Applications of Raman spectroscopy in the diagnosis and monitoring of neurodegenerative diseases.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1301107}, pmid = {38370434}, issn = {1662-4548}, abstract = {Raman scattering is an inelastic light scattering that occurs in a manner reflective of the molecular vibrations of molecular structures and chemical conditions in a given sample of interest. Energy changes in the scattered light can be assessed to determine the vibration mode and associated molecular and chemical conditions within the sample, providing a molecular fingerprint suitable for sample identification and characterization. Raman spectroscopy represents a particularly promising approach to the molecular analysis of many diseases owing to clinical advantages including its instantaneous nature and associated high degree of stability, as well as its ability to yield signal outputs corresponding to a single molecule type without any interference from other molecules as a result of its narrow peak width. This technology is thus ideally suited to the simultaneous assessment of multiple analytes. Neurodegenerative diseases represent an increasingly significant threat to global public health owing to progressive population aging, imposing a severe physical and social burden on affected patients who tend to develop cognitive and/or motor deficits beginning between the ages of 50 and 70. Owing to a relatively limited understanding of the etiological basis for these diseases, treatments are lacking for the most common neurodegenerative diseases, which include Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. The present review was formulated with the goal of briefly explaining the principle of Raman spectroscopy and discussing its potential applications in the diagnosis and evaluation of neurodegenerative diseases, with a particular emphasis on the research prospects of this novel technological platform.}, }
@article {pmid38369520, year = {2024}, author = {Adashek, JJ and Pandya, C and Maragakis, NJ and De, P and Cohen, PR and Kato, S and Kurzrock, R}, title = {Neuregulin-1 and ALS19 (ERBB4): at the crossroads of amyotrophic lateral sclerosis and cancer.}, journal = {BMC medicine}, volume = {22}, number = {1}, pages = {74}, pmid = {38369520}, issn = {1741-7015}, support = {U10 CA180888/CA/NCI NIH HHS/United States ; UG1 CA233198/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *Neoplasms/genetics ; *Neuregulin-1/genetics/metabolism ; *Receptor, ErbB-4/genetics/metabolism ; Signal Transduction ; }, abstract = {BACKGROUND: Neuregulin-1 (NRG1) is implicated in both cancer and neurologic diseases such as amyotrophic lateral sclerosis (ALS); however, to date, there has been little cross-field discussion between neurology and oncology in regard to these genes and their functions.<br><br>MAIN BODY: Approximately 0.15-0.5% of cancers harbor NRG1 fusions that upregulate NRG1 activity and hence that of the cognate ERBB3/ERBB4 (HER3/HER4) receptors; abrogating this activity with small molecule inhibitors/antibodies shows preliminary tissue-agnostic anti-cancer activity. Notably, ERBB/HER pharmacologic suppression is devoid of neurologic toxicity. Even so, in ALS, attenuated ERBB4/HER4 receptor activity (due to loss-of-function germline mutations or other mechanisms in sporadic disease) is implicated; indeed, ERBB4/HER4 is designated ALS19. Further, secreted-type NRG1 isoforms may be upregulated (perhaps via a feedback loop) and could contribute to ALS pathogenesis through aberrant glial cell stimulation via enhanced activity of other (e.g., ERBB1-3/HER1-3) receptors and downstream pathways. Hence, pan-ERBB inhibitors, already in use for cancer, may be agents worthy of testing in ALS.<br><br>CONCLUSION: Common signaling cascades between cancer and ALS may represent novel therapeutic targets for both diseases.}, }
@article {pmid38368936, year = {2024}, author = {Herman, M and Randall, GW and Spiegel, JL and Maldonado, DJ and Simoes, S}, title = {Endo-lysosomal dysfunction in neurodegenerative diseases: opinion on current progress and future direction in the use of exosomes as biomarkers.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {379}, number = {1899}, pages = {20220387}, pmid = {38368936}, issn = {1471-2970}, support = {P30 AG066462/AG/NIA NIH HHS/United States ; R01 AG071868/AG/NIA NIH HHS/United States ; R21 AG070768/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Neurodegenerative Diseases/diagnosis/metabolism ; *Exosomes ; *Alzheimer Disease/diagnosis ; Lysosomes/metabolism ; Biomarkers/metabolism ; }, abstract = {Over the past two decades, increased research has highlighted the connection between endosomal trafficking defects and neurodegeneration. The endo-lysosomal network is an important, complex cellular system specialized in the transport of proteins, lipids, and other metabolites, essential for cell homeostasis. Disruption of this pathway is linked to a wide range of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease and frontotemporal dementia. Furthermore, there is strong evidence that defects in this pathway create opportunities for diagnostic and therapeutic intervention. In this Opinion piece, we concisely address the role of endo-lysosomal dysfunction in five neurodegenerative diseases and discuss how future research can investigate this intracellular pathway, including extracellular vesicles with a specific focus on exosomes for the identification of novel disease biomarkers. This article is part of a discussion meeting issue 'Understanding the endo-lysosomal network in neurodegeneration'.}, }
@article {pmid38367748, year = {2024}, author = {La Cognata, V and Morello, G and Guarnaccia, M and Cavallaro, S}, title = {The multifaceted role of the CXC chemokines and receptors signaling axes in ALS pathophysiology.}, journal = {Progress in neurobiology}, volume = {235}, number = {}, pages = {102587}, doi = {10.1016/j.pneurobio.2024.102587}, pmid = {38367748}, issn = {1873-5118}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; Signal Transduction ; Motor Neurons ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a late-onset motor neuron disease with complex genetic basis and still no clear etiology. Multiple intertwined layers of immune system-related dysfunctions and neuroinflammatory mechanisms are emerging as substantial determinants in ALS onset and progression. In this review, we collect the increasingly arising evidence implicating four main CXC chemokines/cognate receptors signaling axes (CXCR1/2-CXCL1/2/8; CXCR3-CXCL9/10/11; CXCR4/7-CXCL12; CXCR5-CXCL13) in the pathophysiology of ALS. Findings in preclinical models implicate these signaling pathways in motor neuron toxicity and neuroprotection, while in ALS patients dysregulation of CXCLs/CXCRs has been shown at both central and peripheral levels. Immunological monitoring of CXC-ligands in ALS may allow tracking of disease progression, while pharmacological modulation of CXC-receptors provides a novel therapeutic strategy. A deeper understanding of the interplay between CXC-mediated neuroinflammation and ALS is crucial to advance research into treatments for this debilitating uncurable disorder.}, }
@article {pmid38367681, year = {2024}, author = {Arsuffi-Marcon, R and Souza, LG and Santos-Miranda, A and Joviano-Santos, JV}, title = {Neurotoxicity of Pyrethroids in neurodegenerative diseases: From animals' models to humans' studies.}, journal = {Chemico-biological interactions}, volume = {391}, number = {}, pages = {110911}, doi = {10.1016/j.cbi.2024.110911}, pmid = {38367681}, issn = {1872-7786}, mesh = {Animals ; Humans ; *Pyrethrins/toxicity ; *Insecticides/toxicity ; *Neurodegenerative Diseases/chemically induced ; *Neurotoxicity Syndromes ; *Pesticides/toxicity ; Mammals ; }, abstract = {Neurodegenerative diseases are associated with diverse symptoms, both motor and mental. Genetic and environmental factors can trigger neurodegenerative diseases. Chemicals as pesticides are constantly used in agriculture and also domestically. In this regard, pyrethroids (PY), are a class of insecticides in which its main mechanism of action is through disruption of voltage-dependent sodium channels function in insects. However, in mammals, they can also induce oxidative stress and enzyme dysfunction. This review investigates the association between PY and neurodegenerative diseases as Alzheimer's, Huntington's, Parkinson's, Amyotrophic Lateral Sclerosis, and Autism in animal models and humans. Published works using specific and non-specific models for these diseases were selected. We showed a tendency toward the development and/or aggravating of these neurodegenerative diseases following exposure to PYs. In animal models, the biochemical mechanisms of the diseases and their interaction with the insecticides are more deeply investigated. Nonetheless, only a few studies considered the specific model for each type of disease to analyze the impacts of the exposure. The choice of a specific model during the research is an important step and our review highlights the knowledge gaps of PYs effects using these models reinforcing the importance of them during the design of the experiments.}, }
@article {pmid38367047, year = {2024}, author = {Sun, W and Liu, SH and Wei, XJ and Sun, H and Ma, ZW and Yu, XF}, title = {Potential of neuroimaging as a biomarker in amyotrophic lateral sclerosis: from structure to metabolism.}, journal = {Journal of neurology}, volume = {271}, number = {5}, pages = {2238-2257}, pmid = {38367047}, issn = {1432-1459}, support = {No. JLSWSRCZX2023-13//the Medical and Health Talents Special Foundation of Jilin Province/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/diagnostic imaging/metabolism ; Humans ; *Neuroimaging/methods/standards ; *Biomarkers/metabolism ; Brain/diagnostic imaging/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by motor neuron degeneration. The development of ALS involves metabolite alterations leading to tissue lesions in the nervous system. Recent advances in neuroimaging have significantly improved our understanding of the underlying pathophysiology of ALS, with findings supporting the corticoefferent axonal disease progression theory. Current studies on neuroimaging in ALS have demonstrated inconsistencies, which may be due to small sample sizes, insufficient statistical power, overinterpretation of findings, and the inherent heterogeneity of ALS. Deriving meaningful conclusions solely from individual imaging metrics in ALS studies remains challenging, and integrating multimodal imaging techniques shows promise for detecting valuable ALS biomarkers. In addition to giving an overview of the principles and techniques of different neuroimaging modalities, this review describes the potential of neuroimaging biomarkers in the diagnosis and prognostication of ALS. We provide an insight into the underlying pathology, highlighting the need for standardized protocols and multicenter collaborations to advance ALS research.}, }
@article {pmid38364912, year = {2024}, author = {Du, L and Roy, S and Wang, P and Li, Z and Qiu, X and Zhang, Y and Yuan, J and Guo, B}, title = {Unveiling the future: Advancements in MRI imaging for neurodegenerative disorders.}, journal = {Ageing research reviews}, volume = {95}, number = {}, pages = {102230}, doi = {10.1016/j.arr.2024.102230}, pmid = {38364912}, issn = {1872-9649}, mesh = {Humans ; *Diffusion Tensor Imaging/methods ; Artificial Intelligence ; Brain/pathology ; Magnetic Resonance Imaging/methods ; *Neurodegenerative Diseases/pathology ; }, abstract = {Neurodegenerative disorders represent a significant and growing global health challenge, necessitating continuous advancements in diagnostic tools for accurate and early detection. This work explores the recent progress in Magnetic Resonance Imaging (MRI) techniques and their application in the realm of neurodegenerative disorders. The introductory section provides a comprehensive overview of the study's background, significance, and objectives. Recognizing the current challenges associated with conventional MRI, the manuscript delves into advanced imaging techniques such as high-resolution structural imaging (HR-MRI), functional MRI (fMRI), diffusion tensor imaging (DTI), and positron emission tomography-MRI (PET-MRI) fusion. Each technique is critically examined regarding its potential to address theranostic limitations and contribute to a more nuanced understanding of the underlying pathology. A substantial portion of the work is dedicated to exploring the applications of advanced MRI in specific neurodegenerative disorders, including Parkinson's disease, Alzheimer's disease, Huntington's disease, and Amyotrophic Lateral Sclerosis (ALS). In addressing the future landscape, the manuscript examines technological advances, including the integration of machine learning and artificial intelligence in neuroimaging. The conclusion summarizes key findings, outlines implications for future research, and underscores the importance of these advancements in reshaping our understanding and approach to neurodegenerative disorders.}, }
@article {pmid38364750, year = {2024}, author = {Mercier, A and Dorris, L}, title = {A systematic review of psychosocial interventions for children and young people with epilepsy.}, journal = {European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society}, volume = {49}, number = {}, pages = {35-44}, doi = {10.1016/j.ejpn.2024.02.002}, pmid = {38364750}, issn = {1532-2130}, mesh = {Adolescent ; Child ; Humans ; *Epilepsy/psychology/therapy ; *Psychosocial Intervention/methods ; Quality of Life/psychology ; }, abstract = {BACKGROUND: Epilepsy is a lifelong neurological disorder that has a profound impact on the lives of millions of children and young people throughout the world, and is linked with mental ill-health and a poorer quality of life. Psychosocial interventions have showed promise for children and young people with epilepsy (CYPE), however there is an absence of large-scale RCT's that would add robustness to the evidence base. The present systematic review provides an update and extension of findings from an earlier review by Corrigan et al. to assess the state of the literature in 2023.<br><br>METHODS: The present systematic review carried out a search of six electronic databases. Forward and backward chaining was carried out on review articles as well as the studies returned through the search to source additional studies. In total, ten articles were included in this review and appraised for quality using the Crowe Critical Appraisal Tool (CCAT).<br><br>RESULTS: Forty percent (4/10) of the included studies were rated as high quality according to the CCAT, which represents a significant proportional increase since Corrigan et&#xa0;al.'s review. A meta-analysis of results was not possible due to significant methodological heterogeneity, and the variability of outcome measures, however effect sizes were reported or calculated for the majority of studies (7/10), which facilitated comparison. Despite the issues of relatively small samples, there are promising findings with regard to psychosocial interventions increasing epilepsy knowledge, coping strategies, self-efficacy, and quality of life markers.<br><br>CONCLUSIONS: There is a growing evidence base supporting the efficacy of psychosocial interventions for children and young people with epilepsy. This evidence base is also increasing in quality. Particular components of treatment that prove to be effective include psychoeducation, components based on cognitive behavioural therapy principles, as well as mindfulness techniques. This aligns with the evidence-based recommendations for adult populations. Intervention goals centre around improving quality of life, reducing symptom distress, and increasing knowledge and skills. The instruments used to measure these outcomes are predominantly standardised, however remain heterogeneous between studies which impacts the overall robustness of the evidence base.}, }
@article {pmid38357638, year = {2024}, author = {Gerritzen, EV and Lee, AR and McDermott, O and Coulson, N and Orrell, M}, title = {Online peer support for people with Amyotrophic Lateral Sclerosis (ALS): a narrative synthesis systematic review.}, journal = {Frontiers in digital health}, volume = {6}, number = {}, pages = {1138530}, pmid = {38357638}, issn = {2673-253X}, abstract = {BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) significantly impacts the lives of people with the diagnosis and their families. A supportive social environment is important for people with ALS to adopt effective coping strategies and health behaviours, and reduce depressive symptoms. Peer support can provide a supportive social environment and can happen in-person and online. Advantages of online peer support are that people can engage from their own home, at their own time and pace, and that it offers a variety of different platforms and modes of communication.<br><br>OBJECTIVES: To (1) explore the benefits and challenges of online peer support for people with ALS, and (2) identify successful elements of online peer support for people with ALS.<br><br>METHODS: The method selected for this systematic review was a narrative synthesis. Six databases were systematically searched in April 2020 for articles published between 1989 and 2020. The search was updated in June 2022. The quality of the included studies was assessed with the Critical Appraisal Skills Programme qualitative research checklist.<br><br>RESULTS: 10,987 unique articles were identified through the systematic database search. Of those, 9 were included in this review. One of the main benefits of online peer support was that people could communicate using text rather than needing verbal communication, which can be challenging for some with ALS. Successful elements included using profile pages and graphics to identify others with similar or relevant experiences. Challenges included ALS symptoms which could make it difficult to use technological devices.<br><br>CONCLUSIONS: Peer support can provide a non-judgmental and supportive environment for people with ALS, in which they can exchange experiences and emotional support, which can help people in developing adaptive coping strategies. However, ALS symptoms may make it more difficult for people to use technological devices and engage in online peer support. More research is needed to identify what kind of specific barriers people with ALS experience, and how these could be overcome.}, }
@article {pmid38354985, year = {2024}, author = {Zamani, A and Thomas, E and Wright, DK}, title = {Sex biology in amyotrophic lateral sclerosis.}, journal = {Ageing research reviews}, volume = {95}, number = {}, pages = {102228}, doi = {10.1016/j.arr.2024.102228}, pmid = {38354985}, issn = {1872-9649}, mesh = {Humans ; Male ; Female ; *Amyotrophic Lateral Sclerosis/epidemiology/genetics ; Brain/pathology ; Biology ; }, abstract = {Although sex differences in amyotrophic lateral sclerosis (ALS) have not been studied systematically, numerous clinical and preclinical studies have shown sex to be influential in disease prognosis. Moreover, with the development of advanced imaging tools, the difference between male and female brain in structure and function and their response to neurodegeneration are more definitive. As discussed in this review, ALS patients exhibit a sex bias pertaining to the features of the disease, and their clinical, pathological, (and pathophysiological) phenotypes. Several epidemiological studies have indicated that this sex disparity stems from various aetiologies, including sex-specific brain structure and neural functioning, genetic predisposition, age, gonadal hormones, susceptibility to traumatic brain injury (TBI)/head trauma and lifestyle factors.}, }
@article {pmid38350967, year = {2024}, author = {Rodriguez-Mogeda, C and van Ansenwoude, CMJ and van der Molen, L and Strijbis, EMM and Mebius, RE and de Vries, HE}, title = {The role of CD56[bright] NK cells in neurodegenerative disorders.}, journal = {Journal of neuroinflammation}, volume = {21}, number = {1}, pages = {48}, pmid = {38350967}, issn = {1742-2094}, mesh = {Humans ; Killer Cells, Natural ; Cytokines ; Cell Differentiation ; *Antineoplastic Agents ; *Neurodegenerative Diseases ; }, abstract = {Emerging evidence suggests a potential role for natural killer (NK) cells in neurodegenerative diseases, such as multiple sclerosis, Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. However, the precise function of NK cells in these diseases remains ambiguous. The existence of two NK cell subsets, CD56[bright] and CD56[dim] NK cells, complicates the understanding of the contribution of NK cells in neurodegeneration as their functions within the context of neurodegenerative diseases may differ significantly. CD56[bright] NK cells are potent cytokine secretors and are considered more immunoregulatory and less terminally differentiated than their mostly cytotoxic CD56[dim] counterparts. Hence, this review focusses on NK cells, specifically on CD56[bright] NK cells, and their role in neurodegenerative diseases. Moreover, it explores the mechanisms underlying their ability to enter the central nervous system. By consolidating current knowledge, we aim to provide a comprehensive overview on the role of CD56[bright] NK cells in neurodegenerative diseases. Elucidating their impact on neurodegeneration may have implications for future therapeutic interventions, potentially ameliorating disease pathogenesis.}, }
@article {pmid38349514, year = {2024}, author = {Xu, Y and Lin, F and Liao, G and Sun, J and Chen, W and Zhang, L}, title = {Ripks and Neuroinflammation.}, journal = {Molecular neurobiology}, volume = {61}, number = {9}, pages = {6771-6787}, pmid = {38349514}, issn = {1559-1182}, support = {81971098//National Natural Science Foundation of China/ ; 82104144//National Natural Science Foundation of China/ ; }, mesh = {*Receptor-Interacting Protein Serine-Threonine Kinases/metabolism ; Humans ; Animals ; *Neuroinflammatory Diseases/metabolism/pathology ; Inflammation/pathology/metabolism ; }, abstract = {Neuroinflammation is an immune response in the central nervous system and poses a significant threat to human health. Studies have shown that the receptor serine/threonine protein kinase family (RIPK) family, a popular research target in inflammation, has been shown to play an essential role in neuroinflammation. It is significant to note that the previous reviews have only examined the link between RIPK1 and neuroinflammation. However, it has yet to systematically analyze the relationship between the RIPK family and neuroinflammation. Activation of RIPK1 promotes neuroinflammation. RIPK1 and RIPK3 are responsible for the control of cell death, including apoptosis, necrosis, and inflammation. RIPK1 and RIPK3 regulate inflammatory responses through the release of damage in necroptosis. RIPK1 and RIPK3 regulate inflammatory responses by releasing damage-associated molecular patterns (DAMPs) during necrosis. In addition, activated RIPK1 nuclear translocation and its interaction with the BAF complex leads to upregulation of chromatin modification and inflammatory gene expression, thereby triggering inflammation. Although RIPK2 is not directly involved in regulating cell death, it is considered an essential target for treating neurological inflammation. When the peptidoglycan receptor detects peptidoglycan IE-DAP or MDP in bacteria, it prompts NOD1 and NOD2 to recruit RIPK2 and activate the XIAP E3 ligase. This leads to the K63 ubiquitination of RIPK2. This is followed by LUBAC-mediated linear ubiquitination, which activates NF-KB and MAPK pathways to produce cytokines and chemokines. In conclusion, there are seven known members of the RIPK family, but RIPK4, RIPK5, RIPK6, and RIPK7 have not been linked to neuroinflammation. This article seeks to explore the potential of RIPK1, RIPK2, and RIPK3 kinases as therapeutic interventions for neuroinflammation, which is associated with Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), ischemic stroke, Parkinson's disease (PD), multiple sclerosis (MS), and traumatic brain injury (TBI).}, }
@article {pmid38349395, year = {2024}, author = {Soni, S and Lukhey, MS and Thawkar, BS and Chintamaneni, M and Kaur, G and Joshi, H and Ramniwas, S and Tuli, HS}, title = {A current review on P2X7 receptor antagonist patents in the treatment of neuroinflammatory disorders: a patent review on antagonists.}, journal = {Naunyn-Schmiedeberg's archives of pharmacology}, volume = {397}, number = {7}, pages = {4643-4656}, pmid = {38349395}, issn = {1432-1912}, mesh = {*Patents as Topic ; Humans ; *Receptors, Purinergic P2X7/metabolism ; *Purinergic P2X Receptor Antagonists/therapeutic use/pharmacology ; Animals ; *Neuroinflammatory Diseases/drug therapy ; }, abstract = {Chronic inflammation is defined by an activated microglial state linked to all neurological disorders, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (a motor neuron disease that affects the brain and spinal cord). P2X7 receptors (P2X7R) are ATP-activated ion-gated channels present on microglial surfaces. Prolonged ATP release under pathological settings results in sustained P2X7R activation, which leads to inflammasome development and cytokine release. P2X7R and its enabling roles have recently been linked to neurodegenerative diseases, making it a potential research subject. This research provides an overview of current patents for chemicals, biologics, and medicinal applications. The World Intellectual Property Organization (WIPO), European Patent Office (EPO, Espacenet), and the United States Patent and Trademark Office (USPTO) databases were searched for patents using the keywords "P2X7R and Neuroinflammation." During the study period from 2015 to 2021, 103 patents were examined. The countries that protected these innovations were the United States, PCT (Patent Cooperation Treaty states), Europe, Canada, Australia, and India. Janssen Pharmaceutica NV had the most applications, followed by Acetelion Pharmaceuticals LTD., Renovis Inc., Kelly Michael G, Kincaid Jhon, Merck Patent GMBH, H Lundbeck A/S, and many more. The P2X7R is a possible diagnostic and therapeutic target for cancer, pain disorders, and inflammation. For P2X7 R, several compounds have been discovered and are presently the subject of clinical trial investigations. This study featured patents for P2X7R antagonists, which help treat conditions including neuroinflammation.}, }
@article {pmid38348223, year = {2024}, author = {Orfali, R and Alwatban, AZ and Orfali, RS and Lau, L and Chea, N and Alotaibi, AM and Nam, YW and Zhang, M}, title = {Oxidative stress and ion channels in neurodegenerative diseases.}, journal = {Frontiers in physiology}, volume = {15}, number = {}, pages = {1320086}, pmid = {38348223}, issn = {1664-042X}, support = {R33 NS101182/NS/NINDS NIH HHS/United States ; }, abstract = {Numerous neurodegenerative diseases result from altered ion channel function and mutations. The intracellular redox status can significantly alter the gating characteristics of ion channels. Abundant neurodegenerative diseases associated with oxidative stress have been documented, including Parkinson's, Alzheimer's, spinocerebellar ataxia, amyotrophic lateral sclerosis, and Huntington's disease. Reactive oxygen and nitrogen species compounds trigger posttranslational alterations that target specific sites within the subunits responsible for channel assembly. These alterations include the adjustment of cysteine residues through redox reactions induced by reactive oxygen species (ROS), nitration, and S-nitrosylation assisted by nitric oxide of tyrosine residues through peroxynitrite. Several ion channels have been directly investigated for their functional responses to oxidizing agents and oxidative stress. This review primarily explores the relationship and potential links between oxidative stress and ion channels in neurodegenerative conditions, such as cerebellar ataxias and Parkinson's disease. The potential correlation between oxidative stress and ion channels could hold promise for developing innovative therapies for common neurodegenerative diseases.}, }
@article {pmid38347638, year = {2024}, author = {Li, W and Li, HL and Wang, JZ and Liu, R and Wang, X}, title = {Abnormal protein post-translational modifications induces aggregation and abnormal deposition of protein, mediating neurodegenerative diseases.}, journal = {Cell &amp; bioscience}, volume = {14}, number = {1}, pages = {22}, pmid = {38347638}, issn = {2045-3701}, support = {92049107//National Natural Science Foundation of China/ ; 82071440//National Natural Science Foundation of China/ ; 31929002//National Natural Science Foundation of China/ ; }, abstract = {Protein post-translational modifications (PPTMs) refer to a series of chemical modifications that occur after the synthesis of protein. Proteins undergo different modifications such as phosphorylation, acetylation, ubiquitination, and so on. These modifications can alter the protein's structure, function, and interaction, thereby regulating its biological activity. In neurodegenerative diseases, several proteins undergo abnormal post-translational modifications, which leads to aggregation and abnormal deposition of protein, thus resulting in neuronal death and related diseases. For example, the main pathological features of Alzheimer's disease are the aggregation of beta-amyloid protein and abnormal phosphorylation of tau protein. The abnormal ubiquitination and loss of α-synuclein are related to the onset of Parkinson's disease. Other neurodegenerative diseases such as Huntington's disease, amyotrophic lateral sclerosis, and so on are also connected with abnormal PPTMs. Therefore, studying the abnormal PPTMs in neurodegenerative diseases is critical for understanding the mechanism of these diseases and the development of significant therapeutic strategies. This work reviews the implications of PPTMs in neurodegenerative diseases and discusses the relevant therapeutic strategies.}, }
@article {pmid38347315, year = {2024}, author = {Huang, SL and Shen, YL and Peng, WY and Ye, K and Zheng, H}, title = {Edaravone for patients with amyotrophic lateral sclerosis: a systematic review and meta-analysis.}, journal = {Acta neurologica Belgica}, volume = {124}, number = {3}, pages = {895-904}, pmid = {38347315}, issn = {2240-2993}, support = {no. 2021JDTD0007//Sichuan Province Science and Technology Support Program/ ; }, mesh = {*Edaravone/therapeutic use ; Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; Free Radical Scavengers/therapeutic use ; Randomized Controlled Trials as Topic/methods ; Treatment Outcome ; }, abstract = {BACKGROUND AND OBJECTIVE: The effectiveness and long-term efficacy of edaravone, a recommended treatment for amyotrophic lateral sclerosis (ALS), has not been examined in real-world settings. This study aims to evaluate the effectiveness and long-term efficacy of edaravone.<br><br>METHODS: The OVID Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science databases were searched for articles published between January 1, 2000, and May 1, 2023. Two investigators independently screened the retrieved articles for randomized controlled trials (RCTs), cohort studies, or single-arm trials that evaluated the effect of edaravone on amyotrophic lateral sclerosis (ALS). The risk of bias was evaluated using the revised Cochrane Risk-of-Bias (RoB 2.0) tool for randomized controlled trials (RCTs) and the Risk-of-Bias In Non-randomized Studies of Interventions (ROBINS-I) tool for observational studies. The primary outcome was the ALSFRS-R score assessed at month 6, with secondary outcomes including the ALSFRS-R scores evaluated at months 9, 12, and 18, forced vital capacity (FVC), and adverse events. The certainty of evidence was assessed using the GRADE approach.<br><br>RESULTS: The analysis included 16 studies with a total of 4828 participants. Among these, four were randomized controlled trials (RCTs) and 12 were observational studies. Of the RCTs, four were rated as having a low risk of bias, while six of the observational studies were rated as having a low risk of bias. Edaravone was associated with slightly slower progression in the reduction of ALSFRS-R score at month 6 compared to placebo (mean difference 1.01, 95%CI -0.87 to 3.09, p&#x2009;=&#x2009;0.293), as shown by evidence from RCTs. However, observational studies did not show any benefit of adding edaravone to routine practice (mean difference 1.85, 95%CI -2.05 to 5.75, p&#x2009;=&#x2009;0.352). The change from baseline in ALSFRS-R score was -2.1, -4.04, -7.5, -6.82, and -7.9 at months 3, 6, 9, 12, and 18, respectively. The GRADE assessment indicated moderate certainty for evidence from RCTs, while evidence from observational studies had very low certainty.<br><br>CONCLUSION: Due to the limited number of studies and confounding issues in observational studies, further examination of the added benefits of edaravone to routine practice is necessary through RCTs, particularly regarding its long-term efficacy.}, }
@article {pmid38341094, year = {2024}, author = {McKechnie, T and Brennan, K and Eskicioglu, C and Farooq, A and Patel, SV}, title = {Applying the fragility index to randomized controlled trials evaluating total neoadjuvant therapy for rectal cancer: A methodological survey.}, journal = {Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology}, volume = {194}, number = {}, pages = {110148}, doi = {10.1016/j.radonc.2024.110148}, pmid = {38341094}, issn = {1879-0887}, mesh = {Humans ; *Neoadjuvant Therapy ; Randomized Controlled Trials as Topic ; *Rectal Neoplasms/therapy/pathology ; }, abstract = {BACKGROUND: Recently, there has been significant interest in, and adoption of, total neoadjuvant therapy (TNT) for locally advanced rectal cancer (LARC). We designed the present study to assess the robustness of the randomized controlled trials (RCTs) evaluating contemporary TNTs for LARC using the fragility index (FI).<br><br>MATERIALS AND METHODS: Relevant articles were identified through a review article by Johnson et al. in the Canadian Journal of Surgery. Dichotomous outcomes within these RCTs were eligible for inclusion if the reported effect size had a p-value&#xa0;<&#xa0;0.05. The main outcome was FI for each included outcome. Walsh et al.'s method of calculating FI was utilized. Correlations between FI and research characteristics were assessed using the Spearman's rank correlation coefficients. Risk of bias was assessed using Cochrane recommended tools.<br><br>RESULTS: Ten RCTs were identified with 25 outcomes having statistically significant differences between groups. Eleven outcomes were time-to-event outcomes, while the remainder were dichotomous outcomes. Approximately half (n&#xa0;=&#xa0;13) were oncologic outcomes. The median FI was 2 (interquartile range [IQR] 1-16). The number of patients lost to follow-up exceeded the FI in 17 outcomes (68.0&#xa0;%) and thus these results were considered "fragile". Lower FI was associated with high risk of bias (rho&#xa0;=&#xa0;-0.5594) and greater loss to follow-up (rho&#xa0;=&#xa0;-0.4394), while higher FI was associated with large study size (rho&#xa0;=&#xa0;0.5120).<br><br>CONCLUSIONS: The robustness of outcomes from trials assessing TNT for LARC was found to be questionable. Most outcomes were fragile, as determined by the FI. This survey is limited by the number of included studies.}, }
@article {pmid38339149, year = {2024}, author = {Lee, A and Henderson, R and Aylward, J and McCombe, P}, title = {Gut Symptoms, Gut Dysbiosis and Gut-Derived Toxins in ALS.}, journal = {International journal of molecular sciences}, volume = {25}, number = {3}, pages = {}, pmid = {38339149}, issn = {1422-0067}, support = {There were no grant numbers//Wesley Medical Research/ ; There were no grant numbers//MND Research Australia/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/etiology ; Dysbiosis/etiology ; *Gastrointestinal Microbiome/physiology ; Brain ; }, abstract = {Many pathogenetic mechanisms have been proposed for amyotrophic lateral sclerosis (ALS). Recently, there have been emerging suggestions of a possible role for the gut microbiota. Gut microbiota have a range of functions and could influence ALS by several mechanisms. Here, we review the possible role of gut-derived neurotoxins/excitotoxins. We review the evidence of gut symptoms and gut dysbiosis in ALS. We then examine a possible role for gut-derived toxins by reviewing the evidence that these molecules are toxic to the central nervous system, evidence of their association with ALS, the existence of biochemical pathways by which these molecules could be produced by the gut microbiota and existence of mechanisms of transport from the gut to the blood and brain. We then present evidence that there are increased levels of these toxins in the blood of some ALS patients. We review the effects of therapies that attempt to alter the gut microbiota or ameliorate the biochemical effects of gut toxins. It is possible that gut dysbiosis contributes to elevated levels of toxins and that these could potentially contribute to ALS pathogenesis, but more work is required.}, }
@article {pmid38339035, year = {2024}, author = {Sun, Y and Islam, S and Michikawa, M and Zou, K}, title = {Presenilin: A Multi-Functional Molecule in the Pathogenesis of Alzheimer's Disease and Other Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {25}, number = {3}, pages = {}, pmid = {38339035}, issn = {1422-0067}, support = {C19K07846//The Grant-in-Aid for Scientific Research/ ; 22K07352//The Ministry of Education, Culture, Sports, Science, and Technology, Japan./ ; JP20dk0207050h0001 and JP20de010702//AMED/ ; no//The 24th General Assembly of the Japanese Association of Medical Sciences/ ; no//Daiko Foundation/ ; no//Hirose International Scholarship Foundation/ ; no//Hori Sciences and Arts Foundation/ ; no//Daiwa Securities Foundation/ ; no//Hirose Foundation/ ; }, mesh = {Humans ; *Alzheimer Disease/metabolism ; Amyloid beta-Peptides/metabolism ; *Neurodegenerative Diseases/etiology ; Amyloid Precursor Protein Secretases/metabolism ; Presenilin-1/genetics/metabolism ; Amyloid beta-Protein Precursor/metabolism ; Apolipoproteins E ; Presenilin-2/genetics/metabolism ; }, abstract = {Presenilin, a transmembrane protein primarily known for its role in Alzheimer's disease (AD) as part of the γ-secretase complex, has garnered increased attention due to its multifaceted functions in various cellular processes. Recent investigations have unveiled a plethora of functions beyond its amyloidogenic role. This review aims to provide a comprehensive overview of presenilin's diverse roles in AD and other neurodegenerative disorders. It includes a summary of well-known substrates of presenilin, such as its involvement in amyloid precursor protein (APP) processing and Notch signaling, along with other functions. Additionally, it highlights newly discovered functions, such as trafficking function, regulation of ferritin expression, apolipoprotein E (ApoE) secretion, the interaction of ApoE and presenilin, and the Aβ42-to-Aβ40-converting activity of ACE. This updated perspective underscores the evolving landscape of presenilin research, emphasizing its broader impact beyond established pathways. The incorporation of these novel findings accentuates the dynamic nature of presenilin's involvement in cellular processes, further advancing our comprehension of its multifaceted roles in neurodegenerative disorders. By synthesizing evidence from a range of studies, this review sheds light on the intricate web of presenilin functions and their implications in health and disease.}, }
@article {pmid38339026, year = {2024}, author = {Potenza, RL and Armida, M and Popoli, P}, title = {Can Some Anticancer Drugs Be Repurposed to Treat Amyotrophic Lateral Sclerosis? A Brief Narrative Review.}, journal = {International journal of molecular sciences}, volume = {25}, number = {3}, pages = {}, pmid = {38339026}, issn = {1422-0067}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Motor Neuron Disease ; *Antineoplastic Agents/pharmacology/therapeutic use ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a rare progressive motor neuron disease that, due to its high complexity, still lacks effective treatments. Development of a new drug is a highly costly and time-consuming process, and the repositioning of approved drugs can represent an efficient strategy to provide therapeutic opportunities. This is particularly true for rare diseases, which are characterised by small patient populations and therefore attract little commercial interest. Based on the overlap between the biological background of cancer and neurodegeneration, the repurposing of antineoplastic drugs for ALS has been suggested. The objective of this narrative review was to summarise the current experimental evidence on the use of approved anticancer drugs in ALS. Specifically, anticancer drugs belonging to different classes were found to act on mechanisms involved in the ALS pathogenesis, and some of them proved to exert beneficial effects in ALS models. However, additional studies are necessary to confirm the real therapeutic potential of anticancer drugs for repositioning in ALS treatment.}, }
@article {pmid38338912, year = {2024}, author = {Duranti, E and Cordani, N and Villa, C}, title = {Edaravone: A Novel Possible Drug for Cancer Treatment?.}, journal = {International journal of molecular sciences}, volume = {25}, number = {3}, pages = {}, pmid = {38338912}, issn = {1422-0067}, mesh = {Humans ; Edaravone/therapeutic use ; *Neuroprotective Agents/pharmacology ; *Amyotrophic Lateral Sclerosis/drug therapy ; Antioxidants/therapeutic use ; *Neoplasms/drug therapy/chemically induced ; Free Radical Scavengers/pharmacology ; }, abstract = {Despite significant advancements in understanding the causes and progression of tumors, cancer remains one of the leading causes of death worldwide. In light of advances in cancer therapy, there has been a growing interest in drug repurposing, which involves exploring new uses for medications that are already approved for clinical use. One such medication is edaravone, which is currently used to manage patients with cerebral infarction and amyotrophic lateral sclerosis. Due to its antioxidant and anti-inflammatory properties, edaravone has also been investigated for its potential activities in treating cancer, notably as an anti-proliferative and cytoprotective drug against side effects induced by traditional cancer therapies. This comprehensive review aims to provide updates on the various applications of edaravone in cancer therapy. It explores its potential as a standalone antitumor drug, either used alone or in combination with other medications, as well as its role as an adjuvant to mitigate the side effects of conventional anticancer treatments.}, }
@article {pmid38337058, year = {2024}, author = {Choi, BJ and Park, MH and Jin, HK and Bae, JS}, title = {Acid sphingomyelinase as a pathological and therapeutic target in neurological disorders: focus on Alzheimer's disease.}, journal = {Experimental &amp; molecular medicine}, volume = {56}, number = {2}, pages = {301-310}, pmid = {38337058}, issn = {2092-6413}, mesh = {Animals ; Humans ; Mice ; *Alzheimer Disease/drug therapy ; Brain ; *Multiple Sclerosis ; *Nervous System Diseases ; Sphingomyelin Phosphodiesterase/genetics ; }, abstract = {Over the past decade, numerous studies have highlighted the importance of acid sphingomyelinase (ASM) in disease treatment in humans. This enzyme functions primarily to generate ceramide, maintain the cellular membrane, and regulate cellular function. However, in the blood and brain of patients with neurological disorders, including major depression, ischemic stroke, amyotrophic lateral sclerosis, multiple sclerosis, and Alzheimer's disease (AD), elevated ASM levels significantly suggest disease onset or progression. In these diseases, increased ASM is profoundly involved in neuronal death, abnormal autophagy, neuroinflammation, blood-brain barrier disruption, hippocampal neurogenesis loss, and immune cell dysfunction. Moreover, genetic and pharmacological inhibition of ASM can prevent or ameliorate various diseases. The therapeutic effects of ASM inhibition have prompted the urgent need to develop ASM inhibitors, and several ASM inhibitors have been identified. In this review, we summarize the current knowledge on the critical roles and mechanisms of ASM in brain cells and blood that are associated with different neuropathological features, especially those observed in AD. Furthermore, we elucidate the potential possibility and limitations of existing ASM-targeting drugs according to experimental studies in neurological disorder mouse models.}, }
@article {pmid38334818, year = {2024}, author = {Hoek, AG and Dal Canto, E and Wenker, E and Bindraban, N and Handoko, ML and Elders, PJM and Beulens, JWJ}, title = {Epidemiology of heart failure in diabetes: a disease in disguise.}, journal = {Diabetologia}, volume = {67}, number = {4}, pages = {574-601}, pmid = {38334818}, issn = {1432-0428}, support = {91718304/ZONMW_/ZonMw/Netherlands ; }, mesh = {Humans ; *Diabetes Mellitus, Type 2/epidemiology/complications ; *Heart Failure/epidemiology/physiopathology ; Incidence ; Prevalence ; Stroke Volume/physiology ; Ventricular Dysfunction, Left/epidemiology/physiopathology ; Echocardiography ; }, abstract = {Left ventricular diastolic dysfunction (LVDD) without symptoms, and heart failure (HF) with preserved ejection fraction (HFpEF) represent the most common phenotypes of HF in individuals with type 2 diabetes mellitus, and are more common than HF with reduced ejection fraction (HFrEF), HF with mildly reduced ejection fraction (HFmrEF) and left ventricular systolic dysfunction (LVSD) in these individuals. However, diagnostic criteria for HF have changed over the years, resulting in heterogeneity in the prevalence/incidence rates reported in different studies. We aimed to give an overview of the diagnosis and epidemiology of HF in type 2 diabetes, using both a narrative and systematic review approach; we focus narratively on diagnosing (using the 2021 European Society of Cardiology [ESC] guidelines) and screening for HF in type 2 diabetes. We performed an updated (2016-October 2022) systematic review and meta-analysis of studies reporting the prevalence and incidence of HF subtypes in adults ≥18 years with type 2 diabetes, using echocardiographic data. Embase and MEDLINE databases were searched and data were assessed using random-effects meta-analyses, with findings presented as forest plots. From the 5015 studies found, 209 were screened using the full-text article. In total, 57 studies were included, together with 29 studies that were identified in a prior meta-analysis; these studies reported on the prevalence of LVSD (n=25 studies, 24,460 individuals), LVDD (n=65 studies, 25,729 individuals), HFrEF (n=4 studies, 4090 individuals), HFmrEF (n=2 studies, 2442 individuals) and/or HFpEF (n=8 studies, 5292 individuals), and on HF incidence (n=7 studies, 17,935 individuals). Using Hoy et al's risk-of-bias tool, we found that the studies included generally had a high risk of bias. They showed a prevalence of 43% (95% CI 37%, 50%) for LVDD, 17% (95% CI 7%, 35%) for HFpEF, 6% (95% CI 3%, 10%) for LVSD, 7% (95% CI 3%, 15%) for HFrEF, and 12% (95% CI 7%, 22%) for HFmrEF. For LVDD, grade I was found to be most prevalent. Additionally, we reported a higher incidence rate of HFpEF (7% [95% CI 4%, 11%]) than HFrEF 4% [95% CI 3%, 7%]). The evidence is limited by the heterogeneity of the diagnostic criteria over the years. The systematic section of this review provides new insights on the prevalence/incidence of HF in type 2 diabetes, unveiling a large pre-clinical target group with LVDD/HFpEF in which disease progression could be halted by early recognition and treatment.Registration PROSPERO ID CRD42022368035.}, }
@article {pmid38334639, year = {2024}, author = {Cunha-Oliveira, T and Montezinho, L and Simões, RF and Carvalho, M and Ferreiro, E and Silva, FSG}, title = {Mitochondria: A Promising Convergent Target for the Treatment of Amyotrophic Lateral Sclerosis.}, journal = {Cells}, volume = {13}, number = {3}, pages = {}, pmid = {38334639}, issn = {2073-4409}, support = {PTDC/MED-FAR/29391/2017//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e Tecnologia/ ; POCI-01-0145-FEDER-029391//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e Tecnologia/ ; PTDC/BTM-SAL/29297/2017//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e Tecnologia/ ; POCI-01-0145-FEDER-029297//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e Tecnologia/ ; PTDC/BTM-ORG/0055/2021//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e Tecnologia/ ; DL57/2016/CP1448/CT0016//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e Tecnologia/ ; CEECIND/00322/2017//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e Tecnologia/ ; 2022.00011.CEECIND//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e Tecnologia/ ; UIDP/04539/2020//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e Tecnologia/ ; UIDB/04539/2020//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e Tecnologia/ ; UIDB/00081/2020//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e Tecnologia/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; *Neurodegenerative Diseases/metabolism ; Mitochondria/metabolism ; Motor Neurons/pathology ; Apoptosis ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the progressive loss of motor neurons, for which current treatment options are limited. Recent studies have shed light on the role of mitochondria in ALS pathogenesis, making them an attractive therapeutic intervention target. This review contains a very comprehensive critical description of the involvement of mitochondria and mitochondria-mediated mechanisms in ALS. The review covers several key areas related to mitochondria in ALS, including impaired mitochondrial function, mitochondrial bioenergetics, reactive oxygen species, metabolic processes and energy metabolism, mitochondrial dynamics, turnover, autophagy and mitophagy, impaired mitochondrial transport, and apoptosis. This review also highlights preclinical and clinical studies that have investigated various mitochondria-targeted therapies for ALS treatment. These include strategies to improve mitochondrial function, such as the use of dichloroacetate, ketogenic and high-fat diets, acetyl-carnitine, and mitochondria-targeted antioxidants. Additionally, antiapoptotic agents, like the mPTP-targeting agents minocycline and rasagiline, are discussed. The paper aims to contribute to the identification of effective mitochondria-targeted therapies for ALS treatment by synthesizing the current understanding of the role of mitochondria in ALS pathogenesis and reviewing potential convergent therapeutic interventions. The complex interplay between mitochondria and the pathogenic mechanisms of ALS holds promise for the development of novel treatment strategies to combat this devastating disease.}, }
@article {pmid38334609, year = {2024}, author = {Noori, L and Saqagandomabadi, V and Di Felice, V and David, S and Caruso Bavisotto, C and Bucchieri, F and Cappello, F and Conway de Macario, E and Macario, AJL and Scalia, F}, title = {Putative Roles and Therapeutic Potential of the Chaperone System in Amyotrophic Lateral Sclerosis and Multiple Sclerosis.}, journal = {Cells}, volume = {13}, number = {3}, pages = {}, pmid = {38334609}, issn = {2073-4409}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; *Multiple Sclerosis/therapy ; Molecular Chaperones/metabolism ; Heat-Shock Proteins/metabolism ; }, abstract = {The putative pathogenic roles and therapeutic potential of the chaperone system (CS) in amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) are reviewed to provide a bibliographic and conceptual platform for launching research on the diagnostic and therapeutic applications of CS components. Various studies suggest that dysfunction of the CS contributes to the pathogenesis of ALS and MS, and here, we identify some of the implicated CS members. The physiology and pathophysiology of the CS members can be properly understood if they are studied or experimentally or clinically manipulated for diagnostic or therapeutic purposes, bearing in mind that they belong to a physiological system with multiple interacting and dynamic components, widespread throughout the body, intra- and extracellularly. Molecular chaperones, some called heat shock protein (Hsp), are the chief components of the CS, whose canonical functions are cytoprotective. However, abnormal chaperones can be etiopathogenic factors in a wide range of disorders, chaperonopathies, including ALS and MS, according to the data reviewed. Chaperones typically form teams, and these build functional networks to maintain protein homeostasis, the canonical role of the CS. However, members of the CS also display non-canonical functions unrelated to protein homeostasis. Therefore, chaperones and other members of the CS, if abnormal, may disturb not only protein synthesis, maturation, and migration but also other physiological processes. Thus, in elucidating the role of CS components in ALS and MS, one must look at protein homeostasis abnormalities and beyond, following the clues emerging from the works discussed here.}, }
@article {pmid38334254, year = {2024}, author = {Mohammadi, S and Ghaderi, S and Fatehi, F}, title = {MRI biomarkers and neuropsychological assessments of hippocampal and parahippocampal regions affected by ALS: A systematic review.}, journal = {CNS neuroscience &amp; therapeutics}, volume = {30}, number = {2}, pages = {e14578}, pmid = {38334254}, issn = {1755-5949}, mesh = {Humans ; *Hippocampus/diagnostic imaging/pathology ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/psychology/pathology/metabolism ; *Magnetic Resonance Imaging ; *Neuropsychological Tests ; *Biomarkers/metabolism ; Parahippocampal Gyrus/diagnostic imaging/pathology ; }, abstract = {BACKGROUND AND OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a progressive motor and extra-motor neurodegenerative disease. This systematic review aimed to examine MRI biomarkers and neuropsychological assessments of the hippocampal and parahippocampal regions in patients with ALS.<br><br>METHODS: A systematic review was conducted in the Scopus and PubMed databases for studies published between January 2000 and July 2023. The inclusion criteria were (1) MRI studies to assess hippocampal and parahippocampal regions in ALS patients, and (2) studies reporting neuropsychological data in patients with ALS.<br><br>RESULTS: A total of 46 studies were included. Structural MRI revealed hippocampal atrophy, especially in ALS-FTD, involving specific subregions (CA1, dentate gyrus). Disease progression and genetic factors impacted atrophy patterns. Diffusion tensor imaging (DTI) showed increased mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), and decreased fractional anisotropy (FA) in the hippocampal tracts and adjacent regions, indicating loss of neuronal and white matter integrity. Functional MRI (fMRI) revealed reduced functional connectivity (FC) between the hippocampus, parahippocampus, and other regions, suggesting disrupted networks. Perfusion MRI showed hypoperfusion in parahippocampal gyri. Magnetic resonance spectroscopy (MRS) found changes in the hippocampus, indicating neuronal loss. Neuropsychological tests showed associations between poorer memory and hippocampal atrophy or connectivity changes. CA1-2, dentate gyrus, and fimbria atrophy were correlated with worse memory.<br><br>CONCLUSIONS: The hippocampus and the connected regions are involved in ALS. Hippocampal atrophy disrupted connectivity and metabolite changes correlate with cognitive and functional decline. Specific subregions can be particularly affected. The hippocampus is a potential biomarker for disease monitoring and prognosis.}, }
@article {pmid38332485, year = {2024}, author = {Alrashdi, DH and Alyafei, AH and Alanazi, SA and Meyer, C and Gould, RL}, title = {Cultural adaptations of third-wave psychotherapies in Gulf Cooperation Council countries: A systematic review.}, journal = {Transcultural psychiatry}, volume = {61}, number = {2}, pages = {209-228}, pmid = {38332485}, issn = {1461-7471}, mesh = {Humans ; *Psychotherapy ; }, abstract = {The effectiveness of third-wave psychotherapies has been demonstrated in a range of mental and physical health conditions in Western cultures. However, little is known about the cultural appropriateness and effectiveness of third-wave psychotherapies for Gulf Cooperation Council (GCC) populations. This review aimed to critically evaluate cultural adaptations to third-wave psychotherapies and explored the effectiveness of these interventions on physical and mental health outcomes in GCC populations. Five bibliographic databases and grey literature were searched; both English and Arabic studies conducted in the GCC were included. Mental and physical health-related outcomes were included. Eleven studies were identified. The overall degree of cultural adaptation ranged from 2 to 5, based on Bernal et al.'s cultural adaptation framework. Language and assessment tools were most frequently adapted. Several studies incorporated goal, method, and context adaptations, whereas metaphor and content were least frequently adapted. None of the studies incorporated person or concept adaptations. Culturally adapted third-wave psychotherapies were associated with improvement in numerous mental health outcomes, including psychological distress, well-being, and psychological traits. No physical health outcomes were identified. Although findings are promising with respect to the effectiveness of third-wave psychotherapies for GCC populations, they should be interpreted with caution due to the small number of studies conducted, cultural adaptation evaluations relying on explicit reporting in studies, and the weak methodological quality of studies. Future rigorous research is needed in the evaluation of culturally adapted third-wave psychotherapies in GCC populations, with more comprehensive reporting of cultural considerations.}, }
@article {pmid38330934, year = {2024}, author = {Yang, L and Li, Y and Zhang, S and Qian, H and Xu, W and Yu, J}, title = {Efficacy of Acupuncture Combined with Traditional Chinese Medicine Fumigation Therapy in Sequelae of Pelvic Inflammatory Disease: A Systematic Review and Meta-Analysis.}, journal = {Complementary medicine research}, volume = {31}, number = {2}, pages = {175-186}, doi = {10.1159/000536101}, pmid = {38330934}, issn = {2504-2106}, mesh = {Humans ; *Acupuncture Therapy/methods ; *Fumigation/methods ; *Medicine, Chinese Traditional/methods ; *Pelvic Inflammatory Disease/therapy ; Combined Modality Therapy ; Female ; }, abstract = {BACKGROUND AND OBJECTIVE: Acupuncture combined with traditional Chinese medicine fumigation is increasingly being used in treating sequelae of pelvic inflammatory disease (SPID). However, there is a lack of meta-analysis on the effectiveness of acupuncture combined with traditional Chinese medicine fumigation in treating SPID. The aim of this study was to assess the feasibility of combining acupuncture with traditional Chinese medicine fumigation in the treatment of SPID.<br><br>METHODS: We searched eight databases for studies on acupuncture combined with traditional Chinese medicine fumigation for the treatment of SPID from the date of establishment to October 29, 2022. We assessed the quality of included studies by using the Cochrane bias risk tool. Pooled results were expressed as risk ratios (RRs), with a 95% confidence interval (CI). In addition, we identified sources of heterogeneity by sensitivity analysis, assessed publication bias by Egger's test, and assessed the quality of the evidence by Grades of Recommendation, Assessment, Development, and Evaluation (GRADE). All statistical analyses were performed by Review Manager 5.3 and Stata 14.<br><br>RESULTS: Finally, seven studies with a total of 663 participants were included. We found a significant difference in the total effective rate in the acupuncture combined with the fumigation group compared with the acupuncture group in the treatment of SPID (RR = 1.17, 95% CI [1.09, 1.25], p = 0.0001 < 0.05; I2 = 0%; 6 trials), and a significant difference in the total effective rate in the acupuncture combined with fumigation group compared with the fumigation group in the treatment of SPID (RR = 1.42, 95% CI [1.21, 1.66], p = 0.0001 < 0.05; 5 trials).<br><br>CONCLUSION: The clinical efficacy of acupuncture combined with herbal fumigation in the treatment of SPID is relatively good. Larger scale studies are needed in the future.<br><br>UNLABELLED: <title>Hintergrund und Ziel</title>Akupunktur in Kombination mit Fumigation, einem Verfahren der Traditionellen Chinesischen Medizin, wird zunehmend in der Behandlung von Folgeerscheinungen von Beckenentz&#xfc;ndungen (SPID; <italic>sequelae of pelvic inflammatory disease</italic>) eingesetzt. Es mangelt jedoch an Metaanalysen zur Wirksamkeit der Akupunktur in Kombination mit Fumigation gem&#xe4;&#xdf; der Traditionellen Chinesischen Medizin in der Behandlung von SPID. Das Ziel dieser Studie ist die Beurteilung der Machbarkeit der Kombination aus Akupunktur und Fumigation gem&#xe4;&#xdf; der Traditionellen Chinesischen Medizin in der Behandlung von SPID.<title>Methoden</title>Wir durchsuchten acht Datenbanken nach Studien zur Akupunktur in Kombination mit Fumigation gem&#xe4;&#xdf; der Traditionellen Chinesischen Medizin in der Behandlung von Folgeerscheinungen von SPID von der Einrichtung bis zum 29. Oktober 2022. Wir beurteilten die Qualit&#xe4;t der eingeschlossenen Studien mit dem Cochrane-Tool zur Bewertung des Bias-Risikos. Die gepoolten Ergebnisse wurden als Risikoquotient (RR; <italic>risk ratio</italic>) mit 95%-Konfidenzintervall (KI) ausgedr&#xfc;ckt. Zus&#xe4;tzlich identifizierten wir Quellen f&#xfc;r Heterogenit&#xe4;t mittels Sensitivit&#xe4;tsanalyse, beurteilten den Publikations-Bias mittels Egger-Test und bewerteten die Qualit&#xe4;t der Evidenz nach Grad der Empfehlungsst&#xe4;rke, Beurteilung, Entwicklung und Evaluierung (GRADE). Alle statistischen Analysen erfolgten mit Review Manager 5.3 und Stata 14.<title>Ergebnisse</title>Im Endeffekt wurden 7 Studien mit insgesamt 663 Teilnehmern eingeschlossen. Wir fanden einen signifikanten Unterschied in der Gesamt-Effektivit&#xe4;tsrate bei der Gruppe, die zur Behandlung von SPID Akupunktur in Kombination mit Fumigation erhielt, im Vergleich zur reinen Akupunkturgruppe (RR = 1,17; 95%-KI [1,09; 1,25]; <italic>p</italic> = 0,0001 < 0,05; <italic>I</italic>2-Wert = 0%; 6 Studien), und einen signifikanten Unterschied in der Gesamt-Effektivit&#xe4;tsrate bei der Gruppe, die zur Behandlung von SPID Akupunktur in Kombination mit Fumigation erhielt, im Vergleich zur reinen Fumigationsgruppe (RR = 1,42; 95%-KI [1,21; 1,66]; <italic>p</italic> = 0,0001 < 0,05; 5 Studien).<title>Schlussfolgerung</title>Die klinische Wirksamkeit der Akupunktur in Kombination mit Kr&#xe4;uter-Fumigation zur Behandlung von SPID ist relativ gut. Zuk&#xfc;nftig sind gr&#xf6;&#xdf;ere Studien erforderlich.}, }
@article {pmid38330475, year = {2024}, author = {Stavros, K}, title = {Genetic Myelopathies.}, journal = {Continuum (Minneapolis, Minn.)}, volume = {30}, number = {1}, pages = {119-132}, pmid = {38330475}, issn = {1538-6899}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; *Muscular Atrophy, Spinal/diagnosis ; *Spastic Paraplegia, Hereditary/diagnosis ; *Spinal Cord Diseases/diagnosis/genetics/therapy ; }, abstract = {OBJECTIVE: This article provides an overview of genetic myelopathies, a diverse group of inherited, degenerative conditions that may be broadly categorized as motor neuron disorders, disorders of spinocerebellar degeneration, leukodystrophies, and hereditary spastic paraplegia. Clinical examples from each category are provided to illustrate the spectrum of genetic myelopathies and their distinguishing features that aid in differentiating genetic myelopathies from potentially treatable acquired causes of myelopathy.<br><br>LATEST DEVELOPMENTS: Advances in genetic testing have vastly enhanced current knowledge of genetic myelopathies and the ability to diagnose and provide appropriate counseling to patients and their families. However, potential health care disparities in access to genetic testing is a topic that must be further explored. Although treatment for most of these conditions is typically supportive, there have been recent therapeutic breakthroughs in treatments for amyotrophic lateral sclerosis, spinal muscular atrophy, and Friedreich ataxia.<br><br>ESSENTIAL POINTS: Genetic myelopathies may present with chronic and progressive symptoms, a family history of similar symptoms, and involvement of other structures outside of the spinal cord. Imaging often shows spinal cord atrophy, but cord signal change is rare. Exclusion of reversible causes of myelopathy is a key step in the diagnosis. There are many different causes of genetic myelopathies, and in some cases, symptoms may overlap, which underscores the utility of genetic testing in confirming the precise underlying neurologic condition.}, }
@article {pmid38329887, year = {2024}, author = {Sanghai, N and Vuong, B and Burak Berk, A and Afridi, MSK and Tranmer, GK}, title = {Current Small Molecule-Based Medicinal Chemistry Approaches for Neurodegeneration Therapeutics.}, journal = {ChemMedChem}, volume = {19}, number = {9}, pages = {e202300705}, doi = {10.1002/cmdc.202300705}, pmid = {38329887}, issn = {1860-7187}, support = {//Department of Human Anatomy and Cell Science, University of Manitoba/ ; //College of Pharmacy, Department of Pharmacology &amp; Therapeutics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Small Molecule Libraries/chemistry/pharmacology/chemical synthesis ; *Neuroprotective Agents/chemistry/pharmacology/chemical synthesis ; Blood-Brain Barrier/metabolism/drug effects ; Chemistry, Pharmaceutical ; Molecular Structure ; }, abstract = {Neurodegenerative diseases (NDDs) like Alzheimer's disease (AD), Parkinson's disease (PD), and Amyotrophic lateral sclerosis (ALS) possess multifactorial aetiologies. In recent years, our understanding of the biochemical and molecular pathways across NDDs has increased, however, new advances in small molecule-based therapeutic strategies targeting NDDs are obscure and scarce. Moreover, NDDs have been studied for more than five decades, however, there is a paucity of drugs that can treat NDDs. Further, the highly lipoidal blood-brain barrier (BBB) limits the uptake of many therapeutic molecules into the brain and is a complicating factor in the development of new agents to treat neurodegeneration. Considering the highly complex nature of NDDs, the association of multiple risk factors, and the challenges to overcome the BBB junction, medicinal chemists have developed small organic molecule-based novel approaches to target NDDs over the last few decades, such as designing lipophilic molecules and applying prodrug strategies. Attempts have been made to utilize a multitarget approach to modulate different biochemical molecular pathways involved in NDDs, in addition to, medicinal chemists making better decisions in identifying optimized drug candidates for the central nervous system (CNS) by using web-based computational tools. To increase the clinical success of these drug candidates, an in vitro assay modeling the BBB has been utilized by medicinal chemists in the pre-clinical phase as a further screening measure of small organic molecules. Herein, we examine some of the intriguing strategies taken by medicinal chemists to design small organic molecules to combat NDDs, with the intention of increasing our awareness of neurodegenerative therapeutics.}, }
@article {pmid38325473, year = {2024}, author = {Xu, Y and Nie, J and Lu, C and Hu, C and Chen, Y and Ma, Y and Huang, Y and Lu, L}, title = {Effects and mechanisms of bisphenols exposure on neurodegenerative diseases risk: A systemic review.}, journal = {The Science of the total environment}, volume = {919}, number = {}, pages = {170670}, doi = {10.1016/j.scitotenv.2024.170670}, pmid = {38325473}, issn = {1879-1026}, mesh = {Animals ; Humans ; *Neurodegenerative Diseases/chemically induced ; *Alzheimer Disease ; *Parkinson Disease/etiology/metabolism ; Brain/metabolism ; Oxidative Stress/physiology ; }, abstract = {Environmental bisphenols (BPs) pose a global threat to human health because of their extensive use as additives in plastic products. BP residues are increasing in various environmental media (i.e., water, soil, and indoor dust) and biological and human samples (i.e., serum and brain). Both epidemiological and animal studies have determined an association between exposure to BPs and an increased risk of neurodegenerative diseases (e.g., Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis), including cognitive abnormalities and behavioral disturbances. Hence, understanding the biological responses to different BPs is essential for prevention, and treatment. This study provides an overview of the underlying pathogenic molecular mechanisms as a valuable basis for understanding neurodegenerative disease responses to BPs, including accumulation of misfolded proteins, reduction of tyrosine hydroxylase and dopamine, abnormal hormone signaling, neuronal death, oxidative stress, calcium homeostasis, and inflammation. These findings provide new insights into the neurotoxic potential of BPs and ultimately contribute to a comprehensive health risk evaluation.}, }
@article {pmid38323662, year = {2024}, author = {Garcés, P and Amaro, A and Montecino, M and van Zundert, B}, title = {Inorganic polyphosphate: from basic research to diagnostic and therapeutic opportunities in ALS/FTD.}, journal = {Biochemical Society transactions}, volume = {52}, number = {1}, pages = {123-135}, doi = {10.1042/BST20230257}, pmid = {38323662}, issn = {1470-8752}, mesh = {Animals ; Mice ; Humans ; *Frontotemporal Dementia/metabolism/therapy ; *Amyotrophic Lateral Sclerosis/diagnosis/drug therapy/metabolism ; Polyphosphates ; *Alzheimer Disease ; *Parkinson Disease ; Mammals ; }, abstract = {Inorganic polyphosphate (polyP) is a simple, negatively charged biopolymer with chain lengths ranging from just a few to over a thousand ortho-phosphate (Pi) residues. polyP is detected in every cell type across all organisms in nature thus far analyzed. Despite its structural simplicity, polyP has been shown to play important roles in a remarkably broad spectrum of biological processes, including blood coagulation, bone mineralization and inflammation. Furthermore, polyP has been implicated in brain function and the neurodegenerative diseases amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alzheimer's disease and Parkinson's disease. In this review, we first address the challenges associated with identifying mammalian polyP metabolizing enzymes, such as Nudt3, and quantifying polyP levels in brain tissue, cultured neural cells and cerebrospinal fluid. Subsequently, we focus on recent studies that unveil how the excessive release of polyP by human and mouse ALS/FTD astrocytes contributes to these devastating diseases by inducing hyperexcitability, leading to motoneuron death. Potential implications of elevated polyP levels in ALS/FTD patients for innovative diagnostic and therapeutic approaches are explored. It is emphasized, however, that caution is required in targeting polyP in the brain due to its diverse physiological functions, serving as an energy source, a chelator for divalent cations and a scaffold for amyloidogenic proteins. Reducing polyP levels, especially in neurons, might thus have adverse effects in brain functioning. Finally, we discuss how activated mast cells and platelets also can significantly contribute to ALS progression, as they can massively release polyP.}, }
@article {pmid38321352, year = {2024}, author = {Sathyamurthy, VH and Nagarajan, Y and Parvathi, VD}, title = {Mitochondria-Endoplasmic Reticulum Contact Sites (MERCS): A New Axis in Neuronal Degeneration and Regeneration.}, journal = {Molecular neurobiology}, volume = {61}, number = {9}, pages = {6528-6538}, pmid = {38321352}, issn = {1559-1182}, mesh = {Humans ; Animals ; *Mitochondria/metabolism ; *Endoplasmic Reticulum/metabolism ; Nerve Degeneration/pathology ; Nerve Regeneration/physiology ; Neurons/metabolism/pathology ; Neurodegenerative Diseases/metabolism/pathology ; Mitochondria Associated Membranes ; }, abstract = {Mitochondria-Endoplasmic Reticulum Contact Sites (MERCS) are dynamic structures whose physiological interaction is vital to direct life and death of the cell. A bevy of tethering proteins, mitofusin-1/2 (Mfn-1/2), glucose-regulated protein-75 (Grp-75), voltage-dependent anion channel-1 (VDAC1), and dynamic-related protein-1 (Drp1), plays an integral role in establishing and regulating this intricate intracellular communication. Dysregulation of this interplay leads to various neurodegenerative disorders, like Alzheimer's disease (AD), Parkinson's disease (PD), stroke, traumatic brain injury (TBI), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD). Although there is an absence of a well-defined molecular background that dictates the pathway of MERCS, adequate exploration has resulted in preliminary data that suggests its cardinal role in neuroregeneration. The juxtaposition of mitochondria and ER has a critical function in cell senescence, thus regulating regeneration. Axonal regeneration and brain tissue regeneration, using reactive astrocytes, are studied most extensively. Overexpression of Grp-75 promoted axonal regeneration post a nerve injury. Attempts have been made to exploit MERCS as potential therapeutic drug targets for enhancing neuroregeneration and impeding neurodegeneration. Novel strategies have been developed to aid the delivery of mitochondria into the neuronal cell body, which in turn establishes a network with the presiding ER resulting in contact site formation. The fascinating aspect of this mechanism is that despite the lack of inherent regenerative capacity in neurons, it can be induced by modifying MERCS.}, }
@article {pmid38318860, year = {2024}, author = {Jhooty, S and Barkhaus, P and Brown, A and Mascias Cadavid, J and Carter, GT and Crayle, J and Heiman-Patterson, T and Li, X and Mallon, E and Mcdermott, C and Mushannen, T and Pattee, G and Ratner, D and Wicks, P and Wiedau, M and Bedlack, R}, title = {ALSUntangled #74: Withania Somnifera (Ashwagandha).}, journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration}, volume = {25}, number = {7-8}, pages = {805-808}, doi = {10.1080/21678421.2024.2311721}, pmid = {38318860}, issn = {2167-9223}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy ; Humans ; *Withania ; Animals ; *Plant Extracts/therapeutic use ; Phytotherapy/methods ; }, abstract = {ALSUntangled reviews alternative and off-label treatments on behalf of people with ALS (PALS) who ask about them. Here, we review withania somnifera (WS) commonly known as ashwagandha or winter cherry. WS has plausible mechanisms for slowing ALS progression because of its effects on inflammation, oxidative stress, autophagy, mitochondrial function, and apoptosis. Preclinical trials demonstrate that WS slows disease progression in multiple different animal models of ALS. Of the five individuals we found who described using WS for their ALS, two individuals reported moderate benefit while none reported experiencing any significant side effects. There is currently one clinical trial using WS to treat PALS; the results are not yet published. There are no serious side effects associated with WS and the associated cost of this treatment is low. Based on the above information, WS appears to us to be a good candidate for future ALS trials.}, }
@article {pmid38318827, year = {2024}, author = {Motamedy, S and Soltani, B and Kameshki, H and Kermani, AA and Amleshi, RS and Nazeri, M and Shabani, M}, title = {The Therapeutic Potential and Molecular Mechanisms Underlying the Neuroprotective Effects of Sativex[®] - A Cannabis-derived Spray.}, journal = {Mini reviews in medicinal chemistry}, volume = {24}, number = {15}, pages = {1427-1448}, pmid = {38318827}, issn = {1875-5607}, mesh = {Humans ; *Neuroprotective Agents/pharmacology/chemistry ; *Cannabidiol/pharmacology/therapeutic use/chemistry ; *Plant Extracts/chemistry/pharmacology ; *Dronabinol/pharmacology/chemistry/therapeutic use ; Animals ; Multiple Sclerosis/drug therapy ; Cannabis/chemistry ; Drug Combinations ; }, abstract = {Sativex is a cannabis-based medicine that comes in the form of an oromucosal spray. It contains equal amounts of Δ9-tetrahydrocannabinol and cannabidiol, two compounds derived from cannabis plants. Sativex has been shown to have positive effects on symptoms of amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and sleep disorders. It also has analgesic, antiinflammatory, antitumoral, and neuroprotective properties, which make it a potential treatment option for other neurological disorders. The article reviews the results of recent preclinical and clinical studies that support the therapeutic potential of Sativex and the molecular mechanisms behind its neuroprotective benefits in various neurological disorders. The article also discusses the possible advantages and disadvantages of using Sativex as a neurotherapeutic agent, such as its safety, efficacy, availability, and legal status.}, }
@article {pmid38318532, year = {2024}, author = {Geng, Y and Cai, Q}, title = {Role of C9orf72 hexanucleotide repeat expansions in ALS/FTD pathogenesis.}, journal = {Frontiers in molecular neuroscience}, volume = {17}, number = {}, pages = {1322720}, pmid = {38318532}, issn = {1662-5099}, abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are progressive neurological disorders that share neurodegenerative pathways and features. The most prevalent genetic causes of ALS/FTD is the GGGGCC hexanucleotide repeat expansions in the first intron region of the chromosome 9 open reading frame 72 (C9orf72) gene. In this review, we comprehensively summarize the accumulating evidences elucidating the pathogenic mechanism associated with hexanucleotide repeat expansions in ALS/FTD. These mechanisms encompass the structural polymorphism of DNA and transcribed RNA, the formation of RNA foci via phase separation, and the cytoplasmic accumulation and toxicities of dipeptide-repeat proteins. Additionally, the formation of G-quadruplex structures significantly impairs the expression and normal function of the C9orf72 protein. We also discuss the sequestration of specific RNA binding proteins by GGGGCC RNA, which further contributes to the toxicity of C9orf72 hexanucleotide repeat expansions. The deeper understanding of the pathogenic mechanism of hexanucleotide repeat expansions in ALS/FTD provides multiple potential drug targets for these devastating diseases.}, }
@article {pmid38314277, year = {2024}, author = {Mohan, S and Alhazmi, HA and Hassani, R and Khuwaja, G and Maheshkumar, VP and Aldahish, A and Chidambaram, K}, title = {Role of ferroptosis pathways in neuroinflammation and neurological disorders: From pathogenesis to treatment.}, journal = {Heliyon}, volume = {10}, number = {3}, pages = {e24786}, pmid = {38314277}, issn = {2405-8440}, abstract = {Ferroptosis is a newly discovered non-apoptotic and iron-dependent type of cell death. Ferroptosis mainly takes place owing to the imbalance of anti-oxidation and oxidation in the body. It is regulated via a number of factors and pathways both inside and outside the cell. Ferroptosis is closely linked with brain and various neurological disorders (NDs). In the human body, the brain contains the highest levels of polyunsaturated fatty acids, which are known as lipid peroxide precursors. In addition, there is also a connection of glutathione depletion and lipid peroxidation with NDs. There is growing evidence regarding the possible link between neuroinflammation and multiple NDs, such as Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease, and stroke. Recent studies have demonstrated that disruptions of lipid reactive oxygen species (ROS), glutamate excitatory toxicity, iron homeostasis, and various other manifestations linked with ferroptosis can be identified in various neuroinflammation-mediated NDs. It has also been reported that damage-associated molecular pattern molecules including ROS are generated during the events of ferroptosis and can cause glial activation via activating neuroimmune pathways, which subsequently leads to the generation of various inflammatory factors that play a role in various NDs. This review summarizes the regulation pathways of ferroptosis, the link between ferroptosis as well as inflammation in NDs, and the potential of a range of therapeutic agents that can be used to target ferroptosis and inflammation in the treatment of neurological disorders.}, }
@article {pmid38302810, year = {2024}, author = {Teixeira, LCR and Mamede, I and Luizon, MR and Gomes, KB}, title = {Role of long non-coding RNAs in the pathophysiology of Alzheimer's disease and other dementias.}, journal = {Molecular biology reports}, volume = {51}, number = {1}, pages = {270}, pmid = {38302810}, issn = {1573-4978}, mesh = {Humans ; *Alzheimer Disease/genetics ; *RNA, Long Noncoding/genetics ; Amyloid beta-Peptides ; *Frontotemporal Dementia ; }, abstract = {Dementia is the term used to describe a group of cognitive disorders characterized by a decline in memory, thinking, and reasoning abilities that interfere with daily life activities. Examples of dementia include Alzheimer's Disease (AD), Frontotemporal dementia (FTD), Amyotrophic lateral sclerosis (ALS), Vascular dementia (VaD) and Progressive supranuclear palsy (PSP). AD is the most common form of dementia. The hallmark pathology of AD includes formation of β-amyloid (Aβ) oligomers and tau hyperphosphorylation in the brain, which induces neuroinflammation, oxidative stress, synaptic dysfunction, and neuronal apoptosis. Emerging studies have associated long non-coding RNAs (lncRNAs) with the pathogenesis and progression of the neurodegenerative diseases. LncRNAs are defined as RNAs longer than 200 nucleotides that lack the ability to encode functional proteins. LncRNAs play crucial roles in numerous biological functions for their ability to interact with different molecules, such as proteins and microRNAs, and subsequently regulate the expression of their target genes at transcriptional and post-transcriptional levels. In this narrative review, we report the function and mechanisms of action of lncRNAs found to be deregulated in different types of dementia, with the focus on AD. Finally, we discuss the emerging role of lncRNAs as biomarkers of dementias.}, }
@article {pmid38301596, year = {2024}, author = {Wang, H and Liu, YT and Ren, YL and Guo, XY and Wang, Y}, title = {Association of peripheral immune activation with amyotrophic lateral sclerosis and Parkinson's disease: A systematic review and meta-analysis.}, journal = {Journal of neuroimmunology}, volume = {388}, number = {}, pages = {578290}, doi = {10.1016/j.jneuroim.2024.578290}, pmid = {38301596}, issn = {1872-8421}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/immunology ; Biomarkers ; *Neurodegenerative Diseases/immunology ; *Parkinson Disease/immunology ; }, abstract = {BACKGROUND: Recent studies have revealed the link between immune activation and neurodegenerative diseases.<br><br>METHODS: By employing meta-analysis, we estimated the standardized mean difference (SMD) and their corresponding 95% confidence intervals (CIs) between the groups.<br><br>RESULTS: According to the pre-set criteria, a total of 21 published articles including 2377 ALS patients and 1244 HCs, as well as 60 articles including 5111 PD patients and 4237 HCs, were identified. This study provided evidence of peripheral immune activation in the pathogenesis of ALS and PD.<br><br>CONCLUSION: Our results suggested monitoring changes in peripheral blood immune cell populations, particularly lymphocyte subsets, will benefit understanding the developments and exploring reliable and specific biomarkers of these two diseases.}, }
@article {pmid38300375, year = {2024}, author = {Sarkar, S and Patranabis, S}, title = {Emerging Role of Extracellular Vesicles in Intercellular Communication in the Brain: Implications for Neurodegenerative Diseases and Therapeutics.}, journal = {Cell biochemistry and biophysics}, volume = {82}, number = {2}, pages = {379-398}, pmid = {38300375}, issn = {1559-0283}, mesh = {Humans ; *Extracellular Vesicles/metabolism ; *Neurodegenerative Diseases/metabolism/therapy/pathology ; *Cell Communication ; *Brain/metabolism/pathology ; Animals ; }, abstract = {Extracellular vesicles (EVs) are minute lipid-bilayer sacs discharged by cells, encompassing a diverse array of proteins, nucleic acids, and lipids. The identification of EVs as pivotal agents in intercellular communication has sparked compelling research pathways in the realms of cell biology and neurodegenerative diseases. Utilizing EVs for medicinal reasons has garnered interest due to the adaptability of EV-mediated communication. EVs can be classified based on their physical characteristics, biochemical composition, or cell of origin following purification. This review delves into the primary sub-types of EVs, providing an overview of the biogenesis of each type. Additionally, it explores the diverse environmental conditions triggering EV release and the originating cells, including stem cells and those from the Central Nervous System. Within the brain, EVs play a pivotal role as essential mediators of intercellular communication, significantly impacting synaptic plasticity, brain development, and the etiology of neurological diseases. Their potential diagnostic and therapeutic applications in various brain-related conditions are underscored, given their ability to carry specific cargo. Specially engineered EVs hold promise for treating diverse diseases, including neurodegenerative disorders. This study primarily emphasizes the diagnostic and potential therapeutic uses of EVs in neurological disorders such as Alzheimer's Disease, Huntington's Disease, Parkinson's Disease, Amyotrophic Lateral Sclerosis, and Prions disease. It also summarizes innovative techniques for detecting EVs in the brain, suggesting that EVs could serve as non-invasive biomarkers for early detection, disease monitoring, and prognosis in neurological disorders.}, }
@article {pmid38294530, year = {2024}, author = {O'Shea, H and Bek, J}, title = {The complex interplay between perception, cognition, and action: a commentary on Bach et al. 2022.}, journal = {Psychological research}, volume = {88}, number = {6}, pages = {1814-1816}, pmid = {38294530}, issn = {1430-2772}, mesh = {Humans ; *Imagination/physiology ; *Cognition/physiology ; Motor Activity/physiology ; Perception/physiology ; Psychomotor Performance/physiology ; }, abstract = {Bach (Psychological Research 2022, https://doi.org/10.1007/s00426-022-01773-w) offer a re-conceptualisation of motor imagery, influenced by older ideas of ideomotor action and formulated in terms of action effects rather than motor output. We share the view of an essential role of action effect in action planning and motor imagery processes, but we challenge the claim that motor imagery is non-motoric in nature. In the present article, we critically review some of Bach et al.'s proposed ideas and pose questions of whether effect and motor processes are functionally separable, and if not, what mechanisms underlie motor imagery and what terminology best captures its function.}, }
@article {pmid38291418, year = {2024}, author = {Cai, Y and Peng, Z and He, Q and Sun, P}, title = {Behavioral variant frontotemporal dementia associated with GRN and ErbB4 gene mutations: a case report and literature review.}, journal = {BMC medical genomics}, volume = {17}, number = {1}, pages = {43}, pmid = {38291418}, issn = {1755-8794}, mesh = {Male ; Humans ; Middle Aged ; *Frontotemporal Dementia/genetics ; *Amyotrophic Lateral Sclerosis/genetics ; Positron Emission Tomography Computed Tomography ; Progranulins/genetics ; Mutation ; }, abstract = {OBJECTIVE: To report the clinical manifestation and genetic characteristics of a patient having frontotemporal dementia (FTD) with abnormal behavior and unstable walking.<br><br>METHODS: The clinical and imaging features of a patient who was eventually diagnosed with FTD were analyzed. The patient's neuropsychological, PET-CT, electromyography, and genetic data were collected. Furthermore, the patient's blood samples were examined for FTD-related genes.<br><br>RESULTS: The patient was a 52-year-old man with hidden onset. The symptoms progressed gradually, presenting with abnormal behaviors, including repeated shopping, taking away other people's things, constantly eating snacks, and frequently calling friends at night. The patient also exhibited executive dysfunction, such as the inability to cook and multiple driving problems, e.g., constantly deviates from his lane while driving. In addition, the patient showed personality changes such as irritability, indifference, and withdrawal, as well as motor symptoms, including unstable walking and frequent falls when walking. Brain magnetic resonance imaging revealed hippocampal sclerosis along with widening and deepening of the bilateral temporal lobe sulcus. Brain metabolic imaging via PET-CT demonstrated decreased metabolism in the bilateral prefrontal lobe, with the abnormal energy metabolism indicating FTD. Lastly, blood sample analysis detected mutations in the amyotrophic lateral sclerosis (ALS)-related GRN gene c.1352C&#x2009;>&#x2009;T (p.P451L) and ErbB4 gene c.256&#x2009;T&#x2009;>&#x2009;C (p.Y86H).<br><br>CONCLUSION: This is the first case of heterozygous mutations in the GRN and ErbB4 genes in FTD alone. The GRN and ErbB4 genes are likely to be important in the pathogenesis of FTD, expanding the common genetic profile of ALS and FTD.}, }
@article {pmid38290651, year = {2024}, author = {Lõhelaid, H and Saarma, M and Airavaara, M}, title = {CDNF and ER stress: Pharmacology and therapeutic possibilities.}, journal = {Pharmacology &amp; therapeutics}, volume = {254}, number = {}, pages = {108594}, doi = {10.1016/j.pharmthera.2024.108594}, pmid = {38290651}, issn = {1879-016X}, mesh = {Animals ; Humans ; *Parkinson Disease/drug therapy ; Nerve Growth Factors/therapeutic use/metabolism ; Recombinant Proteins/therapeutic use ; }, abstract = {Cerebral dopamine neurotrophic factor (CDNF) is an endogenous protein in humans and other vertebrates, and it has been shown to have protective and restorative effects on cells in various disease models. Although it is named as a neurotrophic factor, its actions are drastically different from classical neurotrophic factors such as neurotrophins or the glial cell line-derived neurotrophic family of proteins. Like all secreted proteins, CDNF has a signal sequence at the N-terminus, but unlike common growth factors it has a KDEL-receptor retrieval sequence at the C-terminus. Thus, CDNF is mainly located in the ER. In response to adverse effects, such as ER stress, the expression of CDNF is upregulated and can alleviate ER stress. Also different from other neurotrophic factors, CDNF reduces protein aggregation and inflammation in disease models. Although it is an ER luminal protein, it can surprisingly directly interact with alpha-synuclein, a protein involved in the pathogenesis of synucleinopathies e.g., Parkinson's disease. Pleiotropic CDNF has therapeutic potential and has been tested as a recombinant human protein and gene therapy. The neuroprotective and neurorestorative effects have been described in a number of preclinical studies of Parkinson's disease, stroke and amyotrophic lateral sclerosis. Currently, it was successfully evaluated for safety in a phase 1/2 clinical trial for Parkinson's disease. Collectively, based on recent findings on the mode of action and therapeutic potential of CDNF, its use as a drug could be expanded to other ER stress-related diseases.}, }
@article {pmid38289193, year = {2024}, author = {Nolan, M and Scott, C and Hof, PR and Ansorge, O}, title = {Betz cells of the primary motor cortex.}, journal = {The Journal of comparative neurology}, volume = {532}, number = {1}, pages = {e25567}, pmid = {38289193}, issn = {1096-9861}, support = {ANSORGE/OCT14/877-792/MNDA_/Motor Neurone Disease Association/United Kingdom ; MR/L022656/1/MRC_/Medical Research Council/United Kingdom ; 14/877-792/MNDA_/Motor Neurone Disease Association/United Kingdom ; }, mesh = {Adult ; Humans ; Animals ; *Motor Cortex ; *Amyotrophic Lateral Sclerosis ; Pyramidal Cells ; Motor Neurons ; Primates ; Mammals ; }, abstract = {Betz cells, named in honor of Volodymyr Betz (1834-1894), who described them as "giant pyramids" in the primary motor cortex of primates and other mammalian species, are layer V extratelencephalic projection (ETP) neurons that directly innervate α-motoneurons of the brainstem and spinal cord. Despite their large volume and circumferential dendritic architecture, to date, no single molecular criterion has been established that unequivocally distinguishes adult Betz cells from other layer V ETP neurons. In primates, transcriptional signatures suggest the presence of at least two ETP neuron clusters that contain mature Betz cells; these are characterized by an abundance of axon guidance and oxidative phosphorylation transcripts. How neurodevelopmental programs drive the distinct positional and morphological features of Betz cells in humans remains unknown. Betz cells display a distinct biphasic firing pattern involving early cessation of firing followed by delayed sustained acceleration in spike frequency and magnitude. Few cell type-specific transcripts and electrophysiological characteristics are conserved between rodent layer V ETP neurons of the motor cortex and primate Betz cells. This has implications for the modeling of disorders that affect the motor cortex in humans, such as amyotrophic lateral sclerosis (ALS). Perhaps vulnerability to ALS is linked to the evolution of neural networks for fine motor control reflected in the distinct morphomolecular architecture of the human motor cortex, including Betz cells. Here, we discuss histological, molecular, and functional data concerning the position of Betz cells in the emerging taxonomy of neurons across diverse species and their role in neurological disorders.}, }
@article {pmid38288970, year = {2024}, author = {Lini, RS and Scanferla, DTP and de Oliveira, NG and Aguera, RG and Santos, TDS and Teixeira, JJV and Kaneshima, AMS and Mossini, SAG}, title = {Fungicides as a risk factor for the development of neurological diseases and disorders in humans: a systematic review.}, journal = {Critical reviews in toxicology}, volume = {54}, number = {1}, pages = {35-54}, doi = {10.1080/10408444.2024.2303481}, pmid = {38288970}, issn = {1547-6898}, mesh = {Humans ; *Fungicides, Industrial/toxicity ; *Nervous System Diseases/chemically induced ; Risk Factors ; Brazil ; }, abstract = {Although studies show that pesticides, especially insecticides, may be toxic to humans, publications on the neurological effects of fungicides are scarce. As fungicides are used widely in Brazil, it is necessary to gather evidence to support actions aimed at safely using of these chemicals. We investigated through a systematic review of publications on the use of fungicides and consequences of exposure related to nervous system diseases or neurological disorders in humans. The protocol review was registered on PROSPERO and followed the guidelines of the PRISMA-Statement. As far as it is known, there is no apparent systematic review in the literature on this topic. The search was comprised of the following databases: PubMed; Web of Science; Scopus and EMBASE, using groups of Mesh terms and strategies specific to each database. Thirteen articles were selected for this review. Regarding the substances analyzed in the studies, some reported the use of fungicides in general, without separating them by type, while others summarized the categories of all pesticides by their function (insecticides, herbicides, fungicides, etc.) or chemical class (dithiocarbamate, dicarboximide, inorganic, etc.). However, most of the articles referred to fungicides that contain the metal manganese (Mn) in their composition. As for neurological disorders, articles addressed Parkinson's disease (PD), neurodevelopmental outcomes, extrapyramidal syndrome resembling PD, cognitive disorders, depression, neural tube defects, motor neurone disease, and amyotrophic lateral sclerosis. Most investigations pointed to exposure to fungicides, mainly maneb and mancozeb, leading to the development of at least one neurological disease, which suggests the need for further multicentric clinical trials and prospective studies for greater clarity of the research problem.}, }
@article {pmid38288843, year = {2024}, author = {Fatima, J and Siddique, YH}, title = {Application of Nanocomposites and Nanoparticles in Treating Neurodegenerative Disorders.}, journal = {CNS &amp; neurological disorders drug targets}, volume = {23}, number = {10}, pages = {1217-1233}, pmid = {38288843}, issn = {1996-3181}, support = {211610179057//University Grants Commission/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy ; *Nanoparticles/therapeutic use ; *Nanocomposites/therapeutic use ; Animals ; Drug Delivery Systems/methods ; Blood-Brain Barrier/drug effects/metabolism ; Neuroprotective Agents/therapeutic use ; }, abstract = {Neurodegenerative diseases represent a formidable global health challenge, affecting millions and imposing substantial burdens on healthcare systems worldwide. Conditions, like Alzheimer's, Parkinson's, and Huntington's diseases, among others, share common characteristics, such as neuronal loss, misfolded protein aggregation, and nervous system dysfunction. One of the major obstacles in treating these diseases is the presence of the blood-brain barrier, limiting the delivery of therapeutic agents to the central nervous system. Nanotechnology offers promising solutions to overcome these challenges. In Alzheimer's disease, NPs loaded with various compounds have shown remarkable promise in preventing amyloid-beta (Aβ) aggregation and reducing neurotoxicity. Parkinson's disease benefits from improved dopamine delivery and neuroprotection. Huntington's disease poses its own set of challenges, but nanotechnology continues to offer innovative solutions. The promising developments in nanoparticle-based interventions for neurodegenerative diseases, like amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS), have offered new avenues for effective treatment. Nanotechnology represents a promising frontier in biomedical research, offering tailored solutions to the complex challenges posed by neurodegenerative diseases. While much progress has been made, ongoing research is essential to optimize nanomaterial designs, improve targeting, and ensure biocompatibility and safety. Nanomaterials possess unique properties that make them excellent candidates for targeted drug delivery and neuroprotection. They can effectively bypass the blood-brain barrier, opening doors to precise drug delivery strategies. This review explores the extensive research on nanoparticles (NPs) and nanocomposites in diagnosing and treating neurodegenerative disorders. These nanomaterials exhibit exceptional abilities to target neurodegenerative processes and halt disease progression.}, }
@article {pmid38287907, year = {2024}, author = {Pan, MT and Zhang, H and Li, XJ and Guo, XY}, title = {Genetically modified non-human primate models for research on neurodegenerative diseases.}, journal = {Zoological research}, volume = {45}, number = {2}, pages = {263-274}, pmid = {38287907}, issn = {2095-8137}, mesh = {Humans ; Animals ; Chlorocebus aethiops ; *Neurodegenerative Diseases/genetics/therapy/veterinary ; Animals, Genetically Modified ; Disease Models, Animal ; *Parkinson Disease/pathology/veterinary ; Macaca mulatta ; }, abstract = {Neurodegenerative diseases (NDs) are a group of debilitating neurological disorders that primarily affect elderly populations and include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). Currently, there are no therapies available that can delay, stop, or reverse the pathological progression of NDs in clinical settings. As the population ages, NDs are imposing a huge burden on public health systems and affected families. Animal models are important tools for preclinical investigations to understand disease pathogenesis and test potential treatments. While numerous rodent models of NDs have been developed to enhance our understanding of disease mechanisms, the limited success of translating findings from animal models to clinical practice suggests that there is still a need to bridge this translation gap. Old World non-human primates (NHPs), such as rhesus, cynomolgus, and vervet monkeys, are phylogenetically, physiologically, biochemically, and behaviorally most relevant to humans. This is particularly evident in the similarity of the structure and function of their central nervous systems, rendering such species uniquely valuable for neuroscience research. Recently, the development of several genetically modified NHP models of NDs has successfully recapitulated key pathologies and revealed novel mechanisms. This review focuses on the efficacy of NHPs in modeling NDs and the novel pathological insights gained, as well as the challenges associated with the generation of such models and the complexities involved in their subsequent analysis.}, }
@article {pmid38287331, year = {2024}, author = {Oh, J and An, J and Park, K and Park, Y}, title = {Psychosocial interventions for people with amyotrophic lateral sclerosis and motor neuron disease and their caregivers: a scoping review.}, journal = {BMC nursing}, volume = {23}, number = {1}, pages = {75}, pmid = {38287331}, issn = {1472-6955}, support = {2022R1F1A1064038//National Research Foundation of Korea grant funded by the Korea government/ ; }, abstract = {BACKGROUND: As amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) is a fatal progressive neurodegenerative disorder, patients experience severe impairments, with patients and family caregivers facing emotional distress and exhaustion. Several psychosocial interventions are aimed at providing tailored support for ALS/MND patients and caregivers. The aim of this study was to conduct a scoping review and present a comprehensive overview of psychosocial interventions designed for individuals and families affected by ALS/MND, while also pinpointing research gaps.<br><br>METHODS: This scoping review utilized Arksey and O'Malley's methodological framework to investigate psychosocial interventions designed for individuals with ALS/MND and their families. The study adhered to the PRISMA-ScR checklist for reporting.<br><br>RESULTS: A total of 27 articles describing 25 interventions met the inclusion criteria. The predominant interventions observed in the research encompassed education-related strategies, closely followed by behavior therapy, counseling, social support interventions, and psychotherapy interventions. Across the majority of the studies, findings indicated promising feasibility and acceptability of these interventions. Notably, a significant proportion of quantitative investigations yielded one or more statistically significant effects, while qualitative studies consistently reported favorable outcomes, including enhancements in well-being and heightened awareness of individual circumstances.<br><br>CONCLUSIONS: Given the progressive and debilitating nature of this condition, coupled with the absence of a cure, the adoption of a psychosocial approach can prove beneficial for both ALS/MND patients and their families. However, high-quality RCTs with a large sample size are recommended to examine and confirm the effectiveness.}, }
@article {pmid38286111, year = {2024}, author = {Wang, M and Wang, T and Gu, F}, title = {Efficacy of Huanglian Jiedu Decoction for Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.}, journal = {Complementary medicine research}, volume = {31}, number = {2}, pages = {187-200}, doi = {10.1159/000536453}, pmid = {38286111}, issn = {2504-2106}, mesh = {*Diabetes Mellitus, Type 2/drug therapy ; Humans ; *Drugs, Chinese Herbal/therapeutic use ; Blood Glucose/drug effects ; Glycated Hemoglobin ; Randomized Controlled Trials as Topic ; *Hypoglycemic Agents/therapeutic use ; }, abstract = {OBJECTIVE: Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disorder, and there is an increasing interest in the potential benefits of traditional Chinese medicine, such as Huanglian Jiedu decoction (HJD), for its management. This meta-analysis aimed to determine the efficacy and safety of HJD in the treatment of T2DM.<br><br>METHODS: A systematic review was conducted across six databases including PubMed, Embase, Cochrane, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang, from their inception to August 24, 2023. We focused on randomized controlled trials (RCTs) that evaluated HJD as both a monotherapy and in combination treatments for T2DM patients. Data analysis was performed using RevMan 5.3 and Stata 17.0, with evaluations for heterogeneity and publication bias. Additionally, subgroup analyses were stratified based on the duration of treatment.<br><br>RESULTS: A total of 40 studies involving 3,934 participants were included in the meta-analysis. Both HJD monotherapy and combined with other therapies significantly reduced hemoglobin A1C (HbA1c) fasting blood glucose (FBG) and 2-h postprandial glucose (2hPG) levels, as well as improved insulin resistance. Furthermore, combination therapy enhanced the efficacy rate and favorably altered lipid profiles, including increasing HDL-C and decreasing LDL-C, TC, and TG levels. It was worth noting that the results of the subgroup analysis indicated that, in terms of reducing HbA1c and 2hPG, the efficacy of HJD alone for a duration of less than 3 months was found to be potentially superior to that observed in treatments exceeding 3 months. Adverse event assessment suggested that HJD did not increase the incidence of side effects, including diarrhea, affirming its safety.<br><br>CONCLUSION: HJD appears to be an effective and safe alternative or adjunctive therapy for T2DM, showing significant improvements in glycemic control and lipid profiles without increasing adverse events. Further rigorous, multicenter RCTs outside China are warranted to validate these findings.<br><br>UNLABELLED: <title>Ziel</title>Diabetes mellitus Typ 2 (DMT2) ist eine weit verbreitete Stoffwechselerkrankung, und es besteht ein steigendes Interesse an den potenziellen Vorteilen der traditionellen chinesischen Medizin, wie beispielsweise Huanglian Jiedu-Dekokt (HJD), zu seiner Behandlung. Mit dieser Metaanalyse sollten die Wirksamkeit und Sicherheit von HJD zur Behandlung von DMT2 ermittelt werden.<title>Methoden</title>Es wurde eine systematische Recherche in sechs Datenbanken durchgef&#xfc;hrt, darunter PubMed, Embase, Cochrane, Web of Science, China National Knowledge Infrastructure (CNKI) und Wanfang, f&#xfc;r die Zeit vom Beginn der Datenbank bis zum 24. August 2023. Dabei lag unser Hauptaugenmerk auf randomisierten kontrollierten Studien (RCTs), die HJD sowohl als Monotherapie als auch in Kombinationstherapien bei Patienten mit DMT2 untersuchten. Die Datenanalyse erfolgte mithilfe von RevMan 5.3 und Stata 17.0 mit Untersuchungen auf Heterogenit&#xe4;t und Publikationsverzerrungen. Dar&#xfc;ber hinaus wurden Subgruppenanalysen stratifiziert nach Behandlungsdauer durchgef&#xfc;hrt.<title>Ergebnisse</title>Insgesamt wurden 40 Studien mit 3.934 Teilnehmern in die Metaanalyse eingeschlossen. HJD f&#xfc;hrte sowohl als Monotherapie als auch in Kombination mit anderen Therapien zu einer signifikanten Senkung des HbA1c-N&#xfc;chternblutzuckerspiegels (fasting blood glucose, FBG) und der postprandialen Blutzuckerwerte 2 Stunden nach dem Essen (2-h postprandial glucose, 2hPG) sowie zu einer Verbesserung der Insulinresistenz. Dar&#xfc;ber hinaus verbesserte die Kombinationstherapie die Wirksamkeitsrate und f&#xfc;hrte zu einer positiven Ver&#xe4;nderung der Lipidprofile, die eine Erh&#xf6;hung der HDL-Cholesterinwerte und eine Senkung der LDL-, Gesamtcholesterin- und Trigylceridwerte einschloss. Erw&#xe4;hnenswert ist, dass nach den Ergebnissen der Subgruppenanalyse die Wirksamkeit von HJD als Monotherapie in Hinblick auf die Senkung der HbA1c- und 2hPG-Werte bei einer Behandlungsdauer von weniger als drei Monaten gegen&#xfc;ber derjenigen von Behandlungen, die l&#xe4;nger als drei Monate dauerten, potenziell &#xfc;berlegen war. Die Bewertung der unerw&#xfc;nschten Ereignisse zeigte, dass HJD nicht zu einem Anstieg der Nebenwirkungen wie Durchfall f&#xfc;hrte, was seine Sicherheit best&#xe4;tigte.<title>Schlussfolgerung</title>HJD scheint eine wirksame und sichere Alternative oder Zusatztherapie bei DMT2 zu sein, die signifikante Verbesserungen der Blutzuckerkontrolle und der Lipidprofile ohne Zunahme der unerw&#xfc;nschten Ereignisse bewirkt. Weitere rigorose, multizentrische RCTs au&#xdf;erhalb Chinas sind erforderlich, um diese Ergebnisse zu validieren.}, }
@article {pmid38276084, year = {2024}, author = {Vacchiano, V and Bonan, L and Liguori, R and Rizzo, G}, title = {Primary Lateral Sclerosis: An Overview.}, journal = {Journal of clinical medicine}, volume = {13}, number = {2}, pages = {}, pmid = {38276084}, issn = {2077-0383}, abstract = {Primary lateral sclerosis (PLS) is a rare neurodegenerative disorder which causes the selective deterioration of the upper motor neurons (UMNs), sparing the lower motor neuron (LMN) system. The clinical course is defined by a progressive motor disability due to muscle spasticity which typically involves lower extremities and bulbar muscles. Although classically considered a sporadic disease, some familiar cases and possible causative genes have been reported. Despite it having been recognized as a rare but distinct entity, whether it actually represents an extreme end of the motor neuron diseases continuum is still an open issue. The main knowledge gap is the lack of specific biomarkers to improve the clinical diagnostic accuracy. Indeed, the diagnostic imprecision, together with some uncertainty about overlap with UMN-predominant ALS and Hereditary Spastic Paraplegia (HSP), has become an obstacle to the development of specific therapeutic trials. In this study, we provided a comprehensive analysis of the existing literature, including neuropathological, clinical, neuroimaging, and neurophysiological features of the disease, and highlighting the controversies still unsolved in the differential diagnoses and the current diagnostic criteria. We also discussed the current knowledge gaps still present in both diagnostic and therapeutic fields when approaching this rare condition.}, }
@article {pmid38270797, year = {2024}, author = {Singh, S and Borkar, MR and Bhatt, LK}, title = {Transposable Elements: Emerging Therapeutic Targets in Neurodegenerative Diseases.}, journal = {Neurotoxicity research}, volume = {42}, number = {1}, pages = {9}, pmid = {38270797}, issn = {1476-3524}, mesh = {Humans ; *Neurodegenerative Diseases/genetics ; DNA Transposable Elements/genetics ; *Amyotrophic Lateral Sclerosis ; *Alzheimer Disease ; *Parkinson Disease ; }, abstract = {Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), are characterized by the progressive loss of neuronal function and structure. While several genetic and environmental factors have been implicated in the pathogenesis of these disorders, emerging evidence suggests that transposable elements (TEs), once considered "junk DNA," play a significant role in their development and progression. TEs are mobile genetic elements capable of moving within the genome, and their dysregulation has been associated with genomic instability, altered gene expression, and neuroinflammation. This review provides an overview of TEs, including long interspersed nuclear elements (LINEs), short interspersed nuclear elements (SINEs), and endogenous retroviruses (ERVs), mechanisms of repression and derepression, and their potential impact on neurodegeneration. The evidence linking TEs to AD, PD, and ALS by shedding light on the complex interactions between TEs and neurodegeneration has been discussed. Furthermore, the therapeutic potential of targeting TEs in neurodegenerative diseases has been explored. Understanding the role of TEs in neurodegeneration holds promise for developing novel therapeutic strategies aimed at mitigating disease progression and preserving neuronal health.}, }
@article {pmid38267984, year = {2024}, author = {Irwin, KE and Sheth, U and Wong, PC and Gendron, TF}, title = {Fluid biomarkers for amyotrophic lateral sclerosis: a review.}, journal = {Molecular neurodegeneration}, volume = {19}, number = {1}, pages = {9}, pmid = {38267984}, issn = {1750-1326}, support = {R01 NS095969/NS/NINDS NIH HHS/United States ; T32 GM136577/GM/NIGMS NIH HHS/United States ; P01NS084974/NH/NIH HHS/United States ; U19AG063911/NH/NIH HHS/United States ; RF1 NS095969/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; *Neurodegenerative Diseases ; Biomarkers ; Motor Neurons ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of upper and lower motor neurons. Presently, three FDA-approved drugs are available to help slow functional decline for patients with ALS, but no cure yet exists. With an average life expectancy of only two to five years after diagnosis, there is a clear need for biomarkers to improve the care of patients with ALS and to expedite ALS treatment development. Here, we provide a review of the efforts made towards identifying diagnostic, prognostic, susceptibility/risk, and response fluid biomarkers with the intent to facilitate a more rapid and accurate ALS diagnosis, to better predict prognosis, to improve clinical trial design, and to inform interpretation of clinical trial results. Over the course of 20 + years, several promising fluid biomarker candidates for ALS have emerged. These will be discussed, as will the exciting new strategies being explored for ALS biomarker discovery and development.}, }
@article {pmid38266701, year = {2024}, author = {Eisen, A and Nedergaard, M and Gray, E and Kiernan, MC}, title = {The glymphatic system and Amyotrophic lateral sclerosis.}, journal = {Progress in neurobiology}, volume = {234}, number = {}, pages = {102571}, doi = {10.1016/j.pneurobio.2024.102571}, pmid = {38266701}, issn = {1873-5118}, mesh = {Humans ; *Glymphatic System/metabolism/pathology ; *Amyotrophic Lateral Sclerosis/metabolism ; Brain/metabolism ; *Alzheimer Disease/metabolism ; Sleep ; }, abstract = {The glymphatic system and the meningeal lymphatic vessels provide a pathway for transport of solutes and clearance of toxic material from the brain. Of specific relevance to ALS, this is applicable for TDP-43 and glutamate, both major elements in disease pathogenesis. Flow is propelled by arterial pulsation, respiration, posture, as well as the positioning and proportion of aquaporin-4 channels (AQP4). Non-REM slow wave sleep is the is key to glymphatic drainage which discontinues during wakefulness. In Parkinson's disease and Alzheimer's disease, sleep impairment is known to predate the development of characteristic clinical features by several years and is associated with progressive accumulation of toxic proteinaceous products. While sleep issues are well described in ALS, consideration of preclinical sleep impairment or the potential of a failing glymphatic system in ALS has rarely been considered. Here we review how the glymphatic system may impact ALS. Preclinical sleep impairment as an unrecognized major risk factor for ALS is considered, while potential therapeutic options to improve glymphatic flow are explored.}, }
@article {pmid38265475, year = {2024}, author = {Xiang, Y and Song, X and Long, D}, title = {Ferroptosis regulation through Nrf2 and implications for neurodegenerative diseases.}, journal = {Archives of toxicology}, volume = {98}, number = {3}, pages = {579-615}, pmid = {38265475}, issn = {1432-0738}, support = {81673227//National Natural Science Foundation of China/ ; 2020JJ4080//Natural Science Foundation of&#xa0;Hunan Province/ ; }, mesh = {Humans ; *Neurodegenerative Diseases ; NF-E2-Related Factor 2/metabolism ; *Ferroptosis ; Oxidative Stress/physiology ; Antioxidants/metabolism ; }, abstract = {This article provides an overview of the background knowledge of ferroptosis in the nervous system, as well as the key role of nuclear factor E2-related factor 2 (Nrf2) in regulating ferroptosis. The article takes Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) as the starting point to explore the close association between Nrf2 and ferroptosis, which is of clear and significant importance for understanding the mechanism of neurodegenerative diseases (NDs) based on oxidative stress (OS). Accumulating evidence links ferroptosis to the pathogenesis of NDs. As the disease progresses, damage to the antioxidant system, excessive OS, and altered Nrf2 expression levels, especially the inhibition of ferroptosis by lipid peroxidation inhibitors and adaptive enhancement of Nrf2 signaling, demonstrate the potential clinical significance of Nrf2 in detecting and identifying ferroptosis, as well as targeted therapy for neuronal loss and mitochondrial dysfunction. These findings provide new insights and possibilities for the treatment and prevention of NDs.}, }
@article {pmid38261034, year = {2024}, author = {Sian-Hulsmann, J and Riederer, P}, title = {Virus-induced brain pathology and the neuroinflammation-inflammation continuum: the neurochemists view.}, journal = {Journal of neural transmission (Vienna, Austria : 1996)}, volume = {131}, number = {12}, pages = {1429-1453}, pmid = {38261034}, issn = {1435-1463}, mesh = {Humans ; *Neuroinflammatory Diseases/pathology/immunology/metabolism ; Animals ; Neurodegenerative Diseases/pathology/metabolism/immunology ; Brain/pathology/metabolism/immunology ; Inflammation/pathology/metabolism/immunology ; }, abstract = {Fascinatingly, an abundance of recent studies has subscribed to the importance of cytotoxic immune mechanisms that appear to increase the risk/trigger for many progressive neurodegenerative disorders, including Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis, and multiple sclerosis. Events associated with the neuroinflammatory cascades, such as ageing, immunologic dysfunction, and eventually disruption of the blood-brain barrier and the "cytokine storm", appear to be orchestrated mainly through the activation of microglial cells and communication with the neurons. The inflammatory processes prompt cellular protein dyshomeostasis. Parkinson's and Alzheimer's disease share a common feature marked by characteristic pathological hallmarks of abnormal neuronal protein accumulation. These Lewy bodies contain misfolded α-synuclein aggregates in PD or in the case of AD, they are Aβ deposits and tau-containing neurofibrillary tangles. Subsequently, these abnormal protein aggregates further elicit neurotoxic processes and events which contribute to the onset of neurodegeneration and to its progression including aggravation of neuroinflammation. However, there is a caveat for exclusively linking neuroinflammation with neurodegeneration, since it's highly unlikely that immune dysregulation is the only factor that contributes to the manifestation of many of these neurodegenerative disorders. It is unquestionably a complex interaction with other factors such as genetics, age, and environment. This endorses the "multiple hit hypothesis". Consequently, if the host has a genetic susceptibility coupled to an age-related weakened immune system, this makes them more susceptible to the virus/bacteria-related infection. This may trigger the onset of chronic cytotoxic neuroinflammatory processes leading to protein dyshomeostasis and accumulation, and finally, these events lead to neuronal destruction. Here, we differentiate "neuroinflammation" and "inflammation" with regard to the involvement of the blood-brain barrier, which seems to be intact in the case of neuroinflammation but defect in the case of inflammation. There is a neuroinflammation-inflammation continuum with regard to virus-induced brain affection. Therefore, we propose a staging of this process, which might be further developed by adding blood- and CSF parameters, their stage-dependent composition and stage-dependent severeness grade. If so, this might be suitable to optimise therapeutic strategies to fight brain neuroinflammation in its beginning and avoid inflammation at all.}, }
@article {pmid38259504, year = {2023}, author = {Rashid, S and Dimitriadi, M}, title = {Autophagy in spinal muscular atrophy: from pathogenic mechanisms to therapeutic approaches.}, journal = {Frontiers in cellular neuroscience}, volume = {17}, number = {}, pages = {1307636}, pmid = {38259504}, issn = {1662-5102}, abstract = {Spinal muscular atrophy (SMA) is a devastating neuromuscular disorder caused by the depletion of the ubiquitously expressed survival motor neuron (SMN) protein. While the genetic cause of SMA has been well documented, the exact mechanism(s) by which SMN depletion results in disease progression remain elusive. A wide body of evidence has highlighted the involvement and dysregulation of autophagy in SMA. Autophagy is a highly conserved lysosomal degradation process which is necessary for cellular homeostasis; defects in the autophagic machinery have been linked with a wide range of neurodegenerative disorders, including amyotrophic lateral sclerosis, Alzheimer's disease and Parkinson's disease. The pathway is particularly known to prevent neurodegeneration and has been suggested to act as a neuroprotective factor, thus presenting an attractive target for novel therapies for SMA patients. In this review, (a) we provide for the first time a comprehensive summary of the perturbations in the autophagic networks that characterize SMA development, (b) highlight the autophagic regulators which may play a key role in SMA pathogenesis and (c) propose decreased autophagic flux as the causative agent underlying the autophagic dysregulation observed in these patients.}, }
@article {pmid38256091, year = {2024}, author = {Iskusnykh, IY and Zakharova, AA and Kryl'skii, ED and Popova, TN}, title = {Aging, Neurodegenerative Disorders, and Cerebellum.}, journal = {International journal of molecular sciences}, volume = {25}, number = {2}, pages = {}, pmid = {38256091}, issn = {1422-0067}, mesh = {Humans ; *Neurodegenerative Diseases ; Cerebellum ; *Alzheimer Disease ; *Huntington Disease ; Aging ; }, abstract = {An important part of the central nervous system (CNS), the cerebellum is involved in motor control, learning, reflex adaptation, and cognition. Diminished cerebellar function results in the motor and cognitive impairment observed in patients with neurodegenerative disorders such as Alzheimer's disease (AD), vascular dementia (VD), Parkinson's disease (PD), Huntington's disease (HD), spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS), Friedreich's ataxia (FRDA), and multiple sclerosis (MS), and even during the normal aging process. In most neurodegenerative disorders, impairment mainly occurs as a result of morphological changes over time, although during the early stages of some disorders such as AD, the cerebellum also serves a compensatory function. Biological aging is accompanied by changes in cerebellar circuits, which are predominantly involved in motor control. Despite decades of research, the functional contributions of the cerebellum and the underlying molecular mechanisms in aging and neurodegenerative disorders remain largely unknown. Therefore, this review will highlight the molecular and cellular events in the cerebellum that are disrupted during the process of aging and the development of neurodegenerative disorders. We believe that deeper insights into the pathophysiological mechanisms of the cerebellum during aging and the development of neurodegenerative disorders will be essential for the design of new effective strategies for neuroprotection and the alleviation of some neurodegenerative disorders.}, }
@article {pmid38256050, year = {2024}, author = {Bruno, A and Milillo, C and Anaclerio, F and Buccolini, C and Dell'Elice, A and Angilletta, I and Gatta, M and Ballerini, P and Antonucci, I}, title = {Perinatal Tissue-Derived Stem Cells: An Emerging Therapeutic Strategy for Challenging Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {25}, number = {2}, pages = {}, pmid = {38256050}, issn = {1422-0067}, mesh = {Female ; Pregnancy ; Humans ; *Neurodegenerative Diseases/therapy ; *Alzheimer Disease ; *Huntington Disease/therapy ; *Parkinson Disease/therapy ; Stem Cells ; }, abstract = {Over the past 20 years, stem cell therapy has been considered a promising option for treating numerous disorders, in particular, neurodegenerative disorders. Stem cells exert neuroprotective and neurodegenerative benefits through different mechanisms, such as the secretion of neurotrophic factors, cell replacement, the activation of endogenous stem cells, and decreased neuroinflammation. Several sources of stem cells have been proposed for transplantation and the restoration of damaged tissue. Over recent decades, intensive research has focused on gestational stem cells considered a novel resource for cell transplantation therapy. The present review provides an update on the recent preclinical/clinical applications of gestational stem cells for the treatment of protein-misfolding diseases including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS). However, further studies should be encouraged to translate this promising therapeutic approach into the clinical setting.}, }
@article {pmid38254647, year = {2023}, author = {Lauria, G and Curcio, R and Tucci, P}, title = {A Machine Learning Approach for Highlighting microRNAs as Biomarkers Linked to Amyotrophic Lateral Sclerosis Diagnosis and Progression.}, journal = {Biomolecules}, volume = {14}, number = {1}, pages = {}, pmid = {38254647}, issn = {2218-273X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics ; Biomarkers ; Machine Learning ; *MicroRNAs/genetics ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons in the brain and spinal cord. The early diagnosis of ALS can be challenging, as it usually depends on clinical examination and the exclusion of other possible causes. In this regard, the analysis of miRNA expression profiles in biofluids makes miRNAs promising non-invasive clinical biomarkers. Due to the increasing amount of scientific literature that often provides controversial results, this work aims to deepen the understanding of the current state of the art on this topic using a machine-learning-based approach. A systematic literature search was conducted to analyze a set of 308 scientific articles using the MySLR digital platform and the Latent Dirichlet Allocation (LDA) algorithm. Two relevant topics were identified, and the articles clustered in each of them were analyzed and discussed in terms of biomolecular mechanisms, as well as in translational and clinical settings. Several miRNAs detected in the tissues and biofluids of ALS patients, including blood and cerebrospinal fluid (CSF), have been linked to ALS diagnosis and progression. Some of them may represent promising non-invasive clinical biomarkers. In this context, future scientific priorities and goals have been proposed.}, }
@article {pmid38254150, year = {2024}, author = {Khalil, B and Linsenmeier, M and Smith, CL and Shorter, J and Rossoll, W}, title = {Nuclear-import receptors as gatekeepers of pathological phase transitions in ALS/FTD.}, journal = {Molecular neurodegeneration}, volume = {19}, number = {1}, pages = {8}, pmid = {38254150}, issn = {1750-1326}, support = {R33NS110960/NS/NINDS NIH HHS/United States ; R21AG061784/AG/NIA NIH HHS/United States ; RF1AG076122/AG/NIA NIH HHS/United States ; R01 GM099836/GM/NIGMS NIH HHS/United States ; R33 NS110960/NS/NINDS NIH HHS/United States ; R21 AG065854/AG/NIA NIH HHS/United States ; R01GM099836/GM/NIGMS NIH HHS/United States ; R21 AG079609/AG/NIA NIH HHS/United States ; R21AG065854/AG/NIA NIH HHS/United States ; R01 AG077771/AG/NIA NIH HHS/United States ; RF1AG068581/AG/NIA NIH HHS/United States ; W81XWH-20&#x2013;1-0242//Department of Defense/ ; }, mesh = {Humans ; *Frontotemporal Dementia ; *Amyotrophic Lateral Sclerosis ; Active Transport, Cell Nucleus ; DNA-Binding Proteins ; *Prions ; }, abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are fatal neurodegenerative disorders on a disease spectrum that are characterized by the cytoplasmic mislocalization and aberrant phase transitions of prion-like RNA-binding proteins (RBPs). The common accumulation of TAR DNA-binding protein-43 (TDP-43), fused in sarcoma (FUS), and other nuclear RBPs in detergent-insoluble aggregates in the cytoplasm of degenerating neurons in ALS/FTD is connected to nuclear pore dysfunction and other defects in the nucleocytoplasmic transport machinery. Recent advances suggest that beyond their canonical role in the nuclear import of protein cargoes, nuclear-import receptors (NIRs) can prevent and reverse aberrant phase transitions of TDP-43, FUS, and related prion-like RBPs and restore their nuclear localization and function. Here, we showcase the NIR family and how they recognize cargo, drive nuclear import, and chaperone prion-like RBPs linked to ALS/FTD. We also discuss the promise of enhancing NIR levels and developing potentiated NIR variants as therapeutic strategies for ALS/FTD and related neurodegenerative proteinopathies.}, }
@article {pmid38254109, year = {2024}, author = {Nagy, ZF and Pál, M and Engelhardt, JI and Molnár, MJ and Klivényi, P and Széll, M}, title = {Beyond C9orf72: repeat expansions and copy number variations as risk factors of amyotrophic lateral sclerosis across various populations.}, journal = {BMC medical genomics}, volume = {17}, number = {1}, pages = {30}, pmid = {38254109}, issn = {1755-8794}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *C9orf72 Protein/genetics ; DNA Copy Number Variations ; Genes, Regulator ; Risk Factors ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder which is characterized by the loss of both upper and lower motor neurons in the central nervous system. In a significant fraction of ALS cases - irrespective of family history- a genetic background may be identified. The genetic background of ALS shows a high variability from one ethnicity to another. The most frequent genetic cause of ALS is the repeat expansion of the C9orf72 gene. With the emergence of next-generation sequencing techniques and copy number alteration calling tools the focus in ALS genetics has shifted from disease causing genes and mutations towards genetic susceptibility and risk factors.In this review we aimed to summarize the most widely recognized and studied ALS linked repeat expansions and copy number variations other than the hexanucleotide repeat expansion in the C9orf72 gene. We compare and contrast their involvement and phenotype modifying roles in ALS among different populations.}, }
@article {pmid38250776, year = {2024}, author = {Du, P and Zhang, X and Lian, X and Hölscher, C and Xue, G}, title = {O-GlcNAcylation and Its Roles in Neurodegenerative Diseases.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {97}, number = {3}, pages = {1051-1068}, doi = {10.3233/JAD-230955}, pmid = {38250776}, issn = {1875-8908}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism ; Protein Processing, Post-Translational ; Proteins/metabolism ; *Alzheimer Disease/pathology ; Acetylglucosamine/metabolism ; Disease Progression ; N-Acetylglucosaminyltransferases/metabolism ; }, abstract = {As a non-classical post-translational modification, O-linked β-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation) is widely found in human organ systems, particularly in our brains, and is indispensable for healthy cell biology. With the increasing age of the global population, the incidence of neurodegenerative diseases is increasing, too. The common characteristic of these disorders is the aggregation of abnormal proteins in the brain. Current research has found that O-GlcNAcylation dysregulation is involved in misfolding or aggregation of these abnormal proteins to mediate disease progression, but the specific mechanism has not been defined. This paper reviews recent studies on O-GlcNAcylation's roles in several neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, Machado-Joseph's disease, and giant axonal neuropathy, and shows that O-GlcNAcylation, as glucose metabolism sensor, mediating synaptic function, participating in oxidative stress response and signaling pathway conduction, directly or indirectly regulates characteristic pathological protein toxicity and affects disease progression. The existing results suggest that targeting O-GlcNAcylation will provide new ideas for clinical diagnosis, prevention, and treatment of neurodegenerative diseases.}, }
@article {pmid38249779, year = {2024}, author = {de Carvalho, M and Swash, M}, title = {[Not Available].}, journal = {Clinical neurophysiology practice}, volume = {9}, number = {}, pages = {27-38}, pmid = {38249779}, issn = {2467-981X}, abstract = {Accurate and rapid diagnosis of amyotrophic lateral sclerosis (ALS) is essential in order to provide accurate information for patient and family, to avoid time-consuming investigations and to permit an appropriate management plan. ALS is variable regarding presentation, disease progression, genetic profile and patient reaction to the diagnosis. It is obviously important to exclude treatable conditions but, in most patients, for experienced neurologists the diagnosis is clear-cut, depending on the presence of progressive upper and lower motor neuron signs. Patients with signs of restricted lower motor neuron (LMN) or upper motor neuron (UMN) dysfunction may present diagnostic difficulty, but electromyography (EMG) is often a determinant diagnostic test since it may exclude other disorders. Transcranial magnetic stimulation may aid detection of UMN dysfunction, and brain and spinal cord MRI, ultrasound and blood neurofilament measurements, have begun to have clinical impact, although none are themselves diagnostic tests. Several sets of diagnostic criteria have been proposed in the past; all rely on clinical LMN and UMN signs in different anatomic territories, EMG changes, exclusion of other disorders, and disease progression, in particular evidence of spreading to other anatomic territories. Fasciculations are a characteristic clinical feature and increased importance is now attached to fasciculation potentials detected by EMG, when associated with classical signs of denervation and reinnervation. The Gold Coast diagnostic criteria rely on the presence of UMN and LMN signs in one (or more) anatomic territory, or LMN signs in two (or more) anatomic territories, recognizing the fundamental clinical requirements of disease progression and exclusion of other diseases. Recent studies confirm a high sensitivity without loss of specificity using these Gold Coast criteria. In considering the diagnosis of ALS a critical question for future understanding is whether ALS should be considered a syndrome or a specific clinico-pathologic entity; this can only be addressed in the light of more complete knowledge.}, }
@article {pmid38249738, year = {2023}, author = {Croucher, KM and Fleming, SM}, title = {ATP13A2 (PARK9) and basal ganglia function.}, journal = {Frontiers in neurology}, volume = {14}, number = {}, pages = {1252400}, pmid = {38249738}, issn = {1664-2295}, support = {R01 ES031124/ES/NIEHS NIH HHS/United States ; }, abstract = {ATP13A2 is a lysosomal protein involved in polyamine transport with loss of function mutations associated with multiple neurodegenerative conditions. These include early onset Parkinson's disease, Kufor-Rakeb Syndrome, neuronal ceroid lipofuscinosis, hereditary spastic paraplegia, and amyotrophic lateral sclerosis. While ATP13A2 mutations may result in clinical heterogeneity, the basal ganglia appear to be impacted in the majority of cases. The basal ganglia is particularly vulnerable to environmental exposures such as heavy metals, pesticides, and industrial agents which are also established risk factors for many neurodegenerative conditions. Not surprisingly then, impaired function of ATP13A2 has been linked to heavy metal toxicity including manganese, iron, and zinc. This review discusses the role of ATP13A2 in basal ganglia function and dysfunction, potential common pathological mechanisms in ATP13A2-related disorders, and how gene x environment interactions may contribute to basal ganglia dysfunction.}, }
@article {pmid38249293, year = {2023}, author = {Krishnamurthy, K and Pradhan, RK}, title = {Emerging perspectives of synaptic biomarkers in ALS and FTD.}, journal = {Frontiers in molecular neuroscience}, volume = {16}, number = {}, pages = {1279999}, pmid = {38249293}, issn = {1662-5099}, abstract = {Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) are debilitating neurodegenerative diseases with shared pathological features like transactive response DNA-binding protein of 43 kDa (TDP-43) inclusions and genetic mutations. Both diseases involve synaptic dysfunction, contributing to their clinical features. Synaptic biomarkers, representing proteins associated with synaptic function or structure, offer insights into disease mechanisms, progression, and treatment responses. These biomarkers can detect disease early, track its progression, and evaluate therapeutic efficacy. ALS is characterized by elevated neurofilament light chain (NfL) levels in cerebrospinal fluid (CSF) and blood, correlating with disease progression. TDP-43 is another key ALS biomarker, its mislocalization linked to synaptic dysfunction. In FTD, TDP-43 and tau proteins are studied as biomarkers. Synaptic biomarkers like neuronal pentraxins (NPs), including neuronal pentraxin 2 (NPTX2), and neuronal pentraxin receptor (NPTXR), offer insights into FTD pathology and cognitive decline. Advanced technologies, like machine learning (ML) and artificial intelligence (AI), aid biomarker discovery and drug development. Challenges in this research include technological limitations in detection, variability across patients, and translating findings from animal models. ML/AI can accelerate discovery by analyzing complex data and predicting disease outcomes. Synaptic biomarkers offer early disease detection, personalized treatment strategies, and insights into disease mechanisms. While challenges persist, technological advancements and interdisciplinary efforts promise to revolutionize the understanding and management of ALS and FTD. This review will explore the present comprehension of synaptic biomarkers in ALS and FTD and discuss their significance and emphasize the prospects and obstacles.}, }
@article {pmid38247879, year = {2024}, author = {Shehjar, F and Almarghalani, DA and Mahajan, R and Hasan, SA and Shah, ZA}, title = {The Multifaceted Role of Cofilin in Neurodegeneration and Stroke: Insights into Pathogenesis and Targeting as a Therapy.}, journal = {Cells}, volume = {13}, number = {2}, pages = {}, pmid = {38247879}, issn = {2073-4409}, support = {R01 NS112642/NS/NINDS NIH HHS/United States ; R01NS112642/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Actin Depolymerizing Factors ; alpha-Synuclein ; *Alzheimer Disease ; *Amyotrophic Lateral Sclerosis ; *Parkinson Disease ; *Stroke/metabolism ; }, abstract = {This comprehensive review explores the complex role of cofilin, an actin-binding protein, across various neurodegenerative diseases (Alzheimer's, Parkinson's, schizophrenia, amyotrophic lateral sclerosis (ALS), Huntington's) and stroke. Cofilin is an essential protein in cytoskeletal dynamics, and any dysregulation could lead to potentially serious complications. Cofilin's involvement is underscored by its impact on pathological hallmarks like Aβ plaques and α-synuclein aggregates, triggering synaptic dysfunction, dendritic spine loss, and impaired neuronal plasticity, leading to cognitive decline. In Parkinson's disease, cofilin collaborates with α-synuclein, exacerbating neurotoxicity and impairing mitochondrial and axonal function. ALS and frontotemporal dementia showcase cofilin's association with genetic factors like C9ORF72, affecting actin dynamics and contributing to neurotoxicity. Huntington's disease brings cofilin into focus by impairing microglial migration and influencing synaptic plasticity through AMPA receptor regulation. Alzheimer's, Parkinson's, and schizophrenia exhibit 14-3-3 proteins in cofilin dysregulation as a shared pathological mechanism. In the case of stroke, cofilin takes center stage, mediating neurotoxicity and neuronal cell death. Notably, there is a potential overlap in the pathologies and involvement of cofilin in various diseases. In this context, referencing cofilin dysfunction could provide valuable insights into the common pathologies associated with the aforementioned conditions. Moreover, this review explores promising therapeutic interventions, including cofilin inhibitors and gene therapy, demonstrating efficacy in preclinical models. Challenges in inhibitor development, brain delivery, tissue/cell specificity, and long-term safety are acknowledged, emphasizing the need for precision drug therapy. The call to action involves collaborative research, biomarker identification, and advancing translational efforts. Cofilin emerges as a pivotal player, offering potential as a therapeutic target. However, unraveling its complexities requires concerted multidisciplinary efforts for nuanced and effective interventions across the intricate landscape of neurodegenerative diseases and stroke, presenting a hopeful avenue for improved patient care.}, }
@article {pmid38247869, year = {2024}, author = {Smeele, PH and Cesare, G and Vaccari, T}, title = {ALS' Perfect Storm: C9orf72-Associated Toxic Dipeptide Repeats as Potential Multipotent Disruptors of Protein Homeostasis.}, journal = {Cells}, volume = {13}, number = {2}, pages = {}, pmid = {38247869}, issn = {2073-4409}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *C9orf72 Protein/genetics ; Dipeptides ; *Frontotemporal Dementia/genetics ; *Proteostasis ; }, abstract = {Protein homeostasis is essential for neuron longevity, requiring a balanced regulation between protein synthesis and degradation. The clearance of misfolded and aggregated proteins, mediated by autophagy and the ubiquitin-proteasome systems, maintains protein homeostasis in neurons, which are post-mitotic and thus cannot use cell division to diminish the burden of misfolded proteins. When protein clearance pathways are overwhelmed or otherwise disrupted, the accumulation of misfolded or aggregated proteins can lead to the activation of ER stress and the formation of stress granules, which predominantly attempt to restore the homeostasis by suppressing global protein translation. Alterations in these processes have been widely reported among studies investigating the toxic function of dipeptide repeats (DPRs) produced by G4C2 expansion in the C9orf72 gene of patients with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). In this review, we outline the modalities of DPR-induced disruptions in protein homeostasis observed in a wide range of models of C9orf72-linked ALS/FTD. We also discuss the relative importance of each DPR for toxicity, possible synergies between DPRs, and discuss the possible functional relevance of DPR aggregation to disease pathogenesis. Finally, we highlight the interdependencies of the observed effects and reflect on the importance of feedback and feedforward mechanisms in their contribution to disease progression. A better understanding of DPR-associated disease pathogenesis discussed in this review might shed light on disease vulnerabilities that may be amenable with therapeutic interventions.}, }
@article {pmid38246117, year = {2024}, author = {de Jonge, S and Potters, WV and Verhamme, C}, title = {Artificial intelligence for automatic classification of needle EMG signals: A scoping review.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {159}, number = {}, pages = {41-55}, doi = {10.1016/j.clinph.2023.12.134}, pmid = {38246117}, issn = {1872-8952}, mesh = {Humans ; *Artificial Intelligence ; *Amyotrophic Lateral Sclerosis ; Electromyography ; Needles ; }, abstract = {OBJECTIVE: This scoping review provides an overview of artificial intelligence (AI), including machine and deep learning techniques, in the interpretation of clinical needle electromyography (nEMG) signals.<br><br>METHODS: A comprehensive search of Medline, Embase and Web of Science was conducted to find peer-reviewed journal articles. All papers published after 2010 were included. The methodological quality of the included studies was assessed with CLAIM (checklist for artificial intelligence in medical imaging).<br><br>RESULTS: 51 studies were identified that fulfilled the inclusion criteria. 61% used open-source EMGlab data set to develop models to classify nEMG signal in healthy, amyotrophic lateral sclerosis (ALS) and myopathy (25 subjects). Only two articles developed models to classify signals recorded at rest. Most articles reported high performance accuracies, but many were subject to bias and overtraining.<br><br>CONCLUSIONS: Current AI-models of nEMG signals are not sufficient for clinical implementation. Suggestions for future research include emphasizing the need for an optimal training and validation approach using large datasets of clinical nEMG data from a diverse patient population.<br><br>SIGNIFICANCE: The outcomes of this study and the suggestions made aim to contribute to developing AI-models that can effectively handle signal quality variability and are suitable for daily clinical practice in interpreting nEMG signals.}, }
@article {pmid38245992, year = {2024}, author = {Robertson, DJ and Jeziorczak, PM and Aprahamian, CJ}, title = {Diaphragmatic pacing for respiratory failure in children.}, journal = {Seminars in pediatric surgery}, volume = {33}, number = {1}, pages = {151386}, doi = {10.1016/j.sempedsurg.2024.151386}, pmid = {38245992}, issn = {1532-9453}, mesh = {Child ; Humans ; *Amyotrophic Lateral Sclerosis/complications ; Diaphragm ; Phrenic Nerve/surgery ; *Respiratory Insufficiency/etiology/therapy ; }, abstract = {Diaphragm pacing is a ventilation strategy in respiratory failure. Most of the literature on pacing involves adults with common indications being spinal cord injury and amyotrophic lateral sclerosis (ALS). Previous reports in pediatric patients consist of case reports or small series; most describe direct phrenic nerve stimulation for central hypoventilation syndrome. This differs from adult reports that focus most commonly on spinal cord injuries and the rehabilitative nature of diaphragm pacing. This review describes the current state of diaphragm pacing in pediatric patients. Indications, current available technologies, surgical techniques, advantages, and pitfalls/problems are discussed.}, }
@article {pmid38244235, year = {2024}, author = {Kim, SH and Oh, KW and Noh, MY and Kwon, MS}, title = {Optimal Therapeutic Strategy of Bone Marrow-Originated Autologous Mesenchymal Stromal/Stem Cells for ALS.}, journal = {Stem cells translational medicine}, volume = {13}, number = {4}, pages = {309-316}, pmid = {38244235}, issn = {2157-6580}, support = {NRF//National Research Foundation/ ; MSIT; RS-2023-00265515//Korean government/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy ; Bone Marrow ; Biomarkers ; *Mesenchymal Stem Cells ; *Mesenchymal Stem Cell Transplantation/methods ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is characterized by selective and progressive neurodegenerative changes in motor neural networks. Given the system complexity, including anatomically distributed sites of degeneration from the motor cortex to the spinal cord and chronic pro-inflammatory conditions, a cell-based therapeutic strategy could be an alternative approach to treating ALS. Lessons from previous mesenchymal stromal/stem cell (MSC) trials in ALS realized the importance of 3 aspects in current and future MSC therapy, including the preparation of MSCs, administration routes and methods, and recipient-related factors. This review briefly describes the current status and future prerequisites for an optimal strategy using bone-marrow-originated MSCs to treat ALS. We suggest mandatory factors in the optimized therapeutic strategy focused on advanced therapy medicinal products produced according to Good Manufacturing Practice, an optimal administration method, the selection of proper patients, and the importance of biomarkers.}, }
@article {pmid38243956, year = {2024}, author = {Singh, S and Ahuja, A and Pathak, S}, title = {Potential Role of Oxidative Stress in the Pathophysiology of Neurodegenerative Disorders.}, journal = {Combinatorial chemistry &amp; high throughput screening}, volume = {27}, number = {14}, pages = {2043-2061}, pmid = {38243956}, issn = {1875-5402}, mesh = {Humans ; *Oxidative Stress/drug effects ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Antioxidants/pharmacology ; Reactive Oxygen Species/metabolism ; Animals ; Neuroprotective Agents/pharmacology/chemistry ; }, abstract = {Neurodegeneration causes premature death in the peripheral and central nervous system. Neurodegeneration leads to the accumulation of oxidative stress, inflammatory responses, and the generation of free radicals responsible for nervous disorders like amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, and Huntington's disorders. Therefore, focus must be diverted towards treating and managing these disorders, as it is very challenging. Furthermore, effective therapies are also lacking, so the growing interest of the global market must be inclined towards developing newer therapeutic approaches that can intercept the progression of neurodegeneration. Emerging evidences of research findings suggest that antioxidant therapy has significant potential in modulating disease phenotypes. This makes them promising candidates for further investigation. This review focuses on the role of oxidative stress and reactive oxygen species in the pathological mechanisms of various neurodegenerative diseases, amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, and Huntington's disorders and their neuroprotection. Additionally, it highlights the potential of antioxidant-based therapeutics in mitigating disease severity in humans and improving patient compliance. Ongoing extensive global research further sheds light on exploring new therapeutic targets for a deeper understanding of disease mechanisms in the field of medicine and biology targeting neurogenerative disorders.}, }
@article {pmid38241161, year = {2024}, author = {Klemmensen, MM and Borrowman, SH and Pearce, C and Pyles, B and Chandra, B}, title = {Mitochondrial dysfunction in neurodegenerative disorders.}, journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics}, volume = {21}, number = {1}, pages = {e00292}, pmid = {38241161}, issn = {1878-7479}, mesh = {Humans ; *Neurodegenerative Diseases/therapy/drug therapy ; Mitochondria ; Reactive Oxygen Species/therapeutic use ; *Alzheimer Disease/pathology ; *Mitochondrial Diseases/genetics/therapy ; }, abstract = {Recent advances in understanding the role of mitochondrial dysfunction in neurodegenerative diseases have expanded the opportunities for neurotherapeutics targeting mitochondria to alleviate symptoms and slow disease progression. In this review, we offer a historical account of advances in mitochondrial biology and neurodegenerative disease. Additionally, we summarize current knowledge of the normal physiology of mitochondria and the pathogenesis of mitochondrial dysfunction, the role of mitochondrial dysfunction in neurodegenerative disease, current therapeutics and recent therapeutic advances, as well as future directions for neurotherapeutics targeting mitochondrial function. A focus is placed on reactive oxygen species and their role in the disruption of telomeres and their effects on the epigenome. The effects of mitochondrial dysfunction in the etiology and progression of Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, and Huntington's disease are discussed in depth. Current clinical trials for mitochondria-targeting neurotherapeutics are discussed.}, }
@article {pmid38239833, year = {2023}, author = {Eck, RJ and Stair, JG and Kraemer, BC and Liachko, NF}, title = {Simple models to understand complex disease: 10 years of progress from Caenorhabditis elegans models of amyotrophic lateral sclerosis and frontotemporal lobar degeneration.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1300705}, pmid = {38239833}, issn = {1662-4548}, support = {RF1 AG078374/AG/NIA NIH HHS/United States ; P40 OD010440/OD/NIH HHS/United States ; F31 AG082391/AG/NIA NIH HHS/United States ; I01 BX005762/BX/BLRD VA/United States ; I01 BX004044/BX/BLRD VA/United States ; RF1 AG055474/AG/NIA NIH HHS/United States ; T32 GM136534/GM/NIGMS NIH HHS/United States ; I01 BX002619/BX/BLRD VA/United States ; R01 AG066729/AG/NIA NIH HHS/United States ; IK6 BX006467/BX/BLRD VA/United States ; R01 NS064131/NS/NINDS NIH HHS/United States ; }, abstract = {The nematode Caenorhabditis elegans are a powerful model system to study human disease, with numerous experimental advantages including significant genetic and cellular homology to vertebrate animals, a short lifespan, and tractable behavioral, molecular biology and imaging assays. Beginning with the identification of SOD1 as a genetic cause of amyotrophic lateral sclerosis (ALS), C. elegans have contributed to a deeper understanding of the mechanistic underpinnings of this devastating neurodegenerative disease. More recently this work has expanded to encompass models of other types of ALS and the related disease frontotemporal lobar degeneration (FTLD-TDP), including those characterized by mutation or accumulation of the proteins TDP-43, C9orf72, FUS, HnRNPA2B1, ALS2, DCTN1, CHCHD10, ELP3, TUBA4A, CAV1, UBQLN2, ATXN3, TIA1, KIF5A, VAPB, GRN, and RAB38. In this review we summarize these models and the progress and insights from the last ten years of using C. elegans to study the neurodegenerative diseases ALS and FTLD-TDP.}, }
@article {pmid38226086, year = {2023}, author = {AlMadan, N and AlMajed, A and AlAbbad, M and AlNashmi, F and Aleissa, A}, title = {Dental Management of Patients With Amyotrophic Lateral Sclerosis.}, journal = {Cureus}, volume = {15}, number = {12}, pages = {e50602}, pmid = {38226086}, issn = {2168-8184}, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects the upper and lower motor neurons with upper and lower motor neuron manifestations. It is divided into two variants: a spinal onset and a bulbar onset. The first starts as focal muscle weakness and wasting that spreads with disease progression, while the second phenotype presents with dysarthria, dysphonia, and dysphagia. Moreover, an extra-motor manifestation could be reported with the most commonly reported symptoms being the change in cognition and sleep disorder. Oral manifestations include increased salivation, limited mouth opening, and dysphagia. Patients with ALS have difficulty maintaining oral hygiene, and it is important for the practitioner and the caregiver to take care of this group of population. We herein provide a short review of the disease with a focus on the oral manifestations and dental considerations for management for this group.}, }
@article {pmid38223824, year = {2024}, author = {Lee, MY and Kim, M}, title = {Effects of Red ginseng on neuroinflammation in neurodegenerative diseases.}, journal = {Journal of ginseng research}, volume = {48}, number = {1}, pages = {20-30}, pmid = {38223824}, issn = {1226-8453}, abstract = {Red ginseng (RG) is widely used as a herbal medicine. As the human lifespan has increased, numerous diseases have developed, and RG has also been used to treat various diseases. Neurodegenerative diseases are major problems that modern people face through their lives. Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis are featured by progressive nerve system damage. Recently, neuroinflammation has emerged as a degenerative factor and is an immune response in which cytokines with nerve cells that constitute the nervous system. RG, a natural herbal medicine with fewer side effects than chemically synthesized drugs, is currently in the spotlight. Therefore, we reviewed studies reporting the roles of RG in treating neuroinflammation and neurodegenerative diseases and found that RG might help alleviate neurodegenerative diseases by regulating neuroinflammation.}, }
@article {pmid38218077, year = {2024}, author = {Di Lazzaro, V and Ranieri, F and Bączyk, M and de Carvalho, M and Dileone, M and Dubbioso, R and Fernandes, S and Kozak, G and Motolese, F and Ziemann, U}, title = {Novel approaches to motoneuron disease/ALS treatment using non-invasive brain and spinal stimulation: IFCN handbook chapter.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {158}, number = {}, pages = {114-136}, doi = {10.1016/j.clinph.2023.12.012}, pmid = {38218077}, issn = {1872-8952}, mesh = {Animals ; Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/therapy ; *Transcranial Direct Current Stimulation ; *Motor Neuron Disease/diagnosis/therapy ; Motor Neurons/physiology ; Brain ; Transcranial Magnetic Stimulation/methods ; }, abstract = {Non-invasive brain stimulation techniques have been exploited in motor neuron disease (MND) with multifold objectives: to support the diagnosis, to get insights in the pathophysiology of these disorders and, more recently, to slow down disease progression. In this review, we consider how neuromodulation can now be employed to treat MND, with specific attention to amyotrophic lateral sclerosis (ALS), the most common form with upper motoneuron (UMN) involvement, taking into account electrophysiological abnormalities revealed by human and animal studies that can be targeted by neuromodulation techniques. This review article encompasses repetitive transcranial magnetic stimulation methods (including low-frequency, high-frequency, and pattern stimulation paradigms), transcranial direct current stimulation as well as experimental findings with the newer approach of trans-spinal direct current stimulation. We also survey and discuss the trials that have been performed, and future perspectives.}, }
@article {pmid38216448, year = {2024}, author = {Van Daele, SH and Masrori, P and Van Damme, P and Van Den Bosch, L}, title = {The sense of antisense therapies in ALS.}, journal = {Trends in molecular medicine}, volume = {30}, number = {3}, pages = {252-262}, doi = {10.1016/j.molmed.2023.12.003}, pmid = {38216448}, issn = {1471-499X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/drug therapy ; Oligonucleotides, Antisense/therapeutic use ; RNA Splicing ; }, abstract = {Treatment of patients with amyotrophic lateral sclerosis (ALS) has entered a new era now that encouraging results about antisense oligonucleotides (ASOs) are becoming available and a first ASO therapy for ALS has been approved by the FDA. Moreover, there is hope not only that ALS can be stopped but also that symptoms can be reversed. Until now, degrading ASOs seemed to be successful mostly for rarer forms of familial ALS. However, the first attempts to correct mis-splicing events in sporadic ALS are underway, as well as a clinical trial examining interference with a genetic modifier. In this review, we discuss the current status of using ASOs in ALS and the possibilities and pitfalls of this therapeutic strategy.}, }
@article {pmid38215538, year = {2024}, author = {Garizoain, G and Parra, RC and Aranda, CM and Luna, LH}, title = {Three decades after the publication of the Lamendin method for adult age-at-death estimation: Methodological evolution of the procedure and interpretations.}, journal = {Forensic science international}, volume = {355}, number = {}, pages = {111917}, doi = {10.1016/j.forsciint.2023.111917}, pmid = {38215538}, issn = {1872-6283}, mesh = {Adult ; Humans ; Middle Aged ; Aged ; *Tooth Root ; Reproducibility of Results ; Bayes Theorem ; *Age Determination by Teeth/methods ; }, abstract = {More than three decades have passed since the publication of Lamendin et al.'s proposal in 1992. Over this time, numerous investigations have been conducted to assess the applicability of the technique in different populations with acceptable results in terms of estimation errors. The proposal by Lamendin and colleagues remains relevant today, and has made a significant contribution to adult age-at-death estimation due to its simplicity, repeatability, replicability, and high performance. Indeed, significant progress towards systematizing and strengthening the procedure has been reported in the published literature. One noteworthy advancement is the development of an international database that supports the use of Bayesian statistics for age-at-death estimation. This resource plays a crucial role in standardizing the methodology and improving the reliability for obtaining more reliable results on a global scale. The aim of this study is to investigate the historical evolution of the technique, to assess the accuracy of the results obtained by different analytic procedures, and to explore its impact in forensic applications through a systematic analysis of the specialized literature on this field. The current state of research indicates that this type of methodological research is an ongoing process, far from being completed. Many questions and challenges that require further attention to address effectively these issues remain unanswered, such as the development of non-linear regressions and probabilistic approaches, the deepening of procedures that improve global approximations, and the intensification of research focused on achieving more accurate estimations among individuals over 70 years-old. However, studies generally agree that the Lamendin technique works well for individuals between the ages of 30-60 years. It is still in force today, although the method has been significantly perfected. Despite the degree of research development in this area, further efforts are needed to improve the understanding and performance of these kinds of procedures. This will ultimately lead to an improvement in the accuracy and reliability of forensic investigation results worldwide.}, }
@article {pmid38214845, year = {2024}, author = {Fang, A and Zhao, Y and Yang, P and Zhang, X and Giovannucci, EL}, title = {Vitamin D and human health: evidence from Mendelian randomization studies.}, journal = {European journal of epidemiology}, volume = {39}, number = {5}, pages = {467-490}, pmid = {38214845}, issn = {1573-7284}, support = {81803219//National Natural Science Foundation of China/ ; 2018A030310335//Natural Science Foundation of Guangdong Province/ ; }, mesh = {Humans ; *Mendelian Randomization Analysis ; *Vitamin D/blood/analogs &amp; derivatives ; Vitamin D Deficiency/epidemiology/complications/genetics ; }, abstract = {We summarized the current evidence on vitamin D and major health outcomes from Mendelian randomization (MR) studies. PubMed and Embase were searched for original MR studies on vitamin D in relation to any health outcome from inception to September 1, 2022. Nonlinear MR findings were excluded due to concerns about the validity of the statistical methods used. A meta-analysis was preformed to synthesize study-specific estimates after excluding overlapping samples, where applicable. The methodological quality of the included studies was evaluated according to the STROBE-MR checklist. A total of 133 MR publications were eligible for inclusion in the analyses. The causal association between vitamin D status and 275 individual outcomes was examined. Linear MR analyses showed genetically high 25-hydroxyvitamin D (25(OH)D) concentrations were associated with reduced risk of multiple sclerosis incidence and relapse, non-infectious uveitis and scleritis, psoriasis, femur fracture, leg fracture, amyotrophic lateral sclerosis, anorexia nervosa, delirium, heart failure, ovarian cancer, non-alcoholic fatty liver disease, dyslipidemia, and bacterial pneumonia, but increased risk of Behçet's disease, Graves' disease, kidney stone disease, fracture of radium/ulna, basal cell carcinoma, and overall cataracts. Stratified analyses showed that the inverse association between genetically predisposed 25(OH)D concentrations and multiple sclerosis risk was significant and consistent regardless of the genetic instruments GIs selected. However, the associations with most of the other outcomes were only pronounced when using genetic variants not limited to those in the vitamin D pathway as GIs. The methodological quality of the included MR studies was substantially heterogeneous. Current evidence from linear MR studies strongly supports a causal role of vitamin D in the development of multiple sclerosis. Suggestive support for a number of other health conditions could help prioritize conditions where vitamin D may be beneficial or harmful.}, }
@article {pmid38213309, year = {2024}, author = {Eisen, A and Vucic, S and Mitsumoto, H}, title = {History of ALS and the competing theories on pathogenesis: IFCN handbook chapter.}, journal = {Clinical neurophysiology practice}, volume = {9}, number = {}, pages = {1-12}, pmid = {38213309}, issn = {2467-981X}, abstract = {Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disorder of the human motor system, first described in the 19th Century. The etiology of ALS appears to be multifactorial, with a complex interaction of genetic, epigenetic, and environmental factors underlying the onset of disease. Importantly, there are no known naturally occurring animal models, and transgenic mouse models fail to faithfully reproduce ALS as it manifests in patients. Debate as to the site of onset of ALS remain, with three competing theories proposed, including (i) the dying-forward hypothesis, whereby motor neuron degeneration is mediated by hyperexcitable corticomotoneurons via an anterograde transsynaptic excitotoxic mechanism, (ii) dying-back hypothesis, proposing the ALS begins in the peripheral nervous system with a toxic factor(s) retrogradely transported into the central nervous system and mediating upper motor neuron dysfunction, and (iii) independent hypothesis, suggesting that upper and lower motor neuron degenerated independently. Transcranial magnetic stimulation studies, along with pathological and genetic findings have supported the dying forward hypothesis theory, although the science is yet to be settled. The review provides a historical overview of ALS, discusses phenotypes and likely pathogenic mechanisms.}, }
@article {pmid38203614, year = {2023}, author = {Wu, Y and Chen, Y and Yu, X and Zhang, M and Li, Z}, title = {Towards Understanding Neurodegenerative Diseases: Insights from Caenorhabditis elegans.}, journal = {International journal of molecular sciences}, volume = {25}, number = {1}, pages = {}, pmid = {38203614}, issn = {1422-0067}, support = {2002472//National Health and Medical Research Council/ ; }, mesh = {Animals ; Caenorhabditis elegans/genetics ; *Neurodegenerative Diseases/genetics ; *Alzheimer Disease ; *Huntington Disease ; *Parkinson Disease ; Mammals ; }, abstract = {The elevated occurrence of debilitating neurodegenerative disorders, such as amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), Alzheimer's disease (AD), Parkinson's disease (PD) and Machado-Joseph disease (MJD), demands urgent disease-modifying therapeutics. Owing to the evolutionarily conserved molecular signalling pathways with mammalian species and facile genetic manipulation, the nematode Caenorhabditis elegans (C. elegans) emerges as a powerful and manipulative model system for mechanistic insights into neurodegenerative diseases. Herein, we review several representative C. elegans models established for five common neurodegenerative diseases, which closely simulate disease phenotypes specifically in the gain-of-function aspect. We exemplify applications of high-throughput genetic and drug screenings to illustrate the potential of C. elegans to probe novel therapeutic targets. This review highlights the utility of C. elegans as a comprehensive and versatile platform for the dissection of neurodegenerative diseases at the molecular level.}, }
@article {pmid38203300, year = {2023}, author = {Wei, J and Wong, LC and Boland, S}, title = {Lipids as Emerging Biomarkers in Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {25}, number = {1}, pages = {}, pmid = {38203300}, issn = {1422-0067}, mesh = {Humans ; *Neurodegenerative Diseases/diagnosis ; *Alzheimer Disease/diagnosis ; *Parkinson Disease ; Biomarkers ; Monoglycerides ; }, abstract = {Biomarkers are molecules that can be used to observe changes in an individual's biochemical or medical status and provide information to aid diagnosis or treatment decisions. Dysregulation in lipid metabolism in the brain is a major risk factor for many neurodegenerative disorders, including frontotemporal dementia, Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Thus, there is a growing interest in using lipids as biomarkers in neurodegenerative diseases, with the anionic phospholipid bis(monoacylglycerol)phosphate and (glyco-)sphingolipids being the most promising lipid classes thus far. In this review, we provide a general overview of lipid biology, provide examples of abnormal lysosomal lipid metabolism in neurodegenerative diseases, and discuss how these insights might offer novel and promising opportunities in biomarker development and therapeutic discovery. Finally, we discuss the challenges and opportunities of lipid biomarkers and biomarker panels in diagnosis, prognosis, and/or treatment response in the clinic.}, }
@article {pmid38202163, year = {2023}, author = {Ueha, R and Cotaoco, C and Kondo, K and Yamasoba, T}, title = {Management and Treatment for Dysphagia in Neurodegenerative Disorders.}, journal = {Journal of clinical medicine}, volume = {13}, number = {1}, pages = {}, pmid = {38202163}, issn = {2077-0383}, abstract = {Patients with neurodegenerative disorders (NDDs) often experience functional dysphagia, which may involve dysfunction in a specific phase of swallowing or in the entire process. This review outlines the approach to dysphagia in the setting of NDDs. Distinguishing the etiology of dysphagia can be difficult, and it is important to always look out for signs pointing to NDD as the cause. Thorough diagnostic work-up is essential, and it includes a comprehensive history and physical examination, alongside swallowing function tests, such as fiberoptic endoscopic evaluation of swallowing, videofluoroscopic swallowing study, and high-resolution manometry. Management requires a multidisciplinary approach with a treatment plan tailored to each patient. This involves dietary guidance, swallowing rehabilitation, and surgery in cases in which improvement with rehabilitation is inadequate. Surgery may involve altering certain pharyngolaryngeal structures to facilitate swallowing and reduce the risk of aspiration (swallowing improvement surgery) or separating the airway and digestive tract while sacrificing laryngeal function, with the main goal of preventing aspiration (aspiration prevention surgery). Proper management stems from recognizing the impact of these disorders on swallowing and consistently finding ways to improve the quality of life of patients.}, }
@article {pmid38201932, year = {2023}, author = {Sharma, H and Sharma, N and An, SSA}, title = {Unique Bioactives from Zombie Fungus (Cordyceps) as Promising Multitargeted Neuroprotective Agents.}, journal = {Nutrients}, volume = {16}, number = {1}, pages = {}, pmid = {38201932}, issn = {2072-6643}, support = {RS-2023-00251396 and 2021R1A6A1A03038996//National Research Foundation of Korea/ ; }, mesh = {*Neuroprotective Agents/pharmacology ; *Cordyceps ; *Agaricales ; Neuroprotection ; Adenosine ; }, abstract = {Cordyceps, also known as "zombie fungus", is a non-poisonous mushroom that parasitizes insects for growth and development by manipulating the host system in a way that makes the victim behave like a "zombie". These species produce promising bioactive metabolites, like adenosine, β-glucans, cordycepin, and ergosterol. Cordyceps has been used in traditional medicine due to its immense health benefits, as it boosts stamina, appetite, immunity, longevity, libido, memory, and sleep. Neuronal loss is the typical feature of neurodegenerative diseases (NDs) (Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS)) and neurotrauma. Both these conditions share common pathophysiological features, like oxidative stress, neuroinflammation, and glutamatergic excitotoxicity. Cordyceps bioactives (adenosine, N[6]-(2-hydroxyethyl)-adenosine, ergosta-7, 9 (11), 22-trien-3β-ol, active peptides, and polysaccharides) exert potential antioxidant, anti-inflammatory, and anti-apoptotic activities and display beneficial effects in the management and/or treatment of neurodegenerative disorders in vitro and in vivo. Although a considerable list of compounds is available from Cordyceps, only a few have been evaluated for their neuroprotective potential and still lack information for clinical trials. In this review, the neuroprotective mechanisms and safety profile of Cordyceps extracts/bioactives have been discussed, which might be helpful in the identification of novel potential therapeutic entities in the future.}, }
@article {pmid38201303, year = {2024}, author = {Chen, L and Zhang, S and Liu, S and Gao, S}, title = {Amyotrophic Lateral Sclerosis Mechanism: Insights from the Caenorhabditis elegans Models.}, journal = {Cells}, volume = {13}, number = {1}, pages = {}, pmid = {38201303}, issn = {2073-4409}, support = {32020103007//Major International (Regional) Joint Research Project/ ; 2022YFA1206001//National Key Research and Development Program of China/ ; 32371189, 32300984//the National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/genetics ; Caenorhabditis elegans ; Motor Neurons ; Protein Aggregates ; Signal Transduction ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a debilitating neurodegenerative condition characterized by the progressive degeneration of motor neurons. Despite extensive research in various model animals, the cellular signal mechanisms of ALS remain elusive, impeding the development of efficacious treatments. Among these models, a well-characterized and diminutive organism, Caenorhabditis elegans (C. elegans), has emerged as a potent tool for investigating the molecular and cellular dimensions of ALS pathogenesis. This review summarizes the contributions of C. elegans models to our comprehension of ALS, emphasizing pivotal findings pertaining to genetics, protein aggregation, cellular pathways, and potential therapeutic strategies. We analyze both the merits and constraints of the C. elegans system in the realm of ALS research and point towards future investigations that could bridge the chasm between C. elegans foundational discoveries and clinical applications.}, }
@article {pmid38195712, year = {2024}, author = {Ravichandran, KA and Heneka, MT}, title = {Inflammasomes in neurological disorders - mechanisms and therapeutic potential.}, journal = {Nature reviews. Neurology}, volume = {20}, number = {2}, pages = {67-83}, pmid = {38195712}, issn = {1759-4766}, mesh = {Humans ; Inflammasomes/metabolism ; *Nervous System Diseases/drug therapy ; *Stroke ; *Multiple Sclerosis ; Brain/metabolism ; }, abstract = {Inflammasomes are molecular scaffolds that are activated by damage-associated and pathogen-associated molecular patterns and form a key element of innate immune responses. Consequently, the involvement of inflammasomes in several diseases that are characterized by inflammatory processes, such as multiple sclerosis, is widely appreciated. However, many other neurological conditions, including Alzheimer disease, Parkinson disease, amyotrophic lateral sclerosis, stroke, epilepsy, traumatic brain injury, sepsis-associated encephalopathy and neurological sequelae of COVID-19, all involve persistent inflammation in the brain, and increasing evidence suggests that inflammasome activation contributes to disease progression in these conditions. Understanding the biology and mechanisms of inflammasome activation is, therefore, crucial for the development of inflammasome-targeted therapies for neurological conditions. In this Review, we present the current evidence for and understanding of inflammasome activation in neurological diseases and discuss current and potential interventional strategies that target inflammasome activation to mitigate its pathological consequences.}, }
@article {pmid38194198, year = {2024}, author = {Xu, A and Luo, Y and Tang, Y and Yang, F and Gao, X and Qiao, G and Zhu, X and Zhou, J}, title = {Chitinases as a potential diagnostic and prognostic biomarker for amyotrophic lateral sclerosis: a systematic review and meta-analysis.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {6}, pages = {2489-2503}, pmid = {38194198}, issn = {1590-3478}, support = {2023AFD128//Hubei Provincial Natural Science Foundation and the Innovation and Development of Traditional Chinese Medicine of China/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/cerebrospinal fluid/diagnosis/blood ; Humans ; *Biomarkers/cerebrospinal fluid/blood ; *Chitinases/cerebrospinal fluid/blood ; Prognosis ; Hexosaminidases/cerebrospinal fluid/blood ; Chitinase-3-Like Protein 1/cerebrospinal fluid/blood ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the degeneration of motor neurons, and there is currently a lack of reliable diagnostic biomarkers. This meta-analysis aimed to evaluate CHIT1, CHI3L1, and CHI3L2 levels in the cerebrospinal fluid (CSF) or blood and their diagnostic potential in ALS patients. A systematic, comprehensive search was performed of peer-reviewed English-language articles published before April 1, 2023, in PubMed, Scopus, Embase, Cochrane Library, and Web of Science. After a thorough screening, 13 primary articles were included, and their chitinases-related data were extracted for systematic review and meta-analysis. In ALS patients, the CSF CHIT1 levels were significantly elevated compared to controls with healthy control (HC) (SMD, 1.92; 95% CI, 0.78 - 3.06; P < 0.001). CHIT1 levels were elevated in the CSF of ALS patients compared to other neurodegenerative diseases (ONDS) control (SMD, 0.74; 95% CI, 0.22 - 1.27; P < 0.001) and exhibited an even more substantial increase when compared to ALS-mimicking diseases (AMDS) (SMD, 1.15; 95% CI, 0.35 - 1.94, P < 0.001). Similarly, the CSF CHI3L1 levels were significantly higher in ALS patients compared to HC (SMD, 3.16; 95% CI, 1.26 - 5.06, P < 0.001). CHI3L1 levels were elevated in the CSF of ALS patients compared to ONDS (SMD, 0.75; 95% CI, 0.32 - 1.19; P = 0.017) and exhibited a more pronounced increase when compared to AMDS (SMD, 1.92; 95% CI, 0.41 - 3.42; P < 0.001). The levels of CSF chitinases in the ALS patients showed a significant increase, supporting the role of CSF chitinases as diagnostic biomarkers for ALS.}, }
@article {pmid38189033, year = {2023}, author = {Moreno-Roco, J and Del Valle, L and Jiménez, D and Acosta, I and Castillo, JL and Dharmadasa, T and Kiernan, MC and Matamala, JM}, title = {Diagnostic utility of transcranial magnetic stimulation for neurodegenerative disease: a critical review.}, journal = {Dementia &amp; neuropsychologia}, volume = {17}, number = {}, pages = {e20230048}, pmid = {38189033}, issn = {1980-5764}, abstract = {Neurodegenerative diseases pose significant challenges due to their impact on brain structure, function, and cognition. As life expectancy rises, the prevalence of these disorders is rapidly increasing, resulting in substantial personal, familial, and societal burdens. Efforts have been made to optimize the diagnostic and therapeutic processes, primarily focusing on clinical, cognitive, and imaging characterization. However, the emergence of non-invasive brain stimulation techniques, specifically transcranial magnetic stimulation (TMS), offers unique functional insights and diagnostic potential. TMS allows direct evaluation of brain function, providing valuable information inaccessible through other methods. This review aims to summarize the current and potential diagnostic utility of TMS in investigating neurodegenerative diseases, highlighting its relevance to the field of cognitive neuroscience. The findings presented herein contribute to the growing body of research focused on improving our understanding and management of these debilitating conditions, particularly in regions with limited resources and a pressing need for innovative approaches.}, }
@article {pmid38188146, year = {2024}, author = {Shao, BZ and Jiang, JJ and Zhao, YC and Zheng, XR and Xi, N and Zhao, GR and Huang, XW and Wang, SL}, title = {Neutrophil extracellular traps in central nervous system (CNS) diseases.}, journal = {PeerJ}, volume = {12}, number = {}, pages = {e16465}, pmid = {38188146}, issn = {2167-8359}, mesh = {Humans ; *Extracellular Traps ; *Central Nervous System Diseases ; *Multiple Sclerosis ; Central Nervous System ; Neutrophils ; }, abstract = {Excessive induction of inflammatory and immune responses is widely considered as one of vital factors contributing to the pathogenesis and progression of central nervous system (CNS) diseases. Neutrophils are well-studied members of inflammatory and immune cell family, contributing to the innate and adaptive immunity. Neutrophil-released neutrophil extracellular traps (NETs) play an important role in the regulation of various kinds of diseases, including CNS diseases. In this review, current knowledge on the biological features of NETs will be introduced. In addition, the role of NETs in several popular and well-studied CNS diseases including cerebral stroke, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis (ALS), and neurological cancers will be described and discussed through the reviewing of previous related studies.}, }
@article {pmid38188011, year = {2023}, author = {Ansari, U and Chen, V and Sedighi, R and Syed, B and Muttalib, Z and Ansari, K and Ansari, F and Nadora, D and Razick, D and Lui, F}, title = {Role of the UNC13 family in human diseases: A literature review.}, journal = {AIMS neuroscience}, volume = {10}, number = {4}, pages = {388-400}, pmid = {38188011}, issn = {2373-7972}, abstract = {This literature review explores the pivotal roles of the Uncoordinated-13 (UNC13) protein family, encompassing UNC13A, UNC13B, UNC13C, and UNC13D, in the pathogenesis of various human diseases. These proteins, which are evolutionarily conserved and crucial for synaptic vesicle priming and exocytosis, have been implicated in a range of disorders, spanning from neurodegenerative diseases like amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) to immune-related conditions such as familial hemophagocytic lymphohistiocytosis (FHL). The involvement of UNC13A in neurotransmitter release and synaptic plasticity is linked to ALS and FTD, with genetic variations affecting disease progression. UNC13B, which is closely related to UNC13A, plays a role in autism spectrum disorders (ASD), epilepsy, and schizophrenia. UNC13C is implicated in oral squamous cell carcinoma (OSCC) and hepatocellular carcinoma (HCC), and has a neuroprotective role in Alzheimer's disease (AD). UNC13D has an essential role in immune cell function, making it a key player in FHL. This review highlights the distinct molecular functions of each UNC13 family member and their implications in disease contexts, shedding light on potential therapeutic strategies and avenues for future research. Understanding these proteins' roles offers new insights into the management and treatment of neurological and immunological disorders.}, }
@article {pmid38188002, year = {2023}, author = {Ansari, U and Wen, J and Taguinod, I and Nadora, D and Nadora, D and Lui, F}, title = {Exploring dietary approaches in the prevention and management of Amyotrophic Lateral Sclerosis: A literature review.}, journal = {AIMS neuroscience}, volume = {10}, number = {4}, pages = {376-387}, pmid = {38188002}, issn = {2373-7972}, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal and complex neurodegenerative disease of upper and lower motor neurons of the central nervous system. The pathogenesis of this multifaceted disease is unknown. However, diet has emerged as a modifiable risk factor that has neuroprotective effects towards other neurological disorders such as Alzheimer's, Parkinson's and dementia. Thus, this review aims to explore how diet can potentially influence ALS onset and/or progression. In this review, five popular diets (Mediterranean, Vegan, Carnivore, Paleolithic and Ketogenic) and their distinct macromolecule composition, nutritional profile, biochemical pathways and their potential therapeutic effects for ALS are thoroughly examined. However, the composition of these diets varies, and the data is controversial, with conflicting studies on the effectiveness of nutrient intake of several of these diets. Although these five diets show that a higher intake of foods containing anti-inflammatory and antioxidant compounds have a positive correlation towards reducing the oxidative stress of ALS, further research is needed to directly compare the effects of these diets and the mechanisms leading to ALS and its progression.}, }
@article {pmid38178841, year = {2023}, author = {Zhao, S and Chen, R and Gao, Y and Lu, Y and Bai, X and Zhang, J}, title = {Fundamental roles of the Optineurin gene in the molecular pathology of Amyotrophic Lateral Sclerosis.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1319706}, pmid = {38178841}, issn = {1662-4548}, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive loss of motor neurons (MNs) in the brain and spinal cord. It is caused by multiple factors, including mutations in any one of several specific genes. Optineurin (OPTN) mutation is an essential cause of some familial and sporadic ALS. Besides, as a multifunctional protein, OPTN is highly expressed and conserved in the central nervous system. OPTN exerts its functions by interacting with various proteins, often acting as an adaptor to provide a link between two or more core proteins related to autophagy and inflammation, etc. OPTN mutation mainly results in its function deficiency, which alters these interactions, leading to functional impairment in many processes. Meanwhile, OPTN immunopositive inclusions are also confirmed in the cases of ALS due to C9ORF72, FUS, TARDBP, and SOD1 mutations. Therefore, OPTN gene may play fundamental roles in the molecular pathology of ALS in addition to OPTN mutation. In this review, we summarize the recent advances in the ALS pathology of OPTN defect, such as mitophagy disorder, neuroinflammation, neuronal axonal degeneration, vesicular transport dysfunction, etc., which will provide a reference for research on the pathogenesis and treatment of ALS.}, }
@article {pmid38176936, year = {2023}, author = {Windhorst, U and Dibaj, P}, title = {Plastic Spinal Motor Circuits in Health and Disease.}, journal = {Journal of integrative neuroscience}, volume = {22}, number = {6}, pages = {167}, doi = {10.31083/j.jin2206167}, pmid = {38176936}, issn = {0219-6352}, mesh = {Animals ; Humans ; Spinal Cord ; *Amyotrophic Lateral Sclerosis ; *Muscular Atrophy, Spinal/pathology ; *Spinal Cord Injuries/pathology ; Disease Models, Animal ; *Stroke/pathology ; }, abstract = {In the past, the spinal cord was considered a hard-wired network responsible for spinal reflexes and a conduit for long-range connections. This view has changed dramatically over the past few decades. It is now recognized as a plastic structure that has the potential to adapt to changing environments. While such changes occur under physiological conditions, the most dramatic alterations take place in response to pathological events. Many of the changes that occur following such pathological events are maladaptive, but some appear to help adapt to the new conditions. Although a number of studies have been devoted to elucidating the underlying mechanisms, in humans and animal models, the etiology and pathophysiology of various diseases impacting the spinal cord are still not well understood. In this review, we summarize current understanding and outstanding challenges for a number of diseases, including spinal muscular atrophy (SMA), amyotrophic laterals sclerosis (ALS), and spinal cord injury (SCI), with occasional relations to stroke. In particular, we focus on changes resulting from SCI (and stroke), and various influencing factors such as cause, site and extent of the afflicted damage.}, }
@article {pmid38158151, year = {2024}, author = {Pesta, D}, title = {Mitochondrial density in skeletal and cardiac muscle.}, journal = {Mitochondrion}, volume = {75}, number = {}, pages = {101838}, doi = {10.1016/j.mito.2023.101838}, pmid = {38158151}, issn = {1872-8278}, mesh = {Humans ; *Mitochondria, Muscle/metabolism ; *Muscle, Skeletal/metabolism ; Muscle Fibers, Skeletal ; Mitochondria ; Myocytes, Cardiac ; Citrate (si)-Synthase/metabolism ; }, abstract = {Kubat et al. provide a review on the role Mitochondrial density in skeletal and cardiac muscle of mitochondrial dysfunction in muscle atrophy. They stress mitochondria's pivotal function, citing a 52 % density in skeletal muscle. However, the reference to Park et al.'s work misinterprets their findings. Park et al. report citrate synthase (CS) activity, indicating mitochondrial density as 222 ± 13 μmol.min[-1].mg[-1] for cardiac muscle and 115 ± 2 μmol.min[-1].mg[-1] for skeletal muscle. Thus, the authors should clarify that skeletal muscle density is approximately 52 % of cardiac muscle, not an absolute 52 %. Mitochondrial volume density assessment, predominantly through TEM, establishes cardiomyocytes at 25-30 % and untrained skeletal muscle at 2-6 %, increasing to 11 % in trained athletes. However, this remains modest compared to myofibrils' 75 %-85 % of muscle fiber volume. Although the utility of CS activity is evident, TEM and other novel approaches such as three-dimensional focused ion beam scanning electron microscopy are likely superior for assessing mitochondrial volume density and morphology.}, }
@article {pmid38151890, year = {2024}, author = {Talebi, S and Khodagholi, F and Bahaeddin, Z and Ansari Dezfouli, M and Zeinaddini-Meymand, A and Berchi Kankam, S and Foolad, F and Alijaniha, F and Fayazi Piranghar, F}, title = {Does hazelnut consumption affect brain health and function against neurodegenerative diseases?.}, journal = {Nutritional neuroscience}, volume = {27}, number = {9}, pages = {1008-1024}, doi = {10.1080/1028415X.2023.2296164}, pmid = {38151890}, issn = {1476-8305}, mesh = {*Corylus ; Humans ; *Neurodegenerative Diseases/prevention &amp; control ; *Brain ; Nuts ; Antioxidants/administration &amp; dosage ; Neuroprotective Agents/administration &amp; dosage ; Animals ; Diet ; Nutritive Value ; }, abstract = {INTRODUCTION: A healthy daily diet and consuming certain nutrients, such as polyphenols, vitamins, and unsaturated fatty acids, may help neuronal health maintenance. Polyphenolic chemicals, which have antioxidant and anti-inflammatory properties, are involved in the neuroprotective pathway. Because of their nutritional value, nuts have been shown in recent research to be helpful in neuroprotection.<br><br>OBJECTIVE: Hazelnut is often consumed worldwide in various items, including processed foods, particularly in bakery, chocolate, and confectionery products. This nut is an excellent source of vitamins, amino acids, tocopherols, phytosterols, polyphenols, minerals, and unsaturated fatty acids. Consuming hazelnut may attenuate the risk of neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, and Huntington's disease due to its anti-inflammatory and anti-oxidant qualities.<br><br>RESULTS: Many documents introduce hazelnut as an excellent choice to provide neuroprotection against neurodegenerative disorders and there is some direct proof of its neuroprotective effects.<br><br>DISCUSSION: So hazelnut consumption in daily diet may reduce neurodegenerative disease risk and be advantageous in reducing the imposed costs of dealing with neurodegenerative diseases.}, }
@article {pmid38151482, year = {2024}, author = {Taha, MA and Morren, JA}, title = {The role of artificial intelligence in electrodiagnostic and neuromuscular medicine: Current state and future directions.}, journal = {Muscle &amp; nerve}, volume = {69}, number = {3}, pages = {260-272}, doi = {10.1002/mus.28023}, pmid = {38151482}, issn = {1097-4598}, mesh = {Humans ; *Artificial Intelligence ; Machine Learning ; *Amyotrophic Lateral Sclerosis/diagnostic imaging ; Brain ; Electromyography ; }, abstract = {The rapid advancements in artificial intelligence (AI), including machine learning (ML), and deep learning (DL) have ushered in a new era of technological breakthroughs in healthcare. These technologies are revolutionizing the way we utilize medical data, enabling improved disease classification, more precise diagnoses, better treatment selection, therapeutic monitoring, and highly accurate prognostication. Different ML and DL models have been used to distinguish between electromyography signals in normal individuals and those with amyotrophic lateral sclerosis and myopathy, with accuracy ranging from 67% to 99.5%. DL models have also been successfully applied in neuromuscular ultrasound, with the use of segmentation techniques achieving diagnostic accuracy of at least 90% for nerve entrapment disorders, and 87% for inflammatory myopathies. Other successful AI applications include prediction of treatment response, and prognostication including prediction of intensive care unit admissions for patients with myasthenia gravis. Despite these remarkable strides, significant knowledge, attitude, and practice gaps persist, including within the field of electrodiagnostic and neuromuscular medicine. In this narrative review, we highlight the fundamental principles of AI and draw parallels with the intricacies of human brain networks. Specifically, we explore the immense potential that AI holds for applications in electrodiagnostic studies, neuromuscular ultrasound, and other aspects of neuromuscular medicine. While there are exciting possibilities for the future, it is essential to acknowledge and understand the limitations of AI and take proactive steps to mitigate these challenges. This collective endeavor holds immense potential for the advancement of healthcare through the strategic and responsible integration of AI technologies.}, }
@article {pmid38147116, year = {2024}, author = {Louro, H and Vettorazzi, A and López de Cerain, A and Spyropoulou, A and Solhaug, A and Straumfors, A and Behr, AC and Mertens, B and Žegura, B and Fæste, CK and Ndiaye, D and Spilioti, E and Varga, E and Dubreil, E and Borsos, E and Crudo, F and Eriksen, GS and Snapkow, I and Henri, J and Sanders, J and Machera, K and Gaté, L and Le Hegarat, L and Novak, M and Smith, NM and Krapf, S and Hager, S and Fessard, V and Kohl, Y and Silva, MJ and Dirven, H and Dietrich, J and Marko, D}, title = {Hazard characterization of Alternaria toxins to identify data gaps and improve risk assessment for human health.}, journal = {Archives of toxicology}, volume = {98}, number = {2}, pages = {425-469}, pmid = {38147116}, issn = {1432-0738}, support = {101057014//European Commission/ ; }, mesh = {Humans ; *Perylene ; Alternaria/metabolism ; *Mycotoxins/toxicity/analysis ; Mutagens/toxicity/metabolism ; Lactones/toxicity/metabolism ; Risk Assessment ; Food Contamination/analysis ; }, abstract = {Fungi of the genus Alternaria are ubiquitous plant pathogens and saprophytes which are able to grow under varying temperature and moisture conditions as well as on a large range of substrates. A spectrum of structurally diverse secondary metabolites with toxic potential has been identified, but occurrence and relative proportion of the different metabolites in complex mixtures depend on strain, substrate, and growth conditions. This review compiles the available knowledge on hazard identification and characterization of Alternaria toxins. Alternariol (AOH), its monomethylether AME and the perylene quinones altertoxin I (ATX-I), ATX-II, ATX-III, alterperylenol (ALP), and stemphyltoxin III (STTX-III) showed in vitro genotoxic and mutagenic properties. Of all identified Alternaria toxins, the epoxide-bearing analogs ATX-II, ATX-III, and STTX-III show the highest cytotoxic, genotoxic, and mutagenic potential in vitro. Under hormone-sensitive conditions, AOH and AME act as moderate xenoestrogens, but in silico modeling predicts further Alternaria toxins as potential estrogenic factors. Recent studies indicate also an immunosuppressive role of AOH and ATX-II; however, no data are available for the majority of Alternaria toxins. Overall, hazard characterization of Alternaria toxins focused, so far, primarily on the commercially available dibenzo-α-pyrones AOH and AME and tenuazonic acid (TeA). Limited data sets are available for altersetin (ALS), altenuene (ALT), and tentoxin (TEN). The occurrence and toxicological relevance of perylene quinone-based Alternaria toxins still remain to be fully elucidated. We identified data gaps on hazard identification and characterization crucial to improve risk assessment of Alternaria mycotoxins for consumers and occupationally exposed workers.}, }
@article {pmid38136659, year = {2023}, author = {Cilleros-Holgado, P and Gómez-Fernández, D and Piñero-Pérez, R and Romero-Domínguez, JM and Reche-López, D and López-Cabrera, A and Álvarez-Córdoba, M and Munuera-Cabeza, M and Talaverón-Rey, M and Suárez-Carrillo, A and Romero-González, A and Sánchez-Alcázar, JA}, title = {Mitochondrial Quality Control via Mitochondrial Unfolded Protein Response (mtUPR) in Ageing and Neurodegenerative Diseases.}, journal = {Biomolecules}, volume = {13}, number = {12}, pages = {}, pmid = {38136659}, issn = {2218-273X}, support = {FIS PI19/00377 and PI22/00142 grants//Instituto de Salud Carlos III/ ; CTS-5725, PY18-850, and UPO-FEDER 2018 (UPO-1380614)//Regional Government of Andalusia/ ; }, mesh = {Animals ; *Neurodegenerative Diseases/metabolism ; Mitochondria/metabolism ; *Mitochondrial Diseases ; Aging ; Unfolded Protein Response ; }, abstract = {Mitochondria play a key role in cellular functions, including energy production and oxidative stress regulation. For this reason, maintaining mitochondrial homeostasis and proteostasis (homeostasis of the proteome) is essential for cellular health. Therefore, there are different mitochondrial quality control mechanisms, such as mitochondrial biogenesis, mitochondrial dynamics, mitochondrial-derived vesicles (MDVs), mitophagy, or mitochondrial unfolded protein response (mtUPR). The last item is a stress response that occurs when stress is present within mitochondria and, especially, when the accumulation of unfolded and misfolded proteins in the mitochondrial matrix surpasses the folding capacity of the mitochondrion. In response to this, molecular chaperones and proteases as well as the mitochondrial antioxidant system are activated to restore mitochondrial proteostasis and cellular function. In disease contexts, mtUPR modulation holds therapeutic potential by mitigating mitochondrial dysfunction. In particular, in the case of neurodegenerative diseases, such as primary mitochondrial diseases, Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Amyotrophic Lateral Sclerosis (ALS), or Friedreich's Ataxia (FA), there is a wealth of evidence demonstrating that the modulation of mtUPR helps to reduce neurodegeneration and its associated symptoms in various cellular and animal models. These findings underscore mtUPR's role as a promising therapeutic target in combating these devastating disorders.}, }
@article {pmid38132330, year = {2023}, author = {Spisni, E and Valerii, MC and Massimino, ML}, title = {Essential Oil Molecules Can Break the Loop of Oxidative Stress in Neurodegenerative Diseases.}, journal = {Biology}, volume = {12}, number = {12}, pages = {}, pmid = {38132330}, issn = {2079-7737}, support = {0000//Xeda international (1397 Route Nationale 7, Zac la Crau, 13670 Saint Andiol, France)./ ; }, abstract = {Essential oils (EOs) are mixtures of volatile compounds, extracted from aromatic plants, with multiple activities including antioxidant and anti-inflammatory ones. EOs are complex mixtures easy to find on the market and with low costs. In this mini narrative review, we have collected the results of in vitro and in vivo studies, which tested these EOs on validated models of neurodegeneration and in particular of the two main neurodegenerative diseases (NDs) that afflict humans: Alzheimer's and Parkinson's. Since EO compositions can vary greatly, depending on the environmental conditions, plant cultivar, and extraction methods, we focused our attention to studies involving single EO molecules, and in particular those that have demonstrated the ability to cross the blood-brain barrier. These single EO molecules, alone or in defined mixtures, could be interesting new therapies to prevent or slow down oxidative and inflammatory processes which are common mechanisms that contribute to neuronal death in all NDs.}, }
@article {pmid38131803, year = {2023}, author = {Miteva, D and Vasilev, GV and Velikova, T}, title = {Role of Specific Autoantibodies in Neurodegenerative Diseases: Pathogenic Antibodies or Promising Biomarkers for Diagnosis.}, journal = {Antibodies (Basel, Switzerland)}, volume = {12}, number = {4}, pages = {}, pmid = {38131803}, issn = {2073-4468}, support = {BG-RRP-2.004-0008//the European Union-NextGenerationEU, through the National Recovery and Resilience Plan of the Republic of Bulgaria/ ; }, abstract = {Neurodegenerative diseases (NDDs) affect millions of people worldwide. They develop due to the pathological accumulation and aggregation of various misfolded proteins, axonal and synaptic loss and dysfunction, inflammation, cytoskeletal abnormalities, defects in DNA and RNA, and neuronal death. This leads to the activation of immune responses and the release of the antibodies against them. Recently, it has become clear that autoantibodies (Aabs) can contribute to demyelination, axonal loss, and brain and cognitive dysfunction. This has significantly changed the understanding of the participation of humoral autoimmunity in neurodegenerative disorders. It is crucial to understand how neuroinflammation is involved in neurodegeneration, to aid in improving the diagnostic and therapeutic value of Aabs in the future. This review aims to provide data on the immune system's role in NDDs, the pathogenic role of some specific Aabs against molecules associated with the most common NDDs, and their potential role as biomarkers for monitoring and diagnosing NDDs. It is suggested that the autoimmune aspects of NDDs will facilitate early diagnosis and help to elucidate previously unknown aspects of the pathobiology of these diseases.}, }
@article {pmid38116771, year = {2023}, author = {Máčová, L and Kancheva, R and Bičíková, M}, title = {Molecular Regulation of the CNS by Vitamin D.}, journal = {Physiological research}, volume = {72}, number = {S4}, pages = {S339-S356}, doi = {10.33549/physiolres.935248}, pmid = {38116771}, issn = {1802-9973}, mesh = {Humans ; Vitamin D/therapeutic use ; Vitamins ; *Alzheimer Disease ; *Nervous System Diseases ; *Parkinson Disease ; }, abstract = {Vitamin D is a lipid-soluble vitamin that can be found in some foods. It is also produced endogenously (in the presence of ultraviolet light), transported through the blood to the targets organs and this is the reason to consider vitamin D as a hormone. It is known that vitamin D has genomic and non-genomic effects. This review is focused mainly on the vitamin D receptors, the importance of vitamin D as a neuromodulator, the role of vitamin D in the pathophysiology of devastating neurological disorders such as Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease and the benefit of vitamin D and its derivates in alleviating these disorders.}, }
@article {pmid38112345, year = {2024}, author = {Battaglini, M and Marino, A and Montorsi, M and Carmignani, A and Ceccarelli, MC and Ciofani, G}, title = {Nanomaterials as Microglia Modulators in the Treatment of Central Nervous System Disorders.}, journal = {Advanced healthcare materials}, volume = {13}, number = {12}, pages = {e2304180}, doi = {10.1002/adhm.202304180}, pmid = {38112345}, issn = {2192-2659}, mesh = {*Microglia/drug effects/metabolism ; Humans ; *Nanostructures/chemistry ; Animals ; *Central Nervous System Diseases/drug therapy/metabolism ; Neurodegenerative Diseases/drug therapy/metabolism ; }, abstract = {Microglia play a pivotal role in the central nervous system (CNS) homeostasis, acting as housekeepers and defenders of the surrounding environment. These cells can elicit their functions by shifting into two main phenotypes: pro-inflammatory classical phenotype, M1, and anti-inflammatory alternative phenotype, M2. Despite their pivotal role in CNS homeostasis, microglia phenotypes can influence the development and progression of several CNS disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, ischemic stroke, traumatic brain injuries, and even brain cancer. It is thus clear that the possibility of modulating microglia activation has gained attention as a therapeutic tool against many CNS pathologies. Nanomaterials are an unprecedented tool for manipulating microglia responses, in particular, to specifically target microglia and elicit an in situ immunomodulation activity. This review focuses the discussion on two main aspects: analyzing the possibility of using nanomaterials to stimulate a pro-inflammatory response of microglia against brain cancer and introducing nanostructures able to foster an anti-inflammatory response for treating neurodegenerative disorders. The final aim is to stimulate the analysis of the development of new microglia nano-immunomodulators, paving the way for innovative and effective therapeutic approaches for the treatment of CNS disorders.}, }
@article {pmid38110839, year = {2024}, author = {Benatar, M and Ostrow, LW and Lewcock, JW and Bennett, F and Shefner, J and Bowser, R and Larkin, P and Bruijn, L and Wuu, J}, title = {Biomarker Qualification for Neurofilament Light Chain in Amyotrophic Lateral Sclerosis: Theory and Practice.}, journal = {Annals of neurology}, volume = {95}, number = {2}, pages = {211-216}, pmid = {38110839}, issn = {1531-8249}, support = {U01 NS107027/NS/NINDS NIH HHS/United States ; U01 NS107027/NH/NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/drug therapy ; Superoxide Dismutase-1 ; Intermediate Filaments ; Biomarkers ; Prognosis ; Neurofilament Proteins ; }, abstract = {OBJECTIVE: To explore whether the utility of neurofilament light chain (NfL), as a biomarker to aid amyotrophic lateral sclerosis (ALS) therapy development, would be enhanced by obtaining formal qualification from the US Food and Drug Administration for a defined context-of-use.<br><br>METHODS: Consensus discussion among academic, industry, and patient advocacy group representatives.<br><br>RESULTS: A wealth of scientific evidence supports the use of NfL as a prognostic, response, and potential safety biomarker in the broad ALS population, and as a risk/susceptibility biomarker among the subset of SOD1 pathogenic variant carriers. Although NfL has not yet been formally qualified for any of these contexts-of-use, the US Food and Drug Administration has provided accelerated approval for an SOD1-lowering antisense oligonucleotide, based partially on the recognition that a reduction in NfL is reasonably likely to predict a clinical benefit.<br><br>INTERPRETATION: The increasing incorporation of NfL into ALS therapy development plans provides evidence that its utility-as a prognostic, response, risk/susceptibility, and/or safety biomarker-is already widely accepted by the community. The willingness of the US Food and Drug Administration to base regulatory decisions on rigorous peer-reviewed data-absent formal qualification, leads us to conclude that formal qualification, despite some benefits, is not essential for ongoing and future use of NfL as a tool to aid ALS therapy development. Although the balance of considerations for and against seeking NfL biomarker qualification will undoubtedly vary across different diseases and contexts-of-use, the robustness of the published data and careful deliberations of the ALS community may offer valuable insights for other disease communities grappling with the same issues. ANN NEUROL 2024;95:211-216.}, }
@article {pmid38108952, year = {2024}, author = {Xiao, X and Rui, Y and Jin, Y and Chen, M}, title = {Relationship of Sleep Disorder with Neurodegenerative and Psychiatric Diseases: An Updated Review.}, journal = {Neurochemical research}, volume = {49}, number = {3}, pages = {568-582}, pmid = {38108952}, issn = {1573-6903}, support = {82371541//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/metabolism ; *Alzheimer Disease/metabolism ; Brain/metabolism ; *Huntington Disease/metabolism ; *Sleep Wake Disorders/metabolism ; }, abstract = {Sleep disorders affect many people worldwide and can accompany neurodegenerative and psychiatric diseases. Sleep may be altered before the clinical manifestations of some of these diseases appear. Moreover, some sleep disorders affect the physiological organization and function of the brain by influencing gene expression, accelerating the accumulation of abnormal proteins, interfering with the clearance of abnormal proteins, or altering the levels of related hormones and neurotransmitters, which can cause or may be associated with the development of neurodegenerative and psychiatric diseases. However, the detailed mechanisms of these effects are unclear. This review mainly focuses on the relationship between and mechanisms of action of sleep in Alzheimer's disease, depression, and anxiety, as well as the relationships between sleep and Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. This summary of current research hotspots may provide researchers with better clues and ideas to develop treatment solutions for neurodegenerative and psychiatric diseases associated with sleep disorders.}, }
@article {pmid38105925, year = {2023}, author = {Mimic, S and Aru, B and Pehlivanoğlu, C and Sleiman, H and Andjus, PR and Yanıkkaya Demirel, G}, title = {Immunology of amyotrophic lateral sclerosis - role of the innate and adaptive immunity.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1277399}, pmid = {38105925}, issn = {1662-4548}, abstract = {This review aims to summarize the latest evidence about the role of innate and adaptive immunity in Amyotrophic Lateral Sclerosis (ALS). ALS is a devastating neurodegenerative disease affecting upper and lower motor neurons, which involves essential cells of the immune system that play a basic role in innate or adaptive immunity, that can be neurotoxic or neuroprotective for neurons. However, distinguishing between the sole neurotoxic or neuroprotective function of certain cells such as astrocytes can be challenging due to intricate nature of these cells, the complexity of the microenvironment and the contextual factors. In this review, in regard to innate immunity we focus on the involvement of monocytes/macrophages, microglia, the complement, NK cells, neutrophils, mast cells, and astrocytes, while regarding adaptive immunity, in addition to humoral immunity the most important features and roles of T and B cells are highlighted, specifically different subsets of CD4[+] as well as CD8[+] T cells. The role of autoantibodies and cytokines is also discussed in distinct sections of this review.}, }
@article {pmid38105307, year = {2024}, author = {Hamad, AA and Amer, BE and Hawas, Y and Mabrouk, MA and Meshref, M}, title = {Masitinib as a neuroprotective agent: a scoping review of preclinical and clinical evidence.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {5}, pages = {1861-1873}, pmid = {38105307}, issn = {1590-3478}, mesh = {Humans ; *Neuroprotective Agents/pharmacology/therapeutic use ; Animals ; *Benzamides/pharmacology/therapeutic use ; *Thiazoles/pharmacology/therapeutic use ; *Piperidines/pharmacology/therapeutic use ; *Pyridines/pharmacology/therapeutic use ; Protein Kinase Inhibitors/pharmacology ; }, abstract = {OBJECTIVES: Masitinib, originally developed as a tyrosine kinase inhibitor for cancer treatment, has shown potential neuroprotective effects in various neurological disorders by modulating key pathways implicated in neurodegeneration. This scoping review aimed to summarize the current evidence of masitinib's neuroprotective activities from preclinical to clinical studies.<br><br>METHODS: This scoping review was conducted following the guidelines described by Arksey and O'Malley and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The inclusion criteria covered all original studies reporting on the neuroprotective effects of masitinib, including clinical studies, animal studies, and in vitro studies.<br><br>RESULTS: A total of 16 studies met the inclusion criteria and were included in the review. These comprised five randomized controlled trials (RCTs), one post-hoc analysis study, one case report, and nine animal studies. The RCTs focused on Alzheimer's disease (two studies), multiple sclerosis (two studies), and amyotrophic lateral sclerosis (one study). Across all included studies, masitinib consistently demonstrated neuroprotective properties. However, the majority of RCTs reported concerns regarding the safety profile of masitinib. Preclinical studies revealed the neuroprotective mechanisms of masitinib, which include inhibition of certain kinases interfering with cell proliferation and survival, reduction of neuroinflammation, and exhibition of antioxidant activity.<br><br>CONCLUSION: The current evidence suggests a promising therapeutic benefit of masitinib in neurodegenerative diseases. However, further research is necessary to validate and expand upon these findings, particularly regarding the precise mechanisms through which masitinib exerts its therapeutic effects. Future studies should also focus on addressing the safety concerns associated with masitinib use.}, }
@article {pmid38105306, year = {2024}, author = {Katerelos, A and Alexopoulos, P and Economou, P and Polychronopoulos, P and Chroni, E}, title = {Cognitive function in amyotrophic lateral sclerosis: a cross-sectional and prospective pragmatic clinical study with review of the literature.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {5}, pages = {2075-2085}, pmid = {38105306}, issn = {1590-3478}, mesh = {Adult ; Humans ; *Amyotrophic Lateral Sclerosis/complications/diagnosis ; *Cognition Disorders/etiology/complications ; Neuropsychological Tests ; Prospective Studies ; Quality of Life ; Cross-Sectional Studies ; Cognition/physiology ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) can present with either bulbar or spinal symptoms, and in some cases, both types of symptoms may be present. In addition, cognitive impairment has been observed in ALS. The study aimed to evaluate the frontal and general cognitive performance in ALS not only cross-sectionally but also longitudinally.<br><br>METHODS AND MATERIALS: The Frontal Assessment Battery (FAB) and the Montreal Cognitive Assessment (MoCA) were employed to assess cognitive function in 52 adults with ALS and 52 cognitively healthy individuals. The statistical analyses encompassed the Pearson Chi square test, the Skillings-Mack test, the Spearman's rank correlation coefficient, and the Proportional Odds Logistic Regression Model (POLR).<br><br>RESULTS: Cross-sectionally, lower cognitive performance was associated with ALS diagnosis, older age, and motor functional decline. The cognitive impairment of individuals with bulbar and spinal-bulbar symptoms showed faster deterioration compared to those with spinal symptoms. The spinal subgroup consistently performed worst in delayed recall and attention, while the spinal-bulbar and bulbar subgroups exhibited inferior scores in delayed recall, attention, visuospatial skills, orientation, and verbal fluency.<br><br>CONCLUSION: The incorporation of cognitive screening in the diagnostic workup of ALS may be beneficial, as early detection can enhance symptom management and improve the quality of life for both individuals with ALS and their care partners.}, }
@article {pmid38103074, year = {2023}, author = {Villavicencio-Tejo, F and Olesen, MA and Navarro, L and Calisto, N and Iribarren, C and García, K and Corsini, G and Quintanilla, RA}, title = {Gut-Brain Axis Deregulation and Its Possible Contribution to Neurodegenerative Disorders.}, journal = {Neurotoxicity research}, volume = {42}, number = {1}, pages = {4}, pmid = {38103074}, issn = {1476-3524}, support = {1200178//Agencia Nacional de Investigaci&#xf3;n y Desarrollo/ ; }, mesh = {Animals ; Humans ; Brain-Gut Axis ; *Amyotrophic Lateral Sclerosis ; *Gastrointestinal Microbiome/physiology ; *Neurodegenerative Diseases/pathology ; Central Nervous System ; *Parkinson Disease/pathology ; *Huntington Disease/pathology ; *Alzheimer Disease ; }, abstract = {The gut-brain axis is an essential communication pathway between the central nervous system (CNS) and the gastrointestinal tract. The human microbiota is composed of a diverse and abundant microbial community that compasses more than 100 trillion microorganisms that participate in relevant physiological functions such as host nutrient metabolism, structural integrity, maintenance of the gut mucosal barrier, and immunomodulation. Recent evidence in animal models has been instrumental in demonstrating the possible role of the microbiota in neurodevelopment, neuroinflammation, and behavior. Furthermore, clinical studies suggested that adverse changes in the microbiota can be considered a susceptibility factor for neurological disorders (NDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). In this review, we will discuss evidence describing the role of gut microbes in health and disease as a relevant risk factor in the pathogenesis of neurodegenerative disorders, including AD, PD, HD, and ALS.}, }
@article {pmid38102945, year = {2024}, author = {Bhamra, IB and Gallagher, JE and Patel, R}, title = {Telehealth technologies in care homes: a gap for dentistry?.}, journal = {Journal of public health (Oxford, England)}, volume = {46}, number = {1}, pages = {e106-e135}, pmid = {38102945}, issn = {1741-3850}, mesh = {Humans ; *Telemedicine ; *Remote Consultation ; Delivery of Health Care ; Health Facilities ; Dentistry ; }, abstract = {BACKGROUND: Telehealth technologies are playing an increasing role in healthcare. This study aimed to review the literature relating to the use of telehealth technologies in care homes with a focus on teledentistry.<br><br>METHODS: Khangura et&#xa0;al.'s (Evidence summaries: the evolution of a rapid review approach. Syst Rev 2012;1:10) rapid review method included an electronic database search on Embase, PubMed, Web of Science and OpenGrey. Out of 1525 papers, 1108 titles and abstracts were screened, and 75 full texts assessed for eligibility. Risk of bias was assessed using the Mixed Methods Assessment Tool 2018.<br><br>RESULTS: Forty-seven papers (40 studies) from 10 countries, published 1997-2021, were included in the review, four studies related to teledentistry. Whilst some preferred in-person consultations, perceived benefits by stakeholders included reduced hospitalization rates (n&#xa0;=&#xa0;14), cost-savings (n&#xa0;=&#xa0;8) and high diagnostic accuracy (n&#xa0;=&#xa0;7). Studies investigating teledentistry using intra-oral cameras reported that teleconsultations were feasible with potentially high diagnostic accuracy (n&#xa0;=&#xa0;2), cost-savings (n&#xa0;=&#xa0;1) and patient acceptability (n&#xa0;=&#xa0;1).<br><br>CONCLUSION: There is limited published research on teledentistry, but wider telehealth research is applicable to teledentistry, with findings suggesting that telehealth technologies play a role in care homes consultations that are acceptable, cost-saving and with potential diagnostic accuracy. Further research is needed on the mode, utility and acceptability of teledentistry in care homes.}, }
@article {pmid38102715, year = {2023}, author = {Stringer, RN and Weiss, N}, title = {Pathophysiology of ion channels in amyotrophic lateral sclerosis.}, journal = {Molecular brain}, volume = {16}, number = {1}, pages = {82}, pmid = {38102715}, issn = {1756-6606}, support = {#22-23242S//Grantov&#xe1; Agentura &#x10c;esk&#xe9; Republiky/ ; VEGA #2/0073/22//Agent&#xfa;ra Ministerstva &#x160;kolstva, Vedy, V&#xfd;skumu a &#x160;portu SR/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; Motor Neurons ; Ion Channels ; Muscle Weakness ; }, abstract = {Amyotrophic lateral sclerosis (ALS) stands as the most prevalent and severe form of motor neuron disease, affecting an estimated 2 in 100,000 individuals worldwide. It is characterized by the progressive loss of cortical, brainstem, and spinal motor neurons, ultimately resulting in muscle weakness and death. Although the etiology of ALS remains poorly understood in most cases, the remodelling of ion channels and alteration in neuronal excitability represent a hallmark of the disease, manifesting not only during the symptomatic period but also in the early pre-symptomatic stages. In this review, we delve into these alterations observed in ALS patients and preclinical disease models, and explore their consequences on neuronal activities. Furthermore, we discuss the potential of ion channels as therapeutic targets in the context of ALS.}, }
@article {pmid38101818, year = {2024}, author = {Ryan, L and Rubinsztein, DC}, title = {The autophagy of stress granules.}, journal = {FEBS letters}, volume = {598}, number = {1}, pages = {59-72}, doi = {10.1002/1873-3468.14787}, pmid = {38101818}, issn = {1873-3468}, support = {//Raymond and Beverly Sackler Fund/ ; NIHR203312//NIHR Cambridge Biomedical Research Centre/ ; //UK Dementia Research Institute/ ; }, mesh = {Humans ; *Stress Granules ; Proteins ; Autophagy ; *Amyotrophic Lateral Sclerosis/genetics ; }, abstract = {Our understanding of stress granule (SG) biology has deepened considerably in recent years, and with this, increased understanding of links has been made between SGs and numerous neurodegenerative diseases. One of the proposed mechanisms by which SGs and any associated protein aggregates may become pathological is based upon defects in their autophagic clearance, and so the precise processes governing the degradation of SGs are important to understand. Mutations and disease-associated variants implicated in amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease and frontotemporal lobar dementia compromise autophagy, whilst autophagy-inhibiting drugs or knockdown of essential autophagy proteins result in the persistence of SGs. In this review, we will consider the current knowledge regarding the autophagy of SG.}, }
@article {pmid38100267, year = {2024}, author = {Qi, S and Peng, Y and Wang, G and Zhang, X and Liu, M and He, L}, title = {A tale of dual functions of SERF family proteins in regulating amyloid formation.}, journal = {Chembiochem : a European journal of chemical biology}, volume = {25}, number = {5}, pages = {e202300727}, doi = {10.1002/cbic.202300727}, pmid = {38100267}, issn = {1439-7633}, support = {2018YFE0202301//National Key R&amp;D Program of China/ ; 2018YFE0202300//National Key R&amp;D Program of China/ ; 22174151//National Natural Sciences Foundation of China/ ; 21991080//National Natural Sciences Foundation of China/ ; XDB0540000//Strategic Priority Research Program of the Chinese Academy of Sciences/ ; 2023AFA041//Hubei Provincial Natural Science Foundation of China/ ; }, mesh = {Animals ; Caenorhabditis elegans ; *Neurodegenerative Diseases ; Amyloidogenic Proteins ; Amyloid beta-Peptides ; *Alzheimer Disease ; *Caenorhabditis elegans Proteins ; }, abstract = {The abnormal aggregation of proteins is a significant pathological hallmark of diseases, such as the amyloid formation associated with fused in sarcoma protein (FUS) in frontotemporal lobar degeneration and amyotrophic lateral sclerosis diseases. Understanding which cellular components and how these components regulate the process of abnormal protein aggregation in living organisms is crucial for the prevention and treatment of neurodegenerative diseases. MOAG-4/SERF is a conserved family of proteins with rich positive charged residues, which was initially identified as an enhancer for the formation of amyloids in C. elegans. Knocking out SERF impedes the amyloid formation of various proteins, including α-synuclein and β-amyloid, which are linked to Parkinson's and Alzheimer's diseases, respectively. However, recent studies revealed SERF exhibited dual functions, as it could both promote and inhibit the fibril formation of the neurodegenerative disease-related amyloidogenic proteins. The connection between functions and structure basis of SERF in regulating the amyloid formation is still unclear. This review will outline the hallmark proteins in neurodegenerative diseases, summarize the contradictory role of the SERF protein family in promoting and inhibiting the aggregation of neurodegenerative proteins, and finally explore the potential structural basis and functional selectivity of the SERF protein.}, }
@article {pmid38100009, year = {2024}, author = {Zhao, DW and Robinson, SG and Pozzar, R and Leiter, R and Walsh, C and Siemens, I and Lovrics, E and Cellarius, V and Mahtani, R and Jia, Z}, title = {The Evolving Roles and Expectations of Inpatient Palliative Care Through COVID-19: a Systematic Review and Meta-synthesis.}, journal = {Journal of general internal medicine}, volume = {39}, number = {4}, pages = {661-682}, pmid = {38100009}, issn = {1525-1497}, mesh = {Humans ; *COVID-19/therapy/epidemiology/psychology ; *Palliative Care/methods ; Inpatients/psychology ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Palliative care performed a central role in responding to the systemic suffering incurred by the COVID-19 pandemic. Yet, few studies have elucidated the inpatient palliative care specialists' experiences and perceptions.<br><br>OBJECTIVE: Systematically review and synthesize the evolving roles and expectations of inpatient palliative care specialists in response to COVID-19.<br><br>DESIGN: A systematic review and meta-synthesis informed by Thomas and Harden's framework and Pozzar et al.'s approach was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines.<br><br>DATA SOURCES: MEDLINE, EMBASE, CINAHL, and PubMed were systematically searched for articles published between December 2019 and March 2023. We included all peer-reviewed qualitative and mixed-method literature studying the roles and expectations of inpatient palliative care specialists. A mixed-method appraisal tool was used for quality assessment.<br><br>RESULTS: Of 3869 unique articles, 52 were included. Studies represented North American (n = 23), European (n = 16), South American (n = 4), Oceanic (n = 2), Asian (n = 2), West African (n = 1), Middle Eastern (n = 1), and inter-continental settings (n = 3). Most were reported in English (n = 50), conducted in 2020 (n = 28), and focused on the perspectives of inpatient palliative care clinicians (n = 28). Three descriptive themes captured the roles and expectations of inpatient palliative care specialists: shifting foundations, reorienting to relationships, and evolving identity. Two analytical themes were synthesized: palliative care propagates compassion through a healing presence, and palliative care enhances the systemic response to suffering through nimble leadership.<br><br>CONCLUSION: Inpatient palliative care specialists responded to the COVID-19 pandemic by establishing their healing presence and leading with their adaptability. To develop institutionally tailored and collaborative responses to future pandemics, future studies are needed to understand how inpatient palliative care clinicians are recognized and valued within their institutions.}, }
@article {pmid38096601, year = {2024}, author = {Chiba, K and Niwa, S}, title = {Autoinhibition and activation of kinesin-1 and their involvement in amyotrophic lateral sclerosis.}, journal = {Current opinion in cell biology}, volume = {86}, number = {}, pages = {102301}, doi = {10.1016/j.ceb.2023.102301}, pmid = {38096601}, issn = {1879-0410}, mesh = {Humans ; *Kinesins/metabolism ; *Amyotrophic Lateral Sclerosis ; Neurons/metabolism ; Biological Transport ; }, abstract = {Kinesin-1, composed of kinesin heavy chain and kinesin light chain, is a founding member of kinesin superfamily and transports various neuronal cargos. Kinesin-1 is one of the most abundant ATPases in the cell and thus need to be tightly regulated to avoid wastage of energy. It has been well established that kinesin-1 is regulated by the autoinhibition mechanism. This review focuses on the recent researches that have contributed to the understanding of mechanisms for the autoinhibition of kinesin-1 and its unlocking. Recent electron microscopic studies have shown an unanticipated structure of autoinhibited kinesin-1. Biochemical reconstitution have revealed detailed molecular mechanisms how the autoinhibition is unlocked. Importantly, misregulation of kinesin-1 is emerging as one of the major causes of amyotrophic lateral sclerosis.}, }
@article {pmid38093670, year = {2024}, author = {Oliveira Santos, M and Swash, M and de Carvalho, M}, title = {Current challenges in primary lateral sclerosis diagnosis.}, journal = {Expert review of neurotherapeutics}, volume = {24}, number = {1}, pages = {45-53}, doi = {10.1080/14737175.2023.2295010}, pmid = {38093670}, issn = {1744-8360}, mesh = {Adult ; Humans ; *Amyotrophic Lateral Sclerosis ; *Motor Neuron Disease/diagnosis ; Neuroimaging ; Diagnosis, Differential ; Biomarkers ; Multicenter Studies as Topic ; }, abstract = {INTRODUCTION: Primary lateral sclerosis (PLS) is a rare, adult-onset and slowly progressive motor neuron disorder whose clinical core is characterized by upper motor neuron (UMN) dysfunction. Its formal diagnosis is clinically based and disease duration-dependent. Differentiating PLS from other disorders involving UMN can be challenging, particularly in the early stages.<br><br>AREAS COVERED: Our review covers and discusses different aspects of the PLS field, including the diagnostic criteria and its limitations, its differential diagnosis and their major pitfalls, and the actual role of neurophysiology, neuroimaging, genetics, and molecular biomarkers. Symptomatic treatment of the different manifestations is also addressed. The authors searched MEDLINE and Scopus. They also searched the reference lists of articles identified by our search strategy and reviewed and selected those deemed relevant. They selected papers and studies based on the quality of the report, significance of the findings, and on the author's critical appraise and expertise.<br><br>EXPERT OPINION: It is important to investigate novel molecular biomarkers and plan multicenter clinical trials for PLS. However, this will require a large international project to recruit enough patients, particularly given the diagnostic uncertainty of the current clinical criteria. A better understanding of PLS pathophysiology is crucial for designing disease-targeted therapies.}, }
@article {pmid38092270, year = {2024}, author = {Deng, C and Chen, H}, title = {Brain-derived neurotrophic factor/tropomyosin receptor kinase B signaling in spinal muscular atrophy and amyotrophic lateral sclerosis.}, journal = {Neurobiology of disease}, volume = {190}, number = {}, pages = {106377}, doi = {10.1016/j.nbd.2023.106377}, pmid = {38092270}, issn = {1095-953X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; Brain-Derived Neurotrophic Factor ; Motor Neurons/physiology ; Tropomyosin ; *Muscular Atrophy, Spinal ; Receptor, trkB ; }, abstract = {Tropomyosin receptor kinase B (TrkB) and its primary ligand brain-derived neurotrophic factor (BDNF) are expressed in the neuromuscular system, where they affect neuronal survival, differentiation, and functions. Changes in BDNF levels and full-length TrkB (TrkB-FL) signaling have been revealed in spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS), two common forms of motor neuron diseases that are characterized by defective neuromuscular junctions in early disease stages and subsequently progressive muscle weakness. This review summarizes the current understanding of BDNF/TrkB-FL-related research in SMA and ALS, with an emphasis on their alterations in the neuromuscular system and possible BDNF/TrkB-FL-targeting therapeutic strategies. The limitations of current studies and future directions are also discussed, giving the hope of discovering novel and effective treatments.}, }
@article {pmid38090405, year = {2023}, author = {Gupta, D and Vagha, S and Dhingra, H and Shirsath, H}, title = {Advances in Understanding and Treating Amyotrophic Lateral Sclerosis (ALS): A Comprehensive Review.}, journal = {Cureus}, volume = {15}, number = {11}, pages = {e48691}, pmid = {38090405}, issn = {2168-8184}, abstract = {Amyotrophic lateral sclerosis (ALS) is a deadly CNS neurodegenerative disease. The way ALS is now managed, from diagnosis to prognosis, is still not ideal despite many studies. Early diagnosis can help ALS patients live longer since prompt treatment can halt the disease's development. Two medications, riluzole and edaravone, have recently been licensed for use in therapy, and they very slightly increase life expectancy. Still, a lot of cutting-edge experimental medications are being developed. In the following article, we give a synopsis of the innovative medications and genetic remodeling that have emerged recently and help to halt the course of the illness. Studies have also been conducted on a few symptomatic and rehabilitative therapies that enhance the quality of life for ALS patients.}, }
@article {pmid38087359, year = {2023}, author = {Nayab, DE and Din, FU and Ali, H and Kausar, WA and Urooj, S and Zafar, M and Khan, I and Shabbir, K and Khan, GM}, title = {Nano biomaterials based strategies for enhanced brain targeting in the treatment of neurodegenerative diseases: an up-to-date perspective.}, journal = {Journal of nanobiotechnology}, volume = {21}, number = {1}, pages = {477}, pmid = {38087359}, issn = {1477-3155}, support = {20-14604/NRPU/R&amp;D/HEC/2021//Higher Education Commision, Pakistan/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy ; Brain ; Blood-Brain Barrier ; Drug Delivery Systems/methods ; Nanotechnology ; }, abstract = {Neurons and their connecting axons gradually degenerate in neurodegenerative diseases (NDs), leading to dysfunctionality of the neuronal cells and eventually their death. Drug delivery for the treatment of effected nervous system is notoriously complicated because of the presence of natural barriers, i.e., the blood-brain barrier and the blood cerebrospinal fluid barrier. Palliative care is currently the standard care for many diseases. Therefore, treatment programs that target the disease's origin rather than its symptoms are recommended. Nanotechnology-based drug delivery platforms offer an innovative way to circumvent these obstacles and deliver medications directly to the central nervous system, thereby enabling treatment of several common neurological problems, i.e., Alzheimer's, Parkinson's, Huntington's, and amyotrophic lateral sclerosis. Interestingly, the combination of nanomedicine and gene therapy enables targeting of selective mutant genes responsible for the progression of NDs, which may provide a much-needed boost in the struggle against these diseases. Herein, we discussed various central nervous system delivery obstacles, followed by a detailed insight into the recently developed techniques to restore neurological function via the differentiation of neural stem cells. Moreover, a comprehensive background on the role of nanomedicine in controlling neurogenesis via differentiation of neural stem cells is explained. Additionally, numerous phytoconstituents with their neuroprotective properties and molecular targets in the identification and management of NDs are also deliberated. Furthermore, a detailed insight of the ongoing clinical trials and currently marketed products for the treatment of NDs is provided in this manuscript.}, }
@article {pmid38079579, year = {2024}, author = {Stefánsdóttir, H and Crowe, K and Magnússon, E and Guiberson, M and Másdóttir, T and Ágústsdóttir, I and Baldursdóttir, &#xd6;V}, title = {Measuring speech intelligibility with deaf and hard-of-hearing children: A systematic review.}, journal = {Journal of deaf studies and deaf education}, volume = {29}, number = {2}, pages = {265-277}, pmid = {38079579}, issn = {1465-7325}, mesh = {Humans ; *Speech Intelligibility/physiology ; Child ; *Deafness/psychology ; Persons with Hearing Disabilities/psychology ; }, abstract = {There is great variability in the ways in which the speech intelligibility of d/Deaf and hard-of-hearing (DHH) children who use spoken language as part, or all, of their communication system is measured. This systematic review examined the measures and methods that have been used when examining the speech intelligibility of children who are DHH and the characteristics of these measures and methods. A systematic database search was conducted of CENTRAL; CINAHL; Cochrane; ERIC; Joanna Briggs; Linguistics, Language and Behavior Abstracts; Medline; Scopus; and Web of Science databases, as well as supplemental searches. A total of 204 included studies reported the use of many different measures/methods which measured segmental aspects of speech, with the most common being Allen et al.'s (2001, The reliability of a rating scale for measuring speech intelligibility following pediatric cochlear implantation. Otology and Neurotology, 22(5), 631-633. https://doi.org/10.1097/00129492-200109000-00012) Speech Intelligibility Rating scale. Many studies included insufficient details to determine the measure that was used. Future research should utilize methods/measures with known psychometric validity, provide clear descriptions of the methods/measures used, and consider using more than one measure to account for limitations inherent in different methods of measuring the speech intelligibility of children who are DHH, and consider and discuss the rationale for the measure/method chosen.}, }
@article {pmid38078970, year = {2024}, author = {Sun, Z and Zhang, B and Peng, Y}, title = {Development of novel treatments for amyotrophic lateral sclerosis.}, journal = {Metabolic brain disease}, volume = {39}, number = {3}, pages = {467-482}, pmid = {38078970}, issn = {1573-7365}, support = {No. 82073835, and 81872855//National Natural Sciences Foundation of China/ ; No. 2021-I2M-1-054//CAMS Innovation Fund for Medical Sciences/ ; 201920200802//Disciplines construction project/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/pathology ; *Neurodegenerative Diseases ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease that causes paralysis whose etiology and pathogenesis have not been fully elucidated. Presently it is incurable and rapidly progressive with a survival of 2-5 years from onset, and no treatments could cure it. Therefore, it is urgent to identify which therapeutic target(s) are more promising to develop treatments that could effectively treat ALS. So far, more than 90 novel treatments for ALS patients have been registered on ClinicalTrials.gov, of which 23 are in clinical trials, 12 have been terminated and the rest suspended. This review will systematically summarize the possible targets of these novel treatments under development or failing based on published literature and information released by sponsors, so as to provide basis and support for subsequent drug research and development.}, }
@article {pmid38072117, year = {2024}, author = {Alaoui Mansouri, M and Kharbach, M and Bouklouze, A}, title = {Current Applications of Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) in Pharmaceutical Analysis: Review.}, journal = {Journal of pharmaceutical sciences}, volume = {113}, number = {4}, pages = {856-865}, doi = {10.1016/j.xphs.2023.12.004}, pmid = {38072117}, issn = {1520-6017}, mesh = {Least-Squares Analysis ; *Biopharmaceutics ; Pharmaceutical Preparations ; Multivariate Analysis ; }, abstract = {The present review encompasses various applications of multivariate curve resolution- alternating least squares (MCR-ALS) as a promising data handling, which is issued by analytical techniques in pharmaceutics. It involves different sections starting from a concise theory of MCR-ALS and four detailed applications in drugs analysis. Dissolution, stability, polymorphism, and quantification are the main four detailed applications. The data generated by analytical techniques associated with MCR-ALS deals accurately with different challenges compared to other chemometric tools. For each reviewed purpose, it was explained how MCR-ALS was applied and detailed information was given. Different approaches were introduced to overcome challenges that limit the use of MCR-ALS efficiently in pharmaceutical mixture were also discussed.}, }
@article {pmid38070961, year = {2023}, author = {Krall, JTW and Chakravartty, A and Caress, JB and Files, DC}, title = {Identification and Management of Acute Neuromuscular Respiratory Failure in the ICU.}, journal = {Chest}, volume = {164}, number = {6}, pages = {1454-1461}, doi = {10.1016/j.chest.2023.09.009}, pmid = {38070961}, issn = {1931-3543}, mesh = {Humans ; *Neuromuscular Diseases/complications/diagnosis/therapy ; *Respiratory Insufficiency/diagnosis/etiology/therapy ; Prognosis ; Intensive Care Units ; }, abstract = {Respiratory failure is a common and potentially life-threatening complication of neuromuscular diseases. Prompt recognition and accurate diagnosis of new or worsening chronic neuromuscular disease have important clinical management and prognostic implications. In this article, we present an approach to the acute presentation of undifferentiated neuromuscular respiratory failure in the ICU and guidance for determination and respiratory management of the underlying disorder.}, }
@article {pmid38070417, year = {2024}, author = {Ur Rahman, S and Han, JC and Ahmad, M and Ashraf, MN and Khaliq, MA and Yousaf, M and Wang, Y and Yasin, G and Nawaz, MF and Khan, KA and Du, Z}, title = {Aluminum phytotoxicity in acidic environments: A comprehensive review of plant tolerance and adaptation strategies.}, journal = {Ecotoxicology and environmental safety}, volume = {269}, number = {}, pages = {115791}, doi = {10.1016/j.ecoenv.2023.115791}, pmid = {38070417}, issn = {1090-2414}, mesh = {*Aluminum/toxicity/metabolism ; Malates/metabolism ; Plant Breeding ; Plants/metabolism ; *Alkaloids/pharmacology ; Organic Chemicals/metabolism ; Soil/chemistry ; Plant Roots/metabolism ; Gene Expression Regulation, Plant ; }, abstract = {Aluminum (Al), a non-essential metal for plant growth, exerts significant phytotoxic effects, particularly on root growth. Anthropogenic activities would intensify Al's toxic effects by releasing Al[3+] into the soil solution, especially in acidic soils with a pH lower than 5.5 and rich mineral content. The severity of Al-induced phytotoxicity varies based on factors such as Al concentration, ionic form, plant species, and growth stages. Al toxicity leads to inhibited root and shoot growth, reduced plant biomass, disrupted water uptake causing nutritional imbalance, and adverse alterations in physiological, biochemical, and molecular processes. These effects collectively lead to diminished plant yield and quality, along with reduced soil fertility. Plants employ various mechanisms to counter Al toxicity under stress conditions, including sequestering Al in vacuoles, exuding organic acids (OAs) like citrate, oxalate, and malate from root tip cells to form Al-complexes, activating antioxidative enzymes, and overexpressing Al-stress regulatory genes. Recent advancements focus on enhancing the exudation of OAs to prevent Al from entering the plant, and developing Al-tolerant varieties. Gene transporter families, such as ATP-Binding Cassette (ABC), Aluminum-activated Malate Transporter (ALMT), Natural resistance-associated macrophage protein (Nramp), Multidrug and Toxic compounds Extrusion (MATE), and aquaporin, play a crucial role in regulating Al toxicity. This comprehensive review examined recent progress in understanding the cytotoxic impact of Al on plants at the cellular and molecular levels. Diverse strategies developed by both plants and scientists to mitigate Al-induced phytotoxicity were discussed. Furthermore, the review explored recent genomic developments, identifying candidate genes responsible for OAs exudation, and delved into genome-mediated breeding initiatives, isolating transgenic and advanced breeding lines to cultivate Al-tolerant plants.}, }
@article {pmid38069329, year = {2023}, author = {Kim, H and Kim, GS and Hyun, SH and Kim, E}, title = {Advancements in 2D and 3D In Vitro Models for Studying Neuromuscular Diseases.}, journal = {International journal of molecular sciences}, volume = {24}, number = {23}, pages = {}, pmid = {38069329}, issn = {1422-0067}, support = {NRF-2021R1C1C2007132//National Research Foundation of Korea/ ; }, mesh = {Humans ; *Neuromuscular Diseases ; Muscle, Skeletal ; Neuromuscular Junction ; Motor Neurons ; Organoids ; }, abstract = {Neuromuscular diseases (NMDs) are a genetically or clinically heterogeneous group of diseases that involve injury or dysfunction of neuromuscular tissue components, including peripheral motor neurons, skeletal muscles, and neuromuscular junctions. To study NMDs and develop potential therapies, remarkable progress has been made in generating in vitro neuromuscular models using engineering approaches to recapitulate the complex physical and biochemical microenvironments of 3D human neuromuscular tissues. In this review, we discuss recent studies focusing on the development of in vitro co-culture models of human motor neurons and skeletal muscles, with the pros and cons of each approach. Furthermore, we explain how neuromuscular in vitro models recapitulate certain aspects of specific NMDs, including amyotrophic lateral sclerosis and muscular dystrophy. Research on neuromuscular organoids (NMO) will continue to co-develop to better mimic tissues in vivo and will provide a better understanding of the development of the neuromuscular tissue, mechanisms of NMD action, and tools applicable to preclinical studies, including drug screening and toxicity tests.}, }
@article {pmid38069154, year = {2023}, author = {Belosludtseva, NV and Matveeva, LA and Belosludtsev, KN}, title = {Mitochondrial Dyshomeostasis as an Early Hallmark and a Therapeutic Target in Amyotrophic Lateral Sclerosis.}, journal = {International journal of molecular sciences}, volume = {24}, number = {23}, pages = {}, pmid = {38069154}, issn = {1422-0067}, support = {23-25-00286//Russian Science Foundation/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/therapy/metabolism ; Mitochondria/metabolism ; Motor Neurons/metabolism ; Energy Metabolism ; Disease Progression ; Superoxide Dismutase-1/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal multisystem disease characterized by progressive death of motor neurons, loss of muscle mass, and impaired energy metabolism. More than 40 genes are now known to be associated with ALS, which together account for the majority of familial forms of ALS and only 10% of sporadic ALS cases. To date, there is no consensus on the pathogenesis of ALS, which makes it difficult to develop effective therapy. Accumulating evidence indicates that mitochondria, which play an important role in cellular homeostasis, are the earliest targets in ALS, and abnormalities in their structure and functions contribute to the development of bioenergetic stress and disease progression. Mitochondria are known to be highly dynamic organelles, and their stability is maintained through a number of key regulatory pathways. Mitochondrial homeostasis is dynamically regulated via mitochondrial biogenesis, clearance, fission/fusion, and trafficking; however, the processes providing "quality control" and distribution of the organelles are prone to dysregulation in ALS. Here, we systematically summarized changes in mitochondrial turnover, dynamics, calcium homeostasis, and alterations in mitochondrial transport and functions to provide in-depth insights into disease progression pathways, which may have a significant impact on current symptomatic therapies and personalized treatment programs for patients with ALS.}, }
@article {pmid38062079, year = {2023}, author = {Bowden, M and Beswick, E and Tam, J and Perry, D and Smith, A and Newton, J and Chandran, S and Watts, O and Pal, S}, title = {A systematic review and narrative analysis of digital speech biomarkers in Motor Neuron Disease.}, journal = {NPJ digital medicine}, volume = {6}, number = {1}, pages = {228}, pmid = {38062079}, issn = {2398-6352}, abstract = {Motor Neuron Disease (MND) is a progressive and largely fatal neurodegeneritve disorder with a lifetime risk of approximately 1 in 300. At diagnosis, up to 25% of people with MND (pwMND) exhibit bulbar dysfunction. Currently, pwMND are assessed using clinical examination and diagnostic tools including the ALS Functional Rating Scale Revised (ALS-FRS(R)), a clinician-administered questionnaire with a single item on speech intelligibility. Here we report on the use of digital technologies to assess speech features as a marker of disease diagnosis and progression in pwMND. Google Scholar, PubMed, Medline and EMBASE were systematically searched. 40 studies were evaluated including 3670 participants; 1878 with a diagnosis of MND. 24 studies used microphones, 5 used smartphones, 6 used apps, 2 used tape recorders and 1 used the Multi-Dimensional Voice Programme (MDVP) to record speech samples. Data extraction and analysis methods varied but included traditional statistical analysis, CSpeech, MATLAB and machine learning (ML) algorithms. Speech features assessed also varied and included jitter, shimmer, fundamental frequency, intelligible speaking rate, pause duration and syllable repetition. Findings from this systematic review indicate that digital speech biomarkers can distinguish pwMND from healthy controls and can help identify bulbar involvement in pwMND. Preliminary evidence suggests digitally assessed acoustic features can identify more nuanced changes in those affected by voice dysfunction. No one digital speech biomarker alone is consistently able to diagnose or prognosticate MND. Further longitudinal studies involving larger samples are required to validate the use of these technologies as diagnostic tools or prognostic biomarkers.}, }
@article {pmid38052682, year = {2024}, author = {Festa, LK and Grinspan, JB and Jordan-Sciutto, KL}, title = {White matter injury across neurodegenerative disease.}, journal = {Trends in neurosciences}, volume = {47}, number = {1}, pages = {47-57}, pmid = {38052682}, issn = {1878-108X}, support = {R01 MH098742/MH/NIMH NIH HHS/United States ; R01 MH126773/MH/NIMH NIH HHS/United States ; R21 MH118121/MH/NIMH NIH HHS/United States ; T32 AI007632/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Neurodegenerative Diseases/metabolism ; *White Matter/metabolism ; *Alzheimer Disease ; *Parkinson Disease ; *Amyotrophic Lateral Sclerosis ; }, abstract = {Oligodendrocytes (OLs), the myelin-generating cells of the central nervous system (CNS), are active players in shaping neuronal circuitry and function. It has become increasingly apparent that injury to cells within the OL lineage plays a central role in neurodegeneration. In this review, we focus primarily on three degenerative disorders in which white matter loss is well documented: Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). We discuss clinical data implicating white matter injury as a key feature of these disorders, as well as shared and divergent phenotypes between them. We examine the cellular and molecular mechanisms underlying the alterations to OLs, including chronic neuroinflammation, aggregation of proteins, lipid dysregulation, and organellar stress. Last, we highlight prospects for therapeutic intervention targeting the OL lineage to restore function.}, }
@article {pmid38049900, year = {2023}, author = {Flynn, R and Cassidy, C and Dobson, L and Al-Rassi, J and Langley, J and Swindle, J and Graham, ID and Scott, SD}, title = {Knowledge translation strategies to support the sustainability of evidence-based interventions in healthcare: a scoping review.}, journal = {Implementation science : IS}, volume = {18}, number = {1}, pages = {69}, pmid = {38049900}, issn = {1748-5908}, mesh = {Humans ; *Translational Science, Biomedical ; *Evidence-Based Medicine ; Delivery of Health Care ; }, abstract = {BACKGROUND: Knowledge translation (KT) strategies are widely used to facilitate the implementation of EBIs into healthcare practices. However, it is unknown what and how KT strategies are used to facilitate the sustainability of EBIs in institutional healthcare settings.<br><br>OBJECTIVES: This scoping review aimed to consolidate the current evidence on (i) what and how KT strategies are being used for the sustainability of EBIs in institutional healthcare settings; (ii) the reported KT strategy outcomes (e.g., acceptability) for EBI sustainability, and (iii) the reported EBI sustainability outcomes (e.g., EBI activities or component of the intervention continue).<br><br>METHODS: We conducted a scoping review of five electronic databases. We included studies describing the use of specific KT strategies to facilitate the sustainability of EBIs (more than 1-year post-implementation). We coded KT strategies using the clustered ERIC taxonomy and AIMD framework, we coded KT strategy outcomes using Tierney et al.'s measures, and EBI sustainability outcomes using Scheirer and Dearing's and Lennox's taxonomy. We conducted descriptive numerical summaries and a narrative synthesis to analyze the results.<br><br>RESULTS: The search identified 3776 studies for review. Following the screening, 25 studies (reported in 27 papers due to two companion reports) met the final inclusion criteria. Most studies used multi-component KT strategies for EBI sustainability (n = 24). The most common ERIC KT strategy clusters were to train and educate stakeholders (n = 38) and develop stakeholder interrelationships (n = 34). Education was the most widely used KT strategy (n = 17). Many studies (n = 11) did not clearly report whether they used different or the same KT strategies between EBI implementation and sustainability. Seven studies adapted KT strategies from implementation to sustainability efforts. Only two studies reported using a new KT strategy for EBI sustainability. The most reported KT strategy outcomes were acceptability (n = 10), sustainability (n = 5); and adoption (n = 4). The most commonly measured EBI sustainability outcome was the continuation of EBI activities or components (n = 23), followed by continued benefits for patients, staff, and stakeholders (n = 22).<br><br>CONCLUSIONS: Our review provides insight into a conceptual problem where initial EBI implementation and sustainability are considered as two discrete time periods. Our findings show we need to consider EBI implementation and sustainability as a continuum and design and select KT strategies with this in mind. Our review has emphasized areas that require further research (e.g., KT strategy adaptation for EBI sustainability). To advance understanding of how to employ KT strategies for EBI sustainability, we recommend clearly reporting the dose, frequency, adaptations, fidelity, and cost of KT strategies. Advancing our understanding in this area would facilitate better design, selection, tailored, and adapted use of KT strategies for EBI sustainability, thereby contributing to improved patient, provider, and health system outcomes.}, }
@article {pmid38046601, year = {2023}, author = {Quan, W and Chan, Z and Wei, P and Mao, Y and Bartels, D and Liu, X}, title = {PHD finger proteins function in plant development and abiotic stress responses: an overview.}, journal = {Frontiers in plant science}, volume = {14}, number = {}, pages = {1297607}, pmid = {38046601}, issn = {1664-462X}, abstract = {The plant homeodomain (PHD) finger with a conserved Cys4-His-Cys3 motif is a common zinc-binding domain, which is widely present in all eukaryotic genomes. The PHD finger is the "reader" domain of methylation marks in histone H3 and plays a role in the regulation of gene expression patterns. Numerous proteins containing the PHD finger have been found in plants. In this review, we summarize the functional studies on PHD finger proteins in plant growth and development and responses to abiotic stresses in recent years. Some PHD finger proteins, such as VIN3, VILs, and Ehd3, are involved in the regulation of flowering time, while some PHD finger proteins participate in the pollen development, for example, MS, TIP3, and MMD1. Furthermore, other PHD finger proteins regulate the plant tolerance to abiotic stresses, including Alfin1, ALs, and AtSIZ1. Research suggests that PHD finger proteins, as an essential transcription regulator family, play critical roles in various plant biological processes, which is helpful in understanding the molecular mechanisms of novel PHD finger proteins to perform specific function.}, }
@article {pmid38037913, year = {2024}, author = {Zhong, G and Wang, X and Li, J and Xie, Z and Wu, Q and Chen, J and Wang, Y and Chen, Z and Cao, X and Li, T and Liu, J and Wang, Q}, title = {Insights Into the Role of Copper in Neurodegenerative Diseases and the Therapeutic Potential of Natural Compounds.}, journal = {Current neuropharmacology}, volume = {22}, number = {10}, pages = {1650-1671}, pmid = {38037913}, issn = {1875-6190}, support = {81973918, 82274616//National Natural Science Foundation of China/ ; 2019KSYS005//Key laboratory project of colleges and universities in Guangdong Province/ ; 2020A0505100052//Guangdong province science and technology plan international cooperation project/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Copper/metabolism ; Animals ; Biological Products/therapeutic use/pharmacology ; Homeostasis/drug effects ; Chelating Agents/therapeutic use/pharmacology ; }, abstract = {Neurodegenerative diseases encompass a collection of neurological disorders originating from the progressive degeneration of neurons, resulting in the dysfunction of neurons. Unfortunately, effective therapeutic interventions for these diseases are presently lacking. Copper (Cu), a crucial trace element within the human body, assumes a pivotal role in various biological metabolic processes, including energy metabolism, antioxidant defense, and neurotransmission. These processes are vital for the sustenance, growth, and development of organisms. Mounting evidence suggests that disrupted copper homeostasis contributes to numerous age-related neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), Wilson's disease (WD), Menkes disease (MD), prion diseases, and multiple sclerosis (MS). This comprehensive review investigates the connection between the imbalance of copper homeostasis and neurodegenerative diseases, summarizing pertinent drugs and therapies that ameliorate neuropathological changes, motor deficits, and cognitive impairments in these conditions through the modulation of copper metabolism. These interventions include Metal-Protein Attenuating Compounds (MPACs), copper chelators, copper supplements, and zinc salts. Moreover, this review highlights the potential of active compounds derived from natural plant medicines to enhance neurodegenerative disease outcomes by regulating copper homeostasis. Among these compounds, polyphenols are particularly abundant. Consequently, this review holds significant implications for the future development of innovative drugs targeting the treatment of neurodegenerative diseases.}, }
@article {pmid38033869, year = {2023}, author = {Vukolova, MN and Yen, LY and Khmyz, MI and Sobolevsky, AI and Yelshanskaya, MV}, title = {Parkinson's disease, epilepsy, and amyotrophic lateral sclerosis-emerging role of AMPA and kainate subtypes of ionotropic glutamate receptors.}, journal = {Frontiers in cell and developmental biology}, volume = {11}, number = {}, pages = {1252953}, pmid = {38033869}, issn = {2296-634X}, support = {R37 NS083660/NS/NINDS NIH HHS/United States ; R01 NS107253/NS/NINDS NIH HHS/United States ; R01 NS083660/NS/NINDS NIH HHS/United States ; R01 AR078814/AR/NIAMS NIH HHS/United States ; R01 CA206573/CA/NCI NIH HHS/United States ; }, abstract = {Ionotropic glutamate receptors (iGluRs) mediate the majority of excitatory neurotransmission and are implicated in various neurological disorders. In this review, we discuss the role of the two fastest iGluRs subtypes, namely, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate receptors, in the pathogenesis and treatment of Parkinson's disease, epilepsy, and amyotrophic lateral sclerosis. Although both AMPA and kainate receptors represent promising therapeutic targets for the treatment of these diseases, many of their antagonists show adverse side effects. Further studies of factors affecting the selective subunit expression and trafficking of AMPA and kainate receptors, and a reasonable approach to their regulation by the recently identified novel compounds remain promising directions for pharmacological research.}, }
@article {pmid38030693, year = {2023}, author = {Vanbilsen, N and Kotz, SA and Rosso, M and Leman, M and Triccas, LT and Feys, P and Moumdjian, L}, title = {Auditory attention measured by EEG in neurological populations: systematic review of literature and meta-analysis.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {21064}, pmid = {38030693}, issn = {2045-2322}, support = {G082021N//Fonds Wetenschappelijk Onderzoek/ ; 1295923N//Fonds Wetenschappelijk Onderzoek/ ; }, mesh = {Humans ; Cross-Sectional Studies ; *Attention ; *Parkinson Disease ; Gait ; Electroencephalography ; }, abstract = {Sensorimotor synchronization strategies have been frequently used for gait rehabilitation in different neurological populations. Despite these positive effects on gait, attentional processes required to dynamically attend to the auditory stimuli needs elaboration. Here, we investigate auditory attention in neurological populations compared to healthy controls quantified by EEG recordings. Literature was systematically searched in databases PubMed and Web of Science. Inclusion criteria were investigation of auditory attention quantified by EEG recordings in neurological populations in cross-sectional studies. In total, 35 studies were included, including participants with Parkinson's disease (PD), stroke, Traumatic Brain Injury (TBI), Multiple Sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS). A meta-analysis was performed on P3 amplitude and latency separately to look at the differences between neurological populations and healthy controls in terms of P3 amplitude and latency. Overall, neurological populations showed impairments in auditory processing in terms of magnitude and delay compared to healthy controls. Consideration of individual auditory processes and thereafter selecting and/or designing the auditory structure during sensorimotor synchronization paradigms in neurological physical rehabilitation is recommended.}, }
@article {pmid38029395, year = {2024}, author = {Song, J}, title = {Molecular Mechanisms of Phase Separation and Amyloidosis of ALS/FTD-linked FUS and TDP-43.}, journal = {Aging and disease}, volume = {15}, number = {5}, pages = {2084-2112}, pmid = {38029395}, issn = {2152-5250}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; *RNA-Binding Protein FUS/metabolism/chemistry/genetics ; *DNA-Binding Proteins/metabolism/chemistry/genetics ; *Frontotemporal Dementia/genetics/metabolism/pathology ; Amyloidosis/metabolism/pathology/genetics ; Phase Separation ; }, abstract = {FUS and TDP-43, two RNA-binding proteins from the heterogeneous nuclear ribonucleoprotein family, have gained significant attention in the field of neurodegenerative diseases due to their association with amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD). They possess folded domains for binding ATP and various nucleic acids including DNA and RNA, as well as substantial intrinsically disordered regions (IDRs) including prion-like domains (PLDs) and RG-/RGG-rich regions. They play vital roles in various cellular processes, including transcription, splicing, microRNA maturation, RNA stability and transport and DNA repair. In particular, they are key components for forming ribonucleoprotein granules and stress granules (SGs) through homotypic or heterotypic liquid-liquid phase separation (LLPS). Strikingly, liquid-like droplets formed by FUS and TDP-43 may undergo aging to transform into less dynamic assemblies such as hydrogels, inclusions, and amyloid fibrils, which are the pathological hallmarks of ALS and FTD. This review aims to synthesize and consolidate the biophysical knowledge of the sequences, structures, stability, dynamics, and inter-domain interactions of FUS and TDP-43 domains, so as to shed light on the molecular mechanisms underlying their liquid-liquid phase separation (LLPS) and amyloidosis. The review further delves into the mechanisms through which ALS-causing mutants of the well-folded hPFN1 disrupt the dynamics of LLPS of FUS prion-like domain, providing key insights into a potential mechanism for misfolding/aggregation-prone proteins to cause neurodegenerative diseases and aging by gain of functions. With better understanding of different biophysical aspects of FUS and TDP-43, the ultimate goal is to develop drugs targeting LLPS and amyloidosis, which could mediate protein homeostasis within cells and lead to new treatments for currently intractable diseases, particularly neurodegenerative diseases such as ALS, FTD and aging. However, the study of membrane-less organelles and condensates is still in its infancy and therefore the review also highlights key questions that require future investigation.}, }
@article {pmid38022117, year = {2023}, author = {Jain, A and Madkan, S and Patil, P}, title = {The Role of Gut Microbiota in Neurodegenerative Diseases: Current Insights and Therapeutic Implications.}, journal = {Cureus}, volume = {15}, number = {10}, pages = {e47861}, pmid = {38022117}, issn = {2168-8184}, abstract = {Small microscopic entities known as microbes, having a population of hundreds of billions or perhaps even in trillions, reside in our gastrointestinal tract. A healthy immune system, digestion, and creation of vitamins and enzymes are all thanks to these microbes. However, new research has shown a hitherto unrecognized connection between the microbiota of the intestines and the genesis of neurodegenerative diseases. Neurons in the CNS gradually deteriorate in neurodegenerative illnesses like multiple sclerosis and Parkinson's disease (PD). This deterioration impairs cognitive and physical function. Amyotrophic lateral sclerosis (ALS), PD, and Alzheimer's disease (AD) are just a few examples of neurodegenerative illnesses that pose a serious threat to world health and have few effective treatments. Recent research suggests that the gut microbiota, a diverse microbial population found in the gastrointestinal system, may substantially impact the cause and development of various diseases. The discovery of altered gut microbiota composition in people with these illnesses is one of the most critical lines of evidence connecting gut microbiota dysbiosis to neurodegenerative diseases. AD patients have a distinct characteristic of having a particular microbiota profile. In addition, an excess population of a specific microbe data profile is seen as compared to a healthy individual. Similar changes in the gut microbiota composition have been noted in people with multiple sclerosis and PD. The latest study indicates the potential that dysbiosis, a condition characterized by alteration in the intestinal microbiota's makeup and functioning, may have an effect on the onset and progression of neurodegenerative diseases, including PD and multiple sclerosis. In order to emphasize any potential underlying mechanisms and examine potential treatment repercussions, the review article's goal is to summarize current knowledge about the connection between gut microbiota and neurodegenerative disorders. The review article aims to summarize current knowledge about the connection between gut microbiota and neurodegenerative disorders, highlighting potential underlying mechanisms and examining potential treatment repercussions.}, }
@article {pmid38020546, year = {2023}, author = {de Brito Siqueira, ALG and Cremasco, PVV and Bahú, JO and Pioli da Silva, A and Melo de Andrade, LR and González, PGA and Crivellin, S and Cárdenas Concha, VO and Krambeck, K and Lodi, L and Severino, P and Souto, EB}, title = {Phytocannabinoids: Pharmacological effects, biomedical applications, and worldwide prospection.}, journal = {Journal of traditional and complementary medicine}, volume = {13}, number = {6}, pages = {575-587}, pmid = {38020546}, issn = {2225-4110}, abstract = {Scientific evidence exists about the association between neurological diseases (i.e., Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), multiple sclerosis, depression, and memory loss) and oxidative damage. The increasing worldwide incidence of such diseases is attracting the attention of researchers to find palliative medications to reduce the symptoms and promote quality of life, in particular, in developing countries, e.g., South America and Africa. Among potential alternatives, extracts of Cannabis Sativa L. are suitable for people who have neurological disorders, spasticity, and pain, nausea, resulting from diseases such as cancer and arthritis. In this review, we discuss the latest developments in the use of Cannabis, its subtypes and constituents, extraction methods, and relevant pharmacological effects. Biomedical applications, marketed products, and prospects for the worldwide use of Cannabis Sativa L. extracts are also discussed, providing the bibliometric maps of scientific literature published in representative countries from South America (i.e., Brazil) and Africa (i.e., South Africa). A lack of evidence on the effectiveness and safety of Cannabis, besides the concerns about addiction and other adverse events, has led many countries to act with caution before changing Cannabis-related regulations. Recent findings are expected to increase the social acceptance of Cannabis, while new technologies seem to boost the global cannabis market because the benefits of (-)-trans-delta-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) use have been proven in several studies in addition to the potential to general new employment.}, }
@article {pmid38018200, year = {2024}, author = {Monteiro, KLC and de Aquino, TM and da Silva-Júnior, EF}, title = {Natural Compounds as Inhibitors of Aβ Peptide and Tau Aggregation.}, journal = {CNS &amp; neurological disorders drug targets}, volume = {23}, number = {10}, pages = {1234-1250}, pmid = {38018200}, issn = {1996-3181}, mesh = {Humans ; *tau Proteins/metabolism/antagonists &amp; inhibitors ; *Amyloid beta-Peptides/metabolism/antagonists &amp; inhibitors ; *Biological Products/pharmacology/therapeutic use ; *Alzheimer Disease/drug therapy/metabolism ; Animals ; Plaque, Amyloid/drug therapy/metabolism ; Protein Aggregation, Pathological/drug therapy ; Neurofibrillary Tangles/drug effects/metabolism ; }, abstract = {Neurodegenerative conditions like Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) encompass disorders characterized by the degeneration of neurons in specific circumstances. The quest for novel agents to influence these diseases, particularly AD, has unearthed various natural compounds displaying multifaceted activities and diverse pharmacological mechanisms. Given the ongoing extensive study of pathways associated with the accumulation of neurofibrillary aggregates and amyloid plaques, this paper aims to comprehensively review around 130 studies exploring natural products. These studies focus on inhibiting the formation of amyloid plaques and tau protein tangles, with the objective of potentially alleviating or delaying AD.}, }
@article {pmid38018119, year = {2024}, author = {Brown, A and Armon, C and Barkhaus, P and Beauchamp, M and Bertorini, T and Bromberg, M and Cadavid, JM and Carter, GT and Crayle, J and Feldman, EL and Heiman-Patterson, T and Jhooty, S and Linares, A and Li, X and Mallon, E and Mcdermott, C and Mushannen, T and Nathaniel, G and Pattee, G and Pierce, K and Ratner, D and Slactova, L and Wicks, P and Bedlack, R}, title = {ALSUntangled #72: Insulin.}, journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration}, volume = {25}, number = {3-4}, pages = {416-419}, doi = {10.1080/21678421.2023.2288110}, pmid = {38018119}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; Insulin/adverse effects ; }, abstract = {ALSUntangled reviews alternative and off-label treatments for people living with amyotrophic lateral sclerosis (PALS). Here we review insulin, which has at least one plausible mechanism for slowing ALS progression. However, pre-clinical studies are limited and there have been no trials in PALS yet. Insulin use in patients without a metabolic need may cause very serious and potentially lethal side effects. While further studies to evaluate potential benefits may be warranted, at this time we cannot endorse insulin treatment to slow ALS progression.}, }
@article {pmid38010626, year = {2024}, author = {Zhong, R and Rua, MT and Wei-LaPierre, L}, title = {Targeting mitochondrial Ca[2+] uptake for the treatment of amyotrophic lateral sclerosis.}, journal = {The Journal of physiology}, volume = {602}, number = {8}, pages = {1519-1549}, pmid = {38010626}, issn = {1469-7793}, support = {R01 NS127858/NS/NINDS NIH HHS/United States ; R21 NS099545/NS/NINDS NIH HHS/United States ; R56 NS117429/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Humans ; *Amyotrophic Lateral Sclerosis/pathology ; Calcium/metabolism ; *Neurodegenerative Diseases ; Motor Neurons/physiology ; Mitochondria/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a rare adult-onset neurodegenerative disease characterized by progressive motor neuron (MN) loss, muscle denervation and paralysis. Over the past several decades, researchers have made tremendous efforts to understand the pathogenic mechanisms underpinning ALS, with much yet to be resolved. ALS is described as a non-cell autonomous condition with pathology detected in both MNs and non-neuronal cells, such as glial cells and skeletal muscle. Studies in ALS patient and animal models reveal ubiquitous abnormalities in mitochondrial structure and function, and disturbance of intracellular calcium homeostasis in various tissue types, suggesting a pivotal role of aberrant mitochondrial calcium uptake and dysfunctional calcium signalling cascades in ALS pathogenesis. Calcium signalling and mitochondrial dysfunction are intricately related to the manifestation of cell death contributing to MN loss and skeletal muscle dysfunction. In this review, we discuss the potential contribution of intracellular calcium signalling, particularly mitochondrial calcium uptake, in ALS pathogenesis. Functional consequences of excessive mitochondrial calcium uptake and possible therapeutic strategies targeting mitochondrial calcium uptake or the mitochondrial calcium uniporter, the main channel mediating mitochondrial calcium influx, are also discussed.}, }
@article {pmid38008065, year = {2024}, author = {Maier, GS and Rosar, G and Dietz, G and Hemken, N and Kafchitsas, K and Seeger, JB and Horas, K}, title = {Effectiveness of Mud-Pack Therapy and Mud-Bath Therapy in Osteoarthritis: A Systematic Review.}, journal = {Complementary medicine research}, volume = {31}, number = {1}, pages = {30-39}, doi = {10.1159/000535437}, pmid = {38008065}, issn = {2504-2106}, mesh = {Humans ; *Mud Therapy ; *Osteoarthritis, Knee ; *Osteoarthritis, Hip ; Quality of Life ; *Low Back Pain ; }, abstract = {OBJECTIVES: Osteoarthritis has a tremendous socioeconomic impact in terms of drug spending, hospital admissions, work productivity, and temporary or permanent incapacity. Mud therapy has been discussed as potential conservative treatment options for osteoarthritis. However, findings from several trials still remain controversial. For this reason, we aimed to systematically review the highest evidence provided by published trials to estimate the clinical effect of mud-pack and mud-bath therapy for the treatment of osteoarthritis.<br><br>METHODS: We searched PubMed, PEDro, and the Cochrane CENTRAL Register for Controlled Trials for articles published between 2000 and 2020 using the terms "orthopedics," "orthopaedics," "musculoskeletal," "osteoarthritis," and "mud bath," "mud pack."<br><br>RESULTS: Of the 19 studies included, 15 examined the effects of mud-bath therapy in knee osteoarthritis treatment. One study focused on the treatment effect of mud bath on hand osteoarthritis, another study examined treatment effects in hip and knee osteoarthritis, and two studies enrolled patients with chronic low back pain caused by lumbar spine osteoarthritis. We systematically reviewed the data obtained from the literature and summarized the results on the basis of the main outcomes. The results show significant improvements in function, quality of life, and perceived pain for patients with osteoarthritis.<br><br>CONCLUSION: Results of randomized controlled trials suggest that mud therapy is part of a promising integrated and synergistic multidisciplinary approach in combination with other treatment forms like pharmacotherapy or physiotherapy.<br><br>UNLABELLED: <title>Ziele</title>Die sozio-&#xf6;konomischen Auswirkungen der Arthrose sind immens. Heiltorfbehandlungen sind seit einiger Zeit als m&#xf6;gliche Erg&#xe4;nzung der konservativen Therapieoptionen dieser Erkrankung Gegenstand wissenschaftlicher Untersuchungen. Ziel dieser Studie war es, die aktuellen Erkenntnisse zur Heiltorftherapie bei Arthrose zusammenzufassen.<title>Methoden</title>Wir f&#xfc;hrten eine systematische Literaturrecherche der Datenbanken Pubmed, PEDro und Cochrane CENTRAL Register of Controlled Trials durch. Hierbei wurden Artikel, die zwischen 2000 und 2020 publiziert wurden und mit den Schlagw&#xf6;rtern &#x201c;orthopedics&#x201d;, &#x201c;orthopaedics&#x201d;, &#x201c;musculoskeletal&#x201d;, &#x201c;osteoarthritis&#x201d; und &#x201c;mud-bath&#x201d;, &#x201c;mud-pack&#x201d; assoziiert waren, erfasst.<title>Ergebnisse</title>Von den 19 n&#xe4;her untersuchten Studien besch&#xe4;ftigten sich 15 mit den Effekten der Heiltorftherapie bei Patienten mit Kniearthrose, eine Studie untersuchte Patienten mit Arthrose der Hand, eine weitere Studie untersuchte die Auswirkung der Therapie bei Arthrose der H&#xfc;fte. 2 Studien untersuchten den Effekt der Moorb&#xe4;der bei Patienten mit chronischen R&#xfc;ckenschmerzen. Insgesamt zeigten sich signifikante Verbesserungen der Funktion, Lebensqualit&#xe4;t und Schmerzlinderung bei den Patienten unter Heiltorftherapie.<title>Zusammenfassung</title>Die Ergebnisse der randomisierten, kontrollierten Studien zeigen, dass die Heiltorftherapie eine vielversprechende Erg&#xe4;nzung in einem multidisziplin&#xe4;ren Ansatz der Arthrosetherapie ist.}, }
@article {pmid38007795, year = {2023}, author = {Feng, T}, title = {Applications of Artificial Intelligence to Diagnosis of Neurodegenerative Diseases.}, journal = {Studies in health technology and informatics}, volume = {308}, number = {}, pages = {648-655}, doi = {10.3233/SHTI230896}, pmid = {38007795}, issn = {1879-8365}, mesh = {Humans ; Artificial Intelligence ; *Neurodegenerative Diseases/diagnostic imaging ; *Alzheimer Disease/diagnostic imaging ; Machine Learning ; Natural Language Processing ; }, abstract = {Artificial Intelligence (AI) is an umbrella term that represents a new technology for simulating and expanding human intelligence by using machines and computer systems. It consists of methods such as machine learning (ML), deep learning (DL), and natural language processing (NLP). In the era of big data, AI has emerged as an essential tool for improving the detection of neurodegenerative diseases, such as Alzheimer's diseases (AD), Parkinson's diseases, amyotrophic lateral sclerosis, etc. AI with its ability to extract critical information from the mass of data has enabled scientists to deal with various types of large-volume data, including genetic data, imaging data, and clinical data, rapidly generated in the course of neurodegenerative disease research. This review provides a comprehensive overview of the literature on current AI applications in the diagnosis of neurodegenerative diseases. Firstly, bioinformatics and AI approaches to identify potential biomarkers for neurodegenerative diseases such as AD are reviewed. Secondly, the use of ML and DL methods to analyze Magnetic Resonance Imaging (MRI) data for a better understanding of disease progression and predicting patient outcomes is discussed. Finally, the use of AI methods including NLP for Electronic Health Record (EHR) data analysis to extract meaningful information and identify patterns that may contribute to early diagnosis and treatment planning are reviewed. The potential benefits of AI-based approaches in improving patient outcomes and the challenges associated with their implementations are also discussed. Overall, this paper highlights the promise of AI in transforming the diagnosis and management of neurodegenerative diseases.}, }
@article {pmid38004577, year = {2023}, author = {Niazi, SK}, title = {Non-Invasive Drug Delivery across the Blood-Brain Barrier: A Prospective Analysis.}, journal = {Pharmaceutics}, volume = {15}, number = {11}, pages = {}, pmid = {38004577}, issn = {1999-4923}, abstract = {Non-invasive drug delivery across the blood-brain barrier (BBB) represents a significant advancement in treating neurological diseases. The BBB is a tightly packed layer of endothelial cells that shields the brain from harmful substances in the blood, allowing necessary nutrients to pass through. It is a highly selective barrier, which poses a challenge to delivering therapeutic agents into the brain. Several non-invasive procedures and devices have been developed or are currently being investigated to enhance drug delivery across the BBB. This paper presents a review and a prospective analysis of the art and science that address pharmacology, technology, delivery systems, regulatory approval, ethical concerns, and future possibilities.}, }
@article {pmid38003309, year = {2023}, author = {Toader, C and Dobrin, N and Brehar, FM and Popa, C and Covache-Busuioc, RA and Glavan, LA and Costin, HP and Bratu, BG and Corlatescu, AD and Popa, AA and Ciurea, AV}, title = {From Recognition to Remedy: The Significance of Biomarkers in Neurodegenerative Disease Pathology.}, journal = {International journal of molecular sciences}, volume = {24}, number = {22}, pages = {}, pmid = {38003309}, issn = {1422-0067}, mesh = {Humans ; *Neurodegenerative Diseases/diagnosis/metabolism ; *Amyotrophic Lateral Sclerosis ; *Parkinson Disease/diagnosis/metabolism ; *Alzheimer Disease/diagnosis ; Biomarkers/metabolism ; }, abstract = {With the inexorable aging of the global populace, neurodegenerative diseases (NDs) like Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) pose escalating challenges, which are underscored by their socioeconomic repercussions. A pivotal aspect in addressing these challenges lies in the elucidation and application of biomarkers for timely diagnosis, vigilant monitoring, and effective treatment modalities. This review delineates the quintessence of biomarkers in the realm of NDs, elucidating various classifications and their indispensable roles. Particularly, the quest for novel biomarkers in AD, transcending traditional markers in PD, and the frontier of biomarker research in ALS are scrutinized. Emergent susceptibility and trait markers herald a new era of personalized medicine, promising enhanced treatment initiation especially in cases of SOD1-ALS. The discourse extends to diagnostic and state markers, revolutionizing early detection and monitoring, alongside progression markers that unveil the trajectory of NDs, propelling forward the potential for tailored interventions. The synergy between burgeoning technologies and innovative techniques like -omics, histologic assessments, and imaging is spotlighted, underscoring their pivotal roles in biomarker discovery. Reflecting on the progress hitherto, the review underscores the exigent need for multidisciplinary collaborations to surmount the challenges ahead, accelerate biomarker discovery, and herald a new epoch of understanding and managing NDs. Through a panoramic lens, this article endeavors to provide a comprehensive insight into the burgeoning field of biomarkers in NDs, spotlighting the promise they hold in transforming the diagnostic landscape, enhancing disease management, and illuminating the pathway toward efficacious therapeutic interventions.}, }
@article {pmid38002924, year = {2023}, author = {Genin, EC and Abou-Ali, M and Paquis-Flucklinger, V}, title = {Mitochondria, a Key Target in Amyotrophic Lateral Sclerosis Pathogenesis.}, journal = {Genes}, volume = {14}, number = {11}, pages = {}, pmid = {38002924}, issn = {2073-4425}, support = {ANR-16-CE16-0024-01//Agence Nationale de la Recherche/ ; MND202004011475//Fondation pour la Recherche M&#xe9;dicale/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology ; Mitochondria/metabolism ; Motor Neurons/metabolism ; Cell Death/genetics ; Mitochondrial Proteins/genetics/metabolism ; }, abstract = {Mitochondrial dysfunction occurs in numerous neurodegenerative diseases, particularly amyotrophic lateral sclerosis (ALS), where it contributes to motor neuron (MN) death. Of all the factors involved in ALS, mitochondria have been considered as a major player, as secondary mitochondrial dysfunction has been found in various models and patients. Abnormal mitochondrial morphology, defects in mitochondrial dynamics, altered activities of respiratory chain enzymes and increased production of reactive oxygen species have been described. Moreover, the identification of CHCHD10 variants in ALS patients was the first genetic evidence that a mitochondrial defect may be a primary cause of MN damage and directly links mitochondrial dysfunction to the pathogenesis of ALS. In this review, we focus on the role of mitochondria in ALS and highlight the pathogenic variants of ALS genes associated with impaired mitochondrial functions. The multiple pathways demonstrated in ALS pathogenesis suggest that all converge to a common endpoint leading to MN loss. This may explain the disappointing results obtained with treatments targeting a single pathological process. Fighting against mitochondrial dysfunction appears to be a promising avenue for developing combined therapies in the future.}, }
@article {pmid38002659, year = {2023}, author = {O'Day, DH}, title = {Protein Biomarkers Shared by Multiple Neurodegenerative Diseases Are Calmodulin-Binding Proteins Offering Novel and Potentially Universal Therapeutic Targets.}, journal = {Journal of clinical medicine}, volume = {12}, number = {22}, pages = {}, pmid = {38002659}, issn = {2077-0383}, abstract = {Seven major neurodegenerative diseases and their variants share many overlapping biomarkers that are calmodulin-binding proteins: Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), frontotemporal lobar dementia (FTD), Huntington's disease (HD), Lewy body disease (LBD), multiple sclerosis (MS), and Parkinson's disease (PD). Calcium dysregulation is an early and persistent event in each of these diseases, with calmodulin serving as an initial and primary target of increased cytosolic calcium. Considering the central role of calcium dysregulation and its downstream impact on calcium signaling, calmodulin has gained interest as a major regulator of neurodegenerative events. Here, we show that calmodulin serves a critical role in neurodegenerative diseases via binding to and regulating an abundance of biomarkers, many of which are involved in multiple neurodegenerative diseases. Of special interest are the shared functions of calmodulin in the generation of protein biomarker aggregates in AD, HD, LBD, and PD, where calmodulin not only binds to amyloid beta, pTau, alpha-synuclein, and mutant huntingtin but also, via its regulation of transglutaminase 2, converts them into toxic protein aggregates. It is suggested that several calmodulin binding proteins could immediately serve as primary drug targets, while combinations of calmodulin binding proteins could provide simultaneous insight into the onset and progression of multiple neurodegenerative diseases.}, }
@article {pmid38002264, year = {2023}, author = {Duranti, E and Villa, C}, title = {Muscle Involvement in Amyotrophic Lateral Sclerosis: Understanding the Pathogenesis and Advancing Therapeutics.}, journal = {Biomolecules}, volume = {13}, number = {11}, pages = {}, pmid = {38002264}, issn = {2218-273X}, mesh = {Animals ; Humans ; *Amyotrophic Lateral Sclerosis/therapy/pathology ; Motor Neurons/metabolism ; Muscle, Skeletal/pathology ; Muscular Atrophy/metabolism ; Paralysis/complications/pathology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal condition characterized by the selective loss of motor neurons in the motor cortex, brainstem, and spinal cord. Muscle involvement, muscle atrophy, and subsequent paralysis are among the main features of this disease, which is defined as a neuromuscular disorder. ALS is a persistently progressive disease, and as motor neurons continue to degenerate, individuals with ALS experience a gradual decline in their ability to perform daily activities. Ultimately, muscle function loss may result in paralysis, presenting significant challenges in mobility, communication, and self-care. While the majority of ALS research has traditionally focused on pathogenic pathways in the central nervous system, there has been a great interest in muscle research. These studies were carried out on patients and animal models in order to better understand the molecular mechanisms involved and to develop therapies aimed at improving muscle function. This review summarizes the features of ALS and discusses the role of muscle, as well as examines recent studies in the development of treatments.}, }
@article {pmid38001967, year = {2023}, author = {Seki, S and Kitaoka, Y and Kawata, S and Nishiura, A and Uchihashi, T and Hiraoka, SI and Yokota, Y and Isomura, ET and Kogo, M and Tanaka, S}, title = {Characteristics of Sensory Neuron Dysfunction in Amyotrophic Lateral Sclerosis (ALS): Potential for ALS Therapy.}, journal = {Biomedicines}, volume = {11}, number = {11}, pages = {}, pmid = {38001967}, issn = {2227-9059}, support = {21K17088//JSPS KAKENHI/ ; 20H03887//JSPS KAKENHI/ ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterised by the progressive degeneration of motor neurons, resulting in muscle weakness, paralysis, and, ultimately, death. Presently, no effective treatment for ALS has been established. Although motor neuron dysfunction is a hallmark of ALS, emerging evidence suggests that sensory neurons are also involved in the disease. In clinical research, 30% of patients with ALS had sensory symptoms and abnormal sensory nerve conduction studies in the lower extremities. Peroneal nerve biopsies show histological abnormalities in 90% of the patients. Preclinical research has reported several genetic abnormalities in the sensory neurons of animal models of ALS, as well as in motor neurons. Furthermore, the aggregation of misfolded proteins like TAR DNA-binding protein 43 has been reported in sensory neurons. This review aims to provide a comprehensive description of ALS-related sensory neuron dysfunction, focusing on its clinical changes and underlying mechanisms. Sensory neuron abnormalities in ALS are not limited to somatosensory issues; proprioceptive sensory neurons, such as MesV and DRG neurons, have been reported to form networks with motor neurons and may be involved in motor control. Despite receiving limited attention, sensory neuron abnormalities in ALS hold potential for new therapies targeting proprioceptive sensory neurons.}, }
@article {pmid38001926, year = {2023}, author = {Reddy, VP}, title = {Oxidative Stress in Health and Disease.}, journal = {Biomedicines}, volume = {11}, number = {11}, pages = {}, pmid = {38001926}, issn = {2227-9059}, abstract = {Oxidative stress, resulting from the excessive intracellular accumulation of reactive oxygen species (ROS), reactive nitrogen species (RNS), and other free radical species, contributes to the onset and progression of various diseases, including diabetes, obesity, diabetic nephropathy, diabetic neuropathy, and neurological diseases, such as Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). Oxidative stress is also implicated in cardiovascular disease and cancer. Exacerbated oxidative stress leads to the accelerated formation of advanced glycation end products (AGEs), a complex mixture of crosslinked proteins and protein modifications. Relatively high levels of AGEs are generated in diabetes, obesity, AD, and other I neurological diseases. AGEs such as N[e]-carboxymethyllysine (CML) serve as markers for disease progression. AGEs, through interaction with receptors for advanced glycation end products (RAGE), initiate a cascade of deleterious signaling events to form inflammatory cytokines, and thereby further exacerbate oxidative stress in a vicious cycle. AGE inhibitors, AGE breakers, and RAGE inhibitors are therefore potential therapeutic agents for multiple diseases, including diabetes and AD. The complexity of the AGEs and the lack of well-established mechanisms for AGE formation are largely responsible for the lack of effective therapeutics targeting oxidative stress and AGE-related diseases. This review addresses the role of oxidative stress in the pathogenesis of AGE-related chronic diseases, including diabetes and neurological disorders, and recent progress in the development of therapeutics based on antioxidants, AGE breakers and RAGE inhibitors. Furthermore, this review outlines therapeutic strategies based on single-atom nanozymes that attenuate oxidative stress through the sequestering of reactive oxygen species (ROS) and reactive nitrogen species (RNS).}, }
@article {pmid38001557, year = {2024}, author = {Genge, A and Wainwright, S and Vande Velde, C}, title = {Amyotrophic lateral sclerosis: exploring pathophysiology in the context of treatment.}, journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration}, volume = {25}, number = {3-4}, pages = {225-236}, doi = {10.1080/21678421.2023.2278503}, pmid = {38001557}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a complex, neurodegenerative disorder in which alterations in structural, physiological, and metabolic parameters act synergistically. Over the last decade there has been a considerable focus on developing drugs to slow the progression of the disease. Despite this, only four disease-modifying therapies are approved in North America. Although additional research is required for a thorough understanding of ALS, we have accumulated a large amount of knowledge that could be better integrated into future clinical trials to accelerate drug development and provide patients with improved treatment options. It is likely that future, successful ALS treatments will take a multi-pronged therapeutic approach, targeting different pathways, akin to personalized medicine in oncology. In this review, we discuss the link between ALS pathophysiology and treatments, looking at the therapeutic failures as learning opportunities that can help us refine and optimize drug development.}, }
@article {pmid37999738, year = {2024}, author = {Ovsepian, SV and O'Leary, VB and Martinez, S}, title = {Selective vulnerability of motor neuron types and functional groups to degeneration in amyotrophic lateral sclerosis: review of the neurobiological mechanisms and functional correlates.}, journal = {Brain structure &amp; function}, volume = {229}, number = {1}, pages = {1-14}, pmid = {37999738}, issn = {1863-2661}, support = {Innovation Fund Award 2022//University of Greenwich/ ; COOPERATIO-207036//VBO, Charles University/ ; SAF2017-83702-R//Una manera de hacer Europa/ ; }, mesh = {Humans ; Animals ; *Amyotrophic Lateral Sclerosis ; Motor Neurons ; Disease Models, Animal ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative condition characterised by a progressive loss of motor neurons controlling voluntary muscle activity. The disease manifests through a variety of motor dysfunctions related to the extent of damage and loss of neurons at different anatomical locations. Despite extensive research, it remains unclear why some motor neurons are especially susceptible to the disease, while others are affected less or even spared. In this article, we review the neurobiological mechanisms, neurochemical profiles, and morpho-functional characteristics of various motor neuron groups and types of motor units implicated in their differential exposure to degeneration. We discuss specific cell-autonomous (intrinsic) and extrinsic factors influencing the vulnerability gradient of motor units and motor neuron types to ALS, with their impact on disease manifestation, course, and prognosis, as revealed in preclinical and clinical studies. We consider the outstanding challenges and emerging opportunities for interpreting the phenotypic and mechanistic variability of the disease to identify targets for clinical interventions.}, }
@article {pmid37992921, year = {2024}, author = {Li, L and Lei, T and Xing, C and Du, H}, title = {Advances in microfluidic chips targeting toxic aggregation proteins for neurodegenerative diseases.}, journal = {International journal of biological macromolecules}, volume = {256}, number = {Pt 2}, pages = {128308}, doi = {10.1016/j.ijbiomac.2023.128308}, pmid = {37992921}, issn = {1879-0003}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism ; Microfluidics ; *Alzheimer Disease ; Amyloid beta-Peptides ; }, abstract = {Neurodegenerative diseases (NDs) are characterized by nervous system damage, often influenced by genetic and aging factors. Pathological analysis frequently reveals the presence of aggregated toxic proteins. The intricate and poorly understood origins of these diseases have hindered progress in early diagnosis and drug development. The development of novel in-vitro and in-vivo models could enhance our comprehension of ND mechanisms and facilitate clinical treatment advancements. Microfluidic chips are employed to establish three-dimensional culture conditions, replicating the human ecological niche and creating a microenvironment conducive to neuronal cell survival. The incorporation of mechatronic controls unifies the chip, cells, and culture medium optimizing living conditions for the cells. This study provides a comprehensive overview of microfluidic chip applications in drug and biomarker screening for neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, and amyotrophic lateral sclerosis. Our Lab-on-a-Chip system releases toxic proteins to simulate the pathological characteristics of neurodegenerative diseases, encompassing β-amyloid, α-synuclein, huntingtin, TAR DNA-binding protein 43, and Myelin Basic Protein. Investigating molecular and cellular interactions in vitro can enhance our understanding of disease mechanisms while minimizing harmful protein levels and can aid in screening potential therapeutic agents. We anticipate that our research will promote the utilization of microfluidic chips in both fundamental research and clinical applications for neurodegenerative diseases.}, }
@article {pmid37988405, year = {2024}, author = {Nusrath, S and Kalluru, P and Shukla, S and Dharanikota, A and Basude, M and Jonnada, P and Abualjadayel, M and Alabbad, S and Mir, TA and Broering, DC and Raju, K and Rao, TS and Vashist, YK}, title = {Current status of indocyanine green fluorescent angiography in assessing perfusion of gastric conduit and oesophago-gastric anastomosis.}, journal = {International journal of surgery (London, England)}, volume = {110}, number = {2}, pages = {1079-1089}, pmid = {37988405}, issn = {1743-9159}, mesh = {Humans ; *Indocyanine Green ; *Coloring Agents ; Angiography/adverse effects ; Anastomotic Leak/diagnostic imaging/etiology ; Anastomosis, Surgical/adverse effects/methods ; Esophagectomy/adverse effects/methods ; Perfusion ; }, abstract = {Anastomotic leak (AL) remains a significant complication after esophagectomy. Indocyanine green fluorescent angiography (ICG-FA) is a promising and safe technique for assessing gastric conduit (GC) perfusion intraoperatively. It provides detailed visualization of tissue perfusion and has demonstrated usefulness in oesophageal surgery. GC perfusion analysis by ICG-FA is crucial in constructing the conduit and selecting the anastomotic site and enables surgeons to make necessary adjustments during surgery to potentially reduce ALs. However, anastomotic integrity involves multiple factors, and ICG-FA must be combined with optimization of patient and procedural factors to decrease AL rates. This review summarizes ICG-FA's current applications in assessing esophago-gastric anastomosis perfusion, including qualitative and quantitative analysis and different imaging systems. It also explores how fluorescent imaging could decrease ALs and aid clinicians in utilizing ICG-FA to improve esophagectomy outcomes.}, }
@article {pmid37982993, year = {2023}, author = {Tsui, A and Kouznetsova, VL and Kesari, S and Fiala, M and Tsigelny, IF}, title = {Role of Senataxin in Amyotrophic Lateral Sclerosis.}, journal = {Journal of molecular neuroscience : MN}, volume = {73}, number = {11-12}, pages = {996-1009}, pmid = {37982993}, issn = {1559-1166}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; Motor Neurons/metabolism ; Gene Expression Regulation ; Mutation ; DNA Helicases/genetics ; RNA Helicases/genetics/metabolism ; Multifunctional Enzymes/genetics/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive, uncurable neurodegenerative disorder characterized by the degradation of motor neurons leading to muscle impairment, failure, and death. Senataxin, encoded by the SETX gene, is a human helicase protein whose mutations have been linked with ALS onset, particularly in its juvenile ALS4 form. Using senataxin's yeast homolog Sen1 as a model for study, it is suggested that senataxin's N-terminus interacts with RNA polymerase II, whilst its C-terminus engages in helicase activity. Senataxin is heavily involved in transcription regulation, termination, and R-loop resolution, enabled by recruitment and interactions with enzymes such as ubiquitin protein ligase SAN1 and ribonuclease H (RNase H). Senataxin also engages in DNA damage response (DDR), primarily interacting with the exosome subunit Rrp45. The Sen1 mutation E1597K, alongside the L389S and R2136H gain-of-function mutations to senataxin, is shown to cause negative structural and thus functional effects to the protein, thus contributing to a disruption in WT functions, motor neuron (MN) degeneration, and the manifestation of ALS clinical symptoms. This review corroborates and summarizes published papers concerning the structure and function of senataxin as well as the effects of their mutations in ALS pathology in order to compile current knowledge and provide a reference for future research. The findings compiled in this review are indicative of the experimental and therapeutic potential of senataxin and its mutations as a target in future ALS treatment/cure discovery, with some potential therapeutic routes also being discussed in the review.}, }
@article {pmid37982655, year = {2024}, author = {Mossa, A and Mayahara, M and Emezue, C and Paun, O}, title = {The Impact of Rapidly Progressing Neurodegenerative Disorders on Caregivers: An Integrative Literature Review.}, journal = {Journal of hospice and palliative nursing : JHPN : the official journal of the Hospice and Palliative Nurses Association}, volume = {26}, number = {2}, pages = {E62-E73}, pmid = {37982655}, issn = {1539-0705}, mesh = {Humans ; *Quality of Life ; Caregivers ; *Amyotrophic Lateral Sclerosis ; Disease Progression ; Death ; }, abstract = {Neurodegenerative disorders affect over 6 million people in the United States. A subset of these patients experiences symptoms that progress rapidly, along with a 5- to 10-year life expectancy (amyotrophic lateral sclerosis). This subgroup often becomes dependent on family caregivers. Managing care demands at the end of life that are brought on by rapid disease progression has a negative impact on caregiver quality of life. The purpose of this integrative review is to highlight the gaps in the existing body of research on the effect of neuropalliative care on quality of life of this caregiver population. A total of 13 articles met inclusion criteria and were selected for review. The most frequently occurring themes and findings in the literature shed light on neuropalliative care and provided some insight into both caregivers and patients' perspective at the end of life. What sets this population apart from caregivers and patients of other terminal diseases is the nature of disease progression and the rapid life adjustments that come along with it. Integration of neuropalliative has shown to provide additional support for caregivers and patients; however, it remains underused. To promote equitable access to these services, it is necessary to address several structural barriers.}, }
@article {pmid37981468, year = {2024}, author = {Sutter, PA and Lavoie, ER and Lombardo, ET and Pinter, MK and Crocker, SJ}, title = {Emerging Role of Astrocyte-Derived Extracellular Vesicles as Active Participants in CNS Neuroimmune Responses.}, journal = {Immunological investigations}, volume = {53}, number = {1}, pages = {26-39}, pmid = {37981468}, issn = {1532-4311}, support = {F30 NS129238/NS/NINDS NIH HHS/United States ; R01 NS131327/NS/NINDS NIH HHS/United States ; R21 NS125332/NS/NINDS NIH HHS/United States ; R56 NS099359/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Astrocytes ; *Extracellular Vesicles ; Cell Communication ; Biomarkers ; }, abstract = {Astrocyte-derived extracellular vesicles (ADEVs) have garnered attention as a fundamental mechanism of intercellular communication in health and disease. In the context of neurological diseases, for which prodromal diagnosis would be advantageous, ADEVs are also being explored for their potential utility as biomarkers. In this review, we provide the current state of data supporting our understanding on the manifold roles of ADEVs in several common neurological disorders. We also discuss these findings from a unique emerging perspective that ADEVs represent a means by which the central nervous system may broadcast influence over other systems in the body to affect neuroinflammatory processes, with both dual potential to either propagate illness or restore health and homeostasis.}, }
@article {pmid37981175, year = {2023}, author = {Wang, C and Cui, Y and Xu, T and Zhou, Y and Yang, R and Wang, T}, title = {New insights into glycogen synthase kinase-3: A common target for neurodegenerative diseases.}, journal = {Biochemical pharmacology}, volume = {218}, number = {}, pages = {115923}, doi = {10.1016/j.bcp.2023.115923}, pmid = {37981175}, issn = {1873-2968}, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/metabolism ; Glycogen Synthase Kinase 3 ; *Parkinson Disease ; *Alzheimer Disease ; *Diabetes Mellitus/drug therapy ; Glycogen Synthase Kinase 3 beta ; }, abstract = {Glycogen synthase kinase 3 (GSK-3) is a highly conserved protein serine/threonine kinase that plays a central role in a wide variety of cellular processes to coordinate catabolic and anabolic pathways and regulate cell growth and fate. There is increasing evidence showing that abnormal glycogen synthase kinase 3 (GSK-3) is associated with the pathogenesis and progression of many disorders, such as cancer, diabetes, psychiatric diseases, and neurodegenerative diseases. In this review, we summarize recent findings about the regulatory role of GSK-3 in the occurrence and development of multiple neurodegenerative diseases, mainly focusing on Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. The aim of this study is to provide new insight into the shared working mechanism of GSK-3 as a therapeutic target of multiple neurodegenerative diseases.}, }
@article {pmid37975798, year = {2024}, author = {Saini, A and Chawla, PA}, title = {Breaking barriers with tofersen: Enhancing therapeutic opportunities in amyotrophic lateral sclerosis.}, journal = {European journal of neurology}, volume = {31}, number = {2}, pages = {e16140}, pmid = {37975798}, issn = {1468-1331}, mesh = {Adult ; Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics ; Superoxide Dismutase-1/genetics ; *Neurodegenerative Diseases ; Oligonucleotides/therapeutic use ; }, abstract = {BACKGROUND AND PURPOSE: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that primarily affects adults, characterized by muscle weakness resulting from the specific death of motor neurons in the spinal cord and brain. The pathogenesis of ALS is associated with the accumulation of mutant superoxide dismutase 1 (SOD1) proteins and neurofilaments in motor neurons, highlighting the critical need for disease-modifying treatments. Current therapies, such as riluzole and edaravone, provide only symptomatic relief. Recently, tofersen gained approval from the US FDA under the brand name Qalsody as the first and only gene therapy for ALS, addressing a significant pathological aspect of the disease.<br><br>METHODS: We carried out a literature survey using PubMed, Scopus, National Institutes of Health, and Biogen for articles published in the English language concerned with "amyotrophic lateral sclerosis", pathophysiology, current treatment, treatment under clinical trial, and the newly approved drug "tofersen" and its detailed summary.<br><br>RESULTS: A comprehensive review of the literature on the pathophysiology, available treatment, and newly approved drug for this condition revealed convincing evidence that we are now able to better monitor and treat ALS.<br><br>CONCLUSIONS: Although treatment of ALS is difficult, the newly approved drug tofersen has emerged as a potential therapy to slow down the progression of ALS by targeting SOD1 mRNA, representing a significant advancement in the treatment of ALS.}, }
@article {pmid37974959, year = {2023}, author = {Bhargava, S and Kulkarni, R and Dewangan, B and Kulkarni, N and Jiaswar, C and Kumar, K and Kumar, A and Bodhe, PR and Kumar, H and Sahu, B}, title = {Microtubule stabilising peptides: new paradigm towards management of neuronal disorders.}, journal = {RSC medicinal chemistry}, volume = {14}, number = {11}, pages = {2192-2205}, pmid = {37974959}, issn = {2632-8682}, abstract = {Neuronal cells made of soma, axon, and dendrites are highly compartmentalized and possess a specialized transport system that can convey long-distance electrical signals for the cross-talk. The transport system is made up of microtubule (MT) polymers and MT-binding proteins. MTs play vital and diverse roles in various cellular processes. Therefore, defects and dysregulation of MTs and their binding proteins lead to many neurological disorders as exemplified by Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, and many others. MT-stabilising agents (MSAs) altering the MT-associated protein connections have shown great potential for several neurodegenerative disorders. Peptides are an important class of molecules with high specificity, biocompatibility and are devoid of side effects. In the past, peptides have been explored in various neuronal disorders as therapeutics. Davunetide, a MT-stabilising octapeptide, has entered into phase II clinical trials for schizophrenia. Numerous examples of peptides emerging as MSAs reflect the emergence of a new paradigm for peptides which can be explored further as drug candidates for neuronal disorders. Although small molecule-based MSAs have been reviewed in the past, there is no systematic review in recent years focusing on peptides as MSAs apart from davunetide in 2013. Therefore, a systematic updated review on MT stabilising peptides may shed light on many hidden aspects and enable researchers to develop new therapies for diseases related to the CNS. In this review we have summarised the recent examples of peptides as MSAs.}, }
@article {pmid37974227, year = {2023}, author = {Awuah, WA and Ahluwalia, A and Ghosh, S and Roy, S and Tan, JK and Adebusoye, FT and Ferreira, T and Bharadwaj, HR and Shet, V and Kundu, M and Yee, ALW and Abdul-Rahman, T and Atallah, O}, title = {The molecular landscape of neurological disorders: insights from single-cell RNA sequencing in neurology and neurosurgery.}, journal = {European journal of medical research}, volume = {28}, number = {1}, pages = {529}, pmid = {37974227}, issn = {2047-783X}, mesh = {Humans ; *Neurosurgery ; Neurosurgical Procedures ; *Neurology ; *Brain Neoplasms/genetics ; Sequence Analysis, RNA ; Tumor Microenvironment ; }, abstract = {Single-cell ribonucleic acid sequencing (scRNA-seq) has emerged as a transformative technology in neurological and neurosurgical research, revolutionising our comprehension of complex neurological disorders. In brain tumours, scRNA-seq has provided valuable insights into cancer heterogeneity, the tumour microenvironment, treatment resistance, and invasion patterns. It has also elucidated the brain tri-lineage cancer hierarchy and addressed limitations of current models. Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis have been molecularly subtyped, dysregulated pathways have been identified, and potential therapeutic targets have been revealed using scRNA-seq. In epilepsy, scRNA-seq has explored the cellular and molecular heterogeneity underlying the condition, uncovering unique glial subpopulations and dysregulation of the immune system. ScRNA-seq has characterised distinct cellular constituents and responses to spinal cord injury in spinal cord diseases, as well as provided molecular signatures of various cell types and identified interactions involved in vascular remodelling. Furthermore, scRNA-seq has shed light on the molecular complexities of cerebrovascular diseases, such as stroke, providing insights into specific genes, cell-specific expression patterns, and potential therapeutic interventions. This review highlights the potential of scRNA-seq in guiding precision medicine approaches, identifying clinical biomarkers, and facilitating therapeutic discovery. However, challenges related to data analysis, standardisation, sample acquisition, scalability, and cost-effectiveness need to be addressed. Despite these challenges, scRNA-seq has the potential to transform clinical practice in neurological and neurosurgical research by providing personalised insights and improving patient outcomes.}, }
@article {pmid37974182, year = {2023}, author = {Soskolne, CL}, title = {Exposing additional authors who suppress evidence about radiation-induced thyroid cancer in children: a Comment adding to Tsuda et al.'s response to Schüz et al. (2023).}, journal = {Environmental health : a global access science source}, volume = {22}, number = {1}, pages = {79}, pmid = {37974182}, issn = {1476-069X}, mesh = {Adult ; Humans ; Child ; *Thyroid Neoplasms/epidemiology/etiology ; Public Health ; *Fukushima Nuclear Accident ; *Neoplasms, Radiation-Induced/epidemiology ; }, abstract = {BACKGROUND: The need to call out and expose authors for their persistence in improperly using epidemiology has been previously noted. Tsuda et al. have done well to expose Schüz et al.'s arguments/assertions in their recent publication in Environmental Heath. In this Comment, I point out that, also warranting being called out, are the arguments/assertions of Cléro et al. who, in their recent response to an article by Tsuda et al., reiterated the conclusions and recommendations derived from their European project, which were published in Environment International in 2021. Tsuda et al. had critiqued the Cléro et al. 2021 publication in their 2022 review article. However, in their response to it, Cléro et al. deflected by not addressing any of the key points that Tsuda et al. had made in their review regarding the aftermath of the Chernobyl and Fukushima nuclear accidents. In this Comment, I critique Cléro et al.'s inadequate response. Publication of this Comment will help in routing out the improper use of epidemiology in the formulation of public health policy and thereby reduce the influence of misinformation on both science and public policy. My critique of Cléro et al. is not dissimilar from Tsuda et al.'s critique of Schüz et al.: in as much as Schüz et al. should withdraw their work, so should Cléro et al.'s article be retracted.<br><br>MAIN BODY: The response by Cl&#xe9;ro et al. consists of four paragraphs. First was their assertion that the purpose of the SHAMISEN project was to make recommendations based on scientific evidence and that it was not a systematic review of all related articles. I point out that the Cl&#xe9;ro et al. recommendations were not based on objective scientific evidence, but on biased studies. In the second paragraph, Cl&#xe9;ro et al. reaffirmed the SHAMISEN Consortium report, which claimed that the overdiagnosis observed in non-exposed adults was applicable to children because children are mirrors of adults. However, the authors of that report withheld statements about secondary examinations in Fukushima that provided evidence against overdiagnosis. In the third paragraph, Cl&#xe9;ro et al. provided an explanation regarding their disclosure of conflicting interests, which was contrary to professional norms for transparency and thus was unacceptable. Finally, their insistence that the Tsuda et al. study was an ecological study susceptible to "the ecological fallacy" indicated their lack of epidemiological knowledge about ecological studies. Ironically, many of the papers cited by Cl&#xe9;ro et al. regarding overdiagnosis were, in fact, ecological studies.<br><br>CONCLUSION: Cl&#xe9;ro et al. and the SHAMISEN Consortium should withdraw their recommendation "not to launch a mass thyroid cancer screening after a nuclear accident, but rather to make it available (with appropriate information counselling) to those who request it." Their recommendation is based on biased evidence and would cause confusion regarding public health measures following a nuclear accident. Those authors should, in my assessment, acquaint themselves with modern epidemiology and evidence-based public health. Like Tsuda et al. recommended of Sch&#xfc;z et al., Cl&#xe9;ro et al. ought also to retract their article.}, }
@article {pmid37973672, year = {2023}, author = {Lo Giudice, M and Cocco, A and Reggiardo, G and Lalli, S and Albanese, A}, title = {Tauro-Urso-Deoxycholic Acid Trials in Amyotrophic Lateral Sclerosis: What is Achieved and What to Expect.}, journal = {Clinical drug investigation}, volume = {43}, number = {12}, pages = {893-903}, pmid = {37973672}, issn = {1179-1918}, support = {755094//Horizon 2020 Framework Programme/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; Phenylbutyrates ; Taurochenodeoxycholic Acid/adverse effects ; }, abstract = {Phase II studies on tauro-urso-deoxycholic acid (TUDCA) raised the promise of safety and efficacy in patients with amyotrophic lateral sclerosis, a currently incurable and devastating disease. We review the available evidence on the efficacy and safety of TUDCA, administered alone or in combination, by analyzing and comparing published and ongoing studies on amyotrophic lateral sclerosis. Two independent phase II studies (using TUDCA solo or combined with sodium phenylbutyrate) showed similar efficacy in slowing disease progression measured by functional scales. One open-label follow-up TUDCA+sodium phenylbutyrate study suggested a benefit on survival. Two subsequent phase III studies with TUDCA (solo or combined with sodium phenylbutyrate) have been initiated and are currently ongoing. Their completion is expected by the end of 2023 and beginning of 2024. Evidence collected by phase II studies indicates that there are no safety concerns in patients with amyotrophic lateral sclerosis. The efficacy shown in phase II studies was considered sufficient to grant approval in some countries but not in others, owing to discrepant views on the strength of evidence. It will be necessary to wait for the results of ongoing phase III studies to attain a full appreciation of these data.}, }
@article {pmid37972860, year = {2023}, author = {Rizzuti, M and Sali, L and Melzi, V and Scarcella, S and Costamagna, G and Ottoboni, L and Quetti, L and Brambilla, L and Papadimitriou, D and Verde, F and Ratti, A and Ticozzi, N and Comi, GP and Corti, S and Gagliardi, D}, title = {Genomic and transcriptomic advances in amyotrophic lateral sclerosis.}, journal = {Ageing research reviews}, volume = {92}, number = {}, pages = {102126}, doi = {10.1016/j.arr.2023.102126}, pmid = {37972860}, issn = {1872-9649}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/therapy ; Transcriptome/genetics ; Gene Expression Profiling/methods ; *MicroRNAs/genetics/metabolism ; Biomarkers ; Epigenomics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder and the most common motor neuron disease. ALS shows substantial clinical and molecular heterogeneity. In vitro and in vivo models coupled with multiomic techniques have provided important contributions to unraveling the pathomechanisms underlying ALS. To date, despite promising results and accumulating knowledge, an effective treatment is still lacking. Here, we provide an overview of the literature on the use of genomics, epigenomics, transcriptomics and microRNAs to deeply investigate the molecular mechanisms developing and sustaining ALS. We report the most relevant genes implicated in ALS pathogenesis, discussing the use of different high-throughput sequencing techniques and the role of epigenomic modifications. Furthermore, we present transcriptomic studies discussing the most recent advances, from microarrays to bulk and single-cell RNA sequencing. Finally, we discuss the use of microRNAs as potential biomarkers and promising tools for molecular intervention. The integration of data from multiple omic approaches may provide new insights into pathogenic pathways in ALS by shedding light on diagnostic and prognostic biomarkers, helping to stratify patients into clinically relevant subgroups, revealing novel therapeutic targets and supporting the development of new effective therapies.}, }
@article {pmid37968433, year = {2024}, author = {Quattrocchi, S and Bonan, L and Cirillo, L and Avoni, P and Di Stasi, V and Rizzo, G and Liguori, R and Vacchiano, V}, title = {Bibrachial amyotrophy as a rare manifestation of intraspinal fluid collection: a case report and systematic review.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {5}, pages = {2279-2288}, pmid = {37968433}, issn = {1590-3478}, mesh = {Humans ; Male ; Middle Aged ; *Magnetic Resonance Imaging ; Electromyography ; Motor Neuron Disease/diagnosis/complications ; }, abstract = {INTRODUCTION: Intraspinal cerebrospinal fluid (CSF) collection has been reported as a rare cause of lower motor neuron (LMN) disorder. We report a case of bibrachial diplegia associated with intraspinal CSF collection and perform a systematic literature review.<br><br>PATIENT AND METHODS: A 52-year-old man developed a bibrachial amyotrophy over 6&#xa0;years, confirmed by the presence of cervical subacute neurogenic changes at electromyography (EMG). Brain magnetic resonance imaging (MRI) revealed cerebral siderosis, while spine MRI showed a ventral longitudinal intraspinal fluid collection (VLISFC) from C2 to L2. No CSF leakage was localized at myelography; a conservative treatment was chosen. We searched for all published cases until 30th April 2023 and extrapolated data of 44 patients reported in 27 publications.<br><br>RESULTS: We observed a male predominance, a younger disease onset compared to amyotrophic lateral sclerosis, and a quite long disease duration, highlighting a slow disease progression. LMN signs were more frequently bilateral, mostly involving C5-C6 myotomes. Around 61% of patients presented additional symptoms, but only three referred to a history of headache. Accordingly, CSF opening pressure was mostly normal. Spinal MRI revealed the presence of VLISFC and in some cases myelomalacia. EMG patterns displayed both chronic and subacute neurogenic change in the cervical region. The disease course mainly depended on the treatment choice, which was mostly represented by a surgical approach when a specific dural defect was detected by imaging.<br><br>CONCLUSION: Bibrachial diplegia due to VLISFC can be a treatable cause of focal amyotrophy and presents some clinical and radiological "red flags" which cannot be missed by a clinical neurologist.}, }
@article {pmid37966813, year = {2024}, author = {Fang, M and Liu, Y and Huang, C and Fan, S}, title = {Targeting stress granules in neurodegenerative diseases: A focus on biological function and dynamics disorders.}, journal = {BioFactors (Oxford, England)}, volume = {50}, number = {3}, pages = {422-438}, doi = {10.1002/biof.2017}, pmid = {37966813}, issn = {1872-8081}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/pathology ; *Stress Granules/metabolism/genetics ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; Alzheimer Disease/metabolism/pathology/genetics ; Huntington Disease/metabolism/genetics/pathology ; Parkinson Disease/metabolism/pathology/genetics ; Animals ; Frontotemporal Dementia/metabolism/pathology/genetics ; Neurons/metabolism/pathology ; }, abstract = {Stress granules (SGs) are membraneless organelles formed by eukaryotic cells in response to stress to promote cell survival through their pleiotropic cytoprotective effects. SGs recruit a variety of components to enhance their physiological function, and play a critical role in the propagation of pathological proteins, a key factor in neurodegeneration. Recent advances indicate that SG dynamic disorders exacerbate neuronal susceptibility to stress in neurodegenerative diseases (NDs) including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Huntington's disease (HD) and Parkinson's disease (PD). Here, we outline the biological functions of SGs, highlight SG dynamic disorders in NDs, and emphasize therapeutic approaches for enhancing SG dynamics to provide new insights into ND intervention.}, }
@article {pmid37966683, year = {2024}, author = {Ansari, MA and Tripathi, T and Venkidasamy, B and Monziani, A and Rajakumar, G and Alomary, MN and Alyahya, SA and Onimus, O and D'souza, N and Barkat, MA and Al-Suhaimi, EA and Samynathan, R and Thiruvengadam, M}, title = {Multifunctional Nanocarriers for Alzheimer's Disease: Befriending the Barriers.}, journal = {Molecular neurobiology}, volume = {61}, number = {5}, pages = {3042-3089}, pmid = {37966683}, issn = {1559-1182}, mesh = {Humans ; *Alzheimer Disease/drug therapy ; Animals ; *Drug Carriers/chemistry ; Drug Delivery Systems/methods ; Blood-Brain Barrier/metabolism/drug effects ; Nanoparticles/chemistry ; Multifunctional Nanoparticles/chemistry ; }, abstract = {Neurodegenerative diseases (NDDs) have been increasing in incidence in recent years and are now widespread worldwide. Neuronal death is defined as the progressive loss of neuronal structure or function which is closely associated with NDDs and represents the intrinsic features of such disorders. Amyotrophic lateral sclerosis, frontotemporal dementia, Alzheimer's, Parkinson's, and Huntington's diseases (AD, PD, and HD, respectively) are considered neurodegenerative diseases that affect a large number of people worldwide. Despite the testing of various drugs, there is currently no available therapy that can remedy or effectively slow the progression of these diseases. Nanomedicine has the potential to revolutionize drug delivery for the management of NDDs. The use of nanoparticles (NPs) has recently been developed to improve drug delivery efficiency and is currently subjected to extensive studies. Nanoengineered particles, known as nanodrugs, can cross the blood-brain barrier while also being less invasive compared to the most treatment strategies in use. Polymeric, magnetic, carbonic, and inorganic NPs are examples of NPs that have been developed to improve drug delivery efficiency. Primary research studies using NPs to cure AD are promising, but thorough research is needed to introduce these approaches to clinical use. In the present review, we discussed the role of metal-based NPs, polymeric nanogels, nanocarrier systems such as liposomes, solid lipid NPs, polymeric NPs, exosomes, quantum dots, dendrimers, polymersomes, carbon nanotubes, and nanofibers and surfactant-based systems for the therapy of neurodegenerative diseases. In addition, we highlighted nanoformulations such as N-butyl cyanoacrylate, poly(butyl cyanoacrylate), D-penicillamine, citrate-coated peptide, magnetic iron oxide, chitosan (CS), lipoprotein, ceria, silica, metallic nanoparticles, cholinesterase inhibitors, an acetylcholinesterase inhibitors, metal chelators, anti-amyloid, protein, and peptide-loaded NPs for the treatment of AD.}, }
@article {pmid37960284, year = {2023}, author = {Zheng, Y and Bonfili, L and Wei, T and Eleuteri, AM}, title = {Understanding the Gut-Brain Axis and Its Therapeutic Implications for Neurodegenerative Disorders.}, journal = {Nutrients}, volume = {15}, number = {21}, pages = {}, pmid = {37960284}, issn = {2072-6643}, support = {Fondi Studenti PhD//University of Camerino/ ; }, mesh = {Humans ; Brain-Gut Axis ; *Neurodegenerative Diseases/therapy ; *Gastrointestinal Microbiome ; *Alzheimer Disease/therapy ; *Parkinson Disease/therapy ; Brain ; Dysbiosis/therapy ; }, abstract = {The gut-brain axis (GBA) is a complex bidirectional communication network connecting the gut and brain. It involves neural, immune, and endocrine communication pathways between the gastrointestinal (GI) tract and the central nervous system (CNS). Perturbations of the GBA have been reported in many neurodegenerative disorders (NDDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), among others, suggesting a possible role in disease pathogenesis. The gut microbiota is a pivotal component of the GBA, and alterations in its composition, known as gut dysbiosis, have been associated with GBA dysfunction and neurodegeneration. The gut microbiota might influence the homeostasis of the CNS by modulating the immune system and, more directly, regulating the production of molecules and metabolites that influence the nervous and endocrine systems, making it a potential therapeutic target. Preclinical trials manipulating microbial composition through dietary intervention, probiotic and prebiotic supplementation, and fecal microbial transplantation (FMT) have provided promising outcomes. However, its clear mechanism is not well understood, and the results are not always consistent. Here, we provide an overview of the major components and communication pathways of the GBA, as well as therapeutic approaches targeting the GBA to ameliorate NDDs.}, }
@article {pmid37958929, year = {2023}, author = {Boylan, MA and Pincetic, A and Romano, G and Tatton, N and Kenkare-Mitra, S and Rosenthal, A}, title = {Targeting Progranulin as an Immuno-Neurology Therapeutic Approach.}, journal = {International journal of molecular sciences}, volume = {24}, number = {21}, pages = {}, pmid = {37958929}, issn = {1422-0067}, mesh = {Humans ; Progranulins/genetics ; Intercellular Signaling Peptides and Proteins/genetics ; *Frontotemporal Dementia/genetics ; Neurons/pathology ; *Amyotrophic Lateral Sclerosis ; }, abstract = {Immuno-neurology is an emerging therapeutic strategy for dementia and neurodegeneration designed to address immune surveillance failure in the brain. Microglia, as central nervous system (CNS)-resident myeloid cells, routinely perform surveillance of the brain and support neuronal function. Loss-of-function (LOF) mutations causing decreased levels of progranulin (PGRN), an immune regulatory protein, lead to dysfunctional microglia and are associated with multiple neurodegenerative diseases, including frontotemporal dementia caused by the progranulin gene (GRN) mutation (FTD-GRN), Alzheimer's disease (AD), Parkinson's disease (PD), limbic-predominant age-related transactivation response deoxyribonucleic acid binding protein 43 (TDP-43) encephalopathy (LATE), and amyotrophic lateral sclerosis (ALS). Immuno-neurology targets immune checkpoint-like proteins, offering the potential to convert aging and dysfunctional microglia into disease-fighting cells that counteract multiple disease pathologies, clear misfolded proteins and debris, promote myelin and synapse repair, optimize neuronal function, support astrocytes and oligodendrocytes, and maintain brain vasculature. Several clinical trials are underway to elevate PGRN levels as one strategy to modulate the function of microglia and counteract neurodegenerative changes associated with various disease states. If successful, these and other immuno-neurology drugs have the potential to revolutionize the treatment of neurodegenerative disorders by harnessing the brain's immune system and shifting it from an inflammatory/pathological state to an enhanced physiological/homeostatic state.}, }
@article {pmid37958596, year = {2023}, author = {Stoka, V and Vasiljeva, O and Nakanishi, H and Turk, V}, title = {The Role of Cysteine Protease Cathepsins B, H, C, and X/Z in Neurodegenerative Diseases and Cancer.}, journal = {International journal of molecular sciences}, volume = {24}, number = {21}, pages = {}, pmid = {37958596}, issn = {1422-0067}, support = {J1-2473, P1-0140//Slovenian Research Agency/ ; }, mesh = {Humans ; *Cysteine Proteases ; *Neurodegenerative Diseases ; Cysteine/metabolism ; Cathepsin B ; *Neoplasms ; Lysosomes/metabolism ; }, abstract = {Papain-like cysteine proteases are composed of 11 human cysteine cathepsins, originally located in the lysosomes. They exhibit broad specificity and act as endopeptidases and/or exopeptidases. Among them, only cathepsins B, H, C, and X/Z exhibit exopeptidase activity. Recently, cysteine cathepsins have been found to be present outside the lysosomes and often participate in various pathological processes. Hence, they have been considered key signalling molecules. Their potentially hazardous proteolytic activities are tightly regulated. This review aims to discuss recent advances in understanding the structural aspects of these four cathepsins, mechanisms of their zymogen activation, regulation of their activities, and functional aspects of these enzymes in neurodegeneration and cancer. Neurodegenerative effects have been evaluated, particularly in Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, and neuropsychiatric disorders. Cysteine cathepsins also participate in tumour progression and metastasis through the overexpression and secretion of proteases, which trigger extracellular matrix degradation. To our knowledge, this is the first review to provide an in-depth analysis regarding the roles of cysteine cathepsins B, H, C, and X in neurodegenerative diseases and cancer. Further advances in understanding the functions of cysteine cathepsins in these conditions will result in the development of novel, targeted therapeutic strategies.}, }
@article {pmid37955299, year = {2023}, author = {Yuan, YH and Mao, ND and Duan, JL and Zhang, H and Garrido, C and Lirussi, F and Gao, Y and Xie, T and Ye, XY}, title = {Recent progress in discovery of novel AAK1 inhibitors: from pain therapy to potential anti-viral agents.}, journal = {Journal of enzyme inhibition and medicinal chemistry}, volume = {38}, number = {1}, pages = {2279906}, pmid = {37955299}, issn = {1475-6374}, mesh = {Humans ; *Protein Serine-Threonine Kinases ; *Antiviral Agents/pharmacology ; Phosphorylation ; Pain ; }, abstract = {Adaptor associated kinase 1 (AAK1), a member of the Ark1/Prk1 family of Ser/Thr kinases, is a specific key kinase regulating Thr156 phosphorylation at the μ2 subunit of the adapter complex-2 (AP-2) protein. Due to their important biological functions, AAK1 systems have been validated in clinics for neuropathic pain therapy, and are being explored as potential therapeutic targets for diseases caused by various viruses such as Hepatitis C (HCV), Dengue, Ebola, and COVID-19 viruses and for amyotrophic lateral sclerosis (ALS). Centreing on the advances of drug discovery programs in this field up to 2023, AAK1 inhibitors are discussed from the aspects of the structure-based rational molecular design, pharmacology, toxicology and synthetic routes for the compounds of interest in this review. The aim is to provide the medicinal chemistry community with up-to-date information and to accelerate the drug discovery programs in the field of AAK1 small molecule inhibitors.}, }
@article {pmid37952981, year = {2023}, author = {Okano, H and Morimoto, S and Kato, C and Nakahara, J and Takahashi, S}, title = {Induced pluripotent stem cells-based disease modeling, drug screening, clinical trials, and reverse translational research for amyotrophic lateral sclerosis.}, journal = {Journal of neurochemistry}, volume = {167}, number = {5}, pages = {603-614}, doi = {10.1111/jnc.16005}, pmid = {37952981}, issn = {1471-4159}, support = {JP21wm0425009//Japan Agency for Medical Research and Development/ ; JP22bm0804003//Japan Agency for Medical Research and Development/ ; JP22ek0109616//Japan Agency for Medical Research and Development/ ; JP23bm1423002//Japan Agency for Medical Research and Development/ ; JP23bm1123046//Japan Agency for Medical Research and Development/ ; JP23kk0305024//Japan Agency for Medical Research and Development/ ; JP20H00485//Japan Society for the Promotion of Science/ ; JP21H05278//Japan Society for the Promotion of Science/ ; JP22K15736//Japan Society for the Promotion of Science/ ; JP22K07500//Japan Society for the Promotion of Science/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; *Induced Pluripotent Stem Cells/metabolism ; Drug Evaluation, Preclinical ; *Neurodegenerative Diseases/metabolism ; Translational Research, Biomedical ; Randomized Controlled Trials as Topic ; }, abstract = {It has been more than 10 years since the hopes for disease modeling and drug discovery using induced pluripotent stem cell (iPSC) technology boomed. Recently, clinical trials have been conducted with drugs identified using this technology, and some promising results have been reported. For amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disease, several groups have identified candidate drugs, ezogabine (retigabine), bosutinib, and ropinirole, using iPSCs-based drug discovery, and clinical trials using these drugs have been conducted, yielding interesting results. In our previous study, an iPSCs-based drug repurposing approach was utilized to show the potential of ropinirole hydrochloride (ROPI) in reducing ALS-specific pathological phenotypes. Recently, a phase 1/2a trial was conducted to investigate the effects of ropinirole on ALS further. This double-blind, randomized, placebo-controlled study confirmed the safety and tolerability of and provided evidence of its ability to delay disease progression and prolong the time to respiratory failure in ALS patients. Furthermore, in the reverse translational research, in vitro characterization of patient-derived iPSCs-motor neurons (MNs) mimicked the therapeutic effects of ROPI in vivo, suggesting the potential application of this technology to the precision medicine of ALS. Interestingly, RNA-seq data showed that ROPI treatment suppressed the sterol regulatory element-binding protein 2-dependent cholesterol biosynthesis pathway. Therefore, this pathway may be involved in the therapeutic effect of ROPI on ALS. The possibility that this pathway may be involved in the therapeutic effect of ALS was demonstrated. Finally, new future strategies for ALS using iPSCs technology will be discussed in this paper.}, }
@article {pmid37952511, year = {2023}, author = {Zhang, X and Qu, X and Zou, Y}, title = {The Effect of Astragalus on Humoral and Cellular Immune Response: A Systematic Review and Meta-Analysis of Human Studies.}, journal = {Complementary medicine research}, volume = {30}, number = {6}, pages = {535-543}, doi = {10.1159/000534826}, pmid = {37952511}, issn = {2504-2106}, mesh = {Humans ; *Interleukin-10 ; *Interleukin-2 ; Interleukin-4 ; Interleukin-6 ; Tumor Necrosis Factor-alpha ; Biomarkers ; }, abstract = {INTRODUCTION: Astragalus is used in traditional Chinese medicine for immune system disorders. Its effect on immune system function is evaluated in multiple studies. The objective of this systematic review and meta-analysis was to evaluate the effect of Astragalus on humoral and cellular immune response in human studies.<br><br>METHODS: A comprehensive search of electronic databases was conducted to identify relevant studies published up to April 2023. Studies that assessed the impact of Astragalus on humoral and cellular immune markers were included. The data were extracted, and a random-effects meta-analysis was performed to determine the overall effect size. Subgroup analyses were conducted based on outcome measures.<br><br>RESULTS: A total of 19 studies, including 1,094 human participants, were included in the meta-analysis. The analysis of humoral immune markers revealed a significant reduction in proinflammatory cytokines, including IL-2, IL-4, IL-6, IL-10, TNF-&#x3b1;, and IFN-&#x3b3;, following Astragalus intervention (SMD -2.8765, 95% CI: -3.2385 to -2.5145, p < 0.0001). In the cellular immunity domain, Astragalus was found to significantly increase CD3 levels and the CD4/CD8 ratio (SMD 2.4629, 95% CI: 1.9598; 2.9661). Subgroup analyses based on outcome measures supported these findings. However, substantial heterogeneity was observed among the included studies.<br><br>CONCLUSION: This systematic review and meta-analysis provide evidence supporting the immunomodulatory effects of Astragalus on humoral and cellular response. Astragalus demonstrated a significant reduction in proinflammatory cytokines and an enhancement of cellular immune markers, suggesting its potential as a therapeutic agent for immune-related disorders.<br><br>UNLABELLED: <title>Einleitung</title>Astragalus wird in der traditionellen chinesischen Medizin bei Erkrankungen des Immunsystems eingesetzt. Seine Wirkung auf das Immunsystem ist in mehreren Studien untersucht worden. Das Ziel dieser systematischen &#xdc;bersichtsarbeit und Metaanalyse ist es, die Wirkung von Astragalus auf die humorale und zellul&#xe4;re Immunantwort in Studien am Menschen zu untersuchen.<title>Methoden</title>Eine umfassende Suche in elektronischen Datenbanken wurde durchgef&#xfc;hrt, um einschl&#xe4;gige Studien zu finden, die bis April 2023 ver&#xf6;ffentlicht wurden. Eingeschlossen wurden Studien, die die Auswirkung von Astragalus auf Marker der humoralen und zellul&#xe4;ren Immunantwort untersuchten. Die Daten wurden extrahiert und eine Random-Effects-Metaanalyse durchgef&#xfc;hrt, um die Gesamt-Effektst&#xe4;rke zu ermitteln. Subgruppenanalysen wurden basierend auf Zielgr&#xf6;&#xdf;en durchgef&#xfc;hrt.<title>Ergebnisse</title>Insgesamt 19 Studien mit 1&#x2019;094 menschlichen Teilnehmern wurden in die Metaanalyse eingeschlossen. Die Analyse der humoralen Immunmarker ergab eine signifikante Abnahme proinflammatorischer Zytokine, darunter IL-2, IL-4, IL-6, IL-10, TNF-&#x3b1; und IFN-&#x3b3;, nach Anwendung von Astragalus (SMD &#x2013;2.8765; 95%-KI: &#x2212;3.2385, &#x2212;2.5145; <italic>p</italic> < 0.0001). Bei der zellul&#xe4;ren Immunit&#xe4;t zeigte Astralagus eine signifikante Erh&#xf6;hung der CD3-Konzentration und des CD4/CD8-Quotienten (SMD 2.4629; 95%-KI: 1.9598, 2.9661). Die Subgruppenanalysen nach Zielgr&#xf6;&#xdf;en best&#xe4;tigten diese Ergebnisse. Zwischen den eingeschlossenen Studien bestand jedoch erhebliche Heterogenit&#xe4;t.<title>Schlussfolgerung</title>Diese systematische &#xdc;bersichtsarbeit und Metaanalyse liefert Belege f&#xfc;r die immunmodulatorischen Effekte von Astragalus auf die humorale und zellul&#xe4;re Immunantwort. Astragalus zeigte eine signifikante Abnahme proinflammatorischer Zytokine und eine Verbesserung von Markern der zellul&#xe4;ren Immunit&#xe4;t, was auf sein Potenzial als Therapeutikum bei immunvermittelten St&#xf6;rungen hindeutet.}, }
@article {pmid37949994, year = {2023}, author = {McMackin, R and Bede, P and Ingre, C and Malaspina, A and Hardiman, O}, title = {Biomarkers in amyotrophic lateral sclerosis: current status and future prospects.}, journal = {Nature reviews. Neurology}, volume = {19}, number = {12}, pages = {754-768}, pmid = {37949994}, issn = {1759-4766}, support = {MALASPINA/APR13/817-791/MNDA_/Motor Neurone Disease Association/United Kingdom ; TURNER/OCT15/972-797/MNDA_/Motor Neurone Disease Association/United Kingdom ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; Biomarkers ; Prognosis ; Disease Progression ; Drug Development ; }, abstract = {Disease heterogeneity in amyotrophic lateral sclerosis poses a substantial challenge in drug development. Categorization based on clinical features alone can help us predict the disease course and survival, but quantitative measures are also needed that can enhance the sensitivity of the clinical categorization. In this Review, we describe the emerging landscape of diagnostic, categorical and pharmacodynamic biomarkers in amyotrophic lateral sclerosis and their place in the rapidly evolving landscape of new therapeutics. Fluid-based markers from cerebrospinal fluid, blood and urine are emerging as useful diagnostic, pharmacodynamic and predictive biomarkers. Combinations of imaging measures have the potential to provide important diagnostic and prognostic information, and neurophysiological methods, including various electromyography-based measures and quantitative EEG-magnetoencephalography-evoked responses and corticomuscular coherence, are generating useful diagnostic, categorical and prognostic markers. Although none of these biomarker technologies has been fully incorporated into clinical practice or clinical trials as a primary outcome measure, strong evidence is accumulating to support their clinical utility.}, }
@article {pmid37947875, year = {2024}, author = {Azaad, S and Sebanz, N}, title = {Potential benefits of synchronous action observation and motor imagery: a commentary on Eaves et al. 2022.}, journal = {Psychological research}, volume = {88}, number = {6}, pages = {1908-1910}, pmid = {37947875}, issn = {1430-2772}, mesh = {Humans ; *Imagination/physiology ; *Psychomotor Performance/physiology ; Motor Activity/physiology ; }, abstract = {In a recent Psychological Research article, Eaves et al. (2022) review the literature on how motor imagery (MI) practice combined with action observation (AO) enhances motor performance. The authors propose that the synchronous form of AO and MI (AOMI) affords unique benefits to performance that are not possible when the two interventions are performed asynchronously. We discuss three questions raised by Eaves et al.'s review: (1) are there any clear advantages to synchronous AOMI? (2) Are there super-additive benefits to AOMI, and if so, are they unique to synchronous AOMI? (3) How might coordinative AOMI, in which people imagine complementary actions, facilitate joint actions?}, }
@article {pmid37946793, year = {2023}, author = {Rogers, ML and Schultz, DW and Karnaros, V and Shepheard, SR}, title = {Urinary biomarkers for amyotrophic lateral sclerosis: candidates, opportunities and considerations.}, journal = {Brain communications}, volume = {5}, number = {6}, pages = {fcad287}, pmid = {37946793}, issn = {2632-1297}, support = {U01 NS107027/NS/NINDS NIH HHS/United States ; }, abstract = {Amyotrophic lateral sclerosis is a relentless neurodegenerative disease that is mostly fatal within 3-5 years and is diagnosed on evidence of progressive upper and lower motor neuron degeneration. Around 15% of those with amyotrophic lateral sclerosis also have frontotemporal degeneration, and gene mutations account for ∼10%. Amyotrophic lateral sclerosis is a variable heterogeneous disease, and it is becoming increasingly clear that numerous different disease processes culminate in the final degeneration of motor neurons. There is a profound need to clearly articulate and measure pathological process that occurs. Such information is needed to tailor treatments to individuals with amyotrophic lateral sclerosis according to an individual's pathological fingerprint. For new candidate therapies, there is also a need for methods to select patients according to expected treatment outcomes and measure the success, or not, of treatments. Biomarkers are essential tools to fulfil these needs, and urine is a rich source for candidate biofluid biomarkers. This review will describe promising candidate urinary biomarkers of amyotrophic lateral sclerosis and other possible urinary candidates in future areas of investigation as well as the limitations of urinary biomarkers.}, }
@article {pmid37946741, year = {2023}, author = {Ebrahimi, A and Kamyab, A and Hosseini, S and Ebrahimi, S and Ashkani-Esfahani, S}, title = {Involvement of Coenzyme Q10 in Various Neurodegenerative and Psychiatric Diseases.}, journal = {Biochemistry research international}, volume = {2023}, number = {}, pages = {5510874}, pmid = {37946741}, issn = {2090-2247}, abstract = {Coenzyme Q10 (CoQ10), commonly known as ubiquinone, is a vitamin-like component generated in mitochondrial inner membranes. This molecule is detected broadly in different parts of the human body in various quantities. This molecule can be absorbed by the digestive system from various nutritional sources as supplements. CoQ10 exists in three states: in a of reduced form (ubiquinol), in a semiquinone radical form, and in oxidized ubiquinone form in different organs of the body, playing a crucial role in electron transportation and contributing to energy metabolism and oxygen utilization, especially in the musculoskeletal and nervous systems. Since the early 1980s, research about CoQ10 has become the interest for two reasons. First, CoQ10 deficiency has been found to have a link with cardiovascular, neurologic, and cancer disorders. Second, this molecule has an antioxidant and free-radical scavenger nature. Since then, several investigations have indicated that the drug may benefit patients with cardiovascular, neuromuscular, and neurodegenerative illnesses. CoQ10 may protect the neurological system from degeneration and degradation due to its antioxidant and energy-regulating activity in mitochondria. This agent has shown its efficacy in preventing and treating neurological diseases such as migraine, Parkinson's disease, Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis, and Friedreich's ataxia. This study reviews the literature to highlight this agent's potential therapeutic effects in the mentioned neurological disorders.}, }
@article {pmid37946655, year = {2023}, author = {Lochbaum, R and Hoffmann, TK and Greve, J and Hahn, J}, title = {[Medikamente als Auslöser Bradykinin-vermittelter Angioödeme - mehr als ACE-Hemmer].}, journal = {Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG}, volume = {21}, number = {11}, pages = {1283-1290}, doi = {10.1111/ddg.15154_g}, pmid = {37946655}, issn = {1610-0387}, }
@article {pmid37944521, year = {2024}, author = {Yang, K and Tang, Z and Xing, C and Yan, N}, title = {STING signaling in the brain: Molecular threats, signaling activities, and therapeutic challenges.}, journal = {Neuron}, volume = {112}, number = {4}, pages = {539-557}, pmid = {37944521}, issn = {1097-4199}, support = {R01 AI151708/AI/NIAID NIH HHS/United States ; R01 NS117424/NS/NINDS NIH HHS/United States ; R01 NS122825/NS/NINDS NIH HHS/United States ; R56 AI151708/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Brain/pathology ; *Nervous System Diseases ; Signal Transduction ; }, abstract = {Stimulator of interferon genes (STING) is an innate immune signaling protein critical to infections, autoimmunity, and cancer. STING signaling is also emerging as an exciting and integral part of many neurological diseases. Here, we discuss recent advances in STING signaling in the brain. We summarize how molecular threats activate STING signaling in the diseased brain and how STING signaling activities in glial and neuronal cells cause neuropathology. We also review human studies of STING neurobiology and consider therapeutic challenges in targeting STING to treat neurological diseases.}, }
@article {pmid37942130, year = {2023}, author = {Piñeros-Fernández, MC}, title = {Artificial Intelligence Applications in the Diagnosis of Neuromuscular Diseases: A Narrative Review.}, journal = {Cureus}, volume = {15}, number = {11}, pages = {e48458}, pmid = {37942130}, issn = {2168-8184}, abstract = {The accurate diagnosis of neuromuscular diseases (NMD) is in many cases difficult; the starting point is the clinical approach based on the course of the disease and a careful physical examination of the patient. Electrodiagnostic tests, imaging, muscle biopsy, and genetics are fundamental complementary studies for the diagnosis of NMD. The large volume of data obtained from such studies makes it necessary to look for efficient solutions, such as artificial intelligence (AI) applications, which can help classify, synthesize, and organize the information of patients with NMD to facilitate their accurate and timely diagnosis. The objective of this study was to describe the usefulness of AI applications in the diagnosis of patients with neuromuscular diseases. A narrative review was done, including publications on artificial intelligence applied to the diagnostic methods of NMD currently existing. Twelve studies were included. Two of the studies focused on muscle ultrasound, five of the studies on muscle MRI, two studies on electromyography, two studies on amyotrophic lateral sclerosis (ALS) biomarkers, and one study on genes related to myopathies. The accuracy of classification using different classification algorithms used in each of the studies included in this narrative review was already 90% in most studies. In conclusion, the future design of more accurate algorithms applied to NMD with greater precision will have an impact on the earlier diagnosis of this group of diseases.}, }
@article {pmid37941028, year = {2023}, author = {Huang, Y and Liu, B and Sinha, SC and Amin, S and Gan, L}, title = {Mechanism and therapeutic potential of targeting cGAS-STING signaling in neurological disorders.}, journal = {Molecular neurodegeneration}, volume = {18}, number = {1}, pages = {79}, pmid = {37941028}, issn = {1750-1326}, support = {R01AG054214/AG/NIA NIH HHS/United States ; R01AG072758/AG/NIA NIH HHS/United States ; R01 AG074541/AG/NIA NIH HHS/United States ; R01 AG072758/AG/NIA NIH HHS/United States ; R01 AG054214/AG/NIA NIH HHS/United States ; R01AG074541/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; Signal Transduction/physiology ; Nucleotidyltransferases/genetics/metabolism ; DNA/metabolism ; *Interferon Type I/genetics/metabolism ; *Nervous System Diseases ; }, abstract = {DNA sensing is a pivotal component of the innate immune system that is responsible for detecting mislocalized DNA and triggering downstream inflammatory pathways. Among the DNA sensors, cyclic GMP-AMP synthase (cGAS) is a primary player in detecting cytosolic DNA, including foreign DNA from pathogens and self-DNA released during cellular damage, culminating in a type I interferon (IFN-I) response through stimulator of interferon genes (STING) activation. IFN-I cytokines are essential in mediating neuroinflammation, which is widely observed in CNS injury, neurodegeneration, and aging, suggesting an upstream role for the cGAS DNA sensing pathway. In this review, we summarize the latest developments on the cGAS-STING DNA-driven immune response in various neurological diseases and conditions. Our review covers the current understanding of the molecular mechanisms of cGAS activation and highlights cGAS-STING signaling in various cell types of central and peripheral nervous systems, such as resident brain immune cells, neurons, and glial cells. We then discuss the role of cGAS-STING signaling in different neurodegenerative conditions, including tauopathies, Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, as well as aging and senescence. Finally, we lay out the current advancements in research and development of cGAS inhibitors and assess the prospects of targeting cGAS and STING as therapeutic strategies for a wide spectrum of neurological diseases.}, }
@article {pmid37939160, year = {2023}, author = {Gendron, TF and Petrucelli, L}, title = {Immunological drivers of amyotrophic lateral sclerosis.}, journal = {Science translational medicine}, volume = {15}, number = {721}, pages = {eadj9332}, doi = {10.1126/scitranslmed.adj9332}, pmid = {37939160}, issn = {1946-6242}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; Biomarkers ; }, abstract = {Amyotrophic lateral sclerosis (ALS), a devastating motor neuron disease involving complex genetic and environmental factors, is associated with neuroinflammation. Preclinical and clinical studies support immune system involvement in ALS pathogenesis, thereby spurring investigations into potential pathogenic mechanisms, immune response biomarkers, and ALS therapeutics.}, }
@article {pmid37938192, year = {2023}, author = {Maharaj, D and Kaur, K and Saltese, A and Gouvea, J}, title = {Personalized Precision Immunotherapy for Amyotrophic Lateral Sclerosis (ALS).}, journal = {Critical reviews in immunology}, volume = {43}, number = {2}, pages = {1-11}, doi = {10.1615/CritRevImmunol.2023048372}, pmid = {37938192}, issn = {1040-8401}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/therapy ; Immunotherapy ; Brain ; Cytokines ; Inflammation ; }, abstract = {Neurological syndrome amyotrophic lateral sclerosis (ALS) affects motor neurons and is characterized by progressive motor neuron loss in the brain and spinal cord. ALS starts with mainly focal onset but when the disease progresses, it spreads to different parts of the body, with survival limits of 2-5 years after disease initiation. To date, only supportive care is provided for ALS patients, and no effective treatment or cure has been discovered. This review is focused on clinical and immunological aspects of ALS patients, based on our case studies, and we discuss the treatment we have provided to those patients based on a detailed evaluation of their peripheral blood immune cells and blood-derived serum secreted factors, cytokines, chemokines and growth factors. We show that using a personalized approach of low dose immunotherapy there is an improvement in the effects on inflammation and immunological dysfunction.}, }
@article {pmid37928737, year = {2023}, author = {Johnson, GA and Krishnamoorthy, RR and Stankowska, DL}, title = {Modulating mitochondrial calcium channels (TRPM2/MCU/NCX) as a therapeutic strategy for neurodegenerative disorders.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1202167}, pmid = {37928737}, issn = {1662-4548}, support = {T32 AG020494/AG/NIA NIH HHS/United States ; }, abstract = {Efficient cellular communication is essential for the brain to regulate diverse functions like muscle contractions, memory formation and recall, decision-making, and task execution. This communication is facilitated by rapid signaling through electrical and chemical messengers, including voltage-gated ion channels and neurotransmitters. These messengers elicit broad responses by propagating action potentials and mediating synaptic transmission. Calcium influx and efflux are essential for releasing neurotransmitters and regulating synaptic transmission. Mitochondria, which are involved in oxidative phosphorylation, and the energy generation process, also interact with the endoplasmic reticulum to store and regulate cytoplasmic calcium levels. The number, morphology, and distribution of mitochondria in different cell types vary based on energy demands. Mitochondrial damage can cause excess reactive oxygen species (ROS) generation. Mitophagy is a selective process that targets and degrades damaged mitochondria via autophagosome-lysosome fusion. Defects in mitophagy can lead to a buildup of ROS and cell death. Numerous studies have attempted to characterize the relationship between mitochondrial dysfunction and calcium dysregulation in neurodegenerative diseases such as Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Amyotrophic lateral sclerosis, spinocerebellar ataxia, and aging. Interventional strategies to reduce mitochondrial damage and accumulation could serve as a therapeutic target, but further research is needed to unravel this potential. This review offers an overview of calcium signaling related to mitochondria in various neuronal cells. It critically examines recent findings, exploring the potential roles that mitochondrial dysfunction might play in multiple neurodegenerative diseases and aging. Furthermore, the review identifies existing gaps in knowledge to guide the direction of future research.}, }
@article {pmid37926865, year = {2024}, author = {Xiao, X and Li, M and Ye, Z and He, X and Wei, J and Zha, Y}, title = {FUS gene mutation in amyotrophic lateral sclerosis: a new case report and systematic review.}, journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration}, volume = {25}, number = {1-2}, pages = {1-15}, doi = {10.1080/21678421.2023.2272170}, pmid = {37926865}, issn = {2167-9223}, mesh = {Humans ; Male ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics ; Mutation/genetics ; Mutation, Missense ; *Neurodegenerative Diseases ; Retrospective Studies ; RNA-Binding Protein FUS/genetics ; }, abstract = {OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease associated with upper and lower motor neuron degeneration and necrosis, characterized by progressive muscle weakness, atrophy, and paralysis. The FUS mutation-associated ALS has been classified as ALS6. We reported a case of ALS6 with de novo mutation and investigated retrospectively the characteristics of cases with FUS mutation.<br><br>METHODS: We reported a male patient with a new heterozygous variant of the FUS gene and comprehensively reviewed 173 ALS cases with FUS mutation. The literature was reviewed from the PubMed MEDLINE electronic database (https://www.ncbi.nlm.nih.gov/pubmed) using "Amyotrophic Lateral Sclerosis and Fus mutation" or "Fus mutation" as key words from 1 January 2009 to 1 January 2022.<br><br>RESULTS: We report a case of ALS6 with a new mutation point (c.1225-1227delGGA) and comprehensively review 173 ALS cases with FUS mutation. Though ALS6 is all with FUS mutation, it is still a highly heterogenous subtype. The average onset age of ALS6 is 35.2&#xa0;&#xb1;&#xa0;1.3 years, which is much lower than the average onset age of ALS (60 years old). Juvenile FUS mutations have an aggressive progression of disease, with an average time from onset to death or tracheostomy of 18.2&#xa0;&#xb1;&#xa0;0.5 months. FUS gene has the characteristics of early onset, faster progress, and shorter survival, especially in deletion mutation p.G504Wfs *12 and missense mutation of p.P525L.<br><br>CONCLUSIONS: ALS6 is a highly heterogenous subtype. Our study could allow clinicians to better understand the non-ALS typical symptoms, phenotypes, and pathophysiology of ALS6.}, }
@article {pmid37922093, year = {2024}, author = {Jellinger, KA}, title = {Understanding depression with amyotrophic lateral sclerosis: a short assessment of facts and perceptions.}, journal = {Journal of neural transmission (Vienna, Austria : 1996)}, volume = {131}, number = {2}, pages = {107-115}, pmid = {37922093}, issn = {1435-1463}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/therapy/diagnosis ; Depression/complications ; Quality of Life ; Affect ; *Neurodegenerative Diseases/complications ; }, abstract = {Depression with an average prevalence of 25-40% is a serious condition in amyotrophic lateral sclerosis (ALS) that can impact quality of life and survival of patients and caregiver burden, yet the underlying neurobiology is poorly understood. Preexisting depression has been associated with a higher risk of developing ALS, while people with ALS have a significantly higher risk of developing depression that can cause multiple complications. Depression may be a prodromal or subclinical symptom prior to motor involvement, although its relations with disease progression and impairment of quality of life are under discussion. Unfortunately, there are no studies existing that explore the pathogenic mechanisms of depression associated with the basic neurodegenerative process, and no specific neuroimaging data or postmortem findings for the combination of ALS and depression are currently available. Experience from other neurodegenerative processes suggests that depressive symptoms in ALS may be the consequence of cortical thinning in prefrontal regions and other cortex areas, disruption of mood-related brain networks, dysfunction of neurotransmitter systems, changing cortisol levels and other, hitherto unknown mechanisms. Treatment of both ALS and depression is a multidisciplinary task, depression generally being treated with a combination of antidepressant medication, physiotherapy, psychological and other interventions, while electroconvulsive therapy and deep brain stimulation might not be indicated in the majority of patients in view of their poor prognosis. Since compared to depression in other neurodegenerative diseases, our knowledge of its molecular basis in ALS is missing, multidisciplinary clinicopathological studies to elucidate the pathomechanism of depression in motor system disorders including ALS are urgently warranted.}, }
@article {pmid37920473, year = {2023}, author = {Lemos, JP and Tenório, LPG and Mouly, V and Butler-Browne, G and Mendes-da-Cruz, DA and Savino, W and Smeriglio, P}, title = {T cell biology in neuromuscular disorders: a focus on Duchenne Muscular Dystrophy and Amyotrophic Lateral Sclerosis.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1202834}, pmid = {37920473}, issn = {1664-3224}, mesh = {Humans ; *Muscular Dystrophy, Duchenne/therapy ; *Amyotrophic Lateral Sclerosis/therapy/genetics ; *Neuromuscular Diseases ; Muscles ; Genetic Therapy/methods ; }, abstract = {Growing evidence demonstrates a continuous interaction between the immune system, the nerve and the muscle in neuromuscular disorders of different pathogenetic origins, such as Duchenne Muscular Dystrophy (DMD) and Amyotrophic Lateral Sclerosis (ALS), the focus of this review. Herein we highlight the complexity of the cellular and molecular interactions involving the immune system in neuromuscular disorders, as exemplified by DMD and ALS. We describe the distinct types of cell-mediated interactions, such as cytokine/chemokine production as well as cell-matrix and cell-cell interactions between T lymphocytes and other immune cells, which target cells of the muscular or nervous tissues. Most of these interactions occur independently of exogenous pathogens, through ligand-receptor binding and subsequent signal transduction cascades, at distinct levels of specificity. Although this issue reveals the complexity of the system, it can also be envisioned as a window of opportunity to design therapeutic strategies (including synthetic moieties, cell and gene therapy, as well as immunotherapy) by acting upon one or more targets. In this respect, we discuss ongoing clinical trials using VLA-4 inhibition in DMD, and in ALS, with a focus on regulatory T cells, both revealing promising results.}, }
@article {pmid37919089, year = {2023}, author = {Moda, F and Ciullini, A and Dellarole, IL and Lombardo, A and Campanella, N and Bufano, G and Cazzaniga, FA and Giaccone, G}, title = {Secondary Protein Aggregates in Neurodegenerative Diseases: Almost the Rule Rather than the Exception.}, journal = {Frontiers in bioscience (Landmark edition)}, volume = {28}, number = {10}, pages = {255}, doi = {10.31083/j.fbl2810255}, pmid = {37919089}, issn = {2768-6698}, mesh = {Humans ; Aged ; *Neurodegenerative Diseases/pathology ; Protein Aggregates ; *Lewy Body Disease/metabolism/pathology ; *Synucleinopathies ; *Alzheimer Disease/metabolism ; *Parkinson Disease/metabolism ; tau Proteins/metabolism ; *Prion Diseases ; Amyloid beta-Peptides ; *Frontotemporal Lobar Degeneration ; }, abstract = {The presence of protein aggregates is a hallmark of many neurodegenerative diseases, including Parkinson's disease (PD), Alzheimer's disease (AD), and frontotemporal lobar degeneration (FTLD). Traditionally, each disease has been associated with the aggregation of specific proteins, which serve as disease-specific biomarkers. For example, aggregates of α-synuclein (α-syn) are found in α-synucleinopathies such as PD, dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Similarly, AD is characterized by aggregates of amyloid-beta (Aβ) and tau proteins. However, it has been observed that these protein aggregates can also occur in other neurodegenerative diseases, contributing to disease progression. For instance, α-syn aggregates have been detected in AD, Down syndrome, Huntington's disease, prion diseases, and various forms of FTLD. Similarly, Aβ aggregates have been found in conditions like DLB and PD. Tau aggregates, in addition to being present in primary tauopathies, have been identified in prion diseases, α-synucleinopathies, and cognitively healthy aged subjects. Finally, aggregates of TDP-43, typically associated with FTLD and amyotrophic lateral sclerosis (ALS), have been observed in AD, progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), MSA, DLB, and other neurodegenerative diseases. These findings highlight the complexity of protein aggregation in neurodegeneration and suggest potential interactions and common mechanisms underlying different diseases. A deeper understating of this complex scenario may eventually lead to the identification of a better elucidation of the pathogenetic mechanisms of these devastating conditions and hopefully new therapeutic stragegies.}, }
@article {pmid37910649, year = {2025}, author = {Franklin, JE}, title = {Palliative hypnosis approaches in the symptomatic treatment of amyotrophic lateral sclerosis (ALS).}, journal = {The American journal of clinical hypnosis}, volume = {67}, number = {1}, pages = {54-68}, doi = {10.1080/00029157.2023.2252875}, pmid = {37910649}, issn = {2160-0562}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/psychology ; *Palliative Care/methods ; *Hypnosis/methods ; Male ; Middle Aged ; Aged ; Female ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a rare, incurable, and ultimately fatal, devastating, progressive degenerative neurologic disease. It causes upheaval in the lives of patients and family caregivers alike. Palliative care can play an important supportive role in the care of patients and families dealing with the devastation of this illness. Clinical hypnosis has demonstrated benefits in treating the symptoms associated with severe chronic illness. There are, however, few studies looking at the benefits of clinical hypnosis in treating the symptom burden of ALS. This article describes palliative care and how it can provide an additional layer of support to seriously ill patients. A brief review of previous studies of hypnosis in the supportive, symptomatic treatment of ALS is provided, followed by a description of a case series of 30 Veterans who received clinical hypnosis and self-hypnosis training as a complementary treatment for the symptoms of ALS. Details of three case histories are included to highlight and discuss specific strategies and emblematic clinical responses. There is evidence that clinical hypnosis can benefit ALS patients and family caregivers struggling with this devastating illness.}, }
@article {pmid37910562, year = {2023}, author = {Lugg, A and Schindle, M and Sivak, A and Tankisi, H and Jones, KE}, title = {Nerve excitability measured with the TROND protocol in amyotrophic lateral sclerosis: a systematic review and meta-analysis.}, journal = {Journal of neurophysiology}, volume = {130}, number = {6}, pages = {1480-1491}, doi = {10.1152/jn.00174.2023}, pmid = {37910562}, issn = {1522-1598}, support = {RGPIN-2017-05624//Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada (NSERC)/ ; }, mesh = {Humans ; Action Potentials/physiology ; *Amyotrophic Lateral Sclerosis ; Axons/physiology ; Biomarkers ; Prospective Studies ; Clinical Protocols ; }, abstract = {This meta-analysis assessed the 30+ nerve excitability indices generated by the TROND protocol to identify potential biomarkers for amyotrophic lateral sclerosis (ALS). A comprehensive search was conducted in multiple databases to identify human studies that tested median motor axons. Forest plot analyses were performed using a random-effects model to determine the pooled effect (Z-score), heterogeneity (I[2]), and Cohen's d for potential biomarker identification. Out of 2,866 studies, 23 studies met the inclusion criteria, incorporating data from 719 controls and 942 patients with ALS. Seven indices emerged as potential biomarkers: depolarizing threshold electrotonus (TEd) 90-100 ms, strength-duration time constant (SDTC), superexcitability, TEd 40-60 ms, resting I/V slope, 50% depolarizing I/V, and subexcitability (ranked by the magnitude of the difference between patients and controls from largest to smallest). In a sensitivity analysis focusing on patients with larger compound muscle action potentials (CMAPs), only four indices were potential biomarkers: TEd 10-20 ms, TEd 90-100 ms, superexcitability, and SDTC. Among the extensive range of 30+ excitability indices generated by the TROND protocol, we have identified seven indices that effectively differentiate patients with ALS from healthy controls. Furthermore, a smaller subset of four indices shows promise as potential biomarkers when the CMAP remains relatively large. However, most studies were considered to be at moderate risk of bias due to case-control designs and absence of sensitivity and specificity calculations, underscoring the need for more prospective diagnostic test-accuracy studies with appropriate disease controls.NEW &amp; NOTEWORTHY This meta-analysis uncovers seven potential axonal excitability biomarkers for lower motor neuron pathology in ALS, shedding light on ion channel dysfunction. The identified dysfunction aligns with the primary pathology-protein homeostasis disruption. These biomarkers could fill a gap to detect presymptomatic spread of the disease in the spinal cord and monitor treatments targeting protein homeostasis and limiting spread, toward enhancing patient care.}, }
@article {pmid37909610, year = {2023}, author = {Reis, AHO and Figalo, LB and Orsini, M and Lemos, B}, title = {The implications of DNA methylation for amyotrophic lateral sclerosis.}, journal = {Anais da Academia Brasileira de Ciencias}, volume = {95}, number = {suppl 2}, pages = {e20230277}, doi = {10.1590/0001-3765202320230277}, pmid = {37909610}, issn = {1678-2690}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; DNA Methylation/genetics ; Mutation/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a complex and serious neurodegenerative disorder that develops in consequence of the progressive loss of the upper and lower motor neurons. Cases of ALS are classified as sporadic (sALS), or familial (fALS). Over 90% of cases are sALS, while roughly 10% are related to inherited genetic mutations (fALS). Approximately 70% of the genetic mutations that contribute to fALS have been identified. On the other hand, the majority of the sALS cases have an undetermined genetic contributor and few mutations have been described, despite the advanced genetic analysis methods. Also, several factors contribute to the onset and progression of ALS. Numerous lines of evidence indicate that epigenetic changes are linked to aging, as well as neurodegenerative disorders, such as ALS. In most cases, they act as the heritable regulation of transcription by DNA methylation, histone modification and expression of noncoding RNAs. Mechanisms involving aberrant DNA methylation could be relevant to human ALS pathobiology and therapeutic targeting. Despite advances in research to find factors associated with ALS and more effective treatments, this disease remains complex and has low patient survival. Here, we provide a narrative review of the role of DNA methylation for this complex neurodegenerative disorder.}, }
@article {pmid37907717, year = {2024}, author = {Yamamoto, K and Itoi, T and Matsunami, Y and Sofuni, A and Tsuchiya, T and Mukai, S and Kojima, H and Minami, H and Nakatsubo, R and Tonozuka, R}, title = {Early and late effects of endoscopic interventions in patients with malignant afferent loop syndrome: A single-center experience and literature review.}, journal = {Journal of hepato-biliary-pancreatic sciences}, volume = {31}, number = {2}, pages = {120-132}, doi = {10.1002/jhbp.1380}, pmid = {37907717}, issn = {1868-6982}, mesh = {Humans ; *Afferent Loop Syndrome/diagnostic imaging/etiology/surgery ; *Cholestasis/etiology ; Drainage ; Endoscopy ; Endosonography ; Liver/pathology ; Retrospective Studies ; Stents/adverse effects ; Treatment Outcome ; }, abstract = {BACKGROUND/PURPOSE: Afferent loop syndrome (ALS) is a rare adverse event after gastrointestinal surgery requiring appropriate early decompression treatment. Several endoscopic interventions have been attempted for treatment, including endoscopic enteral metal stent placement (EMSP), endoscopic ultrasound (EUS)-guided entero-enterostomy (EUS-EE), and EUS-guided hepaticogastrostomy (EUS-HGS). However, there are limited data on outcomes, including duration of stent patency. In this study, we evaluated the usefulness of each endoscopic intervention for malignant ALS.<br><br>METHODS: We retrospectively investigated nine patients with malignant ALS who underwent EMSP, EUS-EE, or EUS-HGS. Information on technical success, clinical efficacy, adverse events, stent dysfunction, and overall survival was collected and analyzed.<br><br>RESULTS: The most common symptoms were abdominal pain and cholangitis. ALS was treated by EMSP in three patients, EUS-EE in three patients, and EUS-HGS in three patients. Stent placement was successful and clinically effective in all patients with no adverse events. During follow-up, stent dysfunction occurred in two patients treated by EUS-HGS. Eight patients died of primary disease during a median follow-up of 157&#x2009;days.<br><br>CONCLUSIONS: Each of the available endoscopic interventions for malignant ALS can be expected to produce similar outcomes, including duration of stent patency. The choice of endoscopic intervention should be made based on the characteristics of each treatment.}, }
@article {pmid37907134, year = {2023}, author = {Birajdar, SV and Mazahir, F and Alam, MI and Kumar, A and Yadav, AK}, title = {Repurposing and clinical attributes of antidiabetic drugs for the treatment of neurodegenerative disorders.}, journal = {European journal of pharmacology}, volume = {961}, number = {}, pages = {176117}, doi = {10.1016/j.ejphar.2023.176117}, pmid = {37907134}, issn = {1879-0712}, mesh = {Humans ; Mice ; Animals ; Hypoglycemic Agents/pharmacology/therapeutic use ; Amyloid beta-Peptides/metabolism ; *Diabetes Mellitus, Type 2/drug therapy ; Drug Repositioning ; Neuroinflammatory Diseases ; *Alzheimer Disease/drug therapy ; Insulin/metabolism ; *Metformin/pharmacology ; }, abstract = {The risk of neurodegeneration was found to be increased among people with type 2 diabetes mellitus (T2DM). Brain disorders like Alzheimer's disease, Parkinson's disease, Huntington's disease, Amyotrophic lateral sclerosis, and others are considered neurodegenerative diseases and can be characterized by progressive loss of neurons. The deficiency of insulin, impaired signaling, and its resistance lead to alteration in the neuronal functioning of the brain. Insulin degrading enzyme (IDE) plays a significant role in the amyloid β metabolism, aggregation, and deposition of misfolded proteins in the brain's hippocampal and cortical neuronal regions. The insulin signaling via IP3 activation upregulates the IDE and could be a promising approach to regulate neurodegeneration. The repurposing of existing antidiabetic drugs such as Metformin, DPP-4 inhibitors, thiazolidinediones, glucagon-like peptides (GLP-1), sodium-glucose co-transport-2 (SGCT-2) inhibitors, and insulin could be an alternative and effective strategy to treat neurodegeneration via modulating insulin signaling, insulin resistance, IDE activity, oxidative stress, mitochondrial dysfunction, serum lipid profile and neuroinflammation in the brain. Antidiabetic medications reduce the risk of neuroinflammation, oxidative stress, and Aβ deposition by enhancing their clearance rate. The downregulation of IDE alters the degradation of Aβ monomers in the Tg2576 APP mice. Also, the treatment with metformin activated the AMPK pathway and suppressed mTOR and BACE-1 protein expression in the APP/PS1-induced mice model. Thus, the primary intention of this review is to explore the link between T2DM and neurodegenerative disorders, and the possible role of various antidiabetic drugs in the management of neurodegenerative disorders.}, }
@article {pmid37906991, year = {2023}, author = {Prohaska, S and Matthias, K}, title = {Effectiveness of Mindfulness-Based Stress Reduction as a Nondrug Preventive Intervention in Patients with Migraine: A Systematic Review with Meta-Analyses.}, journal = {Complementary medicine research}, volume = {30}, number = {6}, pages = {525-534}, doi = {10.1159/000534653}, pmid = {37906991}, issn = {2504-2106}, mesh = {Adult ; Humans ; *Mindfulness ; Treatment Outcome ; *Migraine Disorders/prevention &amp; control ; Headache ; Stress, Psychological ; }, abstract = {INTRODUCTION: Migraine is a neurological disorder characterized by recurrent, severe headaches that are often accompanied by other symptoms. There are various factors that can trigger a migraine in sufferers. Stress can be such a trigger. Drug and nondrug treatments are available for the preventive treatment of migraine. According to a German guideline, mindfulness can be recommended for the prophylaxis of migraine. Therefore, the aim was to investigate the effectiveness of mindfulness-based stress reduction (MBSR) in relation to patient-relevant outcomes in adult patients with migraine. Patient-relevant outcomes in this context are migraine frequency, headache intensity during a migraine attack, depressive symptoms, and quality of life.<br><br>MATERIAL AND METHODS: The conduct of this study was guided by the PRISMA 2020 statement. A systematic literature search for randomized controlled trials (RCTs) of the effectiveness of MBSR in adult migraine patients was conducted in December 2021 in three databases: MEDLINE via PubMed, the Cochrane Library, and Web of Science. In addition, a review of reference lists and a search of study registries were performed. The last search was conducted on October 7, 2022. In a two-step process, studies were selected based on predefined inclusion and exclusion criteria. The potential for bias was assessed using the Cochrane Risk of Bias Tool 2. The results were summarized descriptively and by means of quantitative synthesis.<br><br>RESULTS: Four RCTs with a total of 275 patients and the follow-up publication of one of these studies were included. The risk of bias in one study each was judged to be low or of some concern and high in two studies. Four studies were included in the quantitative analysis. For the endpoint migraine frequency, the meta-analytic summary of three studies failed to show a statistically significant benefit for MBSR (SMD: -0.23; 95% CI: -0.79 to 0.32). For the endpoint depressive symptoms, a meta-analytic summary of three studies showed a statistically significant benefit for MBSR (SMD: -0.59; 95% CI: -0.93 to -0.25). No study had examined the severity of headaches during a migraine episode.<br><br>CONCLUSION: Some results suggest that migraine patients may benefit from MBSR. However, the evidence base is currently insufficient for recommendations on the use of MBSR as a nondrug treatment option. Further adequately powered, high-quality RCTs are needed.<br><br>UNLABELLED: <title>Einleitung</title>Migr&#xe4;ne ist eine neurologische Erkrankung, die durch wiederkehrende, starke Kopfschmerzen gekennzeichnet ist, die h&#xe4;ufig von anderen Symptomen einhergehen. Es gibt verschiedene Faktoren, die bei den Betroffenen eine Migr&#xe4;ne ausl&#xf6;sen k&#xf6;nnen. Ein solcher Ausl&#xf6;ser kann Stress sein. F&#xfc;r die pr&#xe4;ventive Behandlung der Migr&#xe4;ne stehen medikament&#xf6;se und nichtmedikament&#xf6;se Verfahren zur Verf&#xfc;gung. Laut einer deutschen Leitlinie kann Achtsamkeit zur Prophylaxe von Migr&#xe4;ne empfohlen werden. Ziel der Studie war es daher, die Wirksamkeit von achtsamkeitsbasierter Stressreduktion (MBSR) in Bezug auf patientenrelevante Outcomes bei erwachsenen Migr&#xe4;nepatienten zu untersuchen. Patientenrelevante Outcomes in diesem Zusammenhang sind Migr&#xe4;neh&#xe4;ufigkeit, Kopfschmerzintensit&#xe4;t w&#xe4;hrend einer Migr&#xe4;neattacke, depressive Symptome und Lebensqualit&#xe4;t.<title>Methoden</title>Die Durchf&#xfc;hrung dieser Studie orientierte sich am PRISMA-Statement. Eine systematische Literatursuche nach randomisierten kontrollierten Studien zur Wirksamkeit von MBSR bei erwachsenen Migr&#xe4;nepatienten wurde im Dezember 2021 in drei Datenbanken durchgef&#xfc;hrt: MEDLINE &#xfc;ber PubMed, die Cochrane Library und Web of Science. Dar&#xfc;ber hinaus wurden Referenzlisten und Studienregister durchsucht. Die letzte Suche erfolgte am 7. Oktober 2022. In einem zweistufigen Verfahren wurden die Studien anhand von vordefinierten Ein- und Ausschlusskriterien ausgew&#xe4;hlt. Das Verzerrungspotential der Studien wurde mit dem Cochrane Risk of Bias Tool 2 bewertet. Die Ergebnisse wurden deskriptiv und mit Hilfe einer quantitativen Synthese zusammengefasst.<title>Ergebnisse</title>Es wurden vier randomisiert-kontrollierte Studien mit insgesamt 275 Patienten und die Nachfolgepublikation einer dieser Studien eingeschlossen. Das Verzerrungspotential wurde bei je einer Studie als gering oder bedenklich und bei zwei Studien als hoch eingestuft. Vier Studien wurden in die quantitative Analyse einbezogen. F&#xfc;r den Endpunkt Migr&#xe4;neh&#xe4;ufigkeit ergab die metaanalytische Zusammenfassung von drei Studien keinen statistisch signifikanten Vorteil f&#xfc;r MBSR (SMD &#x2212;0.23; 95% CI &#x2212;0.79 bis 0.32). F&#xfc;r den Endpunkt depressive Symptome zeigte eine metaanalytische Zusammenfassung von drei Studien einen statistisch signifikanten Vorteil f&#xfc;r MBSR (SMD &#x2212;0.59; 95% CI &#x2212;0.93 bis &#x2212;0.25). Keine Studie hatte die Schwere der Kopfschmerzen w&#xe4;hrend einer Migr&#xe4;neepisode untersucht.<title>Schlussfolgerung</title>Einige Ergebnisse deuten darauf hin, dass Migr&#xe4;nepatienten von MBSR profitieren k&#xf6;nnen. Allerdings ist die Evidenzbasis derzeit nicht ausreichend, um Empfehlungen f&#xfc;r den Einsatz von MBSR als nichtmedikament&#xf6;se Behandlungsoption abzuleiten. Es werden daher weitere qualitativ hochwertige randomisiert-kontrollierte Studien mit ausreichender statistischer Power ben&#xf6;tigt.}, }
@article {pmid37904013, year = {2024}, author = {Chen, X and Luo, J and Zheng, W and Huang, Q and Du, C and Yuan, H and Xiao, F}, title = {Hyperhidrosis as the initial symptom in FUS mutation-associated amyotrophic lateral sclerosis: a case report and comprehensive literature review.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {4}, pages = {1523-1527}, pmid = {37904013}, issn = {1590-3478}, mesh = {Female ; Humans ; Young Adult ; *Amyotrophic Lateral Sclerosis/complications/diagnosis/genetics ; *Hyperhidrosis/genetics ; Mutation ; *Neurodegenerative Diseases ; Quality of Life ; RNA-Binding Protein FUS/genetics ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that is now recognized to involve autonomic dysfunction. The burden of autonomic dysfunction is an important factor in the quality of life and prognosis of ALS patients. This article presents the clinical characteristics of a young female ALS patient with a fused in sarcoma (FUS) gene mutation and notable hyperhidrosis.<br><br>METHOD: Detailed clinical characteristics of the patients were collected, and comprehensive examinations such as electrophysiological assessment, neuro-ultrasound, genetic testing, and relevant blood tests were conducted.<br><br>RESULT: A 24-year-old female experienced progressive weakness in both lower limbs for over 5 months, along with excessive sweating on both palms and feet. A positive skin iodine-starch test was observed. Electromyography revealed extensive neurogenic damage and prolonged sympathetic skin response (SSR) latency in both lower limbs. Full exon gene sequencing showed a heterozygous mutation c.1574C>T (p.Pro525Leu) in the FUS gene.<br><br>CONCLUSION: The pathogenesis of ALS remains unclear at present. This case underscores the presence of autonomic nervous symptoms in ALS associated with FUS mutation and highlights the importance of early diagnosis and timely treatment intervention to enhance patient prognosis.}, }
@article {pmid37895110, year = {2023}, author = {Provenzano, F and Torazza, C and Bonifacino, T and Bonanno, G and Milanese, M}, title = {The Key Role of Astrocytes in Amyotrophic Lateral Sclerosis and Their Commitment to Glutamate Excitotoxicity.}, journal = {International journal of molecular sciences}, volume = {24}, number = {20}, pages = {}, pmid = {37895110}, issn = {1422-0067}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; Glutamic Acid/metabolism ; Astrocytes/metabolism ; Neuroglia/metabolism ; Neurons/metabolism ; }, abstract = {In the last two decades, there has been increasing evidence supporting non-neuronal cells as active contributors to neurodegenerative disorders. Among glial cells, astrocytes play a pivotal role in driving amyotrophic lateral sclerosis (ALS) progression, leading the scientific community to focus on the "astrocytic signature" in ALS. Here, we summarized the main pathological mechanisms characterizing astrocyte contribution to MN damage and ALS progression, such as neuroinflammation, mitochondrial dysfunction, oxidative stress, energy metabolism impairment, miRNAs and extracellular vesicles contribution, autophagy dysfunction, protein misfolding, and altered neurotrophic factor release. Since glutamate excitotoxicity is one of the most relevant ALS features, we focused on the specific contribution of ALS astrocytes in this aspect, highlighting the known or potential molecular mechanisms by which astrocytes participate in increasing the extracellular glutamate level in ALS and, conversely, undergo the toxic effect of the excessive glutamate. In this scenario, astrocytes can behave as "producers" and "targets" of the high extracellular glutamate levels, going through changes that can affect themselves and, in turn, the neuronal and non-neuronal surrounding cells, thus actively impacting the ALS course. Moreover, this review aims to point out knowledge gaps that deserve further investigation.}, }
@article {pmid37895020, year = {2023}, author = {Davis, SE and Cirincione, AB and Jimenez-Torres, AC and Zhu, J}, title = {The Impact of Neurotransmitters on the Neurobiology of Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {24}, number = {20}, pages = {}, pmid = {37895020}, issn = {1422-0067}, support = {R01 DA057866/DA/NIDA NIH HHS/United States ; F31 DA057163/DA/NIDA NIH HHS/United States ; R01 DA047924/DA/NIDA NIH HHS/United States ; R01 DA035714/DA/NIDA NIH HHS/United States ; DA047924/NH/NIH HHS/United States ; DA035714/NH/NIH HHS/United States ; DA057866/NH/NIH HHS/United States ; DA057163/NH/NIH HHS/United States ; }, mesh = {Humans ; *Neurodegenerative Diseases/pathology ; *Alzheimer Disease/pathology ; Brain/pathology ; *Huntington Disease/pathology ; *HIV Infections/pathology ; }, abstract = {Neurodegenerative diseases affect millions of people worldwide. Neurodegenerative diseases result from progressive damage to nerve cells in the brain or peripheral nervous system connections that are essential for cognition, coordination, strength, sensation, and mobility. Dysfunction of these brain and nerve functions is associated with Alzheimer's disease, Parkinson's disease, Huntington's disease, Amyotrophic lateral sclerosis, and motor neuron disease. In addition to these, 50% of people living with HIV develop a spectrum of cognitive, motor, and/or mood problems collectively referred to as HIV-Associated Neurocognitive Disorders (HAND) despite the widespread use of a combination of antiretroviral therapies. Neuroinflammation and neurotransmitter systems have a pathological correlation and play a critical role in developing neurodegenerative diseases. Each of these diseases has a unique pattern of dysregulation of the neurotransmitter system, which has been attributed to different forms of cell-specific neuronal loss. In this review, we will focus on a discussion of the regulation of dopaminergic and cholinergic systems, which are more commonly disturbed in neurodegenerative disorders. Additionally, we will provide evidence for the hypothesis that disturbances in neurotransmission contribute to the neuronal loss observed in neurodegenerative disorders. Further, we will highlight the critical role of dopamine as a mediator of neuronal injury and loss in the context of NeuroHIV. This review will highlight the need to further investigate neurotransmission systems for their role in the etiology of neurodegenerative disorders.}, }
@article {pmid37894774, year = {2023}, author = {Moțățăianu, A and Șerban, G and Andone, S}, title = {The Role of Short-Chain Fatty Acids in Microbiota-Gut-Brain Cross-Talk with a Focus on Amyotrophic Lateral Sclerosis: A Systematic Review.}, journal = {International journal of molecular sciences}, volume = {24}, number = {20}, pages = {}, pmid = {37894774}, issn = {1422-0067}, support = {PN-III-P1-1.1-TE-2021-0960//Ministry of Research, Innovation and Digitization, CNCS - UEFISCDI/ ; }, mesh = {Humans ; Aged ; *Gastrointestinal Microbiome/physiology ; *Amyotrophic Lateral Sclerosis/metabolism ; *Neurodegenerative Diseases/metabolism ; Brain/metabolism ; Fatty Acids, Volatile/metabolism ; Fatty Acids/metabolism ; }, abstract = {Amyotrophic lateral sclerosis is a devastating neurodegenerative disease characterized by the gradual loss of motor neurons in the brain and spinal cord, leading to progressive motor function decline. Unfortunately, there is no effective treatment, and its increasing prevalence is linked to an aging population, improved diagnostics, heightened awareness, and changing lifestyles. In the gastrointestinal system, the gut microbiota plays a vital role in producing metabolites, neurotransmitters, and immune molecules. Short-chain fatty acids, of interest for their potential health benefits, are influenced by a fiber- and plant-based diet, promoting a diverse and balanced gut microbiome. These fatty acids impact the body by binding to receptors on enteroendocrine cells, influencing hormones like glucagon-like peptide-1 and peptide YY, which regulate appetite and insulin sensitivity. Furthermore, these fatty acids impact the blood-brain barrier, neurotransmitter levels, and neurotrophic factors, and directly stimulate vagal afferent nerves, affecting gut-brain communication. The vagus nerve is a crucial link between the gut and the brain, transmitting signals related to appetite, inflammation, and various processes. Dysregulation of this pathway can contribute to conditions like obesity and irritable bowel syndrome. Emerging evidence suggests the complex interplay among these fatty acids, the gut microbiota, and environmental factors influences neurodegenerative processes via interconnected pathways, including immune function, anti-inflammation, gut barrier, and energy metabolism. Embracing a balanced, fiber-rich diet may foster a diverse gut microbiome, potentially impacting neurodegenerative disease risk. Comprehensive understanding requires further research into interventions targeting the gut microbiome and fatty acid production and their potential therapeutic role in neurodegeneration.}, }
@article {pmid37893165, year = {2023}, author = {De Marchi, F and Munitic, I and Vidatic, L and Papić, E and Rački, V and Nimac, J and Jurak, I and Novotni, G and Rogelj, B and Vuletic, V and Liscic, RM and Cannon, JR and Buratti, E and Mazzini, L and Hecimovic, S}, title = {Overlapping Neuroimmune Mechanisms and Therapeutic Targets in Neurodegenerative Disorders.}, journal = {Biomedicines}, volume = {11}, number = {10}, pages = {}, pmid = {37893165}, issn = {2227-9059}, abstract = {Many potential immune therapeutic targets are similarly affected in adult-onset neurodegenerative diseases, such as Alzheimer's (AD) disease, Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD), as well as in a seemingly distinct Niemann-Pick type C disease with primarily juvenile onset. This strongly argues for an overlap in pathogenic mechanisms. The commonly researched immune targets include various immune cell subsets, such as microglia, peripheral macrophages, and regulatory T cells (Tregs); the complement system; and other soluble factors. In this review, we compare these neurodegenerative diseases from a clinical point of view and highlight common pathways and mechanisms of protein aggregation, neurodegeneration, and/or neuroinflammation that could potentially lead to shared treatment strategies for overlapping immune dysfunctions in these diseases. These approaches include but are not limited to immunisation, complement cascade blockade, microbiome regulation, inhibition of signal transduction, Treg boosting, and stem cell transplantation.}, }
@article {pmid37892126, year = {2023}, author = {Ramos, V and Reis, M and Ferreira, L and Silva, AM and Ferraz, R and Vieira, M and Vasconcelos, V and Martins, R}, title = {Stalling the Course of Neurodegenerative Diseases: Could Cyanobacteria Constitute a New Approach toward Therapy?.}, journal = {Biomolecules}, volume = {13}, number = {10}, pages = {}, pmid = {37892126}, issn = {2218-273X}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism ; Oxidative Stress ; *Parkinson Disease/drug therapy ; Antioxidants/pharmacology ; *Cyanobacteria/metabolism ; }, abstract = {Neurodegenerative diseases (NDs) are characterized by progressive and irreversible neuronal loss, accompanied by a range of pathological pathways, including aberrant protein aggregation, altered energy metabolism, excitotoxicity, inflammation, and oxidative stress. Some of the most common NDs include Alzheimer's Disease (AD), Parkinson's Disease (PD), Multiple Sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS), and Huntington's Disease (HD). There are currently no available cures; there are only therapeutic approaches that ameliorate the progression of symptoms, which makes the search for new drugs and therapeutic targets a constant battle. Cyanobacteria are ancient prokaryotic oxygenic phototrophs whose long evolutionary history has resulted in the production of a plethora of biomedically relevant compounds with anti-inflammatory, antioxidant, immunomodulatory, and neuroprotective properties, that can be valuable in this field. This review summarizes the major NDs and their pathophysiology, with a focus on the anti-neurodegenerative properties of cyanobacterial compounds and their main effects.}, }
@article {pmid37891890, year = {2023}, author = {Korczowska-Łącka, I and Słowikowski, B and Piekut, T and Hurła, M and Banaszek, N and Szymanowicz, O and Jagodziński, PP and Kozubski, W and Permoda-Pachuta, A and Dorszewska, J}, title = {Disorders of Endogenous and Exogenous Antioxidants in Neurological Diseases.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {12}, number = {10}, pages = {}, pmid = {37891890}, issn = {2076-3921}, abstract = {In diseases of the central nervous system, such as Alzheimer's disease (AD), Parkinson's disease (PD), stroke, amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and even epilepsy and migraine, oxidative stress load commonly surpasses endogenous antioxidative capacity. While oxidative processes have been robustly implicated in the pathogenesis of these diseases, the significance of particular antioxidants, both endogenous and especially exogenous, in maintaining redox homeostasis requires further research. Among endogenous antioxidants, enzymes such as catalase, superoxide dismutase, and glutathione peroxidase are central to disabling free radicals, thereby preventing oxidative damage to cellular lipids, proteins, and nucleic acids. Whether supplementation with endogenously occurring antioxidant compounds such as melatonin and glutathione carries any benefit, however, remains equivocal. Similarly, while the health benefits of certain exogenous antioxidants, including ascorbic acid (vitamin C), carotenoids, polyphenols, sulforaphanes, and anthocyanins are commonly touted, their clinical efficacy and effectiveness in particular neurological disease contexts need to be more robustly defined. Here, we review the current literature on the cellular mechanisms mitigating oxidative stress and comment on the possible benefit of the most common exogenous antioxidants in diseases such as AD, PD, ALS, HD, stroke, epilepsy, and migraine. We selected common neurological diseases of a basically neurodegenerative nature.}, }
@article {pmid37890889, year = {2023}, author = {Ilieva, H and Vullaganti, M and Kwan, J}, title = {Advances in molecular pathology, diagnosis, and treatment of amyotrophic lateral sclerosis.}, journal = {BMJ (Clinical research ed.)}, volume = {383}, number = {}, pages = {e075037}, pmid = {37890889}, issn = {1756-1833}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics/therapy ; Pathology, Molecular ; Disease Progression ; }, abstract = {Although the past two decades have produced exciting discoveries in the genetics and pathology of amyotrophic lateral sclerosis (ALS), progress in developing an effective therapy remains slow. This review summarizes the critical discoveries and outlines the advances in disease characterization, diagnosis, imaging, and biomarkers, along with the current status of approaches to ALS care and treatment. Additional knowledge of the factors driving disease progression and heterogeneity will hopefully soon transform the care for patients with ALS into an individualized, multi-prong approach able to prevent disease progression sufficiently to allow for a dignified life with limited disability.}, }
@article {pmid37887017, year = {2023}, author = {You, J and Youssef, MMM and Santos, JR and Lee, J and Park, J}, title = {Microglia and Astrocytes in Amyotrophic Lateral Sclerosis: Disease-Associated States, Pathological Roles, and Therapeutic Potential.}, journal = {Biology}, volume = {12}, number = {10}, pages = {}, pmid = {37887017}, issn = {2079-7737}, abstract = {Microglial and astrocytic reactivity is a prominent feature of amyotrophic lateral sclerosis (ALS). Microglia and astrocytes have been increasingly appreciated to play pivotal roles in disease pathogenesis. These cells can adopt distinct states characterized by a specific molecular profile or function depending on the different contexts of development, health, aging, and disease. Accumulating evidence from ALS rodent and cell models has demonstrated neuroprotective and neurotoxic functions from microglia and astrocytes. In this review, we focused on the recent advancements of knowledge in microglial and astrocytic states and nomenclature, the landmark discoveries demonstrating a clear contribution of microglia and astrocytes to ALS pathogenesis, and novel therapeutic candidates leveraging these cells that are currently undergoing clinical trials.}, }
@article {pmid37872558, year = {2023}, author = {Schmitz, J and Liebold, F and Hinkelbein, J and Nöhl, S and Thal, SC and Sellmann, T}, title = {Cardiopulmonary resuscitation during hyperbaric oxygen therapy: a comprehensive review and recommendations for practice.}, journal = {Scandinavian journal of trauma, resuscitation and emergency medicine}, volume = {31}, number = {1}, pages = {57}, pmid = {37872558}, issn = {1757-7241}, mesh = {Humans ; *Cardiopulmonary Resuscitation ; *Heart Arrest/therapy ; Heart Massage ; *Hyperbaric Oxygenation ; Ventricular Fibrillation ; Practice Guidelines as Topic ; }, abstract = {BACKGROUND: Cardiopulmonary resuscitation (CPR) during hyperbaric oxygen therapy (HBOT) presents unique challenges due to limited access to patients in cardiac arrest (CA) and the distinct physiological conditions present during hyperbaric therapy. Despite these challenges, guidelines specifically addressing CPR during HBOT are lacking. This review aims to consolidate the available evidence and offer recommendations for clinical practice in this context.<br><br>MATERIALS AND METHODS: A comprehensive literature search was conducted in PubMed, EMBASE, Cochrane Library, and CINAHL using the search string: "(pressure chamber OR decompression OR hyperbaric) AND (cardiac arrest OR cardiopulmonary resuscitation OR advanced life support OR ALS OR life support OR chest compression OR ventricular fibrillation OR heart arrest OR heart massage OR resuscitation)". Additionally, relevant publications and book chapters not identified through this search were included.<br><br>RESULTS: The search yielded 10,223 publications, with 41 deemed relevant to the topic. Among these, 18 articles (primarily case reports) described CPR or defibrillation in 22 patients undergoing HBOT. The remaining 23 articles provided information or recommendations pertaining to CPR during HBOT. Given the unique physiological factors during HBOT, the limitations of current resuscitation guidelines are discussed.<br><br>CONCLUSIONS: CPR in the context of HBOT is a rare, yet critical event requiring special considerations. Existing guidelines should be adapted to address these unique circumstances and integrated into regular training for HBOT practitioners. This review serves as a valuable contribution to the literature on "CPR under special circumstances".}, }
@article {pmid37871962, year = {2023}, author = {Lei, F and Chen, WT and Brecht, ML and Zhang, ZF and Hu, Y and Xu, T and Wang, S and Lee, E}, title = {Cross-Cultural Adaptation of Lung Cancer Screening Health Belief Scale in Chinese Americans: A Methodological Study.}, journal = {Journal of nursing measurement}, volume = {31}, number = {4}, pages = {489-501}, doi = {10.1891/JNM-2021-0093}, pmid = {37871962}, issn = {1945-7049}, mesh = {Humans ; *Cross-Cultural Comparison ; Early Detection of Cancer ; *Lung Neoplasms/diagnosis ; Psychometrics ; Reproducibility of Results ; Surveys and Questionnaires ; Asian ; }, abstract = {Background and Purpose: The purpose of this study is to report the process of adapting the existing Lung Cancer Screening Health Belief Scale to be used in Chinese Americans. Methods: Guided by Flaherty et al.'s cross-cultural equivalency model, the methodology used in the adaptation process consists of four steps, including preliminary modification after a comprehensive literature review, forward and backward translation, expert review, and cognitive interviews among participants. Results: The modified culturally fitted Lung Cancer Screening Health Belief Scale included 57 items and 6 subscales, which proved highly reliable and valid through the expert review and participants' review. Conclusions: This study provided an example for a novice cross-cultural researcher to adapt an instrument to be used in another population with a different language. Further research is needed to work out a standard guideline for cross-cultural instrument adaptation.}, }
@article {pmid37870685, year = {2023}, author = {Zhou, L and Chen, W and Jiang, S and Xu, R}, title = {In Vitro Models of Amyotrophic Lateral Sclerosis.}, journal = {Cellular and molecular neurobiology}, volume = {43}, number = {8}, pages = {3783-3799}, pmid = {37870685}, issn = {1573-6830}, support = {30560042//National Natural Science Foundation of China/ ; 81160161//National Natural Science Foundation of China/ ; 81360198//National Natural Science Foundation of China/ ; 82160255//National Natural Science Foundation of China/ ; GJJ13198//Education Department of Jiangxi Province/ ; GJJ170021//Education Department of Jiangxi Province/ ; 20192BAB205043//Jiangxi Provincial Department of Science and Technology/ ; 20181019//Health and Family Planning Commission of Jiangxi Province/ ; 202210002//Health and Family Planning Commission of Jiangxi Province/ ; }, mesh = {Animals ; Humans ; Mice ; *Amyotrophic Lateral Sclerosis/metabolism ; Superoxide Dismutase-1/genetics/metabolism ; Disease Models, Animal ; Motor Neurons/metabolism ; Mutation/genetics ; Superoxide Dismutase/metabolism ; Mice, Transgenic ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is one of the commonest neurodegenerative diseases of adult-onset, which is characterized by the progressive death of motor neurons in the cerebral cortex, brain stem and spinal cord. The dysfunction and death of motor neurons lead to the progressive muscle weakness, atrophy, fasciculations, spasticity and ultimately the whole paralysis of body. Despite the identification of several genetic mutations associated with the pathogenesis of ALS, including mutations in chromosome 9 open reading frame 72 leading to the abnormal expansion of GGGGCC repeat sequence, TAR DNA-binding protein 43, fused in sarcoma/translocated in liposarcoma, copper/zinc superoxide dismutase 1 (SOD1) and TANK-binding kinase 1, the exact mechanisms underlying the specific degeneration of motor neurons that causes ALS remain incompletely understood. At present, since the transgenic model expressed SOD1 mutants was established, multiple in vitro models of ALS have been developed for studying the pathology, pathophysiology and pathogenesis of ALS as well as searching the effective neurotherapeutics. This review reviewed the details of present established in vitro models used in studying the pathology, pathophysiology and pathogenesis of ALS. Meanwhile, we also discussed the advantages, disadvantages, cost and availability of each models.}, }
@article {pmid37868386, year = {2023}, author = {Hoxhaj, P and Hastings, N and Kachhadia, MP and Gupta, R and Sindhu, U and Durve, SA and Azam, A and Auz Vinueza, MJ and Bhuvan,  and Win, SH and Rathod, DC and Afsar, AP}, title = {Exploring Advancements in the Treatment of Amyotrophic Lateral Sclerosis: A Comprehensive Review of Current Modalities and Future Prospects.}, journal = {Cureus}, volume = {15}, number = {9}, pages = {e45489}, pmid = {37868386}, issn = {2168-8184}, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal and incurable disease requiring a multidisciplinary treatment approach and a collaborative therapeutic effort. A combination of both upper and lower motor neuron degeneration ultimately leads to respiratory failure, similar to other dementia-type neurodegenerative diseases. The aim of this paper is to pioneer current ALS research by carrying out a narrative literature review of the current treatment modalities of the disease. Through these efforts, we hope to condense the most pertinent information regarding current treatments and enhance the management of ALS patients as a whole, giving these patients a better quality of life as the search for a cure continues. We used a Pubmed search strategy and specific MeSH terms for the selection of the literature articles using the keywords "ALS," "new treatment," "treatment," and "symptomatic treatment." A combination of pharmaceutical interventions, psychological support, and physical rehabilitation has been most effective in enhancing the quality of life of patients with ALS (PALS). Among potential pharmacological therapies, only a few have been approved by the US Food and Drug Administration(FDA) to be used to treat ALS and its symptoms. Other treatment modalities being considered include gene therapy, cellular therapy, psychological therapy, physical therapy, and speech therapy, alongside robotics, alternative feeding methods, and communication devices.}, }
@article {pmid37865833, year = {2023}, author = {Wu, YK and Wecht, JM and Bloom, OE and Panza, GS and Harel, NY}, title = {Remote Ischemic conditioning as an emerging tool to improve corticospinal transmission in individuals with chronic spinal cord injury.}, journal = {Current opinion in neurology}, volume = {36}, number = {6}, pages = {523-530}, doi = {10.1097/WCO.0000000000001216}, pmid = {37865833}, issn = {1473-6551}, support = {R03 HD097709/HD/NICHD NIH HHS/United States ; }, mesh = {Adult ; Humans ; *Myocardial Infarction ; *Stroke ; *Spinal Cord Injuries ; Hypoxia ; }, abstract = {PURPOSE OF REVIEW: Remote ischemic conditioning (RIC) involves transient blood flow restriction to one limb leading to systemic tissue-protective effects. RIC shares some potential underlying mechanisms with intermittent hypoxia (IH), in which brief bouts of systemic hypoxia trigger increases in growth factor expression and neural plasticity. RIC has shown promise in acute myocardial infarction and stroke but may be applicable toward chronic neuropathology as well. Consequently, this review discusses similarities and differences between RIC and IH and presents preliminary and ongoing research findings regarding RIC.<br><br>RECENT FINDINGS: Several publications demonstrated that combining RIC with motor training may enhance motor learning in adults with intact nervous systems, though the precise mechanisms were unclear. Our own preliminary data has found that RIC, in conjunction with task specific exercise, can increase corticospinal excitability in a subset of people without neurological injury and in those with chronic cervical spinal cord injury or amyotrophic lateral sclerosis.<br><br>SUMMARY: RIC is a low-cost intervention easy to deliver in a clinical or home setting. Its potential application to facilitate neural plasticity and motor learning during rehabilitation training for individuals with chronic neurological disorders is a novel concept requiring further investigation to characterize mechanisms, safety, and efficacy.}, }
@article {pmid37864389, year = {2024}, author = {Xiao, F and He, Z and Wang, S and Li, J and Fan, X and Yan, T and Yang, M and Yang, D}, title = {Regulatory mechanism of circular RNAs in neurodegenerative diseases.}, journal = {CNS neuroscience &amp; therapeutics}, volume = {30}, number = {4}, pages = {e14499}, pmid = {37864389}, issn = {1755-5949}, support = {//China Scholarship Council/ ; //National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/diagnosis/genetics ; RNA, Circular/metabolism ; *MicroRNAs/genetics ; *Alzheimer Disease/genetics ; *Parkinson Disease ; Biomarkers ; }, abstract = {BACKGROUND: Neurodegenerative disease is a collective term for a category of diseases that are caused by neuronal dysfunction, such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Circular RNAs (circRNAs) are a class of non-coding RNAs without the 3' cap and 5' poly(A) and are linked by covalent bonds. CircRNAs are highly expressed in brain neurons and can regulate the pathological process of neurodegenerative diseases by affecting the levels of various deposition proteins.<br><br>AIMS: This review is aiming to suggest that the majority of circRNAs influence neurodegenerative pathologies mainly by affecting the abnormal deposition of proteins in neurodegenerative diseases.<br><br>METHODS: We systematically summarized the pathological features of neurodegenerative diseases and the regulatory mechanisms of circRNAs in various types of neurodegenerative diseases.<br><br>RESULTS: Neurodegenerative disease main features include intercellular ubiquitin-proteasome system abnormalities, changes in cytoskeletal proteins, and the continuous deposition of insoluble protein fragments and inclusion bodies in the cytoplasm or nucleus, resulting in impairment of the normal physiological processes of the neuronal system. CircRNAs have multiple mechanisms, such as acting as microRNA sponges, binding to proteins, and regulating transcription. CircRNAs, which are highly stable molecules, are expected to be potential biomarkers for the pathological detection of neurodegenerative diseases such as AD and PD.<br><br>CONCLUSIONS: In this review, we describe the regulatory roles and mechanisms of circRNAs in neurodegenerative diseases and aim to employ circRNAs as biomarkers for the diagnosis and treatment of neurodegenerative diseases.}, }
@article {pmid37862967, year = {2023}, author = {Rabeh, N and Hajjar, B and Maraka, JO and Sammanasunathan, AF and Khan, M and Alkhaaldi, SMI and Mansour, S and Almheiri, RT and Hamdan, H and Abd-Elrahman, KS}, title = {Targeting mGluR group III for the treatment of neurodegenerative diseases.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {168}, number = {}, pages = {115733}, doi = {10.1016/j.biopha.2023.115733}, pmid = {37862967}, issn = {1950-6007}, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy ; Signal Transduction/physiology ; Glutamic Acid ; Neurotransmitter Agents ; Neurons ; *Receptors, Metabotropic Glutamate/physiology ; }, abstract = {Glutamate, an excitatory neurotransmitter, is essential for neuronal function, and it acts on ionotropic or metabotropic glutamate receptors (mGluRs). A disturbance in glutamatergic signaling is a hallmark of many neurodegenerative diseases. Developing disease-modifying treatments for neurodegenerative diseases targeting glutamate receptors is a promising avenue. The understudied group III mGluR 4, 6-8 are commonly found in the presynaptic membrane, and their activation inhibits glutamate release. Thus, targeted mGluRs therapies could aid in treating neurodegenerative diseases. This review describes group III mGluRs and their pharmacological ligands in the context of amyotrophic lateral sclerosis, Parkinson's, Alzheimer's, and Huntington's diseases. Attempts to evaluate the efficacy of these drugs in clinical trials are also discussed. Despite a growing list of group III mGluR-specific pharmacological ligands, research on the use of these drugs in neurodegenerative diseases is limited, except for Parkinson's disease. Future efforts should focus on delineating the contribution of group III mGluR to neurodegeneration and developing novel ligands with superior efficacy and a favorable side effect profile for the treatment of neurodegenerative diseases.}, }
@article {pmid37858176, year = {2023}, author = {Xie, M and Pallegar, PN and Parusel, S and Nguyen, AT and Wu, LJ}, title = {Regulation of cortical hyperexcitability in amyotrophic lateral sclerosis: focusing on glial mechanisms.}, journal = {Molecular neurodegeneration}, volume = {18}, number = {1}, pages = {75}, pmid = {37858176}, issn = {1750-1326}, support = {R35 NS132326/NS/NINDS NIH HHS/United States ; RF1AG082314/AG/NIA NIH HHS/United States ; RF1 AG082314/AG/NIA NIH HHS/United States ; U19AG 069701/AG/NIA NIH HHS/United States ; R35NS132326/NS/NINDS NIH HHS/United States ; U19 AG069701/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology ; Motor Neurons/pathology ; Neuroglia/pathology ; Microglia/pathology ; Disease Progression ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by the loss of both upper and lower motor neurons, resulting in muscle weakness, atrophy, paralysis, and eventually death. Motor cortical hyperexcitability is a common phenomenon observed at the presymptomatic stage of ALS. Both cell-autonomous (the intrinsic properties of motor neurons) and non-cell-autonomous mechanisms (cells other than motor neurons) are believed to contribute to cortical hyperexcitability. Decoding the pathological relevance of these dynamic changes in motor neurons and glial cells has remained a major challenge. This review summarizes the evidence of cortical hyperexcitability from both clinical and preclinical research, as well as the underlying mechanisms. We discuss the potential role of glial cells, particularly microglia, in regulating abnormal neuronal activity during the disease progression. Identifying early changes such as neuronal hyperexcitability in the motor system may provide new insights for earlier diagnosis of ALS and reveal novel targets to halt the disease progression.}, }
@article {pmid37857264, year = {2024}, author = {Kiene, H and Hamre, HJ}, title = {A Fundamental Question for Complementary Medicine: Are There Other Forces in the Natural World Besides the Physical Forces?.}, journal = {Complementary medicine research}, volume = {31}, number = {1}, pages = {71-77}, doi = {10.1159/000534592}, pmid = {37857264}, issn = {2504-2106}, mesh = {*Complementary Therapies ; *Homeopathy ; DNA ; RNA ; }, abstract = {BACKGROUND: The integration of conventional and complementary medicine reflects the pluralism in science. Still, a critical issue is the conception of the natural world. Many complementary therapy systems seem to contradict the reductionist-atomistic paradigm that all of natural reality is essentially based on the physical interactions of atoms and molecules. Thus, a fundamental question about the natural world is: Do other than the physical forces exist?<br><br>SUMMARY: The assumption that no other than physical forces exist and work in the natural world is not tenable. For example, the formation and maintenance of the functional Gestalt of organisms cannot possibly be explained by molecular processes (e.g., from DNA to RNA and further to amino acids and proteins). The processes on each structural level - from molecules, organelles, cells, organs up to the whole organism - are regulated in regard to the formation of the next higher level. Specific Gestalt-forming forces exist and can be systematically investigated. Their existence implies an extended conception of matter. The Gestalt-forming forces and the extended concept of matter may be relevant for the scientific assessment of complementary therapies.<br><br>KEY MESSAGES: (i) In the natural world, specific Gestalt-forming forces exist in addition to the physical forces, and can be systematically investigated. (ii) The existence of these forces implies an extended conception of matter. (iii) These forces and this extended concept of matter may be relevant for the scientific assessment of complementary therapies, e.g., homeopathy.<br><br>UNLABELLED: <title>Hintergrund</title>In der Integration von konventioneller und komplement&#xe4;rer Medizin spiegelt sich der Methodenpluralismus der Wissenschaft. Die Ontologien vieler komplement&#xe4;rmedizinisches Systeme liegen allerdings au&#xdf;erhalb der Erkl&#xe4;rbarkeit durch die Kr&#xe4;fte der Physik. Eine zentrale Frage ist deshalb: Gibt es Kr&#xe4;fte in der Natur, die eine materielle Wirkung haben, deren Ursprung aber nicht in Atomen oder Molek&#xfc;len und in diesem Sinne nicht in der Materie liegt?<title>Zusammenfassung</title>Die Annahme, dass in der Natur keine anderen als die mit Atomen und Molek&#xfc;len assoziierten physikalischen Kr&#xe4;fte existent und wirksam seien, ist wissenschaftlich nicht begr&#xfc;ndet. Beispielsweise ist die Bildung und Erhaltung der funktionsf&#xe4;higen Gestalt von Organismen nicht durch molekulare Prozesse (z.B. von der DNA zur RNA und weiter zu Aminos&#xe4;uren und Proteinen) erkl&#xe4;rbar. Die Prozesse auf jeder strukturellen Ebene &#x2013; von den Molek&#xfc;len, Organellen, Zellen, Organen bis hinauf zum Gesamtorganismus &#x2013; sind in Hinblick auf die Bildung der funktionsf&#xe4;higen Gestalt der jeweils n&#xe4;chsth&#xf6;heren Ebene gesteuert. F&#xfc;r diese Gestaltbildung gibt es spezifische Kr&#xe4;fte, die systematisch erforscht werden k&#xf6;nnen. Ihre Existenz impliziert eine erweiterte Konzeption von Materie. Diese Gestalt-bildenden Kr&#xe4;fte und dieses erweiterte Konzept von Materie sind relevant f&#xfc;r die wissenschaftliche Erfassung komplement&#xe4;rmedizinischer Systeme.<title>Zentrale Aussagen</title>(i) In der Natur sind au&#xdf;er den physikalischen Kr&#xe4;ften noch weitere spezifische Kr&#xe4;fte wirksam, beispielsweise bei der Bildung und Erhaltung der funktionsf&#xe4;higen Gestalt von Organismen. Diese Kr&#xe4;fte k&#xf6;nnen systematisch erforscht werden. (ii) Die Existenz dieser Kr&#xe4;fte impliziert eine erweitere Konzeption von Materie. (iii) Diese Kr&#xe4;fte und das erweiterte Materiekonzept sind relevant f&#xfc;r die wissenschaftliche Erfassung komplement&#xe4;rmedizinischer Systeme, beispielsweise der Hom&#xf6;opathie.}, }
@article {pmid37855949, year = {2023}, author = {Suh, A and Ong, J and Kamran, SA and Waisberg, E and Paladugu, P and Zaman, N and Sarker, P and Tavakkoli, A and Lee, AG}, title = {Retina Oculomics in Neurodegenerative Disease.}, journal = {Annals of biomedical engineering}, volume = {51}, number = {12}, pages = {2708-2721}, pmid = {37855949}, issn = {1573-9686}, support = {80NSSC20K183//NASA Grant/ ; }, mesh = {Humans ; *Artificial Intelligence ; *Neurodegenerative Diseases/diagnostic imaging ; Quality of Life ; Retina/diagnostic imaging ; Tomography, Optical Coherence/methods ; Biomarkers ; }, abstract = {Ophthalmic biomarkers have long played a critical role in diagnosing and managing ocular diseases. Oculomics has emerged as a field that utilizes ocular imaging biomarkers to provide insights into systemic diseases. Advances in diagnostic and imaging technologies including electroretinography, optical coherence tomography (OCT), confocal scanning laser ophthalmoscopy, fluorescence lifetime imaging ophthalmoscopy, and OCT angiography have revolutionized the ability to understand systemic diseases and even detect them earlier than clinical manifestations for earlier intervention. With the advent of increasingly large ophthalmic imaging datasets, machine learning models can be integrated into these ocular imaging biomarkers to provide further insights and prognostic predictions of neurodegenerative disease. In this manuscript, we review the use of ophthalmic imaging to provide insights into neurodegenerative diseases including Alzheimer Disease, Parkinson Disease, Amyotrophic Lateral Sclerosis, and Huntington Disease. We discuss recent advances in ophthalmic technology including eye-tracking technology and integration of artificial intelligence techniques to further provide insights into these neurodegenerative diseases. Ultimately, oculomics opens the opportunity to detect and monitor systemic diseases at a higher acuity. Thus, earlier detection of systemic diseases may allow for timely intervention for improving the quality of life in patients with neurodegenerative disease.}, }
@article {pmid37855859, year = {2024}, author = {Vieira, TCRG and Barros, CA and Domingues, R and Outeiro, TF}, title = {PrP meets alpha-synuclein: Molecular mechanisms and implications for disease.}, journal = {Journal of neurochemistry}, volume = {168}, number = {8}, pages = {1625-1639}, doi = {10.1111/jnc.15992}, pmid = {37855859}, issn = {1471-4159}, support = {SFB1286 (B8)//Deutsche Forschungsgemeinschaft/ ; EXC 2067/1-390729940//Deutsche Forschungsgemeinschaft/ ; //Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado do Rio de Janeiro (FAPERJ)/ ; //Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico (CNPq)/ ; }, mesh = {Humans ; *alpha-Synuclein/metabolism ; Animals ; Synucleinopathies/metabolism/pathology ; Prion Proteins/metabolism ; }, abstract = {The discovery of prions has challenged dogmas and has revolutionized our understanding of protein-misfolding diseases. The concept of self-propagation via protein conformational changes, originally discovered for the prion protein (PrP), also applies to other proteins that exhibit similar behavior, such as alpha-synuclein (aSyn), a central player in Parkinson's disease and in other synucleinopathies. aSyn pathology appears to spread from one cell to another during disease progression, and involves the misfolding and aggregation of aSyn. How the transfer of aSyn between cells occurs is still being studied, but one important hypothesis involves receptor-mediated transport. Interestingly, recent studies indicate that the cellular prion protein (PrP[C]) may play a crucial role in this process. PrP[C] has been shown to act as a receptor/sensor for protein aggregates in different neurodegenerative disorders, including Alzheimer's disease and amyotrophic lateral sclerosis. Here, we provide a comprehensive overview of the current state of knowledge regarding the interaction between aSyn and PrP[C] and discuss its role in synucleinopathies. We examine the properties of PrP and aSyn, including their structure, function, and aggregation. Additionally, we discuss the current understanding of PrP[C]'s role as a receptor/sensor for aSyn aggregates and identify remaining unanswered questions in this area of research. Ultimately, we posit that exploring the interaction between aSyn and PrP[C] may offer potential treatment options for synucleinopathies.}, }
@article {pmid37851042, year = {2023}, author = {Izenberg, A}, title = {Amyotrophic Lateral Sclerosis and Other Motor Neuron Diseases.}, journal = {Continuum (Minneapolis, Minn.)}, volume = {29}, number = {5}, pages = {1538-1563}, pmid = {37851042}, issn = {1538-6899}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics/therapy ; *Motor Neuron Disease/diagnosis/genetics/therapy ; Biomarkers ; }, abstract = {OBJECTIVE: This article reviews the clinical spectrum of amyotrophic lateral sclerosis (ALS), its variant presentations, and the approach to diagnosis and management. This review includes a detailed discussion of current and emerging disease-modifying therapies and the management of respiratory and bulbar manifestations of disease. An updated review of ALS genetics and pathophysiology is also provided. This article also touches on several other important motor neuron diseases.<br><br>LATEST DEVELOPMENTS: A new set of simplified diagnostic criteria may help identify patients at earlier stages of the disease. A coformulation of sodium phenylbutyrate and tauroursodeoxycholic acid has been shown to have a significant benefit on disease progression and survival, leading to approval by regulatory authorities in the United States and Canada. An oral formulation of edaravone and an antisense oligonucleotide to a SOD1 gene variation (tofersen) have also recently been approved by the US Food and Drug Administration (FDA). Phase 3 trials of intrathecal mesenchymal stem cells failed to meet primary end points for efficacy. Updated American Academy of Neurology quality measures for the care of patients with ALS were published in 2023.<br><br>ESSENTIAL POINTS: There has been continued progress in ALS genetics, diagnosis, and disease-modifying therapies. However, we still lack a definitive biomarker or a treatment that can halt the progression or reverse the course of disease. The evolving understanding of the genetic and pathophysiologic underpinnings of disease offers promise for more effective and clinically meaningful treatments in the future.}, }
@article {pmid37845811, year = {2024}, author = {Holt, MW and Robinson, EC and Shlobin, NA and Hanson, JT and Bozkurt, I}, title = {Intracortical brain-computer interfaces for improved motor function: a systematic review.}, journal = {Reviews in the neurosciences}, volume = {35}, number = {2}, pages = {213-223}, pmid = {37845811}, issn = {2191-0200}, mesh = {Humans ; *Brain-Computer Interfaces ; *Motor Cortex/physiology/physiopathology ; }, abstract = {In this systematic review, we address the status of intracortical brain-computer interfaces (iBCIs) applied to the motor cortex to improve function in patients with impaired motor ability. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 Guidelines for Systematic Reviews. Risk Of Bias In Non-randomized Studies - of Interventions (ROBINS-I) and the Effective Public Health Practice Project (EPHPP) were used to assess bias and quality. Advances in iBCIs in the last two decades demonstrated the use of iBCI to activate limbs for functional tasks, achieve neural typing for communication, and other applications. However, the inconsistency of performance metrics employed by these studies suggests the need for standardization. Each study was a pilot clinical trial consisting of 1-4, majority male (64.28 %) participants, with most trials featuring participants treated for more than 12 months (55.55 %). The systems treated patients with various conditions: amyotrophic lateral sclerosis, stroke, spinocerebellar degeneration without cerebellar involvement, and spinal cord injury. All participants presented with tetraplegia at implantation and were implanted with microelectrode arrays via pneumatic insertion, with nearly all electrode locations solely at the precentral gyrus of the motor cortex (88.88 %). The development of iBCI devices using neural signals from the motor cortex to improve motor-impaired patients has enhanced the ability of these systems to return ability to their users. However, many milestones remain before these devices can prove their feasibility for recovery. This review summarizes the achievements and shortfalls of these systems and their respective trials.}, }
@article {pmid37843219, year = {2024}, author = {Liu, X and Liu, Y and Liu, J and Zhang, H and Shan, C and Guo, Y and Gong, X and Cui, M and Li, X and Tang, M}, title = {Correlation between the gut microbiome and neurodegenerative diseases: a review of metagenomics evidence.}, journal = {Neural regeneration research}, volume = {19}, number = {4}, pages = {833-845}, pmid = {37843219}, issn = {1673-5374}, abstract = {A growing body of evidence suggests that the gut microbiota contributes to the development of neurodegenerative diseases via the microbiota-gut-brain axis. As a contributing factor, microbiota dysbiosis always occurs in pathological changes of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. High-throughput sequencing technology has helped to reveal that the bidirectional communication between the central nervous system and the enteric nervous system is facilitated by the microbiota's diverse microorganisms, and for both neuroimmune and neuroendocrine systems. Here, we summarize the bioinformatics analysis and wet-biology validation for the gut metagenomics in neurodegenerative diseases, with an emphasis on multi-omics studies and the gut virome. The pathogen-associated signaling biomarkers for identifying brain disorders and potential therapeutic targets are also elucidated. Finally, we discuss the role of diet, prebiotics, probiotics, postbiotics and exercise interventions in remodeling the microbiome and reducing the symptoms of neurodegenerative diseases.}, }
@article {pmid37843214, year = {2024}, author = {Wang, X and Hu, Y and Xu, R}, title = {The pathogenic mechanism of TAR DNA-binding protein 43 (TDP-43) in amyotrophic lateral sclerosis.}, journal = {Neural regeneration research}, volume = {19}, number = {4}, pages = {800-806}, pmid = {37843214}, issn = {1673-5374}, abstract = {The onset of amyotrophic lateral sclerosis is usually characterized by focal death of both upper and/or lower motor neurons occurring in the motor cortex, basal ganglia, brainstem, and spinal cord, and commonly involves the muscles of the upper and/or lower extremities, and the muscles of the bulbar and/or respiratory regions. However, as the disease progresses, it affects the adjacent body regions, leading to generalized muscle weakness, occasionally along with memory, cognitive, behavioral, and language impairments; respiratory dysfunction occurs at the final stage of the disease. The disease has a complicated pathophysiology and currently, only riluzole, edaravone, and phenylbutyrate/taurursodiol are licensed to treat amyotrophic lateral sclerosis in many industrialized countries. The TAR DNA-binding protein 43 inclusions are observed in 97% of those diagnosed with amyotrophic lateral sclerosis. This review provides a preliminary overview of the potential effects of TAR DNA-binding protein 43 in the pathogenesis of amyotrophic lateral sclerosis, including the abnormalities in nucleoplasmic transport, RNA function, post-translational modification, liquid-liquid phase separation, stress granules, mitochondrial dysfunction, oxidative stress, axonal transport, protein quality control system, and non-cellular autonomous functions (e.g., glial cell functions and prion-like propagation).}, }
@article {pmid37843208, year = {2024}, author = {King, PH}, title = {Skeletal muscle as a molecular and cellular biomarker of disease progression in amyotrophic lateral sclerosis: a narrative review.}, journal = {Neural regeneration research}, volume = {19}, number = {4}, pages = {747-753}, pmid = {37843208}, issn = {1673-5374}, support = {I01 BX001148/BX/BLRD VA/United States ; I01 BX005899/BX/BLRD VA/United States ; R01 NS092651/NS/NINDS NIH HHS/United States ; R21 NS111275/NS/NINDS NIH HHS/United States ; }, abstract = {Amyotrophic lateral sclerosis is a fatal multisystemic neurodegenerative disease with motor neurons being a primary target. Although progressive weakness is a hallmark feature of amyotrophic lateral sclerosis, there is considerable heterogeneity, including clinical presentation, progression, and the underlying triggers for disease initiation. Based on longitudinal studies with families harboring amyotrophic lateral sclerosis-associated gene mutations, it has become apparent that overt disease is preceded by a prodromal phase, possibly in years, where compensatory mechanisms delay symptom onset. Since 85-90% of amyotrophic lateral sclerosis is sporadic, there is a strong need for identifying biomarkers that can detect this prodromal phase as motor neurons have limited capacity for regeneration. Current Food and Drug Administration-approved therapies work by slowing the degenerative process and are most effective early in the disease. Skeletal muscle, including the neuromuscular junction, manifests abnormalities at the earliest stages of the disease, before motor neuron loss, making it a promising source for identifying biomarkers of the prodromal phase. The accessibility of muscle through biopsy provides a lens into the distal motor system at earlier stages and in real time. The advent of "omics" technology has led to the identification of numerous dysregulated molecules in amyotrophic lateral sclerosis muscle, ranging from coding and non-coding RNAs to proteins and metabolites. This technology has opened the door for identifying biomarkers of disease activity and providing insight into disease mechanisms. A major challenge is correlating the myriad of dysregulated molecules with clinical or histological progression and understanding their relevance to presymptomatic phases of disease. There are two major goals of this review. The first is to summarize some of the biomarkers identified in human amyotrophic lateral sclerosis muscle that have a clinicopathological correlation with disease activity, evidence of a similar dysregulation in the SOD1[G93A] mouse during presymptomatic stages, and evidence of progressive change during disease progression. The second goal is to review the molecular pathways these biomarkers reflect and their potential role in mitigating or promoting disease progression, and as such, their potential as therapeutic targets in amyotrophic lateral sclerosis.}, }
@article {pmid37838979, year = {2024}, author = {Jagadish, A and Shankaranarayana, AM and Natarajan, M and Solomon, JM}, title = {Transcranial direct current stimulation for fatigue in neurological conditions: A systematic scoping review.}, journal = {Physiotherapy research international : the journal for researchers and clinicians in physical therapy}, volume = {29}, number = {1}, pages = {e2054}, doi = {10.1002/pri.2054}, pmid = {37838979}, issn = {1471-2865}, mesh = {Humans ; *Brain Injuries, Traumatic ; Fatigue/therapy/etiology ; *Multiple Sclerosis/complications/therapy ; *Parkinson Disease ; Quality of Life ; *Stroke ; *Transcranial Direct Current Stimulation/adverse effects ; }, abstract = {BACKGROUND AND PURPOSE: Fatigue following neurological conditions negatively impacts daily activities, reducing overall quality of life. Transcranial direct current stimulation (tDCS) for fatigue management is still underexplored. This scoping review explores its use in managing fatigue among various neurological conditions.<br><br>METHODS: A thorough literature search was carried out using PubMed, Scopus, CINAHL, Web of Science, Embase, ProQuest, and the Cochrane Library. Google Scholar and clinicaltrials.gov were manually searched for gray literature and ongoing trials, respectively. Regardless of the study design, all studies utilizing tDCS for the management of fatigue in various neurological conditions were considered. Two reviewers independently screened all the studies, following which the data were retrieved.<br><br>RESULTS: Studies employing tDCS for fatigue management across neurological conditions is as follows: Multiple sclerosis (MS) (n&#xa0;=&#xa0;28, 66%), stroke (n&#xa0;=&#xa0;5, 12%), Parkinson's disease (PD) (n&#xa0;=&#xa0;4, 10%), post-polio syndrome (PPS) (n&#xa0;=&#xa0;2, 5%), traumatic brain injury (TBI) (n&#xa0;=&#xa0;2, 5%), and amyotrophic lateral sclerosis (n&#xa0;=&#xa0;1, 2%). All the studies used anodal stimulation, with the common stimulation site being the left dorsolateral prefrontal cortex for MS, stroke, and PD. A stimulation intensity of 1.0-4.0&#xa0;mA with a duration ranging from 15 to 30&#xa0;min in 1 to 24 sessions were commonly reported. The Fatigue Severity Scale (n&#xa0;=&#xa0;21) and Modified Fatigue Impact Scale (n&#xa0;=&#xa0;17) were frequently implemented outcome measures. Regardless of the study design, 36/42 (85.7%) studies reported an improvement in fatigue scores in the tDCS group. The common adverse events noted were tingling (n&#xa0;=&#xa0;8, 35%), headache (n&#xa0;=&#xa0;6, 26%), and itching (n&#xa0;=&#xa0;6, 26%).<br><br>DISCUSSION: Application of tDCS for fatigue was explored in individuals with stroke, PD, PPS, and TBI after MS. Even though a wide range of treatment parameters and outcome measures were adopted to assess and target fatigue, tDCS proves to have a promising role in alleviating this symptom.}, }
@article {pmid37838538, year = {2024}, author = {Wang, SA and Lee, HW and Ko, YC and Sun, JT and Matsuyama, T and Lin, CH and Hsieh, MJ and Chiang, WC and Ma, MH}, title = {Effect of crew ratio of advanced life support-trained personnel on patients with out-of-hospital cardiac arrest: A systematic review and meta-analysis.}, journal = {Journal of the Formosan Medical Association = Taiwan yi zhi}, volume = {123}, number = {5}, pages = {561-570}, doi = {10.1016/j.jfma.2023.10.008}, pmid = {37838538}, issn = {0929-6646}, mesh = {Humans ; *Out-of-Hospital Cardiac Arrest/therapy/mortality ; *Emergency Medical Services ; *Advanced Cardiac Life Support ; Cardiopulmonary Resuscitation ; Taiwan ; Return of Spontaneous Circulation ; Japan ; }, abstract = {BACKGROUND/PURPOSE: This review aimed to investigate the effect of crew ratios of on-scene advanced life support (ALS)-trained personnel on patients with out-of-hospital cardiac arrest (OHCA).<br><br>METHODS: We systematically searched PubMed, Ovid EMBASE, and the Cochrane Central Register of Controlled Trials databases from the inception date until September 30, 2022, for eligible studies. Two reviewers independently screened the studies for relevance, extracted data, and quality. We compared the effect of the ratio of on-scene ALS-trained personnel >50&#xa0;% to those with a ratio &#x2264;50&#xa0;% among prehospital personnel on the clinical outcomes of OHCA patients. The primary outcome was survival-to-discharge and secondary outcomes were any return of spontaneous circulation (ROSC), sustained ROSC (&#x2265;2&#xa0;h), and favourable neurological outcome at discharge (cerebral performance category scores: 1 or 2). Pooled odds ratios (ORs) were calculated, and the certainty of evidence was assessed.<br><br>RESULTS: From 10,864 references, we identified four non-randomised studies, including 16,475 patients. Two studies were performed in Japan and two in Taiwan. There were significant differences in survival-to-discharge (OR: 1.24, 95&#xa0;% confidence interval [CI]: 1.07-1.44, I[2]: 7&#xa0;%), any ROSC (OR:1.22, 95&#xa0;% CI: 1.04-1.43, I[2]: 74&#xa0;%) and sustained ROSC (OR: 1.39, 95&#xa0;% CI: 1.16-1.65, I[2]: 40&#xa0;%), but insignificant differences in favourable neurological outcome at discharge. The overall certainty of evidence was rated as very low for all outcomes.<br><br>CONCLUSION: Prehospital ALS care with a ratio of on-scene ALS-trained personnel >50&#xa0;% could improve OHCA patient outcomes than crew ratios &#x2264;50&#xa0;%. Further studies are required to reach a robust conclusion.}, }
@article {pmid37837507, year = {2024}, author = {Hamad, AA and Amer, BE and Abbas, NB and Alnajjar, AZ and Meshref, M}, title = {Prevalence and correlates of fatigue in amyotrophic lateral sclerosis: A systematic review and meta-analysis.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {2}, pages = {485-493}, pmid = {37837507}, issn = {1590-3478}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/epidemiology ; Prevalence ; Quality of Life ; Fatigue/etiology/complications ; }, abstract = {OBJECTIVES: This systematic review and meta-analysis aimed to determine the frequency and correlates of fatigue in patients with amyotrophic lateral sclerosis (ALS).<br><br>METHODS: Three databases were searched up to 2nd May 2023 to identify studies reporting fatigue frequency in ALS. Studies included had to identify ALS patients through one of ALS diagnostic criteria and measure fatigue by a validated tool with a specific cut-off value. Meta-analysis was conducted using RStudio's "meta" package with a random-effects model. Subgroup analyses and meta-regression explored the relationship between fatigue frequency in ALS and different covariates.<br><br>RESULTS: Eleven studies, compromising 1072 patients, met the inclusion criteria and were included in our analysis. The pooled frequency of fatigue across all studies was 48% (95% CI&#x2009;=&#x2009;40% to 57%). Our subgroup analysis based on the ALSFRS-R revealed a higher frequency of fatigue in studies with lower scores (<&#x2009;30) compared to those with higher scores (&#x2265;&#x2009;30), with a pooled frequency of 62% (95% CI&#x2009;=&#x2009;43% to 79%) and 43% (95% CI&#x2009;=&#x2009;37% to 49%), respectively. Also, the meta-regression analysis showed a significant negative association between fatigue and ALSFRS-R mean (P&#x2009;=&#x2009;0.02). The included studies reported an association between fatigue and lower functional status and poorer quality of life in patients with ALS.<br><br>CONCLUSION: Our findings suggest that fatigue is prevalent in almost half of ALS patients and is associated with lower functional status and poorer quality of life, highlighting the importance of assessing and managing fatigue in ALS patients.}, }
@article {pmid37834407, year = {2023}, author = {Baj, J and Flieger, W and Barbachowska, A and Kowalska, B and Flieger, M and Forma, A and Teresiński, G and Portincasa, P and Buszewicz, G and Radzikowska-Büchner, E and Flieger, J}, title = {Consequences of Disturbing Manganese Homeostasis.}, journal = {International journal of molecular sciences}, volume = {24}, number = {19}, pages = {}, pmid = {37834407}, issn = {1422-0067}, mesh = {Humans ; Manganese/toxicity/metabolism ; *Diabetes Mellitus, Type 2 ; *Manganese Poisoning/metabolism ; Homeostasis ; *Neurodegenerative Diseases ; }, abstract = {Manganese (Mn) is an essential trace element with unique functions in the body; it acts as a cofactor for many enzymes involved in energy metabolism, the endogenous antioxidant enzyme systems, neurotransmitter production, and the regulation of reproductive hormones. However, overexposure to Mn is toxic, particularly to the central nervous system (CNS) due to it causing the progressive destruction of nerve cells. Exposure to manganese is widespread and occurs by inhalation, ingestion, or dermal contact. Associations have been observed between Mn accumulation and neurodegenerative diseases such as manganism, Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. People with genetic diseases associated with a mutation in the gene associated with impaired Mn excretion, kidney disease, iron deficiency, or a vegetarian diet are at particular risk of excessive exposure to Mn. This review has collected data on the current knowledge of the source of Mn exposure, the experimental data supporting the dispersive accumulation of Mn in the brain, the controversies surrounding the reference values of biomarkers related to Mn status in different matrices, and the competitiveness of Mn with other metals, such as iron (Fe), magnesium (Mg), zinc (Zn), copper (Cu), lead (Pb), calcium (Ca). The disturbed homeostasis of Mn in the body has been connected with susceptibility to neurodegenerative diseases, fertility, and infectious diseases. The current evidence on the involvement of Mn in metabolic diseases, such as type 2 diabetes mellitus/insulin resistance, osteoporosis, obesity, atherosclerosis, and non-alcoholic fatty liver disease, was collected and discussed.}, }
@article {pmid37834374, year = {2023}, author = {Oprisan, AL and Popescu, BO}, title = {Dysautonomia in Amyotrophic Lateral Sclerosis.}, journal = {International journal of molecular sciences}, volume = {24}, number = {19}, pages = {}, pmid = {37834374}, issn = {1422-0067}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology ; *Neurodegenerative Diseases/pathology ; Motor Neurons/pathology ; *Primary Dysautonomias/etiology/pathology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease, characterized in its typical presentation by a combination of lower and upper motor neuron symptoms, with a progressive course and fatal outcome. Due to increased recognition of the non-motor symptoms, it is currently considered a multisystem disorder with great heterogeneity, regarding genetical, clinical, and neuropathological features. Often underestimated, autonomic signs and symptoms have been described in patients with ALS, and various method analyses have been used to assess autonomic nervous system involvement. The aim of this paper is to offer a narrative literature review on autonomic disturbances in ALS, based on the scarce data available to date.}, }
@article {pmid37834128, year = {2023}, author = {Huber, K and Szerenos, E and Lewandowski, D and Toczylowski, K and Sulik, A}, title = {The Role of Adipokines in the Pathologies of the Central Nervous System.}, journal = {International journal of molecular sciences}, volume = {24}, number = {19}, pages = {}, pmid = {37834128}, issn = {1422-0067}, mesh = {Humans ; Adipokines/metabolism ; Central Nervous System/metabolism ; *Alzheimer Disease/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism ; Adipose Tissue/metabolism ; }, abstract = {Adipokines are protein hormones secreted by adipose tissue in response to disruptions in physiological homeostasis within the body's systems. The regulatory functions of adipokines within the central nervous system (CNS) are multifaceted and intricate, and they have been identified in a number of pathologies. Therefore, specific adipokines have the potential to be used as biomarkers for screening purposes in neurological dysfunctions. The systematic review presented herein focuses on the analysis of the functions of various adipokines in the pathogenesis of CNS diseases. Thirteen proteins were selected for analysis through scientific databases. It was found that these proteins can be identified within the cerebrospinal fluid either by their ability to modify their molecular complex and cross the blood-brain barrier or by being endogenously produced within the CNS itself. As a result, this can correlate with their measurability during pathological processes, including Alzheimer's disease, amyotrophic lateral sclerosis, multiple sclerosis, depression, or brain tumors.}, }
@article {pmid37834094, year = {2023}, author = {Jellinger, KA}, title = {The Spectrum of Cognitive Dysfunction in Amyotrophic Lateral Sclerosis: An Update.}, journal = {International journal of molecular sciences}, volume = {24}, number = {19}, pages = {}, pmid = {37834094}, issn = {1422-0067}, support = {000//Society for the Promotion of Research in Experimental Neurology, Vienna, Austria/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *Frontotemporal Dementia/genetics ; Brain/pathology ; *Cognition Disorders/pathology ; *Cognitive Dysfunction/pathology ; *Neurodegenerative Diseases/pathology ; *Pick Disease of the Brain/pathology ; }, abstract = {Cognitive dysfunction is an important non-motor symptom in amyotrophic lateral sclerosis (ALS) that has a negative impact on survival and caregiver burden. It shows a wide spectrum ranging from subjective cognitive decline to frontotemporal dementia (FTD) and covers various cognitive domains, mainly executive/attention, language and verbal memory deficits. The frequency of cognitive impairment across the different ALS phenotypes ranges from 30% to 75%, with up to 45% fulfilling the criteria of FTD. Significant genetic, clinical, and pathological heterogeneity reflects deficits in various cognitive domains. Modern neuroimaging studies revealed frontotemporal degeneration and widespread involvement of limbic and white matter systems, with hypometabolism of the relevant areas. Morphological substrates are frontotemporal and hippocampal atrophy with synaptic loss, associated with TDP-43 and other co-pathologies, including tau deposition. Widespread functional disruptions of motor and extramotor networks, as well as of frontoparietal, frontostriatal and other connectivities, are markers for cognitive deficits in ALS. Cognitive reserve may moderate the effect of brain damage but is not protective against cognitive decline. The natural history of cognitive dysfunction in ALS and its relationship to FTD are not fully understood, although there is an overlap between the ALS variants and ALS-related frontotemporal syndromes, suggesting a differential vulnerability of motor and non-motor networks. An assessment of risks or the early detection of brain connectivity signatures before structural changes may be helpful in investigating the pathophysiological mechanisms of cognitive impairment in ALS, which might even serve as novel targets for effective disease-modifying therapies.}, }
@article {pmid37832609, year = {2023}, author = {Rezaee, D and Saadatpour, F and Akbari, N and Zoghi, A and Najafi, S and Beyranvand, P and Zamani-Rarani, F and Rashidi, MA and Bagheri-Mohammadi, S and Bakhtiari, M}, title = {The role of microRNAs in the pathophysiology of human central nervous system: A focus on neurodegenerative diseases.}, journal = {Ageing research reviews}, volume = {92}, number = {}, pages = {102090}, doi = {10.1016/j.arr.2023.102090}, pmid = {37832609}, issn = {1872-9649}, mesh = {Humans ; *MicroRNAs/genetics/metabolism ; *Neurodegenerative Diseases/metabolism ; Amyloid beta-Peptides ; *Alzheimer Disease/genetics/metabolism ; Central Nervous System/metabolism ; *Neoplasms ; }, abstract = {microRNAs (miRNAs) are suggested to play substantial roles in regulating the development and various physiologic functions of the central nervous system (CNS). These include neurogenesis, cell fate and differentiation, morphogenesis, formation of dendrites, and targeting non-neural mRNAs. Notably, deregulation of an increasing number of miRNAs is associated with several neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis and CNS tumors. They are particularly known to affect the amyloid β (Aβ) cleavage and accumulation, tau protein homeostasis, and expression of alpha-synuclein (α-syn), Parkin, PINK1, and brain-derived neurotrophic factor (BDNF) that play pivotal roles in the pathogenesis of neurodegenerative diseases. These include miR-16, miR-17-5p, miR-20a, miR-106a, miR-106b, miR-15a, miR-15b, miR-103, miR-107, miR-298, miR-328, miR-195, miR-485, and miR-29. In CNS tumors, several miRNAs, including miR-31, miR-16, and miR-21 have been identified to modulate tumorigenesis through impacting tumor invasion and apoptosis. In this review article, we have a look at the recent advances on our knowledge about the role of miRNAs in human brain development and functions, neurodegenerative diseases, and their clinical potentials.}, }
@article {pmid37830099, year = {2023}, author = {Berlowitz, DJ and Mathers, S and Hutchinson, K and Hogden, A and Carey, KA and Graco, M and Whelan, BM and Charania, S and Steyn, F and Allcroft, P and Crook, A and Sheers, NL}, title = {The complexity of multidisciplinary respiratory care in amyotrophic lateral sclerosis.}, journal = {Breathe (Sheffield, England)}, volume = {19}, number = {3}, pages = {220269}, pmid = {37830099}, issn = {1810-6838}, abstract = {UNLABELLED: Motor neurone disease/amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder with no known cure, where death is usually secondary to progressive respiratory failure. Assisting people with ALS through their disease journey is complex and supported by clinics that provide comprehensive multidisciplinary care (MDC). This review aims to apply both a respiratory and a complexity lens to the key roles and areas of practice within the MDC model in ALS. Models of noninvasive ventilation care, and considerations in the provision of palliative therapy, respiratory support, and speech and language therapy are discussed. The impact on people living with ALS of both inequitable funding models and the complexity of clinical care decisions are illustrated using case vignettes. Considerations of the impact of emerging antisense and gene modifying therapies on MDC challenges are also highlighted. The review seeks to illustrate how MDC members contribute to collective decision-making in ALS, how the sum of the parts is greater than any individual care component or health professional, and that the MDC per se adds value to the person living with ALS. Through this approach we hope to support clinicians to navigate the space between what are minimum, guideline-driven, standards of care and what excellent, person-centred ALS care that fully embraces complexity could be.<br><br>EDUCATIONAL AIMS: To highlight the complexities surrounding respiratory care in ALS.To alert clinicians to the risk that complexity of ALS care may modify the effectiveness of any specific, evidence-based therapy for ALS.To describe the importance of person-centred care and shared decision-making in optimising care in ALS.}, }
@article {pmid37828541, year = {2023}, author = {Richardson, PJ and Smith, DP and de Giorgio, A and Snetkov, X and Almond-Thynne, J and Cronin, S and Mead, RJ and McDermott, CJ and Shaw, PJ}, title = {Janus kinase inhibitors are potential therapeutics for amyotrophic lateral sclerosis.}, journal = {Translational neurodegeneration}, volume = {12}, number = {1}, pages = {47}, pmid = {37828541}, issn = {2047-9158}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics/metabolism ; *Janus Kinase Inhibitors/therapeutic use ; *Neurodegenerative Diseases ; Central Nervous System/metabolism ; Janus Kinases/metabolism/therapeutic use ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a poorly treated multifactorial neurodegenerative disease associated with multiple cell types and subcellular organelles. As with other multifactorial diseases, it is likely that drugs will need to target multiple disease processes and cell types to be effective. We review here the role of Janus kinase (JAK)/Signal transducer and activator of transcription (STAT) signalling in ALS, confirm the association of this signalling with fundamental ALS disease processes using the BenevolentAI Knowledge Graph, and demonstrate that inhibitors of this pathway could reduce the ALS pathophysiology in neurons, glia, muscle fibres, and blood cells. Specifically, we suggest that inhibition of the JAK enzymes by approved inhibitors known as Jakinibs could reduce STAT3 activation and modify the progress of this disease. Analysis of the Jakinibs highlights baricitinib as a suitable candidate due to its ability to penetrate the central nervous system and exert beneficial effects on the immune system. Therefore, we recommend that this drug be tested in appropriately designed clinical trials for ALS.}, }
@article {pmid37828358, year = {2023}, author = {Abrahams, S}, title = {Neuropsychological impairment in amyotrophic lateral sclerosis-frontotemporal spectrum disorder.}, journal = {Nature reviews. Neurology}, volume = {19}, number = {11}, pages = {655-667}, pmid = {37828358}, issn = {1759-4766}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/diagnosis ; *Frontotemporal Dementia/complications ; *Neurodegenerative Diseases ; *Cognitive Dysfunction ; *Cognition Disorders/diagnosis/etiology ; Neuropsychological Tests ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a rapid course, characterized by motor neuron dysfunction, leading to progressive disability and death. This Review, which is aimed at neurologists, psychologists and other health professionals who follow evidence-based practice relating to ALS and frontotemporal dementia (FTD), examines the neuropsychological evidence that has driven the reconceptualization of ALS as a spectrum disorder ranging from a pure motor phenotype to ALS-FTD. It focuses on changes in cognition and behaviour, which vary in severity across the spectrum: around 50% individuals with ALS are within the normal range, 15% meet the criteria for ALS-FTD, and the remaining 35% are in the mid-spectrum range with milder and more focal impairments. The cognitive impairments include deficits in verbal fluency, executive functions, social cognition and language, and apathy is the most prevalent behavioural change. The pattern and severity of cognitive and behavioural change predicts underlying regional cerebral dysfunction from brain imaging and post-mortem pathology. Our increased recognition of cognition and behaviour as part of the ALS phenotype has led to the development and standardization of assessment tools, which have been incorporated into research and clinical care. Measuring change over the course of the disease is vital for clinical trials, and neuropsychology is proving to be a biomarker for the earliest preclinical changes.}, }
@article {pmid37827960, year = {2023}, author = {Todd, TW and Shao, W and Zhang, YJ and Petrucelli, L}, title = {The endolysosomal pathway and ALS/FTD.}, journal = {Trends in neurosciences}, volume = {46}, number = {12}, pages = {1025-1041}, pmid = {37827960}, issn = {1878-108X}, support = {R35 NS097273/NS/NINDS NIH HHS/United States ; RF1 AG062171/AG/NIA NIH HHS/United States ; RF1 AG062077/AG/NIA NIH HHS/United States ; R21 NS127331/NS/NINDS NIH HHS/United States ; P01 NS084974/NS/NINDS NIH HHS/United States ; U54 NS123743/NS/NINDS NIH HHS/United States ; R01 NS117461/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; *Frontotemporal Dementia/genetics ; Mutation ; Autophagy ; C9orf72 Protein/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are considered to be part of a disease spectrum that is associated with causative mutations and risk variants in a wide range of genes. Mounting evidence indicates that several of these genes are linked to the endolysosomal system, highlighting the importance of this pathway in ALS/FTD. Although many studies have focused on how disruption of this pathway impacts on autophagy, recent findings reveal that this may not be the whole picture: specifically, disrupting autophagy may not be sufficient to induce disease, whereas disrupting the endolysosomal system could represent a crucial pathogenic driver. In this review we discuss the connections between ALS/FTD and the endolysosomal system, including a breakdown of how disease-associated genes are implicated in this pathway. We also explore the potential downstream consequences of disrupting endolysosomal activity in the brain, outside of an effect on autophagy.}, }
@article {pmid37827904, year = {2023}, author = {Santiago, JA and Karthikeyan, M and Lackey, M and Villavicencio, D and Potashkin, JA}, title = {Diabetes: a tipping point in neurodegenerative diseases.}, journal = {Trends in molecular medicine}, volume = {29}, number = {12}, pages = {1029-1044}, pmid = {37827904}, issn = {1471-499X}, support = {R01 AG062176/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Neurodegenerative Diseases/metabolism ; Mitochondria/metabolism ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; Brain/metabolism ; *Diabetes Mellitus/metabolism ; }, abstract = {Diabetes is associated with an increased risk and progression of Alzheimer's (AD) and Parkinson's (PD) diseases. Conversely, diabetes may confer neuroprotection against amyotrophic lateral sclerosis (ALS). It has been posited that perturbations in glucose and insulin regulation, cholesterol metabolism, and mitochondrial bioenergetics defects may underlie the molecular underpinnings of diabetes effects on the brain. Nevertheless, the precise molecular mechanisms remain elusive. Here, we discuss the evidence from molecular, epidemiological, and clinical studies investigating the impact of diabetes on neurodegeneration and highlight shared dysregulated pathways between these complex comorbidities. We also discuss promising antidiabetic drugs, molecular diagnostics currently in clinical trials, and outstanding questions and challenges for future pursuit.}, }
@article {pmid37827137, year = {2024}, author = {Heckmann, JG and Kiem, M and Immich, G}, title = {Forest Therapy as a Nature-Based Intervention: An Option for Neurological Rehabilitation?.}, journal = {Complementary medicine research}, volume = {31}, number = {1}, pages = {56-63}, doi = {10.1159/000534533}, pmid = {37827137}, issn = {2504-2106}, mesh = {Humans ; *Medicine ; *Neurological Rehabilitation ; *Sleep Wake Disorders ; *Stroke/therapy ; *Dementia ; Observational Studies as Topic ; }, abstract = {BACKGROUND: Forest therapy demonstrates positive effects on mood, immune system, stress levels, and general well-being. Studies on depression, stress-related illnesses, sleep disorders, and arterial hypertension have provided evidence-based proof of this.<br><br>SUMMARY: The aim of this review was to examine the possible effects of forest therapy with regard to its evidence in the treatment of chronic neurological diseases such as stroke in the rehabilitation phase, Parkinson's disease, dementia, and multiple sclerosis. Therefore, the electronic databases Medline, Scopus, and Cochrane were searched for such clinical trials for the years 1970 to mid-2023 without language restriction. The literature search revealed only few studies with positive indications but too few cases to be able to make generalizable evidence-based statements. In terms of improvement in the Hamilton Depression Scale analysis of two studies in stroke patients showed slight benefits in the forest therapy group (standard mean difference -0.43; 95% CI: -0.76 to -0.10; p < 0.01). One observational study revealed a higher rate of stroke survival in patients living in marked greenness. Few nature-based interventions in dementia patients showed certain benefits in particular details.<br><br>KEY MESSAGES: There are no evidence-based results on the benefit of forest therapy for chronic neurological diseases. However, there are hints that forest therapy could have a positive benefit. Therefore, a proposal for forest therapy as a component of multimodal neurological rehabilitation is presented.<br><br>UNLABELLED: <title>Hintergrund</title>Die Waldtherapie zeigt positive Auswirkungen auf die Stimmung, das Immunsystem, das Stressniveau und das allgemeine Wohlbefinden. Studien zu Depressionen, stressbedingten Erkrankungen, Schlafst&#xf6;rungen und arteriellem Bluthochdruck haben dies evidenzbasiert belegt.<title>Zusammenfassung</title>Ziel dieser &#xdc;bersichtsarbeit war es, die m&#xf6;glichen Wirkungen der Waldtherapie im Hinblick auf ihre Evidenz bei der Behandlung chronischer neurologischer Erkrankungen wie Schlaganfall in der Rehabilitationsphase, Morbus Parkinson, Demenz und Multiple Sklerose zu untersuchen. Dazu wurden die elektronischen Datenbanken Medline, Scopus und Cochrane f&#xfc;r die Jahre 1970 bis Mitte 2023 ohne sprachliche Einschr&#xe4;nkung nach solchen klinischen Studien durchsucht. Die Literaturrecherche ergab nur wenige Studien mit positiven Indikationen, aber zu wenigen F&#xe4;llen, um verallgemeinerbare evidenzbasierte Aussagen machen zu k&#xf6;nnen. Im Hinblick auf Verbesserung in der Hamilton Depressionsskala zeigte die Analyse von 2 Studien bei Schlaganfallpatienten leichte Vorteile der Waldtherapiegruppen (Standard Mean Difference &#x2212;0.43; 95% CI: -0.76- -0,10; <italic>p</italic> < 0.01). Eine Beobachtungsstudie ergab eine h&#xf6;here Schlaganfall-&#xdc;berlebensrate bei Patienten, die in ausgepr&#xe4;gtem Gr&#xfc;n leben. Einige naturbasierte Interventionen bei Demenzpatienten zeigten in einzelnen Parametern gewisse Vorteile.<title>Fazit</title>Es gibt bis dato keine verallgemeinerbaren evidenzbasierten Ergebnisse zum Nutzen der Waldtherapie bei chronischen neurologischen Erkrankungen. Es gibt jedoch Hinweise, dass die Waldtherapie einen positiven Nutzen haben k&#xf6;nnte. Es wird daher ein Vorschlag f&#xfc;r eine Waldtherapie als Bestandteil einer multimodalen neurologischen Rehabilitation vorgestellt.}, }
@article {pmid37816542, year = {2024}, author = {McHenry, KL}, title = {Airway Clearance Strategies and Secretion Management in Amyotrophic Lateral Sclerosis.}, journal = {Respiratory care}, volume = {69}, number = {2}, pages = {227-237}, pmid = {37816542}, issn = {1943-3654}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/therapy ; Respiratory Therapy/methods ; *Chest Wall Oscillation ; Bodily Secretions ; *Insufflation/methods ; Cough/etiology ; *Respiratory Insufficiency/therapy ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a rare, neurodegenerative motor neuron disease that affects voluntary muscle movement. Often, difficulty in coughing, breathing, and swallowing are sequela associated with the condition, and the presence of bulbar muscle predominant weakness results in deleterious effects on airway clearance and secretion management. This narrative review will provide practical guidance for clinicians treating this population. Cough insufficiency in this population typically manifests as a prolonged, slow, weak cough effort that impedes the clearability of secretions and airway protection. Dystussia and dysphagia frequently occur simultaneously in bulbar dysfunction, subsequently impacting respiratory health. Measures of respiratory strength should be obtained and monitored every 3-6 months, preferably in a multidisciplinary clinic setting. Cough augmentation, whether manual or mechanical techniques, should be sought as early in the disease progression as possible to adequately control secretions in the proximal airways. This airway clearance strategy can aid in the prevention and treatment of respiratory tract infections (RTIs), which can pose a significant clinical hurdle to those with ALS. The use of mechanical insufflation-exsufflation may be complicated by severe bulbar dysfunction rendering this technique ineffective. Though peripheral airway clearance strategies, such as high-frequency chest-wall compression, have the advantage of being less impacted by bulbar dysfunction, it is only recommended this modality be used in conjunction with, versus in lieu of, proximal strategies. Salivary secretion management includes the use of anticholinergics, botulinum toxin, and radiation therapy depending on severity and desire for relief.}, }
@article {pmid37813308, year = {2023}, author = {Babazadeh, A and Rayner, SL and Lee, A and Chung, RS}, title = {TDP-43 as a therapeutic target in neurodegenerative diseases: Focusing on motor neuron disease and frontotemporal dementia.}, journal = {Ageing research reviews}, volume = {92}, number = {}, pages = {102085}, doi = {10.1016/j.arr.2023.102085}, pmid = {37813308}, issn = {1872-9649}, mesh = {Animals ; Humans ; *Amyotrophic Lateral Sclerosis/therapy ; DNA-Binding Proteins/metabolism ; *Frontotemporal Dementia/therapy ; *Motor Neuron Disease/therapy/pathology ; *Neurodegenerative Diseases/therapy ; }, abstract = {A common feature of adult-onset neurodegenerative diseases is the presence of characteristic pathological accumulations of specific proteins. These pathological protein depositions can vary in their protein composition, cell-type distribution, and intracellular (or extracellular) location. For example, abnormal cytoplasmic protein deposits which consist of the TDP-43 protein are found within motor neurons in patients with amyotrophic lateral sclerosis (ALS, a common form of motor neuron disease) and frontotemporal dementia (FTD). The presence of these insoluble intracellular TDP-43 inclusions suggests that restoring TDP-43 homeostasis represents a potential therapeutical strategy, which has been demonstrated in alleviating neurodegenerative symptoms in cell and animal models of ALS/FTD. We have reviewed the mechanisms that lead to disrupted TDP-43 homeostasis and discussed how small molecule-based therapies could be applied in modulating these mechanisms. This review covers recent advancements and challenges in small molecule-based therapies that could be used to clear pathological forms of TDP-43 through various protein homeostasis mechanisms and advance the way towards finding effective therapeutical drug discoveries for neurodegenerative diseases characterized by TDP-43 proteinopathies, especially ALS and FTD. We also consider the wider insight of these therapeutic strategies for other neurodegenerative diseases.}, }
@article {pmid37807406, year = {2023}, author = {Anderson, G}, title = {Gut Microbiome and Circadian Interactions with Platelets Across Human Diseases, including Alzheimer's Disease, Amyotrophic Lateral Sclerosis, and Cancer.}, journal = {Current topics in medicinal chemistry}, volume = {23}, number = {28}, pages = {2699-2719}, doi = {10.2174/0115680266253465230920114223}, pmid = {37807406}, issn = {1873-4294}, mesh = {Humans ; *Melatonin/metabolism ; *Alzheimer Disease ; *Gastrointestinal Microbiome ; *Amyotrophic Lateral Sclerosis ; *Neoplasms ; Tumor Microenvironment ; }, abstract = {Platelets have traditionally been investigated for their role in clot formation in the course of cardiovascular diseases and strokes. However, recent work indicates platelets to be an integral aspect of wider systemic processes, with relevance to the pathophysiology of a host of diverse medical conditions, including neurodegenerative disorders and cancer. This article reviews platelet function and interactions with the gut microbiome and circadian systems, highlighting the role of the platelet mitochondrial melatonergic pathway in determining platelet activation, fluxes and plasticity. This provides a number of novel conceptualizations of platelet function and mode of interaction with other cell types, including in the pathoetiology and pathophysiology of diverse medical conditions, such as cancer, Alzheimer's disease, and amyotrophic lateral sclerosis. It is proposed that a platelet-gut axis allows platelets to contribute to many of the pathophysiological processes linked to gut dysbiosis and gut permeability. This is at least partly via platelet sphingosine- 1-phosphate release, which regulates enteric glial cells and lymphocyte chemotaxis, indicating an etiological role for platelets in a wide array of medical conditions linked to alterations in the gut microbiome. Platelets are also an important regulator of the various microenvironments that underpin most human medical conditions, including the tumor microenvironment, neurodegenerative diseases, and autoimmune disorders. Platelet serotonin release regulates the availability of the mitochondrial melatonergic pathway systemically, thereby being an important determinant of the dynamic metabolic interactions occurring across cell types that underpin the pathoetiology of many medical conditions. In addition, a number of novel and diverse future research directions and treatment implications are proposed.}, }
@article {pmid37800457, year = {2023}, author = {Billings, JL and Hilton, JBW and Liddell, JR and Hare, DJ and Crouch, PJ}, title = {Fundamental Neurochemistry Review: Copper availability as a potential therapeutic target in progressive supranuclear palsy: Insight from other neurodegenerative diseases.}, journal = {Journal of neurochemistry}, volume = {167}, number = {3}, pages = {337-346}, doi = {10.1111/jnc.15978}, pmid = {37800457}, issn = {1471-4159}, mesh = {Humans ; *Supranuclear Palsy, Progressive/diagnosis/pathology ; Copper ; *Neurodegenerative Diseases/therapy ; Superoxide Dismutase-1 ; *Neurochemistry ; *Parkinson Disease/pathology ; }, abstract = {Since the first description of Parkinson's disease (PD) over two centuries ago, the recognition of rare types of atypical parkinsonism has introduced a spectrum of related PD-like diseases. Among these is progressive supranuclear palsy (PSP), a neurodegenerative condition that clinically differentiates through the presence of additional symptoms uncommon in PD. As with PD, the initial symptoms of PSP generally present in the sixth decade of life when the underpinning neurodegeneration is already significantly advanced. The causal trigger of neuronal cell loss in PSP is unknown and treatment options are consequently limited. However, converging lines of evidence from the distinct neurodegenerative conditions of PD and amyotrophic lateral sclerosis (ALS) are beginning to provide insights into potential commonalities in PSP pathology and opportunity for novel therapeutic intervention. These include accumulation of the high abundance cuproenzyme superoxide dismutase 1 (SOD1) in an aberrant copper-deficient state, associated evidence for altered availability of the essential micronutrient copper, and evidence for neuroprotection using compounds that can deliver available copper to the central nervous system. Herein, we discuss the existing evidence for SOD1 pathology and copper imbalance in PSP and speculate that treatments able to provide neuroprotection through manipulation of copper availability could be applicable to the treatment of PSP.}, }
@article {pmid37797620, year = {2023}, author = {Yonekura, K and Maki-Yonekura, S and Takaba, K}, title = {Applications and limitations of electron 3D crystallography.}, journal = {Structure (London, England : 1993)}, volume = {31}, number = {11}, pages = {1328-1334}, doi = {10.1016/j.str.2023.09.007}, pmid = {37797620}, issn = {1878-4186}, mesh = {Crystallography/methods ; *Electrons ; Crystallography, X-Ray ; *Proteins/chemistry ; Microscopy, Electron, Transmission ; Peptides ; }, abstract = {Three-dimensional electron diffraction (3D ED) is a measurement and analysis technique in transmission electron microscopy that is used for determining atomic structures from small crystals. Diverse targets such as proteins, polypeptides, and organic compounds, whose crystals exist in aqueous solutions and organic solvents, or as dried powders, can be studied with 3D ED. We have been involved in the development of this technique, which can now rapidly process a large number of data collected through AI control, enabling efficient structure determination. Here, we introduce this method and describe our recent results. These include the structures and pathogenic mechanisms of wild-type and mutant polypeptides associated with the debilitating disease amyotrophic lateral sclerosis (ALS), the double helical structure of nanographene promoting nanofiber formation, and the structural properties of an organic semiconductor containing disordered regions. We also discuss the limitations and prospects of 3D ED compared to microcrystallography with X-ray free electron lasers.}, }
@article {pmid37795580, year = {2024}, author = {Rodriguez, P and Blakely, RD}, title = {Sink or swim: Does a worm paralysis phenotype hold clues to neurodegenerative disease?.}, journal = {Journal of cellular physiology}, volume = {239}, number = {6}, pages = {e31125}, doi = {10.1002/jcp.31125}, pmid = {37795580}, issn = {1097-4652}, support = {22A01//Florida Department of Health Ed/ ; }, mesh = {Animals ; *Caenorhabditis elegans/genetics ; *Neurodegenerative Diseases/genetics ; *Phenotype ; Humans ; *Disease Models, Animal ; Caenorhabditis elegans Proteins/genetics/metabolism ; Paralysis/genetics ; Swimming ; Signal Transduction/genetics ; Dopamine/metabolism ; }, abstract = {Receiving a neurodegenerative disease (NDD) diagnosis, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, or amyotrophic lateral sclerosis, is devastating, particularly given the limited options for treatment. Advances in genetic technologies have allowed for efficient modeling of NDDs in animals and brought hope for new disease-modifying medications. The complexity of the mammalian brain and the costs and time needed to identify and develop therapeutic leads limits progress. Modeling NDDs in invertebrates, such as the fruit fly Drosophila melanogaster and the nematode Caenorhabditis elegans, offers orders of magnitude increases in speed of genetic analysis and manipulation, and can be pursued at substantially reduced cost, providing an important, platform complement and inform research with mammalian NDD models. In this review, we describe how our efforts to exploit C. elegans for the study of neural signaling and health led to the discovery of a paralytic phenotype (swimming-induced paralysis) associated with altered dopamine signaling and, surprisingly, to the discovery of a novel gene and pathway whose dysfunction in glial cells triggers neurodegeneration. Research to date on swip-10 and its putative mammalian ortholog MBLAC1, suggests that a tandem analysis will offer insights into NDD mechanisms and insights into novel, disease-modifying therapeutics.}, }
@article {pmid37795273, year = {2023}, author = {Venediktov, AA and Bushueva, OY and Kudryavtseva, VA and Kuzmin, EA and Moiseeva, AV and Baldycheva, A and Meglinski, I and Piavchenko, GA}, title = {Closest horizons of Hsp70 engagement to manage neurodegeneration.}, journal = {Frontiers in molecular neuroscience}, volume = {16}, number = {}, pages = {1230436}, pmid = {37795273}, issn = {1662-5099}, abstract = {Our review seeks to elucidate the current state-of-the-art in studies of 70-kilodalton-weighed heat shock proteins (Hsp70) in neurodegenerative diseases (NDs). The family has already been shown to play a crucial role in pathological aggregation for a wide spectrum of brain pathologies. However, a slender boundary between a big body of fundamental data and its implementation has only recently been crossed. Currently, we are witnessing an anticipated advancement in the domain with dozens of studies published every month. In this review, we briefly summarize scattered results regarding the role of Hsp70 in the most common NDs including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). We also bridge translational studies and clinical trials to portray the output for medical practice. Available options to regulate Hsp70 activity in NDs are outlined, too.}, }
@article {pmid37787835, year = {2024}, author = {Li, S and Zhao, L and Xiao, J and Guo, Y and Fu, R and Zhang, Y and Xu, S}, title = {The gut microbiome: an important role in neurodegenerative diseases and their therapeutic advances.}, journal = {Molecular and cellular biochemistry}, volume = {479}, number = {9}, pages = {2217-2243}, pmid = {37787835}, issn = {1573-4919}, support = {No. 81973626, No. 81774059//National Natural Science Foundation of China/ ; No. 21JCYBJC01620//Tianjin Municipal Science and Technology Commission of China/ ; No. 2021099//Tianjin Health Committee/ ; No. 2021KJ146//Tianjin Education Committee/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Neurodegenerative Diseases/therapy/microbiology ; *Fecal Microbiota Transplantation ; *Probiotics/therapeutic use ; Animals ; Parkinson Disease/therapy/microbiology ; Alzheimer Disease/therapy/microbiology ; }, abstract = {There are complex interactions between the gut and the brain. With increasing research on the relationship between gut microbiota and brain function, accumulated clinical and preclinical evidence suggests that gut microbiota is intimately involved in the pathogenesis of neurodegenerative diseases (NDs). Increasingly studies are beginning to focus on the association between gut microbiota and central nervous system (CNS) degenerative pathologies to find potential therapies for these refractory diseases. In this review, we summarize the changes in the gut microbiota in Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis and contribute to our understanding of the function of the gut microbiota in NDs and its possible involvement in the pathogenesis. We subsequently discuss therapeutic approaches targeting gut microbial abnormalities in these diseases, including antibiotics, diet, probiotics, and fecal microbiota transplantation (FMT). Furthermore, we summarize some completed and ongoing clinical trials of interventions with gut microbes for NDs, which may provide new ideas for studying NDs.}, }
@article {pmid37783557, year = {2023}, author = {Chen, D and Huang, H and Saberi, H and Sharma, HS}, title = {Positive and negative cell therapy in randomized control trials for central nervous system diseases.}, journal = {International review of neurobiology}, volume = {171}, number = {}, pages = {241-254}, doi = {10.1016/bs.irn.2023.05.017}, pmid = {37783557}, issn = {2162-5514}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy ; Quality of Life ; *Central Nervous System Diseases/therapy ; Cell- and Tissue-Based Therapy ; *Parkinson Disease/therapy ; Brain Damage, Chronic ; }, abstract = {Neurorestorative cell therapies have been tested to treat patients with nervous system diseases for over 20 years. Now it is still hard to answer which kinds of cells can really play a role on improving these patients' quality of life. Non-randomized clinical trials or studies could not provide strong evidences in answering this critical question. In this review, we summarized randomized clinical trials of cell therapies for central nervous diseases, such as stroke, spinal cord injury, cerebral palsy (CP), Parkinson's disease (PD), multiple sclerosis (MS), brain trauma, amyotrophic lateral sclerosis (ALS), etc. Most kinds of cell therapies demonstrated negative results for stoke, brain trauma and amyotrophic lateral sclerosis. A few kinds of cell therapies showed neurorestorative effects in this level of evidence-based medicine, such as olfactory ensheating cells for chronic ischemic stroke. Some kinds of cells showed positive or negative effects from different teams in the same or different diseases. We analyzed the possible failed reasons of negative results and the cellular bio-propriety basis of positive results. Based on therapeutic results of randomized control trials and reasonable analysis, we recommend: (1) to further conduct trials for successful cell therapies with positive results to increase neurorestorative effects; (2) to avoid in repeating failed cell therapies with negative results in same diseases because it is nonsense for them to be done with similar treatment methods, such as cell dosage, transplanting way, time of window, etc. Furthermore, we strongly suggest not to do non-randomized clinical trials for cells that had shown negative results in randomized clinical trials.}, }
@article {pmid37782813, year = {2023}, author = {Pennisi, F and Lo Presti, T and Ricciardi, GE and Dalla Valle, Z and Minerva, M and Privitera, G and Signorelli, C}, title = {Training and career opportunities for residencies in Hygiene and Preventive Medicine: results of a survey on 39 Italian schools.}, journal = {Igiene e sanita pubblica}, volume = {80}, number = {4}, pages = {94-100}, pmid = {37782813}, issn = {0019-1639}, mesh = {Humans ; *Internship and Residency ; State Medicine ; Public Health/education ; Hygiene/education ; Universities ; Preventive Medicine/education ; }, abstract = {INTRODUCTION: The Italian National Health Service (SSN) is currently grappling. with a complex situation, characterized by a persistent shortage of medical personnel and the divergent aspirations of young medical graduates. Additionally, recent regulatory developments concerning specialist training further contribute to the intricacies of the landscape, calling for a comprehensive analysis of the challenges and opportunities within the sector. This study aims to provide an updated overview of the current placement of medical graduates, residents and specialists in the specific hygiene and preventive medicine (Public Health) field.<br><br>METHODS: Data on admissions, withdrawals and resignations were obtained from the Ministries of Universities and Health and from the archives of the "Associazione Liberi Specializzandi" (ALS). Information regarding the professional prospects for specialists and residents in the field of Public Health was gathered through a tailored survey conducted by the "Consulta dei Medici in Formazione Specialistica" (Council of Medical Residents) of the Italian Society of Hygiene (SItI).<br><br>RESULTS: In 2022, a total of 483 specialization contracts were granted, indicating a decrease of 37% compared to the previous year. Notably, 85 positions (17.6%) remained unallocated or resulted in dropouts. Six months after completing their residency, 1.5% of hygiene residents were still actively seeking employment. On a positive note, 75.4% of fourth-year residents secured contracts under the "Decreto Calabria". Career opportunities within the Italian SSN have witnessed growth, with a significant proportion of placements in territorial services and hospital medical directorates.<br><br>DISCUSSION AND CONCLUSIONS: The updating of training programs provided by residency schools and the exploration of innovative approaches are of paramount importance to address the urgent need for high-quality training and to cater to the requirements of the national health system.}, }
@article {pmid37781096, year = {2023}, author = {Yu, H and Xiong, M and Zhang, Z}, title = {The role of glycogen synthase kinase 3 beta in neurodegenerative diseases.}, journal = {Frontiers in molecular neuroscience}, volume = {16}, number = {}, pages = {1209703}, pmid = {37781096}, issn = {1662-5099}, abstract = {Neurodegenerative diseases (NDDs) pose an increasingly prevalent threat to the well-being and survival of elderly individuals worldwide. NDDs include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and so on. They are characterized by progressive loss or dysfunction of neurons in the central or peripheral nervous system and share several cellular and molecular mechanisms, including protein aggregation, mitochondrial dysfunction, gene mutations, and chronic neuroinflammation. Glycogen synthase kinase-3 beta (GSK-3β) is a serine/threonine kinase that is believed to play a pivotal role in the pathogenesis of NDDs. Here we summarize the structure and physiological functions of GSK3β and explore its involvement in NDDs. We also discussed its potential as a therapeutic target.}, }
@article {pmid37776476, year = {2023}, author = {Ocharán-Mercado, A and Loaeza-Loaeza, J and Castro-Coronel, Y and Acosta-Saavedra, LC and Hernández-Kelly, LC and Hernández-Sotelo, D and Ortega, A}, title = {RNA-Binding Proteins: A Role in Neurotoxicity?.}, journal = {Neurotoxicity research}, volume = {41}, number = {6}, pages = {681-697}, pmid = {37776476}, issn = {1476-3524}, mesh = {Humans ; Aged ; *Neurodegenerative Diseases/metabolism ; RNA-Binding Proteins/metabolism ; Neurons/metabolism ; *Frontotemporal Dementia ; *Amyotrophic Lateral Sclerosis/metabolism ; }, abstract = {Despite sustained efforts to treat neurodegenerative diseases, little is known at the molecular level to understand and generate novel therapeutic approaches for these malignancies. Therefore, it is not surprising that neurogenerative diseases are among the leading causes of death in the aged population. Neurons require sophisticated cellular mechanisms to maintain proper protein homeostasis. These cells are generally sensitive to loss of gene expression control at the post-transcriptional level. Post-translational control responds to signals that can arise from intracellular processes or environmental factors that can be regulated through RNA-binding proteins. These proteins recognize RNA through one or more RNA-binding domains and form ribonucleoproteins that are critically involved in the regulation of post-transcriptional processes from splicing to the regulation of association of the translation machinery allowing a relatively rapid and precise modulation of the transcriptome. Neurotoxicity is the result of the biological, chemical, or physical interaction of agents with an adverse effect on the structure and function of the central nervous system. The disruption of the proper levels or function of RBPs in neurons and glial cells triggers neurotoxic events that are linked to neurodegenerative diseases such as spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS), fragile X syndrome (FXS), and frontotemporal dementia (FTD) among many others. The connection between RBPs and neurodegenerative diseases opens a new landscape for potentially novel therapeutic targets for the intervention of these neurodegenerative pathologies. In this contribution, a summary of the recent findings of the molecular mechanisms involved in the plausible role of RBPs in RNA processing in neurodegenerative disease is discussed.}, }
@article {pmid37770379, year = {2023}, author = {Souza, INO and Roychaudhuri, R and de Belleroche, J and Mothet, JP}, title = {d-Amino acids: new clinical pathways for brain diseases.}, journal = {Trends in molecular medicine}, volume = {29}, number = {12}, pages = {1014-1028}, doi = {10.1016/j.molmed.2023.09.001}, pmid = {37770379}, issn = {1471-499X}, mesh = {Humans ; *Amino Acids/metabolism ; Critical Pathways ; Central Nervous System/metabolism ; Brain/metabolism ; *Alzheimer Disease/metabolism ; }, abstract = {Free d-amino acids (d-AAs) are emerging as a novel and important class of signaling molecules in many organs, including the brain and endocrine systems. There has been considerable progress in our understanding of the fundamental roles of these atypical messengers, with increasingly recognized implications in a wide range of neuropathologies, including schizophrenia (SCZ), epilepsy, Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), substance abuse, and chronic pain, among others. Research has enabled the discovery that d-serine, d-aspartate and more recently d-cysteine are essential for the healthy development and function of the central nervous system (CNS). We discuss recent progress that has profoundly transformed our vision of numerous physiological processes but has also shown how d-AAs are now offering therapeutic promise in clinical settings for several human diseases.}, }
@article {pmid37762599, year = {2023}, author = {Taneva, SG and Todinova, S and Andreeva, T}, title = {Morphometric and Nanomechanical Screening of Peripheral Blood Cells with Atomic Force Microscopy for Label-Free Assessment of Alzheimer's Disease, Parkinson's Disease, and Amyotrophic Lateral Sclerosis.}, journal = {International journal of molecular sciences}, volume = {24}, number = {18}, pages = {}, pmid = {37762599}, issn = {1422-0067}, support = {KP-06-H31/8//Bulgarian Science Fund/ ; funding programme Open Access Publishing//Baden-W&#xfc;rttemberg Ministry of Science, Research and Culture/ ; }, mesh = {Humans ; *Parkinson Disease/diagnosis ; *Amyotrophic Lateral Sclerosis/diagnosis ; *Alzheimer Disease/diagnosis ; Microscopy, Atomic Force ; Blood Cells ; }, abstract = {Neurodegenerative disorders (NDDs) are complex, multifactorial disorders with significant social and economic impact in today's society. NDDs are predicted to become the second-most common cause of death in the next few decades due to an increase in life expectancy but also to a lack of early diagnosis and mainly symptomatic treatment. Despite recent advances in diagnostic and therapeutic methods, there are yet no reliable biomarkers identifying the complex pathways contributing to these pathologies. The development of new approaches for early diagnosis and new therapies, together with the identification of non-invasive and more cost-effective diagnostic biomarkers, is one of the main trends in NDD biomedical research. Here we summarize data on peripheral biomarkers, biofluids (cerebrospinal fluid and blood plasma), and peripheral blood cells (platelets (PLTs) and red blood cells (RBCs)), reported so far for the three most common NDDs-Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). PLTs and RBCs, beyond their primary physiological functions, are increasingly recognized as valuable sources of biomarkers for NDDs. Special attention is given to the morphological and nanomechanical signatures of PLTs and RBCs as biophysical markers for the three pathologies. Modifications of the surface nanostructure and morphometric and nanomechanical signatures of PLTs and RBCs from patients with AD, PD, and ALS have been revealed by atomic force microscopy (AFM). AFM is currently experiencing rapid and widespread adoption in biomedicine and clinical medicine, in particular for early diagnostics of various medical conditions. AFM is a unique instrument without an analog, allowing the generation of three-dimensional cell images with extremely high spatial resolution at near-atomic scale, which are complemented by insights into the mechanical properties of cells and subcellular structures. Data demonstrate that AFM can distinguish between the three pathologies and the normal, healthy state. The specific PLT and RBC signatures can serve as biomarkers in combination with the currently used diagnostic tools. We highlight the strong correlation of the morphological and nanomechanical signatures between RBCs and PLTs in PD, ALS, and AD.}, }
@article {pmid37762112, year = {2023}, author = {Gimenez, J and Spalloni, A and Cappelli, S and Ciaiola, F and Orlando, V and Buratti, E and Longone, P}, title = {TDP-43 Epigenetic Facets and Their Neurodegenerative Implications.}, journal = {International journal of molecular sciences}, volume = {24}, number = {18}, pages = {}, pmid = {37762112}, issn = {1422-0067}, support = {PathensTDP//Fondazione Italiana di Ricerca per la Sclerosi Laterale Amiotrofica/ ; JPND2020-568-078//EU Joint Programme - Neurodegenerative Disease Research/ ; }, mesh = {Humans ; *Chromatin ; Cytoplasm ; *DNA-Binding Proteins/genetics ; Epigenesis, Genetic ; Epigenomics ; }, abstract = {Since its initial involvement in numerous neurodegenerative pathologies in 2006, either as a principal actor or as a cofactor, new pathologies implicating transactive response (TAR) DNA-binding protein 43 (TDP-43) are regularly emerging also beyond the neuronal system. This reflects the fact that TDP-43 functions are particularly complex and broad in a great variety of human cells. In neurodegenerative diseases, this protein is often pathologically delocalized to the cytoplasm, where it irreversibly aggregates and is subjected to various post-translational modifications such as phosphorylation, polyubiquitination, and cleavage. Until a few years ago, the research emphasis has been focused particularly on the impacts of this aggregation and/or on its widely described role in complex RNA splicing, whether related to loss- or gain-of-function mechanisms. Interestingly, recent studies have strengthened the knowledge of TDP-43 activity at the chromatin level and its implication in the regulation of DNA transcription and stability. These discoveries have highlighted new features regarding its own transcriptional regulation and suggested additional mechanistic and disease models for the effects of TPD-43. In this review, we aim to give a comprehensive view of the potential epigenetic (de)regulations driven by (and driving) this multitask DNA/RNA-binding protein.}, }
@article {pmid37761265, year = {2023}, author = {Anghel, L and Ciubară, A and Nechita, A and Nechita, L and Manole, C and Baroiu, L and Ciubară, AB and Mușat, CL}, title = {Sleep Disorders Associated with Neurodegenerative Diseases.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {13}, number = {18}, pages = {}, pmid = {37761265}, issn = {2075-4418}, abstract = {Sleep disturbances are common in various neurological pathologies, including amyotrophic lateral sclerosis (ALS), multiple system atrophy (MSA), hereditary ataxias, Huntington's disease (HD), progressive supranuclear palsy (PSP), and dementia with Lewy bodies (DLB). This article reviews the prevalence and characteristics of sleep disorders in these conditions, highlighting their impact on patients' quality of life and disease progression. Sleep-related breathing disorders, insomnia, restless legs syndrome (RLS), periodic limb movement syndrome (PLMS), and rapid eye movement sleep behavior disorder (RBD) are among the common sleep disturbances reported. Both pharmacological and non-pharmacological interventions play crucial roles in managing sleep disturbances and enhancing overall patient care.}, }
@article {pmid37760050, year = {2023}, author = {Rubino, V and La Rosa, G and Pipicelli, L and Carriero, F and Damiano, S and Santillo, M and Terrazzano, G and Ruggiero, G and Mondola, P}, title = {Insights on the Multifaceted Roles of Wild-Type and Mutated Superoxide Dismutase 1 in Amyotrophic Lateral Sclerosis Pathogenesis.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {12}, number = {9}, pages = {}, pmid = {37760050}, issn = {2076-3921}, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a progressive motor neurodegenerative disease. Cell damage in ALS is the result of many different, largely unknown, pathogenetic mechanisms. Astrocytes and microglial cells play a critical role also for their ability to enhance a deranged inflammatory response. Excitotoxicity, due to excessive glutamate levels and increased intracellular Ca[2+] concentration, has also been proposed to play a key role in ALS pathogenesis/progression. Reactive Oxygen Species (ROS) behave as key second messengers for multiple receptor/ligand interactions. ROS-dependent regulatory networks are usually mediated by peroxides. Superoxide Dismutase 1 (SOD1) physiologically mediates intracellular peroxide generation. About 10% of ALS subjects show a familial disease associated with different gain-of-function SOD1 mutations. The occurrence of sporadic ALS, not clearly associated with SOD1 defects, has been also described. SOD1-dependent pathways have been involved in neuron functional network as well as in immune-response regulation. Both, neuron depolarization and antigen-dependent T-cell activation mediate SOD1 exocytosis, inducing increased interaction of the enzyme with a complex molecular network involved in the regulation of neuron functional activity and immune response. Here, alteration of SOD1-dependent pathways mediating increased intracellular Ca[2+] levels, altered mitochondria functions and defective inflammatory process regulation have been proposed to be relevant for ALS pathogenesis/progression.}, }
@article {pmid37759656, year = {2023}, author = {Angelopoulou, E and Pyrgelis, ES and Ahire, C and Suman, P and Mishra, A and Piperi, C}, title = {Functional Implications of Protein Arginine Methyltransferases (PRMTs) in Neurodegenerative Diseases.}, journal = {Biology}, volume = {12}, number = {9}, pages = {}, pmid = {37759656}, issn = {2079-7737}, abstract = {During the aging of the global population, the prevalence of neurodegenerative diseases will be continuously growing. Although each disorder is characterized by disease-specific protein accumulations, several common pathophysiological mechanisms encompassing both genetic and environmental factors have been detected. Among them, protein arginine methyltransferases (PRMTs), which catalyze the methylation of arginine of various substrates, have been revealed to regulate several cellular mechanisms, including neuronal cell survival and excitability, axonal transport, synaptic maturation, and myelination. Emerging evidence highlights their critical involvement in the pathophysiology of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal dementia-amyotrophic lateral sclerosis (FTD-ALS) spectrum, Huntington's disease (HD), spinal muscular atrophy (SMA) and spinal and bulbar muscular atrophy (SBMA). Underlying mechanisms include the regulation of gene transcription and RNA splicing, as well as their implication in various signaling pathways related to oxidative stress responses, apoptosis, neuroinflammation, vacuole degeneration, abnormal protein accumulation and neurotransmission. The targeting of PRMTs is a therapeutic approach initially developed against various forms of cancer but currently presents a novel potential strategy for neurodegenerative diseases. In this review, we discuss the accumulating evidence on the role of PRMTs in the pathophysiology of neurodegenerative diseases, enlightening their pathogenesis and stimulating future research.}, }
@article {pmid37759540, year = {2023}, author = {Sanghai, N and Tranmer, GK}, title = {Biochemical and Molecular Pathways in Neurodegenerative Diseases: An Integrated View.}, journal = {Cells}, volume = {12}, number = {18}, pages = {}, pmid = {37759540}, issn = {2073-4409}, abstract = {Neurodegenerative diseases (NDDs) like Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) are defined by a myriad of complex aetiologies. Understanding the common biochemical molecular pathologies among NDDs gives an opportunity to decipher the overlapping and numerous cross-talk mechanisms of neurodegeneration. Numerous interrelated pathways lead to the progression of neurodegeneration. We present evidence from the past pieces of literature for the most usual global convergent hallmarks like ageing, oxidative stress, excitotoxicity-induced calcium butterfly effect, defective proteostasis including chaperones, autophagy, mitophagy, and proteosome networks, and neuroinflammation. Herein, we applied a holistic approach to identify and represent the shared mechanism across NDDs. Further, we believe that this approach could be helpful in identifying key modulators across NDDs, with a particular focus on AD, PD, and ALS. Moreover, these concepts could be applied to the development and diagnosis of novel strategies for diverse NDDs.}, }
@article {pmid37755677, year = {2024}, author = {Hu, C and Yan, Y and Jin, Y and Yang, J and Xi, Y and Zhong, Z}, title = {Decoding the Cellular Trafficking of Prion-like Proteins in Neurodegenerative Diseases.}, journal = {Neuroscience bulletin}, volume = {40}, number = {2}, pages = {241-254}, pmid = {37755677}, issn = {1995-8218}, mesh = {Humans ; *Prions ; *Neurodegenerative Diseases/pathology ; Amyloid beta-Peptides ; *Alzheimer Disease ; alpha-Synuclein ; tau Proteins ; *Parkinson Disease ; }, abstract = {The accumulation and spread of prion-like proteins is a key feature of neurodegenerative diseases (NDs) such as Alzheimer's disease, Parkinson's disease, or Amyotrophic Lateral Sclerosis. In a process known as 'seeding', prion-like proteins such as amyloid beta, microtubule-associated protein tau, α-synuclein, silence superoxide dismutase 1, or transactive response DNA-binding protein 43 kDa, propagate their misfolded conformations by transforming their respective soluble monomers into fibrils. Cellular and molecular evidence of prion-like propagation in NDs, the clinical relevance of their 'seeding' capacities, and their levels of contribution towards disease progression have been intensively studied over recent years. This review unpacks the cyclic prion-like propagation in cells including factors of aggregate internalization, endo-lysosomal leaking, aggregate degradation, and secretion. Debates on the importance of the role of prion-like protein aggregates in NDs, whether causal or consequent, are also discussed. Applications lead to a greater understanding of ND pathogenesis and increased potential for therapeutic strategies.}, }
@article {pmid37751856, year = {2023}, author = {Martin Schaff, C and Kurent, JE and Kolodziejczak, S and Milic, M and Foster, LA and Mehta, AK}, title = {Neuroprognostication for Patients with Amyotrophic Lateral Sclerosis: An Updated, Evidence-Based Review.}, journal = {Seminars in neurology}, volume = {43}, number = {5}, pages = {776-790}, doi = {10.1055/s-0043-1775595}, pmid = {37751856}, issn = {1098-9021}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/therapy ; Quality of Life ; Prognosis ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disorder that presents and progresses in various ways, making prognostication difficult. Several paradigms exist for providers to elucidate prognosis in a way that addresses not only the amount of time a patient has to live, but also a patient's quality of their life moving forward. Prognostication, with regard to both survivability and quality of life, is impacted by several features that include, but are not limited to, patient demographics, clinical features on presentation, and over time, access to therapy, and access to multidisciplinary clinics. An understanding of the impact that these features have on the life of a patient with ALS can help providers to develop a better and more personalized approach for patients related to their clinical prognosis after a diagnosis is made. The ultimate goal of prognostication is to empower patients with ALS to take control and make decisions with their care teams to ensure that their goals are addressed and met.}, }
@article {pmid37751804, year = {2023}, author = {Wang, Z and Zhang, C and Fan, C and Liu, Y}, title = {Post-translational modifications in stress granule and their implications in neurodegenerative diseases.}, journal = {Biochimica et biophysica acta. Gene regulatory mechanisms}, volume = {1866}, number = {4}, pages = {194989}, doi = {10.1016/j.bbagrm.2023.194989}, pmid = {37751804}, issn = {1876-4320}, mesh = {Humans ; *Neurodegenerative Diseases/genetics/metabolism ; Stress Granules ; Protein Processing, Post-Translational ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; RNA, Messenger/metabolism ; }, abstract = {Stress granules (SGs) arise as formations of mRNAs and proteins in response to translation initiation inhibition during stress. These dynamic compartments adopt a fluidic nature through liquid-liquid phase separation (LLPS), exhibiting a composition subject to constant change within cellular contexts. Research has unveiled an array of post-translational modifications (PTMs) occurring on SG proteins, intricately orchestrating SG dynamics. In the realm of neurodegenerative diseases, pathological mutant proteins congregate into insoluble aggregates alongside numerous SG proteins, manifesting resilience against disassembly. Specific PTMs conspicuously label these aggregates, designating them for subsequent degradation. The strategic manipulation of aberrant SGs via PTMs emerges as a promising avenue for therapeutic intervention. This review discerns recent strides in comprehending the impact of PTMs on LLPS behavior and the assembly/disassembly kinetics of SGs. By delving into the roles of PTMs in governing SG dynamics, we augment our cognizance of the molecular underpinnings of neurodegeneration. Furthermore, we offer invaluable insights into potential targets for therapeutic intervention in neurodegenerative afflictions, encompassing conditions like amyotrophic lateral sclerosis and frontotemporal dementia.}, }
@article {pmid37748443, year = {2024}, author = {Jütte, R}, title = {Involving Voters and Consumers in Decision-Making about the Health Care System - The Swiss Case: A Review.}, journal = {Complementary medicine research}, volume = {31}, number = {1}, pages = {78-83}, doi = {10.1159/000534268}, pmid = {37748443}, issn = {2504-2106}, mesh = {Humans ; Switzerland ; *Voting ; *Complementary Therapies ; Evidence-Based Medicine ; }, abstract = {BACKGROUND: Behind the principle of involving users and voters directly in decision-making about the health care system are ideas relating to empowerment. This implies a challenge to the traditional view that scientific knowledge is generally believed to be of higher value than empirical knowledge, as it is the case with CAM. The objectives of this review are (a) to show that this assumption disregards the fact that CAM is as scientific as conventional medicine but has different basic assumptions what the world is being made of and consequently uses different/adapted scientific methods; (b) to demonstrate how a perspective of the history of medicine and science as well as direct democracy mechanisms such as stipulated in the Swiss constitution can be used to achieve the acceptance of CAM in a modern medical health care system. A public health care system financed by levies from the population should also reflect the widely documented desire in the population for medical pluralism (provided that therapeutical alternatives are not risky). Otherwise, the problem of social inequality arises because only people with a good financial background can afford this medicine.<br><br>SUMMARY: From the perspective of scientific theory and the history of science, the answer to the question of whether complementary medicine and conventional medical procedures must provide proof of efficacy according to a uniform scientific is quite controversial according to epistemologically oriented studies on this issue.<br><br>KEY MESSAGES: This review found strong evidence for involving voters and consumers directly in decision-making about the provision of CAM in the health care system. It also seems necessary to step back in the debate on evidence-based medicine, taking a history of medicine and science perspective, as the role which the proper method occupies and plays in medicine is defined by the scientific nature of the world view.<br><br>UNLABELLED: Hinter dem Grundsatz, Nutzer und W&#xe4;hler direkt in die Entscheidungsfindung &#xfc;ber das Gesundheitssystem einzubeziehen, stehen Vorstellungen von Empowerment. Dies impliziert eine Infragestellung der traditionellen Ansicht, dass wissenschaftliches Wissen im Allgemeinen als wertvoller angesehen wird als empirisches Wissen und erprobte Erfahrung, wie es bei der Komplement&#xe4;rmedizin der Fall ist. Die Ziele dieser &#xdc;bersichtsarbeit sind: (a) zu zeigen, dass diese Annahme die Tatsache au&#xdf;er Acht l&#xe4;sst, dass die Komplement&#xe4;rmedizin ebenso wissenschaftlich ist wie die Schulmedizin, aber von anderen Grundannahmen ausgeht, wie die Welt beschaffen ist, und folglich andere/angepasste wissenschaftliche Methoden anwendet; (b) aufzuzeigen, wie eine medizin- und wissenschaftsgeschichtliche Perspektive sowie Mechanismen der direkten Demokratie, wie sie in der Schweizer Verfassung vorgesehen sind, genutzt werden k&#xf6;nnen, um die Akzeptanz der Komplement&#xe4;rmedizin in einem modernen medizinischen Gesundheitssystem zu erreichen. Ein &#xf6;ffentliches, durch Abgaben der Bev&#xf6;lkerung finanziertes Gesundheitssystem sollte auch dem vielfach dokumentierten Wunsch der Bev&#xf6;lkerung nach medizinischem Pluralismus Rechnung tragen (sofern die therapeutischen Alternativen nicht riskant sind). Andernfalls stellt sich das Problem der sozialen Ungleichheit, weil sich nur Menschen mit einem guten finanziellen Hintergrund diese Medizin leisten k&#xf6;nnen.}, }
@article {pmid37746513, year = {2023}, author = {Singh, A and Arora, S and Chavan, M and Shahbaz, S and Jabeen, H}, title = {An Overview of the Neurotrophic and Neuroprotective Properties of the Psychoactive Drug Lithium as an Autophagy Modulator in Neurodegenerative Conditions.}, journal = {Cureus}, volume = {15}, number = {8}, pages = {e44051}, pmid = {37746513}, issn = {2168-8184}, abstract = {For both short-term and long-term treatment of bipolar disorder, lithium is a prototypical mood stabilizer. Lithium's neuroprotective properties were revealed by cumulative translational research, which opened the door to reforming the chemical as a treatment for neurodegenerative illnesses. The control of homeostatic systems such as oxidative stress, autophagy, apoptosis, mitochondrial function, and inflammation underlies lithium's neuroprotective characteristics. The fact that lithium inhibits the enzymes inositol monophosphatase (IMPase) and glycogen synthase kinase (GSK)-3 may be the cause of the various intracellular reactions. In this article, we review lithium's neurobiological properties, as demonstrated by its neurotrophic and neuroprotective capabilities, as well as translational studies in cells in culture and in animal models of Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Prion disease, amyotrophic lateral sclerosis (ALS), ischemic stroke, and neuronal ceroid lipofuscinosis (NCL), discussing the justification for the drug's use in the treatment of these neurodegenerative disorders.}, }
@article {pmid37741764, year = {2024}, author = {Ducharme, S and Pijnenburg, Y and Rohrer, JD and Huey, E and Finger, E and Tatton, N}, title = {Identifying and Diagnosing TDP-43 Neurodegenerative Diseases in Psychiatry.}, journal = {The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry}, volume = {32}, number = {1}, pages = {98-113}, pmid = {37741764}, issn = {1545-7214}, support = {U01 AG079850/AG/NIA NIH HHS/United States ; R01 MH120794/MH/NIMH NIH HHS/United States ; R01 AG062268/AG/NIA NIH HHS/United States ; MR/T046015/1/MRC_/Medical Research Council/United Kingdom ; MR/M008525/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics ; DNA-Binding Proteins/genetics ; *Frontotemporal Dementia/diagnosis/genetics ; *Neurodegenerative Diseases/diagnosis/genetics ; *Psychiatry ; }, abstract = {Neuropsychiatric symptoms (NPS) are common manifestations of neurodegenerative disorders and are often early signs of those diseases. Among those neurodegenerative diseases, TDP-43 proteinopathies are an increasingly recognized cause of early neuropsychiatric manifestations. TDP-43-related diseases include frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), and Limbic-Predominant Age-Related TDP-43 Encephalopathy (LATE). The majority of TDP-43-related diseases are sporadic, but a significant proportion is hereditary, with progranulin (GRN) mutations and C9orf72 repeat expansions as the most common genetic etiologies. Studies reveal that NPS can be the initial manifestation of those diseases or can complicate disease course, but there is a lack of awareness among clinicians about TDP-43-related diseases, which leads to common diagnostic mistakes or delays. There is also emerging evidence that TDP-43 accumulations could play a role in late-onset primary psychiatric disorders. In the absence of robust biomarkers for TDP-43, the diagnosis remains primarily based on clinical assessment and neuroimaging. Given the association with psychiatric symptoms, clinical psychiatrists have a key role in the early identification of patients with TDP-43-related diseases. This narrative review provides a comprehensive overview of the pathobiology of TDP-43, resulting clinical presentations, and associated neuropsychiatric manifestations to help guide clinical practice.}, }
@article {pmid37739217, year = {2023}, author = {Chakraborty, J and Chakraborty, S and Chakraborty, S and Narayan, MN}, title = {Entanglement of MAPK pathways with gene expression and its omnipresence in the etiology for cancer and neurodegenerative disorders.}, journal = {Biochimica et biophysica acta. Gene regulatory mechanisms}, volume = {1866}, number = {4}, pages = {194988}, doi = {10.1016/j.bbagrm.2023.194988}, pmid = {37739217}, issn = {1876-4320}, mesh = {Humans ; Mitogen-Activated Protein Kinases ; MAP Kinase Signaling System/genetics ; *Neoplasms/genetics/drug therapy ; *Neurodegenerative Diseases/genetics ; Gene Expression ; }, abstract = {Mitogen Activated Protein Kinase (MAPK) is one of the most well characterized cellular signaling pathways that controls fundamental cellular processes including proliferation, differentiation, and apoptosis. These cellular functions are consequences of transcription of regulatory genes that are influenced and regulated by the MAP-Kinase signaling cascade. MAP kinase components such as Receptor Tyrosine Kinases (RTKs) sense external cues or ligands and transmit these signals via multiple protein complexes such as RAS-RAF, MEK, and ERKs and eventually modulate the transcription factors inside the nucleus to induce transcription and other regulatory functions. Aberrant activation, dysregulation of this signaling pathway, and genetic alterations in any of these components results in the developmental disorders, cancer, and neurodegenerative disorders. Over the years, the MAPK pathway has been a prime pharmacological target, to treat complex human disorders that are genetically linked such as cancer, Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. The current review re-visits the mechanism of MAPK pathways in gene expression regulation. Further, a current update on the progress of the mechanistic understanding of MAPK components is discussed from a disease perspective.}, }
@article {pmid37738797, year = {2023}, author = {Dong, W and Peng, Q and Liu, Z and Xie, Z and Guo, X and Li, Y and Chen, C}, title = {Estrogen plays an important role by influencing the NLRP3 inflammasome.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {167}, number = {}, pages = {115554}, doi = {10.1016/j.biopha.2023.115554}, pmid = {37738797}, issn = {1950-6007}, abstract = {The nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome is an important part of the natural immune system that plays an important role in many diseases. Estrogen is a sex hormone that plays an important role in controlling reproduction and regulates many physiological and pathological processes. Recent studies have indicated that estrogen is associated with disease progression. Estrogen can ameliorate some diseases (e. g, sepsis, mood disturbances, cerebral ischemia, some hepatopathy, Parkinson's disease, amyotrophic lateral sclerosis, inflammatory bowel disease, spinal cord injury, multiple sclerosis, myocardial ischemia/reperfusion injury, osteoarthritis, and renal fibrosis) by inhibiting the NLRP3 inflammasome. Estrogen can also promote the development of diseases (e.g., ovarian endometriosis, dry eye disease, and systemic lupus erythematosus) by upregulating the NLRP3 inflammasome. In addition, estrogen has a dual effect on the development of cancers and asthma. However, the mechanism of these effects is not summarized. This article reviewed the progress in understanding the effects of estrogen on the NLRP3 inflammasome and its mechanisms in recent years to provide a theoretical basis for an in-depth study.}, }
@article {pmid37735909, year = {2023}, author = {Irie, T and Sawa, M}, title = {CDC7 kinase inhibitors: a survey of recent patent literature (2017-2022).}, journal = {Expert opinion on therapeutic patents}, volume = {33}, number = {7-8}, pages = {493-501}, doi = {10.1080/13543776.2023.2262138}, pmid = {37735909}, issn = {1744-7674}, mesh = {Humans ; *Cell Cycle Proteins/metabolism ; Patents as Topic ; Protein Serine-Threonine Kinases ; DNA Replication ; *Neoplasms ; }, abstract = {INTRODUCTION: CDC7 is a serine/threonine kinase which plays an important role in DNA replication. Inhibition of CDC7 in cancer cells causes lethal S phase or M phase progression, whereas inhibition of CDC7 in normal cells does not cause cell death and only leads to cell cycle arrest at the DNA replication checkpoint. Therefore, CDC7 has been recognized as a potential target for novel therapeutic interventions in cancers.<br><br>AREAS COVERED: Patent literature claiming novel small molecule compounds inhibiting CDC7 disclosed from 2017 to 2022.<br><br>EXPERT OPINION: Despite the indisputable positive impact of CDC7 as a drug target, there have been reported only a handful of chemical scaffolds as CDC7 inhibitors. Several CDC7 inhibitors have been progressed into clinical trials for cancer treatments, but they did not result in satisfactory efficacies in those trials. One possible reason for the failure might be due to the dose-limiting toxicities, and some of the observed toxicities were thought to be not related to CDC7 inhibition, suggesting it should be important to identify novel chemical scaffolds to eliminate unwanted toxicities. Another important factor is the patient stratification that would enable greater response, and the identification of such predictive biomarkers should be the key to success for the development of CDC7 inhibitors.}, }
@article {pmid37735622, year = {2023}, author = {Sarkar, S and Elliott, EC and Henry, HR and Ludovico, ID and Melchior, JT and Frazer-Abel, A and Webb-Robertson, BJ and Davidson, WS and Holers, VM and Rewers, MJ and Metz, TO and Nakayasu, ES}, title = {Systematic review of type 1 diabetes biomarkers reveals regulation in circulating proteins related to complement, lipid metabolism, and immune response.}, journal = {Clinical proteomics}, volume = {20}, number = {1}, pages = {38}, pmid = {37735622}, issn = {1542-6416}, support = {P30 DK116073/DK/NIDDK NIH HHS/United States ; R01 DK032493/DK/NIDDK NIH HHS/United States ; U01 DK127505/DK/NIDDK NIH HHS/United States ; U01 DK127786/DK/NIDDK NIH HHS/United States ; }, abstract = {BACKGROUND: Type 1 diabetes (T1D) results from an autoimmune attack of the pancreatic β cells that progresses to dysglycemia and symptomatic hyperglycemia. Current biomarkers to track this evolution are limited, with development of islet autoantibodies marking the onset of autoimmunity and metabolic tests used to detect dysglycemia. Therefore, additional biomarkers are needed to better track disease initiation and progression. Multiple clinical studies have used proteomics to identify biomarker candidates. However, most of the studies were limited to the initial candidate identification, which needs to be further validated and have assays developed for clinical use. Here we curate these studies to help prioritize biomarker candidates for validation studies and to obtain a broader view of processes regulated during disease development.<br><br>METHODS: This systematic review was registered with Open Science Framework (https://doi.org/10.17605/OSF.IO/N8TSA). Using PRISMA guidelines, we conducted a systematic search of proteomics studies of T1D in the PubMed to identify putative protein biomarkers of the disease. Studies that performed mass spectrometry-based untargeted/targeted proteomic analysis of human serum/plasma of control, pre-seroconversion, post-seroconversion, and/or T1D-diagnosed subjects were included. For unbiased screening, 3 reviewers screened all the articles independently using the pre-determined criteria.<br><br>RESULTS: A total of 13 studies met our inclusion criteria, resulting in the identification of 266 unique proteins, with 31 (11.6%) being identified across 3 or more studies. The circulating protein biomarkers were found to be enriched in complement, lipid metabolism, and immune response pathways, all of which are found to be dysregulated in different phases of T1D development. We found 2 subsets: 17 proteins (C3, C1R, C8G, C4B, IBP2, IBP3, ITIH1, ITIH2, BTD, APOE, TETN, C1S, C6A3, SAA4, ALS, SEPP1 and PI16) and 3 proteins (C3, CLUS and C4A) have consistent regulation in at least 2 independent studies at post-seroconversion and post-diagnosis compared to controls, respectively, making them strong candidates for clinical assay development.<br><br>CONCLUSIONS: Biomarkers analyzed in this systematic review highlight alterations in specific biological processes in T1D, including complement, lipid metabolism, and immune response pathways, and may have potential for further use in the clinic as prognostic or diagnostic assays.}, }
@article {pmid37735487, year = {2023}, author = {Gao, C and Jiang, J and Tan, Y and Chen, S}, title = {Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets.}, journal = {Signal transduction and targeted therapy}, volume = {8}, number = {1}, pages = {359}, pmid = {37735487}, issn = {2059-3635}, mesh = {Animals ; *Neurodegenerative Diseases/genetics ; Microglia ; Neuroinflammatory Diseases ; Protein Aggregates ; *Alzheimer Disease/genetics ; }, abstract = {Microglia activation is observed in various neurodegenerative diseases. Recent advances in single-cell technologies have revealed that these reactive microglia were with high spatial and temporal heterogeneity. Some identified microglia in specific states correlate with pathological hallmarks and are associated with specific functions. Microglia both exert protective function by phagocytosing and clearing pathological protein aggregates and play detrimental roles due to excessive uptake of protein aggregates, which would lead to microglial phagocytic ability impairment, neuroinflammation, and eventually neurodegeneration. In addition, peripheral immune cells infiltration shapes microglia into a pro-inflammatory phenotype and accelerates disease progression. Microglia also act as a mobile vehicle to propagate protein aggregates. Extracellular vesicles released from microglia and autophagy impairment in microglia all contribute to pathological progression and neurodegeneration. Thus, enhancing microglial phagocytosis, reducing microglial-mediated neuroinflammation, inhibiting microglial exosome synthesis and secretion, and promoting microglial conversion into a protective phenotype are considered to be promising strategies for the therapy of neurodegenerative diseases. Here we comprehensively review the biology of microglia and the roles of microglia in neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, multiple system atrophy, amyotrophic lateral sclerosis, frontotemporal dementia, progressive supranuclear palsy, corticobasal degeneration, dementia with Lewy bodies and Huntington's disease. We also summarize the possible microglia-targeted interventions and treatments against neurodegenerative diseases with preclinical and clinical evidence in cell experiments, animal studies, and clinical trials.}, }
@article {pmid37734696, year = {2024}, author = {Kumar, N and Rauf, SA and Rajendar, R and Arbab, S}, title = {Cost-Effectiveness Analysis of Sacubitril/Valsartan for Reducing the Use of Implantable Cardioverter-Defibrillator (ICD) and the Risk of Death in ICD-Eligible Heart Failure Patients With Reduced Ejection Fraction.}, journal = {Current problems in cardiology}, volume = {49}, number = {1 Pt B}, pages = {102093}, doi = {10.1016/j.cpcardiol.2023.102093}, pmid = {37734696}, issn = {1535-6280}, mesh = {Humans ; Stroke Volume ; Cost-Effectiveness Analysis ; *Defibrillators, Implantable ; Tetrazoles/therapeutic use ; Valsartan ; *Heart Failure/therapy ; *Ventricular Dysfunction, Left/chemically induced ; }, abstract = {This critical review of Kaddoura et al.'s article on sacubitril/valsartan in heart failure patients underscores the importance of considering potential adverse effects, including renal failure, hyperkalemia, angioedema, and increased reports of sudden cardiac death. It highlights the need for rigorous monitoring and precise treatment regimens, especially in diabetic heart failure patients. Additionally, the review questions the generalizability of the study's results to diverse healthcare settings and emphasizes the importance of grounded patient follow-up data for accurate long-term assessment. These considerations are vital for informed decision-making regarding sacubitril/valsartan use in heart failure management.}, }
@article {pmid37734449, year = {2023}, author = {Hayashi, K and Sasaki, K}, title = {Number of kinesins engaged in axonal cargo transport: A novel biomarker for neurological disorders.}, journal = {Neuroscience research}, volume = {197}, number = {}, pages = {25-30}, doi = {10.1016/j.neures.2023.09.004}, pmid = {37734449}, issn = {1872-8111}, mesh = {Humans ; *Kinesins/metabolism ; Axonal Transport/physiology ; Axons/metabolism ; Dyneins/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism ; }, abstract = {Kinesin motor proteins play crucial roles in anterograde transport of cargo vesicles in neurons, moving them along axons from the cell body towards the synaptic region. Not only the transport force and velocity of single motor protein, but also the number of kinesin molecules involved in transporting a specific cargo, is pivotal for synapse formation. This collective transport by multiple kinesins ensures stable and efficient cargo transport in neurons. Abnormal increases or decreases in the number of engaged kinesin molecules per cargo could potentially act as biomarkers for neurodegenerative diseases such as Alzheimer's, Parkinson's, amyotrophic lateral sclerosis (ALS), spastic paraplegia, polydactyly syndrome, and virus transport disorders. We review here a model constructed using physical measurements to quantify the number of kinesin molecules associated with their cargo, which could shed light on the molecular mechanisms of neurodegenerative diseases related to axonal transport.}, }
@article {pmid37730668, year = {2023}, author = {Zhu, L and Li, S and Li, XJ and Yin, P}, title = {Pathological insights from amyotrophic lateral sclerosis animal models: comparisons, limitations, and challenges.}, journal = {Translational neurodegeneration}, volume = {12}, number = {1}, pages = {46}, pmid = {37730668}, issn = {2047-9158}, mesh = {Humans ; Animals ; Swine ; *Amyotrophic Lateral Sclerosis/genetics ; *Neurodegenerative Diseases ; Brain ; }, abstract = {In order to dissect amyotrophic lateral sclerosis (ALS), a multigenic, multifactorial, and progressive neurodegenerative disease with heterogeneous clinical presentations, researchers have generated numerous animal models to mimic the genetic defects. Concurrent and comparative analysis of these various models allows identification of the causes and mechanisms of ALS in order to finally obtain effective therapeutics. However, most genetically modified rodent models lack overt pathological features, imposing challenges and limitations in utilizing them to rigorously test the potential mechanisms. Recent studies using large animals, including pigs and non-human primates, have uncovered important events that resemble neurodegeneration in patients' brains but could not be produced in small animals. Here we describe common features as well as discrepancies among these models, highlighting new insights from these models. Furthermore, we will discuss how to make rodent models more capable of recapitulating important pathological features based on the important pathogenic insights from large animal models.}, }
@article {pmid37726779, year = {2023}, author = {Wang, Y and Wong, EL and Nilsen, P and Chung, VC and Tian, Y and Yeoh, EK}, title = {A scoping review of implementation science theories, models, and frameworks - an appraisal of purpose, characteristics, usability, applicability, and testability.}, journal = {Implementation science : IS}, volume = {18}, number = {1}, pages = {43}, pmid = {37726779}, issn = {1748-5908}, mesh = {Humans ; *Implementation Science ; Databases, Factual ; }, abstract = {BACKGROUND: A proliferation of theories, models, and frameworks (TMFs) have been developed in the implementation science field to facilitate the implementation process. The basic features of these TMFs have been identified by several reviews. However, systematic appraisals on the quality of these TMFs are inadequate. To fill this gap, this study aimed to assess the usability, applicability, and testability of the current TMFs in a structured way.<br><br>METHODS: A scoping review method was employed. Electronic databases were searched to locate English and Chinese articles published between January 2000 and April 2022. Search terms were specific to implementation science. Additionally, hand searches were administered to identify articles from related reviews. Purpose and characteristics such as the type of TMF, analytical level, and observation unit were extracted. Structured appraisal criteria were adapted from Birken et al.'s Theory Comparison and Selection Tool (T-CaST) to conduct an in-depth analysis of the TMFs' usability, applicability, and testability.<br><br>RESULTS: A total of 143 TMFs were included in this analysis. Among them, the most common purpose was to identify barriers and facilitators. Most TMFs applied the descriptive method to summarize the included constructs or the prescriptive method to propose courses of implementation actions. TMFs were mainly mid-range theories built on existing conceptual frameworks or demonstrated grand theories. The usability of the TMFs needs to be improved in terms of the provision of conceptually matched strategies to barriers and facilitators and instructions on the TMFs usage. Regarding the applicability, little attention was paid to the constructs of macro-level context, stages of scale-up and sustainability, and implementation outcomes like feasibility, cost, and penetration. Also, fewer TMFs could propose recommended research and measurement methods to apply the TMFs. Lastly, explicit hypotheses or propositions were lacking in most of the TMFs, and empirical evidence was lacking to support the claimed mechanisms between framework elements in testability.<br><br>CONCLUSIONS: Common limitations were found in the usability, application, and testability of the current TMFs. The findings of this review could provide insights for developers of TMFs for future theoretical advancements.}, }
@article {pmid37725878, year = {2023}, author = {Singh, N and Vishwas, S and Kaur, A and Kaur, H and Kakoty, V and Khursheed, R and Chaitanya, MVNL and Babu, MR and Awasthi, A and Corrie, L and Harish, V and Yanadaiah, P and Gupta, S and Sayed, AA and El-Sayed, A and Ali, I and Kensara, OA and Ghaboura, N and Gupta, G and Dou, AM and Algahtani, M and El-Kott, AF and Dua, K and Singh, SK and Abdel-Daim, MM}, title = {Harnessing role of sesamol and its nanoformulations against neurodegenerative diseases.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {167}, number = {}, pages = {115512}, doi = {10.1016/j.biopha.2023.115512}, pmid = {37725878}, issn = {1950-6007}, abstract = {Sesamol is a lignan of sesame seeds and a natural phenolic molecule that has emerged as a useful medical agent. Sesamol is a non-toxic phytoconstituent, which exerts certain valuable effects in the management of cancer, diabetes, cardiovascular diseases, neurodegenerative diseases (NDs), etc. Sesamol is known to depict its neuroprotective role by various mechanisms, such as metabolic regulators, action on oxidative stress, neuroinflammation, etc. However, its poor oral bioavailability, rapid excretion (as conjugates), and susceptibility to gastric irritation/toxicity (particularly in rats' forestomach) may restrict its effectiveness. To overcome the associated limitations, novel drug delivery system-based formulations of sesamol are emerging and being researched extensively. These can conjugate with sesamol and enhance the bioavailability and solubility of free sesamol, along with delivery at the target site. In this review, we have summarized various research works highlighting the role of sesamol on various NDs, including Alzheimer's disease, Huntington's disease, Amyotrophic lateral sclerosis, and Parkinson's disease. Moreover, the formulation strategies and neuroprotective role of sesamol-based nano-formulations have also been discussed.}, }
@article {pmid37725216, year = {2024}, author = {Dar, NJ and John, U and Bano, N and Khan, S and Bhat, SA}, title = {Oxytosis/Ferroptosis in Neurodegeneration: the Underlying Role of Master Regulator Glutathione Peroxidase 4 (GPX4).}, journal = {Molecular neurobiology}, volume = {61}, number = {3}, pages = {1507-1526}, pmid = {37725216}, issn = {1559-1182}, mesh = {Humans ; Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism ; *Ferroptosis ; Cell Death ; Oxidation-Reduction ; *Neurodegenerative Diseases ; Glutathione Peroxidase/metabolism ; Glutathione/metabolism ; Lipid Peroxidation ; }, abstract = {Oxytosis/ferroptosis is an iron-dependent oxidative form of cell death triggered by lethal accumulation of phospholipid hydroperoxides (PLOOHs) in membranes. Failure of the intricate PLOOH repair system is a principle cause of ferroptotic cell death. Glutathione peroxidase 4 (GPX4) is distinctly vital for converting PLOOHs in membranes to non-toxic alcohols. As such, GPX4 is known as the master regulator of oxytosis/ferroptosis. Ferroptosis has been implicated in a number of disorders such as neurodegenerative diseases (amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD), etc.), ischemia/reperfusion injury, and kidney degeneration. Reduced function of GPX4 is frequently observed in degenerative disorders. In this study, we examine how diminished GPX4 function may be a critical event in triggering oxytosis/ferroptosis to perpetuate or initiate the neurodegenerative diseases and assess the possible therapeutic importance of oxytosis/ferroptosis in neurodegenerative disorders. These discoveries are important for advancing our understanding of neurodegenerative diseases because oxytosis/ferroptosis may provide a new target to slow the course of the disease.}, }
@article {pmid37721281, year = {2024}, author = {Jourdi, G and Fleury, S and Boukhatem, I and Lordkipanidzé, M}, title = {Soluble p75 neurotrophic receptor as a reliable biomarker in neurodegenerative diseases: what is the evidence?.}, journal = {Neural regeneration research}, volume = {19}, number = {3}, pages = {536-541}, pmid = {37721281}, issn = {1673-5374}, abstract = {Neurodegenerative diseases are often misdiagnosed, especially when the diagnosis is based solely on clinical symptoms. The p75 neurotrophic receptor (p75[NTR]) has been studied as an index of sensory and motor nerve development and maturation. Its cleavable extracellular domain (ECD) is readily detectable in various biological fluids including plasma, serum and urine. There is evidence for increased p75[NTR] ECD levels in neurodegenerative diseases such as Alzheimer's disease, amyotrophic lateral sclerosis, age-related dementia, schizophrenia, and diabetic neuropathy. Whether p75[NTR] ECD could be used as a biomarker for diagnosis and/or prognosis in these disorders, and whether it could potentially lead to the development of targeted therapies, remains an open question. In this review, we present and discuss published studies that have evaluated the relevance of this emerging biomarker in the context of various neurodegenerative diseases. We also highlight areas that require further investigation to better understand the role of p75[NTR] ECD in the clinical diagnosis and management of neurodegenerative disorders.}, }
@article {pmid37720552, year = {2023}, author = {Naskar, A and Nayak, A and Salaikumaran, MR and Vishal, SS and Gopal, PP}, title = {Phase separation and pathologic transitions of RNP condensates in neurons: implications for amyotrophic lateral sclerosis, frontotemporal dementia and other neurodegenerative disorders.}, journal = {Frontiers in molecular neuroscience}, volume = {16}, number = {}, pages = {1242925}, pmid = {37720552}, issn = {1662-5099}, support = {R01 NS122907/NS/NINDS NIH HHS/United States ; }, abstract = {Liquid-liquid phase separation results in the formation of dynamic biomolecular condensates, also known as membrane-less organelles, that allow for the assembly of functional compartments and higher order structures within cells. Multivalent, reversible interactions between RNA-binding proteins (RBPs), including FUS, TDP-43, and hnRNPA1, and/or RNA (e.g., RBP-RBP, RBP-RNA, RNA-RNA), result in the formation of ribonucleoprotein (RNP) condensates, which are critical for RNA processing, mRNA transport, stability, stress granule assembly, and translation. Stress granules, neuronal transport granules, and processing bodies are examples of cytoplasmic RNP condensates, while the nucleolus and Cajal bodies are representative nuclear RNP condensates. In neurons, RNP condensates promote long-range mRNA transport and local translation in the dendrites and axon, and are essential for spatiotemporal regulation of gene expression, axonal integrity and synaptic function. Mutations of RBPs and/or pathologic mislocalization and aggregation of RBPs are hallmarks of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimer's disease. ALS/FTD-linked mutations of RBPs alter the strength and reversibility of multivalent interactions with other RBPs and RNAs, resulting in aberrant phase transitions. These aberrant RNP condensates have detrimental functional consequences on mRNA stability, localization, and translation, and ultimately lead to compromised axonal integrity and synaptic function in disease. Pathogenic protein aggregation is dependent on various factors, and aberrant dynamically arrested RNP condensates may serve as an initial nucleation step for pathologic aggregate formation. Recent studies have focused on identifying mechanisms by which neurons resolve phase transitioned condensates to prevent the formation of pathogenic inclusions/aggregates. The present review focuses on the phase separation of neurodegenerative disease-linked RBPs, physiological functions of RNP condensates, and the pathologic role of aberrant phase transitions in neurodegenerative disease, particularly ALS/FTD. We also examine cellular mechanisms that contribute to the resolution of aberrant condensates in neurons, and potential therapeutic approaches to resolve aberrantly phase transitioned condensates at a molecular level.}, }
@article {pmid37720544, year = {2023}, author = {McGoldrick, P and Robertson, J}, title = {Unraveling the impact of disrupted nucleocytoplasmic transport systems in C9orf72-associated ALS.}, journal = {Frontiers in cellular neuroscience}, volume = {17}, number = {}, pages = {1247297}, pmid = {37720544}, issn = {1662-5102}, abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two adult-onset neurodegenerative diseases that are part of a common disease spectrum due to clinical, genetic, and pathological overlap. A prominent genetic factor contributing to both diseases is a hexanucleotide repeat expansion in a non-coding region of the C9orf72 gene. This mutation in C9orf72 leads to nuclear depletion and cytoplasmic aggregation of Tar DNA-RNA binding protein 43 (TDP-43). TDP-43 pathology is characteristic of the majority of ALS cases, irrespective of disease causation, and is present in ~50% of FTD cases. Defects in nucleocytoplasmic transport involving the nuclear pore complex, the Ran-GTPase cycle, and nuclear transport factors have been linked with the mislocalization of TDP-43. Here, we will explore and discuss the implications of these system abnormalities of nucleocytoplasmic transport in C9orf72-ALS/FTD, as well as in other forms of familial and sporadic ALS.}, }
@article {pmid37712858, year = {2024}, author = {Al-Kuraishy, HM and Jabir, MS and Al-Gareeb, AI and Saad, HM and Batiha, GE and Klionsky, DJ}, title = {The beneficial role of autophagy in multiple sclerosis: Yes or No?.}, journal = {Autophagy}, volume = {20}, number = {2}, pages = {259-274}, pmid = {37712858}, issn = {1554-8635}, support = {R35 GM131919/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Mice ; *Multiple Sclerosis/metabolism ; Leukocytes, Mononuclear/metabolism ; Autophagy ; Central Nervous System ; *Encephalomyelitis, Autoimmune, Experimental ; Mice, Inbred C57BL ; }, abstract = {Multiple sclerosis (MS) is a chronic progressive demyelinating disease of the central nervous system (CNS) due to an increase of abnormal peripherally auto-reactive T lymphocytes which elicit autoimmunity. The main pathophysiology of MS is myelin sheath damage by immune cells and a defect in the generation of myelin by oligodendrocytes. Macroautophagy/autophagy is a critical degradation process that eliminates dysfunctional or superfluous cellular components. Autophagy has the property of a double-edged sword in MS in that it may have both beneficial and detrimental effects on MS neuropathology. Therefore, this review illustrates the protective and harmful effects of autophagy with regard to this disease. Autophagy prevents the progression of MS by reducing oxidative stress and inflammatory disorders. In contrast, over-activated autophagy is associated with the progression of MS neuropathology and in this case the use of autophagy inhibitors may alleviate the pathogenesis of MS. Furthermore, autophagy provokes the activation of different immune and supporting cells that play an intricate role in the pathogenesis of MS. Autophagy functions in the modulation of MS neuropathology by regulating cell proliferation related to demyelination and remyelination. Autophagy enhances remyelination by increasing the activity of oligodendrocytes, and astrocytes. However, autophagy induces demyelination by activating microglia and T cells. In conclusion, specific autophagic activators of oligodendrocytes, and astrocytes, and specific autophagic inhibitors of dendritic cells (DCs), microglia and T cells induce protective effects against the pathogenesis of MS.Abbreviations: ALS: amyotrophic lateral sclerosis; APCs: antigen-presenting cells; BBB: blood-brain barrier; CSF: cerebrospinal fluid; CNS: central nervous system; DCs: dendritic cells; EAE: experimental autoimmune encephalomyelitis; ER: endoplasmic reticulum; LAP: LC3-associated phagocytosis; MS: multiple sclerosis; NCA: non-canonical autophagy; OCBs: oligoclonal bands; PBMCs: peripheral blood mononuclear cells; PD: Parkinson disease; ROS: reactive oxygen species; UPR: unfolded protein response.}, }
@article {pmid37710261, year = {2023}, author = {Zeng, Q and Wang, K and Liu, WX and Zeng, JZ and Li, XL and Zhang, QF and Ren, SQ and Xu, WM}, title = {Efficacy of high-fidelity simulation in advanced life support training: a systematic review and meta-analysis of randomized controlled trials.}, journal = {BMC medical education}, volume = {23}, number = {1}, pages = {664}, pmid = {37710261}, issn = {1472-6920}, support = {2023NSFSC1475//Sichuan Province Science and Technology Support Program/ ; 2023-207//Health Commission of Sichuan Province/ ; 2021ZX01//Sichuan Provincial People's Hospital/ ; KLET-202104//Ministry of Education Hainan Medical University/ ; R2021012//Peking Union Medical Foundation/ ; }, mesh = {Humans ; Computer Simulation ; Educational Status ; *High Fidelity Simulation Training ; Randomized Controlled Trials as Topic ; }, abstract = {BACKGROUND: Simulation is an increasingly used novel method for the education of medical professionals. This study aimed to systematically review the efficacy of high-fidelity (HF) simulation compared with low-fidelity (LF) simulation or no simulation in advanced life support (ALS) training.<br><br>METHODS: A comprehensive search of the PubMed, Chinese Biomedicine Database, Embase, CENTRAL, ISI, and China Knowledge Resource Integrated Database was performed to identify randomized controlled trials (RCTs) that evaluated the use of HF simulation in ALS training. Quality assessment was based on the Cochrane Handbook for Systematic Reviews of Interventions version 5.0.1. The primary outcome was the improvement of knowledge and skill performance. The secondary outcomes included the participants' confidence and satisfaction at the course conclusion, skill performance at one year, skill performance in actual resuscitation, and patient outcomes. Data were synthesized using the RevMan 5.4 software.<br><br>RESULTS: Altogether, 25 RCTs with a total of 1,987 trainees were included in the meta-analysis. In the intervention group, 998 participants used HF manikins, whereas 989 participants received LF simulation-based or traditional training (classical training without simulation). Pooled data from the RCTs demonstrated a benefit in improvement of knowledge [standardized mean difference (SMD)&#x2009;=&#x2009;0.38; 95% confidence interval (CI): 0.18-0.59, P&#x2009;=&#x2009;0.0003, I[2]&#x2009;=&#x2009;70%] and skill performance (SMD&#x2009;=&#x2009;0.63; 95% CI: 0.21-1.04, P&#x2009;=&#x2009;0.003, I[2]&#x2009;=&#x2009;92%) for HF simulation when compared with LF simulation and traditional training. The subgroup analysis revealed a greater benefit in knowledge with HF simulation compared with traditional training at the course conclusion (SMD&#x2009;=&#x2009;0.51; 95% CI: 0.20-0.83, P&#x2009;=&#x2009;0.003, I[2]&#x2009;=&#x2009;61%). Studies measuring knowledge at three months, skill performance at one year, teamwork behaviors, participants' satisfaction and confidence demonstrated no significant benefit for HF simulation.<br><br>CONCLUSIONS: Learners using HF simulation more significantly benefited from the ALS training in terms of knowledge and skill performance at the course conclusion. However, further research is necessary to enhance long-term retention of knowledge and skill in actual resuscitation and patient's outcomes.}, }
@article {pmid37709948, year = {2023}, author = {Goutman, SA and Savelieff, MG and Jang, DG and Hur, J and Feldman, EL}, title = {The amyotrophic lateral sclerosis exposome: recent advances and future directions.}, journal = {Nature reviews. Neurology}, volume = {19}, number = {10}, pages = {617-634}, pmid = {37709948}, issn = {1759-4766}, support = {R01 TS000327/TS/ATSDR CDC HHS/United States ; K23 ES027221/ES/NIEHS NIH HHS/United States ; R01 ES030049/ES/NIEHS NIH HHS/United States ; R01 NS120926/NS/NINDS NIH HHS/United States ; R01 NS127188/NS/NINDS NIH HHS/United States ; R01 TS000289/TS/ATSDR CDC HHS/United States ; R01TS000289/ACL/ACL HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/etiology/genetics ; *Exposome ; Environmental Exposure/adverse effects ; Mutation ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal disease of motor neuron degeneration with typical survival of only 2-5 years from diagnosis. The causes of ALS are multifactorial: known genetic mutations account for only around 70% of cases of familial ALS and 15% of sporadic cases, and heritability estimates range from 8% to 61%, indicating additional causes beyond genetics. Consequently, interest has grown in environmental contributions to ALS risk and progression. The gene-time-environment hypothesis posits that ALS onset occurs through an interaction of genes with environmental exposures during ageing. An alternative hypothesis, the multistep model of ALS, suggests that several hits, at least some of which could be environmental, are required to trigger disease onset, even in the presence of highly penetrant ALS-associated mutations. Studies have sought to characterize the ALS exposome - the lifetime accumulation of environmental exposures that increase disease risk and affect progression. Identifying the full scope of environmental toxicants that enhance ALS risk raises the prospect of preventing disease by eliminating or mitigating exposures. In this Review, we summarize the evidence for an ALS exposome, discussing the strengths and limitations of epidemiological studies that have identified contributions from various sources. We also consider potential mechanisms of exposure-mediated toxicity and suggest future directions for ALS exposome research.}, }
@article {pmid37706096, year = {2023}, author = {Stipa, G and Ancidoni, A and Vanacore, N and Bellomo, G}, title = {Raw Water and ALS: A Unifying Hypothesis for the Environmental Agents Involved in ALS.}, journal = {Annals of neurosciences}, volume = {30}, number = {2}, pages = {124-132}, pmid = {37706096}, issn = {0972-7531}, abstract = {Different studies identified the presence of several altered genes in familial and sporadic amyotrophic lateral sclerosis (ALS) forms. The experimental data, together with the epidemiological data, would seem to suggest the existence of molecular mechanisms (e.g., axonal transport) related to these genes, together with a susceptibility of the same genes to certain environmental factors that would therefore suggest an impact of the environment on the etiopathogenesis of ALS. In our review, we considered the most relevant environmental clusters around the world, collecting different hypotheses and underlining common environmental factors among the different clusters. Moreover, further epidemiological data identified a higher risk of ALS in professional athletes and, in particular, in soccer and football players. Despite this increased risk of ALS highlighted by the epidemiological evidence in aforementioned sports, the mechanisms remain unclear. At last, the use of raw water has been associated with ALS risk. The aim of the present review is to characterize a possible relationship between these clusters, to be explored in the context of the interaction between genetic and environmental factors on the etiopathogenesis of ALS.}, }
@article {pmid37697342, year = {2023}, author = {Li, Z and Wang, X and Wang, X and Yi, X and Wong, YK and Wu, J and Xie, F and Hu, D and Wang, Q and Wang, J and Zhong, T}, title = {Research progress on the role of extracellular vesicles in neurodegenerative diseases.}, journal = {Translational neurodegeneration}, volume = {12}, number = {1}, pages = {43}, pmid = {37697342}, issn = {2047-9158}, mesh = {Humans ; *Neurodegenerative Diseases/diagnosis/therapy ; *Extracellular Vesicles ; *Alzheimer Disease ; *Parkinson Disease ; *Amyotrophic Lateral Sclerosis ; }, abstract = {Neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease, affect millions of people worldwide. Tremendous efforts have been put into disease-related research, but few breakthroughs have been made in diagnostic and therapeutic approaches. Extracellular vesicles (EVs) are heterogeneous cell-derived membrane structures that arise from the endosomal system or are directly separated from the plasma membrane. EVs contain many biomolecules, including proteins, nucleic acids, and lipids, which can be transferred between different cells, tissues, or organs, thereby regulating cross-organ communication between cells during normal and pathological processes. Recently, EVs have been shown to participate in various aspects of neurodegenerative diseases. Abnormal secretion and levels of EVs are closely related to the pathogenesis of neurodegenerative diseases and contribute to disease progression. Numerous studies have proposed EVs as therapeutic targets or biomarkers for neurodegenerative diseases. In this review, we summarize and discuss the advanced research progress on EVs in the pathological processes of several neurodegenerative diseases. Moreover, we outline the latest research on the roles of EVs in neurodegenerative diseases and their therapeutic potential for the diseases.}, }
@article {pmid37694369, year = {2023}, author = {Verde, F and Aiello, EN and Adobbati, L and Poletti, B and Solca, F and Tiloca, C and Sangalli, D and Maranzano, A and Muscio, C and Ratti, A and Zago, S and Ticozzi, N and Frisoni, GB and Silani, V}, title = {Coexistence of Amyotrophic Lateral Sclerosis and Alzheimer's Disease: Case Report and Review of the Literature.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {95}, number = {4}, pages = {1383-1399}, doi = {10.3233/JAD-230562}, pmid = {37694369}, issn = {1875-8908}, mesh = {Humans ; Female ; Male ; *Amyotrophic Lateral Sclerosis/complications/diagnosis/genetics ; *Alzheimer Disease/diagnosis/diagnostic imaging ; *Cognitive Dysfunction/complications ; Brain/diagnostic imaging ; *Frontotemporal Dementia/complications/diagnostic imaging/genetics ; }, abstract = {We describe a case of amyotrophic lateral sclerosis (ALS) associated with Alzheimer's disease (AD) and review the literature about the coexistence of the two entities, highlighting the following: mean age at onset is 63.8 years, with slight female predominance; ALS tends to manifest after cognitive impairment and often begins in the bulbar region; average disease duration is 3 years; cognitive phenotype is mostly amnestic; the pattern of brain involvement is, in most cases, consistent with AD. Our case and the reviewed ones suggest that patients with ALS and dementia lacking unequivocal features of FTD should undergo additional examinations in order to recognize AD.}, }
@article {pmid37692101, year = {2023}, author = {Stansberry, WM and Pierchala, BA}, title = {Neurotrophic factors in the physiology of motor neurons and their role in the pathobiology and therapeutic approach to amyotrophic lateral sclerosis.}, journal = {Frontiers in molecular neuroscience}, volume = {16}, number = {}, pages = {1238453}, pmid = {37692101}, issn = {1662-5099}, support = {R01 NS089585/NS/NINDS NIH HHS/United States ; }, abstract = {The discovery of the neurotrophins and their potent survival and trophic effects led to great enthusiasm about their therapeutic potential to rescue dying neurons in neurodegenerative diseases. The further discovery that brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF) and glial cell line-derived neurotrophic factor (GDNF) had potent survival-promoting activity on motor neurons led to the proposal for their use in motor neuron diseases such as amyotrophic lateral sclerosis (ALS). In this review we synthesize the literature pertaining to the role of NGF, BDNF, CNTF and GDNF on the development and physiology of spinal motor neurons, as well as the preclinical studies that evaluated their potential for the treatment of ALS. Results from the clinical trials of these molecules will also be described and, with the aid of decades of hindsight, we will discuss what can reasonably be concluded and how this information can inform future clinical development of neurotrophic factors for ALS.}, }
@article {pmid37691335, year = {2023}, author = {Corcoran, J and Kluger, BM}, title = {Prognosis in chronic progressive neurologic disease: a narrative review.}, journal = {Annals of palliative medicine}, volume = {12}, number = {5}, pages = {952-962}, doi = {10.21037/apm-22-1338}, pmid = {37691335}, issn = {2224-5839}, mesh = {Humans ; *Parkinson Disease/diagnosis/therapy ; *Nervous System Diseases ; Prognosis ; Palliative Care ; Chronic Disease ; *Dementia ; }, abstract = {BACKGROUND AND OBJECTIVE: Prognostication is the process of predicting a patient's likely outcome from their medical condition, and consists of determining both how well and how long a patient may live. There are few disease-specific prognostic tools to estimate a patient's individualized prognosis in terms of symptom burden and mortality. Here we summarize relevant literature on prognosis in four progressive neurologic diseases-dementia, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis-as well as on best practices on communicating prognosis with patients and care partners.<br><br>METHODS: We conducted a PubMed search for terms including "prognosis", "mortality" and "prognostic indicators" in addition to specific diseases, and for terms including "prognosis AND communication". Only English-language papers were included in this review. The time frame of our literature search was 1965 through March 1, 2023.<br><br>KEY CONTENT AND FINDINGS: There is some literature to help clinicians in predicting disease progression and survival. These include both general factors (e.g., age, medical co-morbidities) and disease-specific factors (e.g., postural instability in Parkinson's disease). There is also literature on communication of prognosis in neurologic and non-neurologic disease which demonstrates that many patients and care partners prefer to hear prognosis early after diagnosis and to have prognosis discussed as a roadmap of disease.<br><br>CONCLUSIONS: More work is needed to develop tools for individualized prognostication and communication for patients with neurologic disease. While there is limited literature on disease-specific prognostic models, existing literature combined with palliative care approaches may improve prognostic guidance for patients.}, }
@article {pmid37691199, year = {2024}, author = {Bhat, MA and Dhaneshwar, S}, title = {Neurodegenerative Diseases: New Hopes and Perspectives.}, journal = {Current molecular medicine}, volume = {24}, number = {8}, pages = {1004-1032}, pmid = {37691199}, issn = {1875-5666}, mesh = {Humans ; *Neurodegenerative Diseases/therapy/pathology ; Animals ; }, abstract = {Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis, Huntington's disease, and Friedrich ataxia are all incurable neurodegenerative diseases defined by the continuous progressive loss of distinct neuronal subtypes. Despite their rising prevalence among the world's ageing population, fewer advances have been made in the concurrent massive efforts to develop newer drugs. Recently, there has been a shift in research focus towards the discovery of new therapeutic agents for neurodegenerative diseases. In this review, we have summarized the recently developed therapies and their status in the management of neurodegenerative diseases.}, }
@article {pmid37689642, year = {2023}, author = {Bustamante-Barrientos, FA and Luque-Campos, N and Araya, MJ and Lara-Barba, E and de Solminihac, J and Pradenas, C and Molina, L and Herrera-Luna, Y and Utreras-Mendoza, Y and Elizondo-Vega, R and Vega-Letter, AM and Luz-Crawford, P}, title = {Mitochondrial dysfunction in neurodegenerative disorders: Potential therapeutic application of mitochondrial transfer to central nervous system-residing cells.}, journal = {Journal of translational medicine}, volume = {21}, number = {1}, pages = {613}, pmid = {37689642}, issn = {1479-5876}, mesh = {Humans ; Mitochondria ; *Neurodegenerative Diseases/therapy ; *Alzheimer Disease ; *Parkinson Disease ; Central Nervous System ; }, abstract = {Mitochondrial dysfunction is reiteratively involved in the pathogenesis of diverse neurodegenerative diseases. Current in vitro and in vivo approaches support that mitochondrial dysfunction is branded by several molecular and cellular defects, whose impact at different levels including the calcium and iron homeostasis, energetic balance and/or oxidative stress, makes it difficult to resolve them collectively given their multifactorial nature. Mitochondrial transfer offers an overall solution since it contains the replacement of damage mitochondria by healthy units. Therefore, this review provides an introducing view on the structure and energy-related functions of mitochondria as well as their dynamics. In turn, we summarize current knowledge on how these features are deregulated in different neurodegenerative diseases, including frontotemporal dementia, multiple sclerosis, amyotrophic lateral sclerosis, Friedreich ataxia, Alzheimer´s disease, Parkinson´s disease, and Huntington's disease. Finally, we analyzed current advances in mitochondrial transfer between diverse cell types that actively participate in neurodegenerative processes, and how they might be projected toward developing novel therapeutic strategies.}, }
@article {pmid37689321, year = {2023}, author = {Donini, L and Tanel, R and Zuccarino, R and Basso, M}, title = {Protein biomarkers for the diagnosis and prognosis of Amyotrophic Lateral Sclerosis.}, journal = {Neuroscience research}, volume = {197}, number = {}, pages = {31-41}, doi = {10.1016/j.neures.2023.09.002}, pmid = {37689321}, issn = {1872-8111}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/metabolism ; Prognosis ; Biomarkers ; Disease Progression ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is the most common motor neuron disease, still incurable. The disease is highly heterogenous both genetically and phenotypically. Therefore, developing efficacious treatments is challenging in many aspects because it is difficult to predict the rate of disease progression and stratify the patients to minimize statistical variability in clinical studies. Moreover, there is a lack of sensitive measures of therapeutic effect to assess whether a pharmacological intervention ameliorates the disease. There is also urgency of markers that reflect a molecular mechanism dysregulated by ALS pathology and can be rescued when a treatment relieves the condition. Here, we summarize and discuss biomarkers tested in multicentered studies and across different laboratories like neurofilaments, the most used marker in ALS clinical studies, neuroinflammatory-related proteins, p75[ECD], p-Tau/t-Tau, and UCHL1. We also explore the applicability of muscle proteins and extracellular vesicles as potential biomarkers.}, }
@article {pmid37688751, year = {2023}, author = {Khakha, N and Khan, H and Kaur, A and Singh, TG}, title = {Therapeutic implications of phosphorylation- and dephosphorylation-dependent factors of cAMP-response element-binding protein (CREB) in neurodegeneration.}, journal = {Pharmacological reports : PR}, volume = {75}, number = {5}, pages = {1152-1165}, pmid = {37688751}, issn = {2299-5684}, mesh = {Animals ; *Alzheimer Disease/drug therapy ; Cyclic AMP Response Element-Binding Protein/metabolism ; *Neurodegenerative Diseases/drug therapy/genetics ; Phosphorylation ; Response Elements ; Humans ; }, abstract = {Neurodegeneration is a condition of the central nervous system (CNS) characterized by loss of neural structures and function. The most common neurodegenerative disorders (NDDs) include Alzheimer's disease (AD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), multiple sclerosis (MS), motor neuron disorders, psychological disorders, dementia with vascular dementia (VaD), Lewy body dementia (DLB), epilepsy, cerebral ischemia, mental illness, and behavioral disorders. CREB (cAMP-response element-binding protein) represent a nuclear protein that regulates gene transcriptional activity. The primary focus of the review pertains to the exploration of CREB expression and activation within the context of neurodegenerative diseases, specifically in relation to the phosphorylation and dephosphorylation events that occur within the CREB signaling pathway under normal physiological conditions. The findings mentioned have contributed to the elucidation of the regulatory mechanisms governing CREB activity. Additionally, they have provided valuable insights into the potential mediation of diverse biological processes, such as memory consolidation and neuroprotective effects, by various related studies. The promotion of synaptic plasticity and neurodevelopment in the central nervous system through the targeting of CREB proteins has the potential to contribute to the prevention or delay of the onset of neurodegenerative disorders. Multiple drugs have been found to initiate downstream signaling pathways, leading to neuroprotective advantages in both animal model studies and clinical trials. The clinical importance of the cAMP-response element-binding protein (CREB) is examined in this article, encompassing its utility as both a predictive/prognostic marker and a target for therapeutic interventions.}, }
@article {pmid37686737, year = {2023}, author = {Zhou, J and Zhang, W and Cao, Z and Lian, S and Li, J and Nie, J and Huang, Y and Zhao, K and He, J and Liu, C}, title = {Association of Selenium Levels with Neurodegenerative Disease: A Systemic Review and Meta-Analysis.}, journal = {Nutrients}, volume = {15}, number = {17}, pages = {}, pmid = {37686737}, issn = {2072-6643}, support = {81903294//National Natural Science Foundation of China/ ; 202102020120//Guangzhou Basic and Applied Basic Research Foundation/ ; A2022080//Medical Scientific Research Foundation of Guangdong Province of China/ ; }, mesh = {Humans ; *Selenium ; *Neurodegenerative Diseases ; *Alzheimer Disease ; *Amyotrophic Lateral Sclerosis ; Databases, Factual ; }, abstract = {BACKGROUND: Neurodegenerative diseases (NDs) have posed significant challenges to public health, and it is crucial to understand their mechanisms in order to develop effective therapeutic strategies. Recent studies have highlighted the potential role of selenium in ND pathogenesis, as it plays a vital role in maintaining cellular homeostasis and preventing oxidative damage. However, a comprehensive analysis of the association between selenium and NDs is still lacking.<br><br>METHOD: Five public databases, namely PubMed, Web of Science, EMBASE, Cochrane and Clinical Trials, were searched in our research. Random model effects were chosen, and Higgins inconsistency analyses (I[2]), Cochrane's Q test and Tau2 were calculated to evaluate the heterogeneity.<br><br>RESULT: The association of selenium in ND patients with Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD) was studied. A statistically significant relationship was only found for AD patients (SMD = -0.41, 95% CI (-0.64, -0.17), p < 0.001), especially for erythrocytes. However, no significant relationship was observed in the analysis of the other four diseases.<br><br>CONCLUSION: Generally, this meta-analysis indicated that AD patients are strongly associated with lower selenium concentrations compared with healthy people, which may provide a clinical reference in the future. However, more studies are urgently needed for further study and treatment of neurodegenerative diseases.}, }
@article {pmid37681887, year = {2023}, author = {Vasconcelos, CFM and Ribas, VT and Petrs-Silva, H}, title = {Shared Molecular Pathways in Glaucoma and Other Neurodegenerative Diseases: Insights from RNA-Seq Analysis and miRNA Regulation for Promising Therapeutic Avenues.}, journal = {Cells}, volume = {12}, number = {17}, pages = {}, pmid = {37681887}, issn = {2073-4409}, mesh = {Humans ; *Neurodegenerative Diseases/genetics/therapy ; RNA-Seq ; Homeostasis ; *Glaucoma/genetics/therapy ; *MicroRNAs/genetics ; }, abstract = {Advances in RNA-sequencing technologies have led to the identification of molecular biomarkers for several diseases, including neurodegenerative diseases, such as Alzheimer's, Parkinson's, Huntington's diseases and Amyotrophic Lateral Sclerosis. Despite the nature of glaucoma as a neurodegenerative disorder with several similarities with the other above-mentioned diseases, transcriptional data about this disease are still scarce. microRNAs are small molecules (~17-25 nucleotides) that have been found to be specifically expressed in the CNS as major components of the system regulating the development signatures of neurodegenerative diseases and the homeostasis of the brain. In this review, we sought to identify similarities between the functional mechanisms and the activated pathways of the most common neurodegenerative diseases, as well as to discuss how those mechanisms are regulated by miRNAs, using RNA-Seq as an approach to compare them. We also discuss therapeutically suitable applications for these disease hallmarks in clinical future studies.}, }
@article {pmid37680538, year = {2023}, author = {Dunn, E and Zhang, B and Sahota, VK and Augustin, H}, title = {Potential benefits of medium chain fatty acids in aging and neurodegenerative disease.}, journal = {Frontiers in aging neuroscience}, volume = {15}, number = {}, pages = {1230467}, pmid = {37680538}, issn = {1663-4365}, abstract = {Neurodegenerative diseases are a large class of neurological disorders characterized by progressive dysfunction and death of neurones. Examples include Alzheimer's disease, Parkinson's disease, frontotemporal dementia, and amyotrophic lateral sclerosis. Aging is the primary risk factor for neurodegeneration; individuals over 65 are more likely to suffer from a neurodegenerative disease, with prevalence increasing with age. As the population ages, the social and economic burden caused by these diseases will increase. Therefore, new therapies that address both aging and neurodegeneration are imperative. Ketogenic diets (KDs) are low carbohydrate, high-fat diets developed initially as an alternative treatment for epilepsy. The classic ketogenic diet provides energy via long-chain fatty acids (LCFAs); naturally occurring medium chain fatty acids (MCFAs), on the other hand, are the main components of the medium-chain triglyceride (MCT) ketogenic diet. MCT-based diets are more efficient at generating the ketone bodies that are used as a secondary energy source for neurones and astrocytes. However, ketone levels alone do not closely correlate with improved clinical symptoms. Recent findings suggest an alternative mode of action for the MCFAs, e.g., via improving mitochondrial biogenesis and glutamate receptor inhibition. MCFAs have been linked to the treatment of both aging and neurodegenerative disease via their effects on metabolism. Through action on multiple disease-related pathways, MCFAs are emerging as compounds with notable potential to promote healthy aging and ameliorate neurodegeneration. MCFAs have been shown to stimulate autophagy and restore mitochondrial function, which are found to be disrupted in aging and neurodegeneration. This review aims to provide insight into the metabolic benefits of MCFAs in neurodegenerative disease and healthy aging. We will discuss the use of MCFAs to combat dysregulation of autophagy and mitochondrial function in the context of "normal" aging, Parkinson's disease, amyotrophic lateral sclerosis and Alzheimer's disease.}, }
@article {pmid37679883, year = {2024}, author = {de Boer, EMJ and Demaegd, KC and de Bie, CI and Veldink, JH and van den Berg, LH and van Es, MA}, title = {Familial motor neuron disease: co-occurrence of PLS and ALS (-FTD).}, journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration}, volume = {25}, number = {1-2}, pages = {53-60}, doi = {10.1080/21678421.2023.2255621}, pmid = {37679883}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/epidemiology/genetics ; *Frontotemporal Dementia/genetics ; Prospective Studies ; *Motor Neuron Disease/epidemiology/genetics/pathology ; *Muscular Atrophy, Spinal/epidemiology/genetics ; }, abstract = {OBJECTIVE: To report the frequency and characteristics of patients diagnosed with primary lateral sclerosis (PLS) with a positive family history for motor neuron diseases (MND) in the Netherlands and to compare our findings to the literature.<br><br>METHODS: Patients were identified through our ongoing, prospective population-based study on MND in The Netherlands, which also includes a standardized collection of patient characteristics, genetic testing, and family history. Only patients meeting the latest consensus criteria for definite PLS were included. The family history was considered positive for MND if any family members had been diagnosed with PLS, amyotrophic lateral sclerosis (ALS)(-FTD), or progressive muscular atrophy (PMA). Additionally, the literature was reviewed on PLS cases in which MND co-occurred within the same family.<br><br>RESULTS: We identified 392 definite PLS cases, resulting in 9 families with a PLS patient and a positive family history for MND (2.3%). In only one of these pedigrees, a pathogenic variant (C9orf72 repeat expansion) was found. Our literature review revealed 23 families with a co-occurrence of PLS and MND, with 12 of them having a potentially pathogenic genetic variant.<br><br>CONCLUSIONS: The consistent observation of PLS patients with a positive family history for MND, evident in both our study and the literature, implies the presence of shared underlying genetic factors between PLS and ALS. However, these factors are yet to be elucidated.}, }
@article {pmid37679738, year = {2023}, author = {Birkeli, CN and Normand, C and Rø, KI and Kvernenes, M}, title = {Educational supervision in internal medicine residency training - a scoping review.}, journal = {BMC medical education}, volume = {23}, number = {1}, pages = {644}, pmid = {37679738}, issn = {1472-6920}, mesh = {Humans ; *Internship and Residency ; Educational Status ; Learning ; *Mentoring ; Internal Medicine ; }, abstract = {BACKGROUND: Although supervision is an important part of residency training, its scope and how it relates to other types of support, such as mentoring, precepting and feedback, remain unclear. While clinical supervision consists of ongoing instructions and feedback in the workplace setting, educational supervision is a formalized component of postgraduate medical educational and supports the process that facilitates a trainee's progression throughout their training. Since medical specialties have different supervisory traditions, this study focuses on educational supervision in internal medicine. Our aim was to investigate what is known about educational supervision practices in internal medicine and the role of educational supervision in supporting residents' learning.<br><br>METHODS: We conducted a scoping review of the literature on educational supervision in residency training in internal medicine based on Levac et al.'s modification of Arksey and O'Malley's six-step framework. The literature search was performed in the following databases: Medline, Embase, Web of Science and the Educational Resources Information Center. In addition, we conducted a handsearch in Medical Teacher and Google Scholar. We followed the PRISMA guidelines for systematic research.<br><br>RESULTS: Eighteen of the 3,284 identified articles were included in the analysis. We found few empirical studies describing how educational supervision is conducted and what effect routine educational supervision has on residents' learning. Our findings suggest that the terminology can be confusing and that educational supervision practices in internal medicine has a weak theoretical foundation.<br><br>CONCLUSION: The distinction between educational supervision and other support structures, such as mentoring and feedback, has not been clearly defined in the research literature. We argue that shared terminology is needed to better understand current educational practices and to facilitate clear communication about how to help residents learn.}, }
@article {pmid37671427, year = {2023}, author = {Gastelum, S and Michael, AF and Bolger, TA}, title = {Saccharomyces cerevisiae as a research tool for RNA-mediated human disease.}, journal = {Wiley interdisciplinary reviews. RNA}, volume = {}, number = {}, pages = {e1814}, doi = {10.1002/wrna.1814}, pmid = {37671427}, issn = {1757-7012}, support = {R01 GM136827/GM/NIGMS NIH HHS/United States ; GM136827/GM/NIGMS NIH HHS/United States ; }, abstract = {The budding yeast, Saccharomyces cerevisiae, has been used for decades as a powerful genetic tool to study a broad spectrum of biological topics. With its ease of use, economic utility, well-studied genome, and a highly conserved proteome across eukaryotes, it has become one of the most used model organisms. Due to these advantages, it has been used to study an array of complex human diseases. From broad, complex pathological conditions such as aging and neurodegenerative disease to newer uses such as SARS-CoV-2, yeast continues to offer new insights into how cellular processes are affected by disease and how affected pathways might be targeted in therapeutic settings. At the same time, the roles of RNA and RNA-based processes have become increasingly prominent in the pathology of many of these same human diseases, and yeast has been utilized to investigate these mechanisms, from aberrant RNA-binding proteins in amyotrophic lateral sclerosis to translation regulation in cancer. Here we review some of the important insights that yeast models have yielded into the molecular pathology of complex, RNA-based human diseases. This article is categorized under: RNA in Disease and Development > RNA in Disease.}, }
@article {pmid37666602, year = {2023}, author = {Chen, X and Ma, Y and Huang, M and Li, W and Zeng, D and Li, J and Wang, Y}, title = {Multiple herbicide resistance in a Cyperus difformis population in rice field from China.}, journal = {Pesticide biochemistry and physiology}, volume = {195}, number = {}, pages = {105576}, doi = {10.1016/j.pestbp.2023.105576}, pmid = {37666602}, issn = {1095-9939}, mesh = {*Oryza/genetics ; *2-Methyl-4-chlorophenoxyacetic Acid ; *Cyperus ; Herbicide Resistance/genetics ; China ; ATP-Binding Cassette Transporters ; *Acetolactate Synthase/genetics ; *Herbicides/pharmacology ; Indoleacetic Acids ; }, abstract = {Herbicide resistance is rapidly emerging in Cyperus difformis in rice fields across China. The response of a C. difformis population GX-35 was tested against five acetolactate synthase (ALS)-inhibiting herbicides, auxin herbicide MCPA and photosynthesis II (PSII)-inhibitor bentazone. Population GX-35 evolved multiple resistance to ALS-inhibiting herbicides (penoxsulam, bispyribac‑sodium, pyrazosulfuron-ethyl, halosulfuron-methly and imazapic) and auxin herbicide MCPA, with resistance levels of 140-, 1253-, 578-, 18-, 13-, and 21-fold, respectively, compared to the susceptible population. In this population, ALS gene expression was similar to that of the susceptible population. However, an Asp376Glu mutation in ALS gene was observed, leading to reduced inhibition of in-vitro ALS activities by five ALS-inhibiting herbicides. Furthermore, CYP71D8, CYP77A3, CYP78A5 and three ABC transporter genes (cluster-14412.23067, cluster-14412.25321, and cluster-14412.24716) over-expressed in absence of penoxsulam. On the other hand, an UGT73C1 and an ABC transporter (cluster-14412.25038) were induced by penoxsulam. Additionally, both over-expression and induction were observed for CYP74, CYP71A1, UGT88A1 and an ABC transporter (cluster-14412.21723). The GX-35 population has indeed evolved multiple herbicide resistance in China. Therefore, a diverse range of weed control tactics should be implemented in rice field.}, }
@article {pmid37666564, year = {2023}, author = {Odland, ML and Abdul-Latif, AM and Ignatowicz, A and Bekele, A and Chu, K and Howard, A and Tabiri, S and Byiringiro, JC and Davies, J and , }, title = {Governance for injury care systems in Ghana, South Africa and Rwanda: development and pilot testing of an assessment tool.}, journal = {BMJ open}, volume = {13}, number = {9}, pages = {e074088}, pmid = {37666564}, issn = {2044-6055}, support = {130036/DH_/Department of Health/United Kingdom ; }, mesh = {Humans ; Ghana ; Rwanda ; South Africa ; Africa, Northern ; *Consensus ; }, abstract = {OBJECTIVES: This study aims to evaluate health systems governance for injury care in three sub-Saharan countries from policymakers' and injury care providers' perspectives.<br><br>SETTING: Ghana, Rwanda and South Africa.<br><br>DESIGN: Based on Siddiqi et al's framework for governance, we developed an online assessment tool for health system governance for injury with 37 questions covering health policy and implementation under 10 overarching principles of strategic vision, participation and consensus orientation, rule of law, transparency, responsiveness of institutions, equity, effectiveness or efficiency, accountability, ethics and intelligence and information. A literature review was also done to support the scoring. We derived scores using two methods-investigator scores and respondent scores.<br><br>PARTICIPANTS: The tool was sent out to purposively selected stakeholders, including policymakers and injury care providers in Ghana, Rwanda and South Africa. Data were collected between October 2020 and February 2021.<br><br>Investigator-weighted and respondent percentage scores for health system governance for injury care. This was calculated for each country in total and per principle.<br><br>RESULTS: Rwanda had the highest overall investigator-weighted percentage score (70%), followed by South Africa (59%). Ghana had the lowest overall investigator score (48%). The overall results were similar for the respondent scores. Some areas, such as participation and consensus, scored high in all three countries, while other areas, such as transparency, scored very low.<br><br>CONCLUSION: In this multicountry governance survey, we provide insight into and evaluation of health system governance for trauma in three low- and middle-income countries (LMICs) in sub-Saharan Africa. It highlights areas of improvement that need to be prioritised, such as transparency, to meet the high burden of trauma and injuries in LMICs.}, }
@article {pmid37664456, year = {2023}, author = {Garodia, P and Hegde, M and Kunnumakkara, AB and Aggarwal, BB}, title = {Curcumin, inflammation, and neurological disorders: How are they linked?.}, journal = {Integrative medicine research}, volume = {12}, number = {3}, pages = {100968}, pmid = {37664456}, issn = {2213-4220}, abstract = {BACKGROUND: Despite the extensive research in recent years, the current treatment modalities for neurological disorders are suboptimal. Curcumin, a polyphenol found in Curcuma genus, has been shown to mitigate the pathophysiology and clinical sequalae involved in neuroinflammation and neurodegenerative diseases.<br><br>METHODS: We searched PubMed database for relevant publications on curcumin and its uses in treating neurological diseases. We also reviewed relevant clinical trials which appeared on searching PubMed database using 'Curcumin and clinical trials'.<br><br>RESULTS: This review details the pleiotropic immunomodulatory functions and neuroprotective properties of curcumin, its derivatives and formulations in various preclinical and clinical investigations. The effects of curcumin on neurodegenerative diseases such as Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), brain tumors, epilepsy, Huntington's disorder (HD), ischemia, Parkinson's disease (PD), multiple sclerosis (MS), and traumatic brain injury (TBI) with a major focus on associated signalling pathways have been thoroughly discussed.<br><br>CONCLUSION: This review demonstrates curcumin can suppress spinal neuroinflammation by modulating diverse astroglia mediated cascades, ensuring the treatment of neurological disorders.}, }
@article {pmid37662922, year = {2023}, author = {Cao, W and Fan, D}, title = {Neutrophils: a subgroup of neglected immune cells in ALS.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1246768}, pmid = {37662922}, issn = {1664-3224}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; Neutrophils ; *Neurodegenerative Diseases ; Motor Neurons ; Immunity, Innate ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a chronic, progressive neurodegenerative disease characterized by the loss of motor neurons. Dysregulated peripheral immunity has been identified as a hallmark of ALS. Neutrophils, as the front-line responders of innate immunity, contribute to host defense through pathogen clearance. However, they can concurrently play a detrimental role in chronic inflammation. With the unveiling of novel functions of neutrophils in neurodegenerative diseases, it becomes essential to review our current understanding of neutrophils and to recognize the gap in our knowledge about their role in ALS. Thus, a detailed comprehension of the biological processes underlying neutrophil-induced pathogenesis in ALS may assist in identifying potential cell-based therapeutic strategies to delay disease progression.}, }
@article {pmid37658972, year = {2023}, author = {Singh, S and Shukla, R}, title = {Nanovesicular-Mediated Intranasal Drug Therapy for Neurodegenerative Disease.}, journal = {AAPS PharmSciTech}, volume = {24}, number = {7}, pages = {179}, pmid = {37658972}, issn = {1530-9932}, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy ; Nose ; Drug Delivery Systems ; Brain ; *Glioblastoma ; }, abstract = {Numerous neurodegenerative conditions, such as Alzheimer's, Huntington's, Parkinson's, amyotrophic lateral sclerosis, and glioblastoma multiform are now becoming significant concerns of global health. Formulation-related issues, physiological and anatomical barriers, post-administration obstacles, physical challenges, regulatory limitations, environmental hurdles, and health and safety issues have all hindered successful delivery and effective outcomes despite a variety of treatment options. In the current review, we covered the intranasal route, an alternative strategic route targeting brain for improved delivery across the BBB. The trans-nasal pathway is non-invasive, directing therapeutics directly towards brain, circumventing the barrier and reducing peripheral exposure. The delivery of nanosized vesicles loaded with drugs was also covered in the review. Nanovesicle systems are organised in concentric bilayered lipid membranes separated with aqueous layers. These carriers surmount the disadvantages posed by intranasal delivery of rapid mucociliary clearance and enzymatic degradation, and enhance retention of drug to reach the site of target. In conclusion, the review covers in-depth conclusions on numerous aspects of formulation of drug-loaded vesicular system delivery across BBB, current marketed nasal devices, significant jeopardies, potential therapeutic aids, and current advancements followed by future perspectives.}, }
@article {pmid37657967, year = {2023}, author = {Ryan, SK and Ugalde, CL and Rolland, AS and Skidmore, J and Devos, D and Hammond, TR}, title = {Therapeutic inhibition of ferroptosis in neurodegenerative disease.}, journal = {Trends in pharmacological sciences}, volume = {44}, number = {10}, pages = {674-688}, doi = {10.1016/j.tips.2023.07.007}, pmid = {37657967}, issn = {1873-3735}, support = {MC_PC_19032/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *Ferroptosis ; *Neurodegenerative Diseases/drug therapy ; Iron ; }, abstract = {Iron accumulation has been associated with the etiology and progression of multiple neurodegenerative diseases (NDDs). The exact role of iron in these diseases is not fully understood, but an iron-dependent form of regulated cell death called ferroptosis could be key. Although there is substantial preclinical and clinical evidence that ferroptosis plays a role in NDD, there are still questions regarding how to target ferroptosis therapeutically, including which proteins to target, identification of clinically relevant biomarkers, and which patients might benefit most. Clinical trials of iron- and ferroptosis-targeted therapies are beginning to provide some answers, but there is growing interest in developing new ferroptosis inhibitors. We describe newly identified ferroptosis targets, opportunities, and challenges in NDD, as well as key considerations for progressing new therapeutics to the clinic.}, }
@article {pmid37657945, year = {2023}, author = {Cristi, AC and Rapuri, S and Coyne, AN}, title = {Nuclear pore complex and nucleocytoplasmic transport disruption in neurodegeneration.}, journal = {FEBS letters}, volume = {597}, number = {20}, pages = {2546-2566}, pmid = {37657945}, issn = {1873-3468}, support = {R00 NS123242/NS/NINDS NIH HHS/United States ; R01 NS132836/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Nuclear Pore/metabolism ; Active Transport, Cell Nucleus/physiology ; Nuclear Envelope ; Nuclear Pore Complex Proteins/genetics/metabolism ; Endosomal Sorting Complexes Required for Transport/genetics/metabolism ; *Neurodegenerative Diseases/metabolism ; }, abstract = {Nuclear pore complexes (NPCs) play a critical role in maintaining the equilibrium between the nucleus and cytoplasm, enabling bidirectional transport across the nuclear envelope, and are essential for proper nuclear organization and gene regulation. Perturbations in the regulatory mechanisms governing NPCs and nuclear envelope homeostasis have been implicated in the pathogenesis of several neurodegenerative diseases. The ESCRT-III pathway emerges as a critical player in the surveillance and preservation of well-assembled, functional NPCs, as well as nuclear envelope sealing. Recent studies have provided insights into the involvement of nuclear ESCRT-III in the selective reduction of specific nucleoporins associated with neurodegenerative pathologies. Thus, maintaining quality control of the nuclear envelope and NPCs represents a pivotal element in the pathological cascade leading to neurodegenerative diseases. This review describes the constituents of the nuclear-cytoplasmic transport machinery, encompassing the nuclear envelope, NPC, and ESCRT proteins, and how their structural and functional alterations contribute to the development of neurodegenerative diseases.}, }
@article {pmid37657764, year = {2023}, author = {Zhou, S and Zhou, Y and Zhong, W and Su, Z and Qin, Z}, title = {Involvement of protein L-isoaspartyl methyltransferase in the physiopathology of neurodegenerative diseases: Possible substrates associated with synaptic function.}, journal = {Neurochemistry international}, volume = {170}, number = {}, pages = {105606}, doi = {10.1016/j.neuint.2023.105606}, pmid = {37657764}, issn = {1872-9754}, mesh = {Humans ; *Protein D-Aspartate-L-Isoaspartate Methyltransferase/metabolism ; *Neurodegenerative Diseases/metabolism ; Proteins/metabolism ; Isoaspartic Acid/metabolism ; Aspartic Acid/metabolism ; }, abstract = {Synaptic dysfunction is a typical pathophysiologic change in neurodegenerative diseases (NDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), Hintington's disease (HD) and amyotrophic lateral sclerosis (ALS), which involves protein post-translational modifications (PTMs) including L-isoaspartate (L-isoAsp) formed by isomerization of aspartate or deamidation of asparagine. The formation of L-isoAsp could be repaired by protein L-isoaspartyl methyltransferase (PIMT). Some synaptic proteins have been identified as PIMT potential substrates and play an essential role in ensuring synaptic function. In this review, we discuss the role of certain synaptic proteins as PIMT substrates in neurodegenerative disease, thus providing therapeutic synapse-centered targets for the treatment of NDs.}, }
@article {pmid37654673, year = {2023}, author = {Fischetti, F and Poli, L and De Tommaso, M and Paolicelli, D and Greco, G and Cataldi, S}, title = {The role of exercise parameters on small extracellular vesicles and microRNAs cargo in preventing neurodegenerative diseases.}, journal = {Frontiers in physiology}, volume = {14}, number = {}, pages = {1241010}, pmid = {37654673}, issn = {1664-042X}, abstract = {Physical activity (PA), which includes exercise, can reduce the risk of developing various non-communicable diseases, including neurodegenerative diseases (NDs), and mitigate their adverse effects. However, the mechanisms underlying this ability are not yet fully understood. Among several possible mechanisms proposed, such as the stimulation of brain-derived neurotrophic factor (BDNF), endothelial nitric oxide synthase (eNOS), insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), and nerve growth factor (NGF), the possible involvement of particular vesicular structures enclosed in lipid membranes known as extracellular vesicles (EVs) has recently been investigated. These EVs would appear to exert a paracrine and systemic action through their ability to carry various molecules, particularly so-called microRNAs (miRNAs), performing a function as mediators of intercellular communication. Interestingly, EVs and miRNAs are differentially expressed following PA, but evidence on how different exercise parameters may differentially affect EVs and the miRNAs they carry is still scarce. In this review we summarized the current human findings on the effects of PA and different exercise parameters exerted on EVs and their cargo, focusing on miRNAs molecules, and discussing how this may represent one of the biological mechanisms through which exercise contributes to preventing and slowing NDs.}, }
@article {pmid37651420, year = {2023}, author = {Williams, W and Theron, E and Khan, W and Stassen, W}, title = {Developing a South African curriculum for education in neonatal critical care retrieval: An initial exploration.}, journal = {PloS one}, volume = {18}, number = {8}, pages = {e0290972}, pmid = {37651420}, issn = {1932-6203}, mesh = {Infant, Newborn ; Humans ; South Africa ; Retrospective Studies ; Educational Status ; *Curriculum ; *Critical Care ; }, abstract = {BACKGROUND: Owing to limited or centralised neonatal critical care resources, the interfacility transfer of neonates is inevitable. In many high-income settings, dedicated Critical Care Retrieval Services (CCRS) with additional education and training undertake neonatal critical care retrieval (CCR). In South Africa, however, these transfers are mostly conducted by advanced paramedics with limited education in neonatal care, and this may lead to high adverse event rates. In SA, a shortage of skilled neonatal interfacility transport services has been identified as one of the top ten avoidable causes of under-5 mortality. In order to address this gap in neonatal transfer education for paramedics in South Africa, the aim of this study is to develop a curriculum for neonatal critical care retrieval in South Africa.<br><br>METHODS: Using Kern's approach to curriculum development, a general and targeted needs assessment was conducted through semi-structured interviews with experts in the field and a focus group discussion with a prospective student group. Interviews were preceded and informed by a literature review and retrospective chart review of neonates who underwent CCR in SA over a one-year period. Audio recordings of interviews were transcribed verbatim and subjected to inductive-dominant content analysis. Finally, qualitative codes were expanded into course outcome and a curriculum map was developed.<br><br>RESULTS: Six experts in neonatal critical care and retrieval participated in semi-structured interviews with a mean duration of 59 minutes. Following transcription and analysis, 372 codes were developed. Seven prehospital providers (prospective students) who are involved in neonatal transfers in South Africa participated in a focus group discussion with a duration of 91 minutes. The audio recording was transcribed and analysed with 97 codes extracted. The main categories were: Current status of neonatal CCR in South Africa; learning and education in neonatal CCR; and proposed curriculum structure. The proposed curriculum structure described 13 broad course outcomes to be delivered as a blended postgraduate programme. Participants noted that funding, employer buy-in and internet resources would be required. The targeted prospective student group should be all Advanced Life Support (ALS) providers with a change in their scope of practice on completion.<br><br>CONCLUSION: This study described the need for additional education in neonatal critical care retrieval due to the limitations in the current and past education systems. This study provides a curriculum structure with course outcomes that can be used as a basis for the development of a complete curriculum for education in neonatal CCR, with the potential to greatly reduce adverse event rates.}, }
@article {pmid37646130, year = {2023}, author = {Pattee, GL and Genge, A and Couratier, P and Lunetta, C and Sobue, G and Aoki, M and Yoshino, H and Jackson, CE and Wymer, J and Salah, A and Nelson, S}, title = {Oral Edaravone - Introducing a Flexible Treatment Option for Amyotrophic Lateral Sclerosis.}, journal = {Expert review of neurotherapeutics}, volume = {23}, number = {10}, pages = {859-866}, doi = {10.1080/14737175.2023.2251687}, pmid = {37646130}, issn = {1744-8360}, mesh = {Humans ; Edaravone/pharmacokinetics ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Neurodegenerative Diseases/drug therapy ; Free Radical Scavengers/pharmacology ; Administration, Intravenous ; }, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a progressive and incurable neurodegenerative disease. While pharmacotherapy options remain limited, the Food and Drug Administration (FDA) approved intravenous (IV) and oral edaravone for the treatment of ALS in 2017 and 2022, respectively. With the addition of oral edaravone, patients with ALS may exclusively use oral medications.<br><br>AREAS COVERED: The authors performed a review of the published literature using the United States (US) National Library of Medicine's PubMed.gov resource to describe the pharmacokinetics, pharmacodynamics, safety, and efficacy of oral edaravone, as well as pertinent completed and ongoing clinical trials, including the oral edaravone clinical trial development program. The clinical profile of oral edaravone is also discussed.<br><br>EXPERT OPINION: Edaravone has been shown to slow the rate of motor function deterioration experienced by patients with ALS. As the oral formulation has been approved, patients with ALS may use it alone or in combination with other approved therapeutics. Additional clinical trials and real-world evidence are ongoing to gain further understanding of the clinical profile of oral edaravone.}, }
@article {pmid37642362, year = {2023}, author = {Bireley, JD and Morren, JA}, title = {CNM-Au8: an experimental agent for the treatment of amyotrophic lateral sclerosis (ALS).}, journal = {Expert opinion on investigational drugs}, volume = {32}, number = {8}, pages = {677-683}, doi = {10.1080/13543784.2023.2252738}, pmid = {37642362}, issn = {1744-7658}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; Edaravone/pharmacokinetics/therapeutic use ; *Neuroprotective Agents/pharmacology/therapeutic use ; Quality of Life ; Drugs, Investigational/therapeutic use ; }, abstract = {INTRODUCTION: Two established disease-specific therapies for the treatment of amyotrophic lateral sclerosis (ALS) are riluzole and edaravone. Limitations of these medications include minimal progression slowing or survival benefit, and effectiveness only in selected populations, particularly for edaravone. AMX0035 and tofersen received US FDA approval in September 2022 and April 2023, respectively. However, phase 3 trials, further examining both medications' efficacy, are ongoing. CNM-Au8 is an efficient catalyst of energy metabolism and is therefore a potential disease-modifying treatment for ALS, a neurodegenerative condition in which there is bioenergetics impairment.<br><br>AREAS COVERED: In this review, we provide an overview of the current ALS treatment market, followed by a description of the pharmacodynamics and pharmacokinetics of CNM-Au8. The main preclinical and available early clinical evidence of CNM-Au8 is then described, as well as its potential as an ALS treatment.<br><br>EXPERT OPINION: Oral treatment with CNM-Au8 failed to meet primary clinical and electrodiagnostic endpoints in phase 2/3 clinical trials. Despite this failure, a number of exploratory endpoints included in phase 2/3 trials suggest CNM-Au8 has the potential to significantly slow clinical worsening, improve quality of life, and prolong survival in ALS. Further study of CNM-Au8 in a phase 3 clinical trial is currently underway.}, }
@article {pmid37642165, year = {2023}, author = {Shelash Al-Hawary, SI and Yahya Ali, A and Mustafa, YF and Margiana, R and Maksuda Ilyasovna, S and Ramadan, MF and Almalki, SG and Alwave, M and Alkhayyat, S and Alsalamy, A}, title = {The microRNAs (miRs) overexpressing mesenchymal stem cells (MSCs) therapy in neurological disorders; hope or hype.}, journal = {Biotechnology progress}, volume = {39}, number = {6}, pages = {e3383}, doi = {10.1002/btpr.3383}, pmid = {37642165}, issn = {1520-6033}, mesh = {Humans ; *MicroRNAs/genetics/metabolism ; *Nervous System Diseases/genetics/therapy/metabolism ; *Mesenchymal Stem Cells/metabolism ; *Parkinson Disease/therapy ; Neurogenesis ; }, abstract = {Altered expression of multiple miRNAs was found to be extensively involved in the pathogenesis of different neurological disorders including Alzheimer's disease, Parkinson's disease, stroke, epilepsy, multiple sclerosis, amyotrophic lateral sclerosis, and Huntington's disease. One of the biggest concerns within gene-based therapy is the delivery of the therapeutic microRNAs to the intended place, which is obligated to surpass the biological barriers without undergoing degradation in the bloodstream or renal excretion. Hence, the delivery of modified and unmodified miRNA molecules using excellent vehicles is required. In this light, mesenchymal stem cells (MSCs) have attracted increasing attention. The MSCs can be genetically modified to express or overexpress a particular microRNA aimed with promote neurogenesis and neuroprotection. The current review has focused on the therapeutic capabilities of microRNAs-overexpressing MSCs to ameliorate functional deficits in neurological conditions.}, }
@article {pmid37641631, year = {2023}, author = {Fetit, R}, title = {Celebrating the life and research of BNA Past-President Colin Blakemore.}, journal = {Brain and neuroscience advances}, volume = {7}, number = {}, pages = {23982128231195514}, pmid = {37641631}, issn = {2398-2128}, abstract = {Professor Sir Colin Blakemore was a remarkable neuroscientist, persuasive communicator, and brave advocate for animal research who, sadly, passed away in June 2022 from amyotrophic lateral sclerosis. His work helped establish the concept of neuronal plasticity, which was fundamental to our understanding of the postnatal brain and continues to impact our outlook on neurodegenerative disorders. The BNA2023 Festival of Neuroscience dedicated its last plenary session in his honour, bringing together five prominent neuroscientists whose careers were shaped by Professor Blakemore. Here, we summarise the speakers' reflections on how Colin's support, generosity, and foresight influenced their academic paths, inspired their research, and changed their outlook on life.}, }
@article {pmid37641443, year = {2023}, author = {Maragakis, NJ and de Carvalho, M and Weiss, MD}, title = {Therapeutic targeting of ALS pathways: Refocusing an incomplete picture.}, journal = {Annals of clinical and translational neurology}, volume = {10}, number = {11}, pages = {1948-1971}, pmid = {37641443}, issn = {2328-9503}, support = {R01 NS117604/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology ; *Neurodegenerative Diseases ; Biomarkers ; }, abstract = {Numerous potential amyotrophic lateral sclerosis (ALS)-relevant pathways have been hypothesized and studied preclinically, with subsequent translation to clinical trial. However, few successes have been observed with only modest effects. Along with an improved but incomplete understanding of ALS as a neurodegenerative disease is the evolution of more sophisticated and diverse in vitro and in vivo preclinical modeling platforms, as well as clinical trial designs. We highlight proposed pathological pathways that have been major therapeutic targets for investigational compounds. It is likely that the failures of so many of these therapeutic compounds may not have occurred because of lack of efficacy but rather because of a lack of preclinical modeling that would help define an appropriate disease pathway, as well as a failure to establish target engagement. These challenges are compounded by shortcomings in clinical trial design, including lack of biomarkers that could predict clinical success and studies that are underpowered. Although research investments have provided abundant insights into new ALS-relevant pathways, most have not yet been developed more fully to result in clinical study. In this review, we detail some of the important, well-established pathways, the therapeutics targeting them, and the subsequent clinical design. With an understanding of some of the shortcomings in translational efforts over the last three decades of ALS investigation, we propose that scientists and clinicians may choose to revisit some of these therapeutic pathways reviewed here with an eye toward improving preclinical modeling, biomarker development, and the investment in more sophisticated clinical trial designs.}, }
@article {pmid37638324, year = {2023}, author = {Zhou, W and Xu, R}, title = {Current insights in the molecular genetic pathogenesis of amyotrophic lateral sclerosis.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1189470}, pmid = {37638324}, issn = {1662-4548}, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease that leads to the massive loss of motor neurons in cerebrum, brain stem and spinal cord. It affects not only motor neurons but also other neurons and glial cells, resulting in the progressive muscle atrophy, the severe disability and the eventual death due to the respiratory failure. The pathogenesis of ALS is not fully understood. Currently, several factors are considered to be involved in the pathogenesis of ALS, such as genetic factors, imbalances in protein homeostasis, RNA metabolism disorders, mitochondrial dysfunctions, glutamate-mediated excitatory toxicities and intra-neuronal material transport disorders in neurons. The study of genetic mutations related to ALS pathogenesis will link the molecular and cellular mechanisms of the disease, thus enhancing the understanding of its occurrence and progression, thereby providing new insights for the pathogenesis of ALS. This review summarizes the current insights in the molecular genetic pathogenesis of ALS.}, }
@article {pmid37636591, year = {2023}, author = {Jamali, AM and Kethamreddy, M and Burkett, BJ and Port, JD and Pandey, MK}, title = {PET and SPECT Imaging of ALS: An Educational Review.}, journal = {Molecular imaging}, volume = {2023}, number = {}, pages = {5864391}, pmid = {37636591}, issn = {1536-0121}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging ; Positron-Emission Tomography ; Tomography, Emission-Computed, Single-Photon ; Brain/diagnostic imaging ; Fluorodeoxyglucose F18 ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a disease leading to progressive motor degeneration and ultimately death. It is a complex disease that can take a significantly long time to be diagnosed, as other similar pathological conditions must be ruled out for a definite diagnosis of ALS. Noninvasive imaging of ALS has shed light on disease pathology and altered biochemistry in the ALS brain. Other than magnetic resonance imaging (MRI), two types of functional imaging, positron emission tomography (PET) and single photon emission computed tomography (SPECT), have provided valuable data about what happens in the brain of ALS patients compared to healthy controls. PET imaging has revealed a specific pattern of brain metabolism through [[18]F]FDG, while other radiotracers have uncovered neuroinflammation, changes in neuronal density, and protein aggregation. SPECT imaging has shown a general decrease in regional cerebral blood flow (rCBF) in ALS patients. This educational review summarizes the current state of ALS imaging with various PET and SPECT radiopharmaceuticals to better understand the pathophysiology of ALS.}, }
@article {pmid37636024, year = {2023}, author = {Nouri Nojadeh, J and Bildiren Eryilmaz, NS and Ergüder, BI}, title = {CRISPR/Cas9 genome editing for neurodegenerative diseases.}, journal = {EXCLI journal}, volume = {22}, number = {}, pages = {567-582}, pmid = {37636024}, issn = {1611-2156}, abstract = {Gene therapy has emerged as a promising therapeutic strategy for various conditions, including blood disorders, ocular disease, cancer, and nervous system disorders. The advent of gene editing techniques has facilitated the ability of researchers to specifically target and modify the eukaryotic cell genome, making it a valuable tool for gene therapy. This can be performed through either in vivo or ex vivo approaches. Gene editing tools, such as zinc finger nucleases, transcription activator-like effector nucleases, and CRISPR-Cas-associated nucleases, can be employed for gene therapy purposes. Among these tools, CRISPR-Cas-based gene editing stands out because of its ability to introduce heritable genome changes by designing short guide RNAs. This review aims to provide an overview of CRISPR-Cas technology and summarizes the latest research on the application of CRISPR/Cas9 genome editing technology for the treatment of the most prevalent neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, Amyotrophic lateral sclerosis, and Spinocerebellar ataxia.}, }
@article {pmid37633753, year = {2023}, author = {Singh, J and Habean, ML and Panicker, N}, title = {Inflammasome assembly in neurodegenerative diseases.}, journal = {Trends in neurosciences}, volume = {46}, number = {10}, pages = {814-831}, pmid = {37633753}, issn = {1878-108X}, support = {R00 AG066862/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Neurodegenerative Diseases ; Inflammasomes ; *Alzheimer Disease ; *Parkinson Disease ; *Amyotrophic Lateral Sclerosis ; }, abstract = {Neurodegenerative disorders are characterized by the progressive dysfunction and death of selectively vulnerable neuronal populations, often associated with the accumulation of aggregated host proteins. Sustained brain inflammation and hyperactivation of inflammasome complexes have been increasingly demonstrated to contribute to neurodegenerative disease progression. Here, we review molecular mechanisms leading to inflammasome assembly in neurodegeneration. We focus primarily on four degenerative brain disorders in which inflammasome hyperactivation has been well documented: Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and the spectrum of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). We discuss shared and divergent principles of inflammasome assembly across these disorders, and underscore the differences between neurodegeneration-associated inflammasome activation pathways and their peripheral-immune counterparts. We examine how aberrant assembly of inflammasome complexes may amplify pathology in neurodegeneration, including misfolded protein aggregation, and highlight prospects for neurotherapeutic interventions based on targeting inflammasome pathways.}, }
@article {pmid37631001, year = {2023}, author = {Yan, J and Bading, H}, title = {The Disruption of NMDAR/TRPM4 Death Signaling with TwinF Interface Inhibitors: A New Pharmacological Principle for Neuroprotection.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {16}, number = {8}, pages = {}, pmid = {37631001}, issn = {1424-8247}, abstract = {With the discovery that the acquisition of toxic features by extrasynaptic NMDA receptors (NMDARs) involves their physical interaction with the non-selective cation channel, TRPM4, it has become possible to develop a new pharmacological principle for neuroprotection, namely the disruption of the NMDAR/TRPM4 death signaling complex. This can be accomplished through the expression of the TwinF domain, a 57-amino-acid-long stretch of TRPM4 that mediates its interaction with NMDARs, but also using small molecule TwinF interface (TI) inhibitors, also known as NMDAR/TRPM4 interaction interface inhibitors. Both TwinF and small molecule TI inhibitors detoxify extrasynaptic NMDARs without interfering with synaptic NMDARs, which serve important physiological functions in the brain. As the toxic signaling of extrasynaptic NMDARs contributes to a wide range of neurodegenerative conditions, TI inhibitors may offer therapeutic options for currently untreatable human neurodegenerative diseases including Amyotrophic Lateral Sclerosis, Alzheimer's disease, and Huntington's disease.}, }
@article {pmid37629277, year = {2023}, author = {Fernandes, F and Barbalho, I and Bispo Júnior, A and Alves, L and Nagem, D and Lins, H and Arrais Júnior, E and Coutinho, KD and Morais, AHF and Santos, JPQ and Machado, GM and Henriques, J and Teixeira, C and Dourado Júnior, MET and Lindquist, ARR and Valentim, RAM}, title = {Digital Alternative Communication for Individuals with Amyotrophic Lateral Sclerosis: What We Have.}, journal = {Journal of clinical medicine}, volume = {12}, number = {16}, pages = {}, pmid = {37629277}, issn = {2077-0383}, support = {132/2018//Brazilian Ministry of Health/ ; 132/2018//Norte-Grandense Foundation for Research and Culture and the Federal University of Rio Grande do Norte (FUNPEC)/ ; }, abstract = {Amyotrophic Lateral Sclerosis is a disease that compromises the motor system and the functional abilities of the person in an irreversible way, causing the progressive loss of the ability to communicate. Tools based on Augmentative and Alternative Communication are essential for promoting autonomy and improving communication, life quality, and survival. This Systematic Literature Review aimed to provide evidence on eye-image-based Human-Computer Interaction approaches for the Augmentative and Alternative Communication of people with Amyotrophic Lateral Sclerosis. The Systematic Literature Review was conducted and guided following a protocol consisting of search questions, inclusion and exclusion criteria, and quality assessment, to select primary studies published between 2010 and 2021 in six repositories: Science Direct, Web of Science, Springer, IEEE Xplore, ACM Digital Library, and PubMed. After the screening, 25 primary studies were evaluated. These studies showcased four low-cost, non-invasive Human-Computer Interaction strategies employed for Augmentative and Alternative Communication in people with Amyotrophic Lateral Sclerosis. The strategies included Eye-Gaze, which featured in 36% of the studies; Eye-Blink and Eye-Tracking, each accounting for 28% of the approaches; and the Hybrid strategy, employed in 8% of the studies. For these approaches, several computational techniques were identified. For a better understanding, a workflow containing the development phases and the respective methods used by each strategy was generated. The results indicate the possibility and feasibility of developing Human-Computer Interaction resources based on eye images for Augmentative and Alternative Communication in a control group. The absence of experimental testing in people with Amyotrophic Lateral Sclerosis reiterates the challenges related to the scalability, efficiency, and usability of these technologies for people with the disease. Although challenges still exist, the findings represent important advances in the fields of health sciences and technology, promoting a promising future with possibilities for better life quality.}, }
@article {pmid37628709, year = {2023}, author = {De Marchi, F and Tondo, G and Corrado, L and Menegon, F and Aprile, D and Anselmi, M and D'Alfonso, S and Comi, C and Mazzini, L}, title = {Neuroinflammatory Pathways in the ALS-FTD Continuum: A Focus on Genetic Variants.}, journal = {Genes}, volume = {14}, number = {8}, pages = {}, pmid = {37628709}, issn = {2073-4425}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *Frontotemporal Dementia/genetics ; Neuroinflammatory Diseases ; Oxidative Stress ; Astrocytes ; Mitochondrial Proteins ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal dementia (FDT) are progressive neurodegenerative disorders that, in several cases, overlap in clinical presentation, and genetic and pathological disease mechanisms. About 10-15% of ALS cases and up to 40% of FTD are familial, usually with dominant traits. ALS and FTD, in several cases, share common gene mutations, such as in C9ORF72, TARDBP, SQSTM-1, FUS, VCP, CHCHD10, and TBK-1. Also, several mechanisms are involved in ALS and FTD pathogenesis, such as protein misfolding, oxidative stress, and impaired axonal transport. In addition, neuroinflammation and neuroinflammatory cells, such as astrocytes, oligodendrocytes, microglia, and lymphocytes and, overall, the cellular microenvironment, have been proposed as pivotal players in the pathogenesis the ALS-FTD spectrum disorders. This review overviews the current evidence regarding neuroinflammatory markers in the ALS/FTD continuum, focusing on the neuroinflammatory pathways involved in the genetic cases, moving from post-mortem reports to in vivo biofluid and neuroimaging data. We further discuss the potential link between genetic and autoimmune disorders and potential therapeutic implications.}, }
@article {pmid37627588, year = {2023}, author = {Giménez-Bejarano, A and Alegre-Cortés, E and Yakhine-Diop, SMS and Gómez-Suaga, P and Fuentes, JM}, title = {Mitochondrial Dysfunction in Repeat Expansion Diseases.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {12}, number = {8}, pages = {}, pmid = {37627588}, issn = {2076-3921}, support = {CIBERNED CB06/05/0041//Instituto de Salud Carlos III/ ; }, abstract = {Repeat expansion diseases are a group of neuromuscular and neurodegenerative disorders characterized by expansions of several successive repeated DNA sequences. Currently, more than 50 repeat expansion diseases have been described. These disorders involve diverse pathogenic mechanisms, including loss-of-function mechanisms, toxicity associated with repeat RNA, or repeat-associated non-ATG (RAN) products, resulting in impairments of cellular processes and damaged organelles. Mitochondria, double membrane organelles, play a crucial role in cell energy production, metabolic processes, calcium regulation, redox balance, and apoptosis regulation. Its dysfunction has been implicated in the pathogenesis of repeat expansion diseases. In this review, we provide an overview of the signaling pathways or proteins involved in mitochondrial functioning described in these disorders. The focus of this review will be on the analysis of published data related to three representative repeat expansion diseases: Huntington's disease, C9orf72-frontotemporal dementia/amyotrophic lateral sclerosis, and myotonic dystrophy type 1. We will discuss the common effects observed in all three repeat expansion disorders and their differences. Additionally, we will address the current gaps in knowledge and propose possible new lines of research. Importantly, this group of disorders exhibit alterations in mitochondrial dynamics and biogenesis, with specific proteins involved in these processes having been identified. Understanding the underlying mechanisms of mitochondrial alterations in these disorders can potentially lead to the development of neuroprotective strategies.}, }
@article {pmid37627315, year = {2023}, author = {Kandeel, M and Morsy, MA and Alkhodair, KM and Alhojaily, S}, title = {Mesenchymal Stem Cell-Derived Extracellular Vesicles: An Emerging Diagnostic and Therapeutic Biomolecules for Neurodegenerative Disabilities.}, journal = {Biomolecules}, volume = {13}, number = {8}, pages = {}, pmid = {37627315}, issn = {2218-273X}, mesh = {Adult ; Humans ; *Amyotrophic Lateral Sclerosis ; *Mesenchymal Stem Cells ; *Adult Stem Cells ; *Alzheimer Disease ; *Extracellular Vesicles ; *Huntington Disease ; *Multiple Sclerosis ; *Parkinson Disease/diagnosis/therapy ; }, abstract = {Mesenchymal stem cells (MSCs) are a type of versatile adult stem cells present in various organs. These cells give rise to extracellular vesicles (EVs) containing a diverse array of biologically active elements, making them a promising approach for therapeutics and diagnostics. This article examines the potential therapeutic applications of MSC-derived EVs in addressing neurodegenerative disorders such as Alzheimer's disease (AD), multiple sclerosis (MS), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD). Furthermore, the present state-of-the-art for MSC-EV-based therapy in AD, HD, PD, ALS, and MS is discussed. Significant progress has been made in understanding the etiology and potential treatments for a range of neurodegenerative diseases (NDs) over the last few decades. The contents of EVs are carried across cells for intercellular contact, which often results in the control of the recipient cell's homeostasis. Since EVs represent the therapeutically beneficial cargo of parent cells and are devoid of many ethical problems connected with cell-based treatments, they offer a viable cell-free therapy alternative for tissue regeneration and repair. Developing innovative EV-dependent medicines has proven difficult due to the lack of standardized procedures in EV extraction processes as well as their pharmacological characteristics and mechanisms of action. However, recent biotechnology and engineering research has greatly enhanced the content and applicability of MSC-EVs.}, }
@article {pmid37627263, year = {2023}, author = {Rühmkorf, A and Harbauer, AB}, title = {Role of Mitochondria-ER Contact Sites in Mitophagy.}, journal = {Biomolecules}, volume = {13}, number = {8}, pages = {}, pmid = {37627263}, issn = {2218-273X}, mesh = {Humans ; *Mitophagy ; Mitochondria ; Mitochondrial Membranes ; *Amyotrophic Lateral Sclerosis ; Apoptosis ; Mitochondrial Proteins ; Receptors, Estrogen ; }, abstract = {Mitochondria are often referred to as the "powerhouse" of the cell. However, this organelle has many more functions than simply satisfying the cells' metabolic needs. Mitochondria are involved in calcium homeostasis and lipid metabolism, and they also regulate apoptotic processes. Many of these functions require contact with the ER, which is mediated by several tether proteins located on the respective organellar surfaces, enabling the formation of mitochondria-ER contact sites (MERCS). Upon damage, mitochondria produce reactive oxygen species (ROS) that can harm the surrounding cell. To circumvent toxicity and to maintain a functional pool of healthy organelles, damaged and excess mitochondria can be targeted for degradation via mitophagy, a form of selective autophagy. Defects in mitochondria-ER tethers and the accumulation of damaged mitochondria are found in several neurodegenerative diseases, including Parkinson's disease and amyotrophic lateral sclerosis, which argues that the interplay between the two organelles is vital for neuronal health. This review provides an overview of the different mechanisms of mitochondrial quality control that are implicated with the different mitochondria-ER tether proteins, and also provides a novel perspective on how MERCS are involved in mediating mitophagy upon mitochondrial damage.}, }
@article {pmid37626421, year = {2023}, author = {Wang, S and Sun, S}, title = {Translation dysregulation in neurodegenerative diseases: a focus on ALS.}, journal = {Molecular neurodegeneration}, volume = {18}, number = {1}, pages = {58}, pmid = {37626421}, issn = {1750-1326}, support = {R21 AG072078/AG/NIA NIH HHS/United States ; R01 NS107347/NS/NINDS NIH HHS/United States ; RF1 NS113820/NS/NINDS NIH HHS/United States ; RF1 NS127925/NS/NINDS NIH HHS/United States ; R01 AG078948/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Neurodegenerative Diseases/genetics ; *Amyotrophic Lateral Sclerosis/genetics ; Nerve Degeneration ; Homeostasis ; RNA ; }, abstract = {RNA translation is tightly controlled in eukaryotic cells to regulate gene expression and maintain proteome homeostasis. RNA binding proteins, translation factors, and cell signaling pathways all modulate the translation process. Defective translation is involved in multiple neurological diseases including amyotrophic lateral sclerosis (ALS). ALS is a progressive neurodegenerative disorder and poses a major public health challenge worldwide. Over the past few years, tremendous advances have been made in the understanding of the genetics and pathogenesis of ALS. Dysfunction of RNA metabolisms, including RNA translation, has been closely associated with ALS. Here, we first introduce the general mechanisms of translational regulation under physiological and stress conditions and review well-known examples of translation defects in neurodegenerative diseases. We then focus on ALS-linked genes and discuss the recent progress on how translation is affected by various mutant genes and the repeat expansion-mediated non-canonical translation in ALS.}, }
@article {pmid37622689, year = {2024}, author = {Dey, B and Kumar, A and Patel, AB}, title = {Pathomechanistic Networks of Motor System Injury in Amyotrophic Lateral Sclerosis.}, journal = {Current neuropharmacology}, volume = {22}, number = {11}, pages = {1778-1806}, pmid = {37622689}, issn = {1875-6190}, support = {DST/CSRI/2017/258//Department of Science and Technology (DST), Govt. of India/ ; DBT/JRF/BET-17/1/2017/AL/400//Department of Biotechnology (DBT), Govt. of India/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics/metabolism ; Humans ; Animals ; Gene-Environment Interaction ; Motor Neurons/metabolism/pathology ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is the most common, adult-onset, progressive motor neurodegenerative disorder that results in death within 3 years of the clinical diagnosis. Due to the clinicopathological heterogeneity, any reliable biomarkers for diagnosis or prognosis of ALS have not been identified till date. Moreover, the only three clinically approved treatments are not uniformly effective in slowing the disease progression. Over the last 15 years, there has been a rapid advancement in research on the complex pathomechanistic landscape of ALS that has opened up new avenues for successful clinical translation of targeted therapeutics. Multiple studies suggest that the age-dependent interaction of risk-associated genes with environmental factors and endogenous modifiers is critical to the multi-step process of ALS pathogenesis. In this review, we provide an updated discussion on the dysregulated cross-talk between intracellular homeostasis processes, the unique molecular networks across selectively vulnerable cell types, and the multisystemic nature of ALS pathomechanisms. Importantly, this work highlights the alteration in epigenetic and epitranscriptomic landscape due to gene-environment interactions, which have been largely overlooked in the context of ALS pathology. Finally, we suggest that precision medicine research in ALS will be largely benefitted from the stratification of patient groups based on the clinical phenotype, onset and progression, genome, exposome, and metabolic identities.}, }
@article {pmid37621279, year = {2023}, author = {Thijs, Z and Dumican, M}, title = {Laryngeal symptoms related to motor phenotypes in Parkinson's disease: A systematic review.}, journal = {Laryngoscope investigative otolaryngology}, volume = {8}, number = {4}, pages = {970-979}, pmid = {37621279}, issn = {2378-8038}, abstract = {OBJECTIVE: This study aimed to systematically review the associations between motor clinical phenotypes in Parkinson's disease (PD) and laryngeal disease symptoms. Laryngeal dysfunctions such as dysphonia and dysphagia are ubiquitous in people with Parkinson's disease (PwPD). Similar to other disease symptoms, they manifest variably across PwPD. Some of the variability within PD has been explained by clinical phenotypes. However, it is unclear how laryngeal symptoms of PD express themselves across these phenotypes.<br><br>METHODS: Five databases were searched (MEDLINE, CINAHL, Web of Science, Embase, Scopus) in May 2022. After the removal of duplicates, all retrieved records were screened. Cohort, case-control, and cross-sectional studies in English discussing laryngeal symptoms and clinical PD phenotypes were included. Data were extracted, tabulated, and assessed using Moola et al.'s (2021) appraisal tool for systematic reviews of risk and etiology.<br><br>RESULTS: The search retrieved 2370 records, representing 540 PwPD. After the removal of duplicates and screening, eight articles were included for review. The most common phenotype categories were tremor-dominant and postural-instability gait disordered (PIGD). Five studies addressed vocal characteristics, while four considered swallowing. Differences and lack of rigor in methodology across studies complicated conclusions, but a tendency for tremor-dominant phenotypes to present with less severe laryngeal symptoms was found.<br><br>CONCLUSION: Some minor differences in laryngeal function were found between tremor-dominant and PIGD phenotypes in PD. However, there is a need for more standardized and high-quality studies when comparing motor phenotypes for laryngeal function.}, }
@article {pmid37620293, year = {2023}, author = {Kuiper, EFE and Prophet, SM and Schlieker, C}, title = {Coordinating nucleoporin condensation and nuclear pore complex assembly.}, journal = {FEBS letters}, volume = {597}, number = {20}, pages = {2534-2545}, doi = {10.1002/1873-3468.14725}, pmid = {37620293}, issn = {1873-3468}, support = {//Dystonia Medical Research Foundation/ ; ALTF 910-2022//European Molecular Biology Organization/ ; 019.222EN.007//Nederlandse Organisatie voor Wetenschappelijk Onderzoek/ ; PR200788//U.S. Department of Defense/ ; }, abstract = {The nuclear pore complex (NPC) is among the most elaborate protein complexes in eukaryotes. While ribosomes and proteasomes are known to require dedicated assembly machinery, our understanding of NPC assembly is at a relatively early stage. Defects in NPC assembly or homeostasis are tied to movement disorders, including dystonia and amyotrophic lateral sclerosis (ALS), as well as aging, requiring a better understanding of these processes to enable therapeutic intervention. Here, we discuss recent progress in the understanding of NPC assembly and highlight how related defects in human disorders can shed light on NPC biogenesis. We propose that the condensation of phenylalanine-glycine repeat nucleoporins needs to be carefully controlled during NPC assembly to prevent aberrant condensation, aggregation, or amyloid formation.}, }
@article {pmid37620092, year = {2023}, author = {Fink, JK}, title = {The hereditary spastic paraplegias.}, journal = {Handbook of clinical neurology}, volume = {196}, number = {}, pages = {59-88}, doi = {10.1016/B978-0-323-98817-9.00022-3}, pmid = {37620092}, issn = {0072-9752}, mesh = {Child, Preschool ; Humans ; *Spastic Paraplegia, Hereditary/genetics ; Biological Transport ; *Cerebral Palsy ; Exercise ; Family ; }, abstract = {The hereditary spastic paraplegias (HSPs) are a group of more than 90 genetic disorders in which lower extremity spasticity and weakness are either the primary neurologic impairments ("uncomplicated HSP") or when accompanied by other neurologic deficits ("complicated HSP"), important features of the clinical syndrome. Various genetic types of HSP are inherited such as autosomal dominant, autosomal recessive, X-linked, and maternal (mitochondrial) traits. Symptoms that begin in early childhood may be nonprogressive and resemble spastic diplegic cerebral palsy. Symptoms that begin later, typically progress insidiously over a number of years. Genetic testing is able to confirm the diagnosis for many subjects. Insights from gene discovery indicate that abnormalities in diverse molecular processes underlie various forms of HSP, including disturbance in axon transport, endoplasmic reticulum morphogenesis, vesicle transport, lipid metabolism, and mitochondrial function. Pathologic studies in "uncomplicated" HSP have shown axon degeneration particularly involving the distal ends of corticospinal tracts and dorsal column fibers. Treatment is limited to symptom reduction including amelioration of spasticity, reducing urinary urgency, proactive physical therapy including strengthening, stretching, balance, and agility exercise.}, }
@article {pmid37620088, year = {2023}, author = {Muzio, L and Ghirelli, A and Agosta, F and Martino, G}, title = {Novel therapeutic approaches for motor neuron disease.}, journal = {Handbook of clinical neurology}, volume = {196}, number = {}, pages = {523-537}, doi = {10.1016/B978-0-323-98817-9.00027-2}, pmid = {37620088}, issn = {0072-9752}, mesh = {Animals ; Humans ; *Neurodegenerative Diseases ; *Motor Neuron Disease/therapy ; *Amyotrophic Lateral Sclerosis/therapy ; Motor Neurons ; Cognition ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that leads to the neurodegeneration and death of upper and lower motor neurons (MNs). Although MNs are the main cells involved in the process of neurodegeneration, a growing body of evidence points toward other cell types as concurrent to disease initiation and propagation. Given the current absence of effective therapies, the quest for other therapeutic targets remains open and still challenges the scientific community. Both neuronal and extra-neuronal mechanisms of cellular stress and damage have been studied and have posed the basis for the development of novel therapies that have been investigated on both animal models and humans. In this chapter, a thorough review of the main mechanisms of cellular damage and the respective therapeutic attempts targeting them is reported. The main areas covered include neuroinflammation, protein aggregation, RNA metabolism, and oxidative stress.}, }
@article {pmid37620070, year = {2023}, author = {Younger, DS and Brown, RH}, title = {Amyotrophic lateral sclerosis.}, journal = {Handbook of clinical neurology}, volume = {196}, number = {}, pages = {203-229}, doi = {10.1016/B978-0-323-98817-9.00031-4}, pmid = {37620070}, issn = {0072-9752}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/therapy ; Motor Neurons ; Syndrome ; }, abstract = {The scientific landscape surrounding amyotrophic lateral sclerosis has shifted immensely with a number of well-defined ALS disease-causing genes, each with related phenotypical and cellular motor neuron processes that have come to light. Yet in spite of decades of research and clinical investigation, there is still no etiology for sporadic amyotrophic lateral sclerosis, and treatment options even for those with well-defined familial syndromes are still limited. This chapter provides a comprehensive review of the genetic basis of amyotrophic lateral sclerosis, highlighting factors that contribute to its heritability and phenotypic manifestations, and an overview of past, present, and upcoming therapeutic strategies.}, }
@article {pmid37619957, year = {2023}, author = {Chaves-Filho, AB and Diniz, LS and Santos, RS and Lima, RS and Oreliana, H and Pinto, IFD and Dantas, LS and Inague, A and Faria, RL and Medeiros, MHG and Glezer, I and Festuccia, WT and Yoshinaga, MY and Miyamoto, S}, title = {Plasma oxylipin profiling by high resolution mass spectrometry reveal signatures of inflammation and hypermetabolism in amyotrophic lateral sclerosis.}, journal = {Free radical biology &amp; medicine}, volume = {208}, number = {}, pages = {285-298}, doi = {10.1016/j.freeradbiomed.2023.08.019}, pmid = {37619957}, issn = {1873-4596}, mesh = {Rats ; Humans ; Animals ; Mice ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; Oxylipins ; *Neurodegenerative Diseases ; Mass Spectrometry ; Superoxide Dismutase-1/genetics/metabolism ; Inflammation ; Disease Models, Animal ; Mice, Transgenic ; Superoxide Dismutase/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive loss of motor neurons, systemic hypermetabolism, and inflammation. In this context, oxylipins have been investigated as signaling molecules linked to neurodegeneration, although their specific role in ALS remains unclear. Importantly, most methods focused on oxylipin analysis are based on low-resolution mass spectrometry, which usually confers high sensitivity, but not great accuracy for molecular characterization, as provided by high-resolution MS (HRMS). Here, we established an ultra-high performance liquid chromatography HRMS (LC-HRMS) method for simultaneous analysis of 126 oxylipins in plasma. Intra- and inter-day method validation showed high sensitivity (0.3-25 pg), accuracy and precision for more than 90% of quality controls. This method was applied in plasma of ALS rats overexpressing the mutant human Cu/Zn-superoxide dismutase gene (SOD1-G93A) at asymptomatic (ALS 70 days old) and symptomatic stages (ALS 120 days old), and their respective age-matched wild type controls. From the 56 oxylipins identified in plasma, 17 species were significantly altered. Remarkably, most of oxylipins linked to inflammation and oxidative stress derived from arachidonic acid (AA), like prostaglandins and mono-hydroxides, were increased in ALS 120 d rats. In addition, ketones derived from AA and linoleic acid (LA) were increased in both WT 120 d and ALS 120 d groups, supporting that age also modulates oxylipin metabolism in plasma. Interestingly, the LA-derived diols involved in fatty acid uptake and β-oxidation, 9(10)-DiHOME and 12(13)-DiHOME, were decreased in ALS 120 d rats and showed significant synergic effects between age and disease factors. In summary, we validated a high-throughput LC-HRMS method for oxylipin analysis and provided a comprehensive overview of plasma oxylipins involved in ALS disease progression. Noteworthy, the oxylipins altered in plasma have potential to be investigated as biomarkers for inflammation and hypermetabolism in ALS.}, }
@article {pmid37619619, year = {2023}, author = {Wang, Y and Lv, MN and Zhao, WJ}, title = {Research on ferroptosis as a therapeutic target for the treatment of neurodegenerative diseases.}, journal = {Ageing research reviews}, volume = {91}, number = {}, pages = {102035}, doi = {10.1016/j.arr.2023.102035}, pmid = {37619619}, issn = {1872-9649}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism ; *Ferroptosis ; *Alzheimer Disease/drug therapy ; *Parkinson Disease/drug therapy ; *Huntington Disease ; }, abstract = {Ferroptosis is an iron- and lipid peroxidation (LPO)-mediated programmed cell death type. Recently, mounting evidence has indicated the involvement of ferroptosis in neurodegenerative diseases, especially in Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and so on. Treating ferroptosis presents opportunities as well as challenges for neurodegenerative diseases. This review provides a comprehensive overview of typical features of ferroptosis and the underlying mechanisms that contribute to its occurrence, as well as their implications in the pathogenesis and advancement of major neurodegenerative disorders. Meanwhile, we summarize the utilization of ferroptosis inhibition in both experimental and clinical approaches for the treatment of major neurodegenerative disorders. In addition, we specifically summarize recent advances in developing therapeutic means targeting ferroptosis in these diseases, which may guide future approaches for the effective management of these devastating medical conditions.}, }
@article {pmid37614471, year = {2023}, author = {Bhattacharya, MRC}, title = {A nerve-wracking buzz: lessons from Drosophila models of peripheral neuropathy and axon degeneration.}, journal = {Frontiers in aging neuroscience}, volume = {15}, number = {}, pages = {1166146}, pmid = {37614471}, issn = {1663-4365}, support = {R01 NS105680/NS/NINDS NIH HHS/United States ; }, abstract = {The degeneration of axons and their terminals occurs following traumatic, toxic, or genetically-induced insults. Common molecular mechanisms unite these disparate triggers to execute a conserved nerve degeneration cascade. In this review, we will discuss how models of peripheral nerve injury and neuropathy in Drosophila have led the way in advancing molecular understanding of axon degeneration and nerve injury pathways. Both neuron-intrinsic as well as glial responses to injury will be highlighted. Finally, we will offer perspective on what additional questions should be answered to advance these discoveries toward clinical interventions for patients with neuropathy.}, }
@article {pmid37614251, year = {2023}, author = {Hussein, S and Pingili, S and Makkena, VK and Jaramillo, AP and Awosusi, BL and Ayyub, J and Dabhi, KN and Gohil, NV and Tanveer, N and Hamid, P}, title = {The Impact of Serum Uric Acid on the Progression of Amyotrophic Lateral Sclerosis in Adults Aged 18 and Older: A Systematic Review.}, journal = {Cureus}, volume = {15}, number = {7}, pages = {e42312}, pmid = {37614251}, issn = {2168-8184}, abstract = {We have conducted this review to see if serum uric acid (UA) is associated with slowing amyotrophic lateral sclerosis (ALS) progression in adult patients who are at least 18 years old. Understanding the effects of this biomarker for future use is critical because of its easy accessibility. This systematic review paper examined five previous years of recent studies and reports, published in English and limited to human investigations from the Cochrane, PubMed, and Google Scholar databases. Using instruments for assessing the eligibility and quality of systematic and narrative reviews, we narrowed our search to 11 reports that show evidence of a positive association between high blood uric acid and the progression of ALS. However, this claim still needs confirmation by future studies to confirm that possibility. The results of this systematic review may provide a strong foundation for future studies on this biomarker, demonstrating the significance of blood uric acid levels in ALS and highlighting the necessity of using that biomarker to track the disease's progression.}, }
@article {pmid37611905, year = {2024}, author = {Huang, Q and Wang, Y and Chen, S and Liang, F}, title = {Glycometabolic Reprogramming of Microglia in Neurodegenerative Diseases: Insights from Neuroinflammation.}, journal = {Aging and disease}, volume = {15}, number = {3}, pages = {1155-1175}, pmid = {37611905}, issn = {2152-5250}, mesh = {*Microglia/metabolism ; Humans ; *Neurodegenerative Diseases/metabolism/pathology ; *Glucose/metabolism ; Neuroinflammatory Diseases/metabolism/immunology ; Animals ; }, abstract = {Neurodegenerative diseases (ND) are conditions defined by progressive deterioration of the structure and function of the nervous system. Some major examples include Alzheimer's disease (AD), Parkinson's disease (PD), and Amyotrophic lateral sclerosis (ALS). These diseases lead to various dysfunctions, like impaired cognition, memory, and movement. Chronic neuroinflammation may underlie numerous neurodegenerative disorders. Microglia, an important immunocell in the brain, plays a vital role in defending against neuroinflammation. When exposed to different stimuli, microglia are activated and assume different phenotypes, participating in immune regulation of the nervous system and maintaining tissue homeostasis. The immunological activity of activated microglia is affected by glucose metabolic alterations. However, in the context of chronic neuroinflammation, specific alterations of microglial glucose metabolism and their mechanisms of action remain unclear. Thus, in this paper, we review the glycometabolic reprogramming of microglia in ND. The key molecular targets and main metabolic pathways are the focus of this research. Additionally, this study explores the mechanisms underlying microglial glucose metabolism reprogramming in ND and offers an analysis of the most recent therapeutic advancements. The ultimate aim is to provide insights into the development of potential treatments for ND.}, }
@article {pmid37610446, year = {2023}, author = {Bombaci, A and Lupica, A and Pozzi, FE and Remoli, G and Manera, U and Di Stefano, V}, title = {Sensory neuropathy in amyotrophic lateral sclerosis: a systematic review.}, journal = {Journal of neurology}, volume = {270}, number = {12}, pages = {5677-5691}, pmid = {37610446}, issn = {1432-1459}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/diagnosis/epidemiology ; *Neurodegenerative Diseases ; Quality of Life ; Motor Neurons/physiology ; Electromyography ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the degeneration of both upper and lower motoneurons, leading to motor and non-motor symptoms. Recent evidence suggests that ALS is indeed a multisystem disorder, associated with cognitive impairment, dysautonomia, pain and fatigue, excess of secretions, and sensory symptoms. To evaluate whether sensory neuropathy could broaden its spectrum, we systematically reviewed its presence and characteristics in ALS, extracting data on epidemiological, clinical, neurophysiological, neuropathological, and genetic features. Sensory neuropathy can be found in up to 20% of ALS patients, affecting both large and small fibers, although there is a great heterogeneity related to different techniques used for its detection (electromyography vs skin biopsy vs nerve biopsy). Moreover, the association between CIDP-like neuropathy and ALS needs to be better explored, although it could be interpreted as part of the neuroinflammatory process in the latter disease. Sensory neuropathy in ALS may be associated with a spinal onset and might be more frequent in SOD1 patients. Moreover, it seems mutually exclusive with cognitive impairment. No associations with sex and other genetic mutation were observed. All these data in the literature reveal the importance of actively looking for sensory neuropathy in ALS patients, and suggest including sensory neuropathy among ALS non-motor features, as it may explain sensory symptoms frequently reported throughout the course of the disease. Its early identification could help avoid diagnostic delays and improve patients' treatment and quality of life.}, }
@article {pmid37598759, year = {2023}, author = {Rani, N and Alam, MM and Jamal, A and Bin Ghaffar, U and Parvez, S}, title = {Caenorhabditis elegans: A transgenic model for studying age-associated neurodegenerative diseases.}, journal = {Ageing research reviews}, volume = {91}, number = {}, pages = {102036}, doi = {10.1016/j.arr.2023.102036}, pmid = {37598759}, issn = {1872-9649}, mesh = {Animals ; Humans ; *Neurodegenerative Diseases/genetics ; Caenorhabditis elegans/metabolism ; *Alzheimer Disease/genetics ; *Parkinson Disease ; *Huntington Disease/genetics ; }, abstract = {Neurodegenerative diseases (NDs) are a heterogeneous group of aging-associated ailments characterized by interrupting cellular proteostasic machinery and the misfolding of distinct proteins to form toxic aggregates in neurons. Neurodegenerative diseases, which include Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and others, are becoming an increasing threat to human health worldwide. The degeneration and death of certain specific groups of neurons are the hallmarks of these diseases. Over the past decades, Caenorhabditis eleganshas beenwidely used as a transgenic model to investigate biological processes related to health and disease. The nematode Caenorhabditis elegans (C. elegans) has developed as a powerful tool for studying disease mechanisms due to its ease of genetic handling and instant cultivation while providing a whole-animal system amendable to several molecular and biochemical techniques. In this review, we elucidate the potential of C. elegans as a versatile platform for systematic dissection of the molecular basis of human disease, focusing on neurodegenerative disorders, and may help better our understanding of the disease mechanisms and search for new therapeutics for these devastating diseases.}, }
@article {pmid37592793, year = {2024}, author = {Manera, U and Matteoni, E and Canosa, A and Callegaro, S and Casale, F and Marchis, D and Vasta, R and Moglia, C and Chiò, A and Calvo, A}, title = {Mycotoxins and Amyotrophic Lateral Sclerosis: Food Exposure, Nutritional Implications and Dietary Solutions.}, journal = {CNS &amp; neurological disorders drug targets}, volume = {23}, number = {5}, pages = {562-572}, pmid = {37592793}, issn = {1996-3181}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology ; *Mycotoxins/toxicity ; Animals ; Environmental Exposure/adverse effects ; Food Contamination ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder determined by a combination of both genetic and environmental factors. Despite wide investigations, the role of chronic exposure to environmental pollutants is still rather unknown. Among natural toxins, the mycotoxins have received major attention only in the last few years, due to both technical and scientific achievements that allowed to disentangle many important features of the complex fungal biology. Whereas the effects of acute and high-dose mycotoxin exposure are well known, the potential effects of chronic and low-dose exposure on neurodegeneration have not been broadly elucidated. In this review, we have summarized all the studies concerning environmental exposure to unknown substances that caused ALS outbreaks all over the world, reinterpreting in light of the new scientific acquisitions and highlighting the potential and neglected role of mycotoxins. Then, we focused on recent papers about food exposure to mycotoxin, mycobiome and fungal infections in ALS and other neurodegenerative diseases. We analyzed the gaps of current literature that lead to an undervaluation of mycotoxins as detrimental molecules. By listing all the most important mycotoxins and analyzing all the biological pathways that they can affect, we explained the reasons why they need to be considered in the next epidemiological studies on ALS and other neurodegenerative and neuroinflammatory diseases. In conclusion, after suggesting some possible solutions to mitigate mycotoxin exposure risk, we affirm that future collaborations between scientists and policymakers are important to develop sustainable interventions and promote health through dietary diversity.}, }
@article {pmid37590965, year = {2023}, author = {Rani, A and Saini, V and Patra, P and Prashar, T and Pandey, RK and Mishra, A and Jha, HC}, title = {Epigallocatechin Gallate: A Multifaceted Molecule for Neurological Disorders and Neurotropic Viral Infections.}, journal = {ACS chemical neuroscience}, volume = {14}, number = {17}, pages = {2968-2980}, doi = {10.1021/acschemneuro.3c00368}, pmid = {37590965}, issn = {1948-7193}, mesh = {Humans ; *Alzheimer Disease ; *Epstein-Barr Virus Infections ; Glycogen Synthase Kinase 3 ; Phosphatidylinositol 3-Kinases ; *Zika Virus Infection ; Herpesvirus 4, Human ; *Zika Virus ; *Nervous System Diseases ; }, abstract = {Epigallocatechin-3-gallate (EGCG), a polyphenolic moiety found in green tea extracts, exhibits pleiotropic bioactivities to combat many diseases including neurological ailments. These neurological diseases include Alzheimer's disease, multiple sclerosis, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. For instance, in the case of Alzheimer's disease, the formation of a β-sheet in the region of the 10th-21st amino acids was significantly reduced in EGCG-induced oligomeric samples of Aβ40. Its interference induces the formation of Aβ structures with an increase in intercenter-of-mass distances, reduction in interchain/intrachain contacts, reduction in β-sheet propensity, and increase in α-helix. Besides, numerous neurotropic viruses are known to instigate or aggravate neurological ailments. It exerts an effect on the oxidative damage caused in neurodegenerative disorders by acting on GSK3-β, PI3K/Akt, and downstream signaling pathways via caspase-3 and cytochrome-c. EGCG also diminishes these viral-mediated effects, such as EGCG delayed HSV-1 infection by blocking the entry for virions, inhibitory effects on NS3/4A protease or NS5B polymerase of HCV and potent inhibitor of ZIKV NS2B-NS3pro/NS3 serine protease (NS3-SP). It showed a reduction in the neurotoxic properties of HIV-gp120 and Tat in the presence of IFN-γ. EGCG also involves numerous viral-mediated inflammatory cascades, such as JAK/STAT. Nonetheless, it also inhibits the Epstein-Barr virus replication protein (Zta and Rta). Moreover, it also impedes certain viruses (influenza A and B strains) by hijacking the endosomal and lysosomal compartments. Therefore, the current article aims to describe the importance of EGCG in numerous neurological diseases and its inhibitory effect against neurotropic viruses.}, }
@article {pmid37587387, year = {2023}, author = {Hamad, AA and Amer, BE and Al Mawla, AM and Goufa, E and Abdelwahab, MM and Serag, I}, title = {Clinical characteristics, course, and outcomes of amyotrophic lateral sclerosis overlapping with pregnancy: a systematic review of 38 published cases.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {44}, number = {12}, pages = {4219-4231}, pmid = {37587387}, issn = {1590-3478}, mesh = {Female ; Infant, Newborn ; Humans ; Pregnancy ; *Amyotrophic Lateral Sclerosis/complications/diagnosis ; *Neurodegenerative Diseases/complications ; Prognosis ; Health Status ; Databases, Factual ; }, abstract = {OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a rare and fatal neurodegenerative disease that can overlap with pregnancy, but little is known about its clinical characteristics, course, and outcomes in this context. This systematic review aimed to synthesize the current evidence on ALS overlapping with pregnancy.<br><br>METHODS: We comprehensively searched four databases on February 2, 2023, to identify case studies reporting cases of ALS overlapping with pregnancy. Joanna Brigs Institute tool was followed to assess the quality of the included studies.<br><br>RESULTS: Twenty-six articles reporting 38 cases were identified and included in our study. Out of the 38 cases, 18 were aged&#x2009;<&#x2009;30&#xa0;years. The onset of ALS was before pregnancy in 18 cases, during pregnancy in 16 cases, and directly after pregnancy in 4 cases. ALS progression course was rapid or severe in 55% of the cases during pregnancy, and this percentage reached 61% in cases with an onset of ALS before pregnancy. While ALS progression course after pregnancy was rapid or severe in 63% and stable in 37% of the cases. Most cases (95%) were able to complete the pregnancy and gave live birth. However, preterm delivery was common. For neonates, 86% were healthy without any complications.<br><br>CONCLUSION: While pregnancy with ALS is likely to survive and result in giving birth to healthy infants, it could be associated with rapid or severe progression of ALS and result in a worse prognosis, highlighting the importance of close monitoring and counselling for patients and healthcare providers.}, }
@article {pmid37579835, year = {2023}, author = {Yadav, H and Jaldhi,  and Bhardwaj, R and Anamika,  and Bakshi, A and Gupta, S and Maurya, SK}, title = {Unveiling the role of gut-brain axis in regulating neurodegenerative diseases: A comprehensive review.}, journal = {Life sciences}, volume = {330}, number = {}, pages = {122022}, doi = {10.1016/j.lfs.2023.122022}, pmid = {37579835}, issn = {1879-0631}, mesh = {Humans ; *Neurodegenerative Diseases ; Brain-Gut Axis ; *Parkinson Disease/therapy ; *Gastrointestinal Microbiome/physiology ; *Probiotics/therapeutic use ; Brain ; }, abstract = {Emerging evidence have shown the importance of gut microbiota in regulating brain functions. The diverse molecular mechanisms involved in cross-talk between gut and brain provide insight into importance of this communication in maintenance of brain homeostasis. It has also been observed that disturbed gut microbiota contributes to neurological diseases such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis and aging. Recently, gut microbiome-derived exosomes have also been reported to play an essential role in the development and progression of neurodegenerative diseases and could thereby act as a therapeutic target. Further, pharmacological interventions including antibiotics, prebiotics and probiotics can influence gut microbiome-mediated management of neurological diseases. However, extensive research is warranted to better comprehend this interconnection in maintenance of brain homeostasis and its implication in neurological diseases. Thus, the present review is aimed to provide a detailed understanding of gut-brain axis followed by possibilities to target the gut microbiome for improving neurological health.}, }
@article {pmid37579081, year = {2023}, author = {Sulistyo, A and Abrahao, A and Freitas, ME and Ritsma, B and Zinman, L}, title = {Enteral tube feeding for amyotrophic lateral sclerosis/motor neuron disease.}, journal = {The Cochrane database of systematic reviews}, volume = {8}, number = {8}, pages = {CD004030}, pmid = {37579081}, issn = {1469-493X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/therapy ; *Deglutition Disorders/therapy/complications ; Enteral Nutrition/methods ; Intubation, Gastrointestinal ; *Motor Neuron Disease/complications ; }, abstract = {BACKGROUND: Maintaining adequate nutrition is critical for people with amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND). Enteral tube feeding is offered to people experiencing difficulty swallowing (dysphagia) to prevent weight loss and aspiration pneumonia. Among the types of enteral tube feeding, percutaneous endoscopic gastrostomy (PEG) is the typical procedure offered to people with ALS and will be mainly discussed here.<br><br>OBJECTIVES: To examine the effectiveness of percutaneous endoscopic gastrostomy or other enteral tube feeding in people with ALS, compared to oral feeds without enteral tube feeding on: 1. survival; 2. nutritional status; 3. quality of life. To examine the incidence of minor and major complications of percutaneous endoscopic gastrostomy (PEG) and other enteral tube feeding procedures in people with ALS.<br><br>SEARCH METHODS: On 3 January 2020 and 6 February 2021, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE. Embase, ClinicalTrials.gov and WHO ICTRP. We screened the results to identify randomized controlled studies on enteral tube feeding in ALS. We reviewed all references from the search in published articles to identify any additional references.<br><br>SELECTION CRITERIA: We included randomized controlled trials (RCTs), quasi-RCTs, and cross-over trials evaluating the effectiveness and complications of PEG or other enteral tube feeding placement in ALS.<br><br>DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane.<br><br>MAIN RESULTS: We found no RCTs or quasi-RCTs comparing the effectiveness of enteral tube feeding versus oral feeds without enteral tube feeding.<br><br>AUTHORS' CONCLUSIONS: There are no RCTs or quasi-RCTs to indicate whether enteral tube feeding is effective compared to continuation of oral feeding for any of the outcome measures. Such RCTs are very unlikely to be performed for ethical reasons. RCTs evaluating the effect of different enteral tube insertion techniques and timings of tube placement on survival and quality of life of people with ALS dysphagia are feasible and warranted.}, }
@article {pmid37575992, year = {2023}, author = {Mohammadi, M and Yarmohammadi, A and Salehi-Abargouei, A and Ghasemirad, H and Shirvani, M and Ghoshouni, H}, title = {Uric acid and glaucoma: a systematic review and meta-analysis.}, journal = {Frontiers in medicine}, volume = {10}, number = {}, pages = {1159316}, pmid = {37575992}, issn = {2296-858X}, abstract = {BACKGROUND: Glaucoma, the leading cause of irreversible blindness, is a common disorder that contributes to gradual optic nerve degeneration. The beneficial impacts of uric acid (UA) have been reported in some neurodegenerative conditions such as Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis. But the results of current studies about the association between serum UA level and glaucoma are conflicting. The present meta-analysis was conducted to provide a better understanding of the association between serum UA level and glaucoma.<br><br>METHODS: We searched the databases of PubMed, Scopus, Web of Science, and Google Scholar systematically until November 20, 2022 to identify case-control studies, comparing the serum UA concentrations of the patients with glaucoma and controls. The mean &#xb1; standard division difference was used to assess the difference in serum UA concentrations between the glaucoma patients and controls.<br><br>RESULTS: Six studies involving 1,221 glaucoma patients and 1,342 control group were included in the present meta-analysis. This meta-analysis using a random effect model indicated that the mean UA level in glaucoma patients was 0.13 (I[2] = 91.92%, 95% CI = -0.42 to 0.68) higher than the controls; however, it was not statistically significant.<br><br>CONCLUSIONS: Our findings provide evidence that glaucoma patients have a higher serum UA level compared to the controls, but this difference is not statistically significant. Prospective studies are needed to determine the possible association between increased UA and glaucoma pathogenesis.<br><br>https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022364055, identifier: CRD42022364055.}, }
@article {pmid37575227, year = {2023}, author = {Terrabuio, E and Zenaro, E and Constantin, G}, title = {The role of the CD8+ T cell compartment in ageing and neurodegenerative disorders.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1233870}, pmid = {37575227}, issn = {1664-3224}, mesh = {Humans ; *CD8-Positive T-Lymphocytes ; Cytokines ; Central Nervous System ; *Amyotrophic Lateral Sclerosis ; }, abstract = {CD8+ lymphocytes are adaptive immunity cells with the particular function to directly kill the target cell following antigen recognition in the context of MHC class I. In addition, CD8+ T cells may release pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), and a plethora of other cytokines and chemoattractants modulating immune and inflammatory responses. A role for CD8+ T cells has been suggested in aging and several diseases of the central nervous system (CNS), including Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, limbic encephalitis-induced temporal lobe epilepsy and Susac syndrome. Here we discuss the phenotypic and functional alterations of CD8+ T cell compartment during these conditions, highlighting similarities and differences between CNS disorders. Particularly, we describe the pathological changes in CD8+ T cell memory phenotypes emphasizing the role of senescence and exhaustion in promoting neuroinflammation and neurodegeneration. We also discuss the relevance of trafficking molecules such as selectins, mucins and integrins controlling the extravasation of CD8+ T cells into the CNS and promoting disease development. Finally, we discuss how CD8+ T cells may induce CNS tissue damage leading to neurodegeneration and suggest that targeting detrimental CD8+ T cells functions may have therapeutic effect in CNS disorders.}, }
@article {pmid37573779, year = {2023}, author = {Zhang, Z and Zhu, Y and Zhu, C and Li, S and Zhao, Y and Yang, J and Qin, Y and Hou, J and Zhang, J and Han, C}, title = {Effects of Dihuang Yinzi Decoction on Alzheimer's Disease: A Systematic Review and Meta-Analysis.}, journal = {Complementary medicine research}, volume = {30}, number = {5}, pages = {440-452}, doi = {10.1159/000531931}, pmid = {37573779}, issn = {2504-2106}, mesh = {Humans ; *Alzheimer Disease/drug therapy ; Treatment Outcome ; *Medicine ; Medicine, Chinese Traditional ; China ; }, abstract = {OBJECTIVE: The aim of this study was to systematically evaluate the therapeutic effects of Dihuang Yinzi decoction on Alzheimer's disease (AD) and provide a medical evidence-based clinical application of traditional Chinese medicine (TCM).<br><br>METHODS: A comprehensive search was conducted across multiple databases, including PubMed, Embase, Cochrane Library, China National Journals Full-text Database, VIP Database for Chinese Technical Periodicals, Wan Fang database, and SinoMed database, to collect clinical randomized controlled trials of Dihuang Yinzi decoction in the treatment of AD. Strict literature screening was performed based on predefined inclusion and exclusion criteria. The Cochrane Collaboration risk of bias assessment tool and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system recommendation-level method was used to assess the quality of the included studies. Review Manager 5.4 and Stata 17 software were used for data synthesis and processing, while GRADE Profiler 3.6 software was used to evaluate the quality of evidence for outcome indicators (risk ratio, standardized mean difference, and weighted mean difference).<br><br>RESULTS: A total of 11 studies involving 798 patients met the inclusion criteria. Dihuang Yinzi decoction, whether used alone or in combination with conventional Western medicine, demonstrated superior efficacy compared to conventional Western medicine alone in improving the clinical effective rate, TCM syndrome score, activity of daily living score, Mini-Mental State Examination score, and Hasegawa Dementia Scale score in AD treatment. Furthermore, it exhibited a favorable safety profile. However, the GRADE evidence quality rating for the included studies was low.<br><br>CONCLUSIONS: Dihuang Yinzi decoction, either used alone or in combination with conventional Western medicine, shows promising results in enhancing cognitive and memory functions as well as the self-care ability of patients with AD. However, the low GRADE evidence quality rating highlights the need for focused advancements in the planning and execution of clinical randomized controlled trials during future research attempts.<br><br>UNLABELLED: <title>ZIEL</title>Ziel dieser Studie ist es, die therapeutischen Effekte von Dihuang Yinzi-Dekokt auf die Alzheimer-Krankheit systematisch zu bewerten und eine evidenzbasierte klinische Anwendung der traditionellen chinesischen Medizin (TCM) bereitzustellen.<title>Methoden</title>Es wurde eine umfassende Suche in mehreren Datenbanken, darunter PubMed, Embase, Cochrane Library, China National Journals Volltext-Datenbank, VIP Database for Chinese Technical Periodicals, Wan Fang Datenbank und SinoMed-Datenbank durchgef&#xfc;hrt, um randomisierte, kontrollierte klinische Studien zu Dihuang Yinzi-Dekokt in der Behandlung der Alzheimer-Krankheit zu erfassen. Die strenge Literatursuche erfolgte auf Grundlage von vordefinierten Ein-und Ausschlusskriterien. Zur Bewertung der Qualit&#xe4;t der eingeschlossenen Studien wurden das Risk-of-Bias-Tool von Cochrane und das GRADE (Grading of Recommendations Assessment, Development, and Evaluation)-System zur Beurteilung der Empfehlungsgrade herangezogen. Die Datensynthese und -verarbeitung erfolgten mithilfe der Review Manager 5.4- und der Stata 17-Software, w&#xe4;hrend f&#xfc;r die Bewertung der Evidenzqualit&#xe4;t der Outcome-Indikatoren (Risikoverh&#xe4;ltnis, standardisierte Mittelwertdifferenz und gewichtete Mittelwertdifferenz) die Software GRADE Profiler 3.6 verwendet wurde.<title>Ergebnisse</title>Insgesamt erf&#xfc;llten 11 Studien, an denen 798 Patienten teilnahmen, die Einschlusskriterien. Dihuang Yinzi-Dekokt zeigte allein oder in Kombination mit konventioneller westlicher Medizin eine &#xfc;berlegene Wirksamkeit gegen&#xfc;ber der alleinigen Verwendung von konventioneller westlicher Medizin in Bezug auf die klinische Gesamtwirksamkeitsrate, den TCM-Syndrom-Score, den Score f&#xfc;r die Alltagsaktivit&#xe4;ten, den Mini-Mental State Examination-Score und den Score der Hasegawa-Demenz-Skala in der Behandlung der Alzheimer-Krankheit. Dar&#xfc;ber hinaus wies es ein g&#xfc;nstiges Sicherheitsprofil auf. Die Evidenzqualit&#xe4;t der eingeschlossenen Studien gem&#xe4;&#xdf; GRADE wurde jedoch als gering eingestuft.<title>Schlussfolgerungen</title>Dihuang Yinzi-Dekokt zeigt allein oder in Kombination mit konventioneller westlicher Medizin vielversprechende Ergebnisse in Bezug auf die Verbesserung der kognitiven und Ged&#xe4;chtnisfunktionen sowie die Selbstversorgungsf&#xe4;higkeit von Alzheimer-Patienten. Die niedrige Bewertung der Evidenzqualit&#xe4;t gem&#xe4;&#xdf; GRADE unterstreicht jedoch die Notwendigkeit von zielgerichteten Weiterentwicklungen bei der Planung und Durchf&#xfc;hrung von randomisierten, kontrollierten klinischen Studien in zuk&#xfc;nftigen Forschungsunternehmungen.}, }
@article {pmid37572163, year = {2023}, author = {Teli, P and Kale, V and Vaidya, A}, title = {Beyond animal models: revolutionizing neurodegenerative disease modeling using 3D in vitro organoids, microfluidic chips, and bioprinting.}, journal = {Cell and tissue research}, volume = {394}, number = {1}, pages = {75-91}, pmid = {37572163}, issn = {1432-0878}, abstract = {Neurodegenerative diseases (NDs) are characterized by uncontrolled loss of neuronal cells leading to a progressive deterioration of brain functions. The transition rate of numerous neuroprotective drugs against Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease, leading to FDA approval, is only 8-14% in the last two decades. Thus, in spite of encouraging preclinical results, these drugs have failed in human clinical trials, demonstrating that traditional cell cultures and animal models cannot accurately replicate human pathophysiology. Hence, in vitro three-dimensional (3D) models have been developed to bridge the gap between human and animal studies. Such technological advancements in 3D culture systems, such as human-induced pluripotent stem cell (iPSC)-derived cells/organoids, organ-on-a-chip technique, and 3D bioprinting, have aided our understanding of the pathophysiology and underlying mechanisms of human NDs. Despite these recent advances, we still lack a 3D model that recapitulates all the key aspects of NDs, thus making it difficult to study the ND's etiology in-depth. Hence in this review, we propose developing a combinatorial approach that allows the integration of patient-derived iPSCs/organoids with 3D bioprinting and organ-on-a-chip technique as it would encompass the neuronal cells along with their niche. Such a 3D combinatorial approach would characterize pathological processes thoroughly, making them better suited for high-throughput drug screening and developing effective novel therapeutics targeting NDs.}, }
@article {pmid37570771, year = {2023}, author = {Liu, X and Zhao, X and He, J and Wang, S and Shen, X and Liu, Q and Wang, S}, title = {Advances in the Structure of GGGGCC Repeat RNA Sequence and Its Interaction with Small Molecules and Protein Partners.}, journal = {Molecules (Basel, Switzerland)}, volume = {28}, number = {15}, pages = {}, pmid = {37570771}, issn = {1420-3049}, support = {22274050//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; *Frontotemporal Dementia/genetics ; Base Sequence ; DNA Repeat Expansion ; RNA/genetics/chemistry ; RNA-Binding Proteins/genetics/metabolism ; }, abstract = {The aberrant expansion of GGGGCC hexanucleotide repeats within the first intron of the C9orf72 gene represent the predominant genetic etiology underlying amyotrophic lateral sclerosis (ALS) and frontal temporal dementia (FTD). The transcribed r(GGGGCC)n RNA repeats form RNA foci, which recruit RNA binding proteins and impede their normal cellular functions, ultimately resulting in fatal neurodegenerative disorders. Furthermore, the non-canonical translation of the r(GGGGCC)n sequence can generate dipeptide repeats, which have been postulated as pathological causes. Comprehensive structural analyses of r(GGGGCC)n have unveiled its polymorphic nature, exhibiting the propensity to adopt dimeric, hairpin, or G-quadruplex conformations, all of which possess the capacity to interact with RNA binding proteins. Small molecules capable of binding to r(GGGGCC)n have been discovered and proposed as potential lead compounds for the treatment of ALS and FTD. Some of these molecules function in preventing RNA-protein interactions or impeding the phase transition of r(GGGGCC)n. In this review, we present a comprehensive summary of the recent advancements in the structural characterization of r(GGGGCC)n, its propensity to form RNA foci, and its interactions with small molecules and proteins. Specifically, we emphasize the structural diversity of r(GGGGCC)n and its influence on partner binding. Given the crucial role of r(GGGGCC)n in the pathogenesis of ALS and FTD, the primary objective of this review is to facilitate the development of therapeutic interventions targeting r(GGGGCC)n RNA.}, }
@article {pmid37567819, year = {2024}, author = {Marrie, RA and Maxwell, CJ and Rotstein, DL and Tsai, CC and Tremlett, H}, title = {Prodromes in demyelinating disorders, amyotrophic lateral sclerosis, Parkinson disease, and Alzheimer's dementia.}, journal = {Revue neurologique}, volume = {180}, number = {3}, pages = {125-140}, doi = {10.1016/j.neurol.2023.07.002}, pmid = {37567819}, issn = {0035-3787}, mesh = {Humans ; *Alzheimer Disease/diagnosis ; *Parkinson Disease/complications/diagnosis ; *Amyotrophic Lateral Sclerosis/diagnosis ; Biomarkers ; *Multiple Sclerosis ; Prodromal Symptoms ; }, abstract = {A prodrome is an early set of symptoms, which indicates the onset of a disease; these symptoms are often non-specific. Prodromal phases are now recognized in multiple central nervous system diseases. The depth of understanding of the prodromal phase varies across diseases, being more nascent for multiple sclerosis for example, than for Parkinson disease or Alzheimer's disease. Key challenges when identifying the prodromal phase of a disease include the lack of specificity of prodromal symptoms, and consequent need for accessible and informative biomarkers. Further, heterogeneity of the prodromal phase may be influenced by age, sex, genetics and other poorly understood factors. Nonetheless, recognition that an individual is in the prodromal phase of disease offers the opportunity for earlier diagnosis and with it the opportunity for earlier intervention.}, }
@article {pmid37566027, year = {2023}, author = {Bagyinszky, E and Hulme, J and An, SSA}, title = {Studies of Genetic and Proteomic Risk Factors of Amyotrophic Lateral Sclerosis Inspire Biomarker Development and Gene Therapy.}, journal = {Cells}, volume = {12}, number = {15}, pages = {}, pmid = {37566027}, issn = {2073-4409}, mesh = {Humans ; Child ; *Amyotrophic Lateral Sclerosis/genetics/therapy/metabolism ; *Neurodegenerative Diseases ; Proteomics ; DNA-Binding Proteins/metabolism ; Superoxide Dismutase-1 ; Biomarkers ; Risk Factors ; DNA Helicases ; RNA Helicases ; Multifunctional Enzymes ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease affecting the upper and lower motor neurons, leading to muscle weakness, motor impairments, disabilities and death. Approximately 5-10% of ALS cases are associated with positive family history (familial ALS or fALS), whilst the remainder are sporadic (sporadic ALS, sALS). At least 50 genes have been identified as causative or risk factors for ALS. Established pathogenic variants include superoxide dismutase type 1 (SOD1), chromosome 9 open reading frame 72 (c9orf72), TAR DNA Binding Protein (TARDBP), and Fused In Sarcoma (FUS); additional ALS-related genes including Charged Multivesicular Body Protein 2B (CHMP2B), Senataxin (SETX), Sequestosome 1 (SQSTM1), TANK Binding Kinase 1 (TBK1) and NIMA Related Kinase 1 (NEK1), have been identified. Mutations in these genes could impair different mechanisms, including vesicle transport, autophagy, and cytoskeletal or mitochondrial functions. So far, there is no effective therapy against ALS. Thus, early diagnosis and disease risk predictions remain one of the best options against ALS symptomologies. Proteomic biomarkers, microRNAs, and extracellular vehicles (EVs) serve as promising tools for disease diagnosis or progression assessment. These markers are relatively easy to obtain from blood or cerebrospinal fluids and can be used to identify potential genetic causative and risk factors even in the preclinical stage before symptoms appear. In addition, antisense oligonucleotides and RNA gene therapies have successfully been employed against other diseases, such as childhood-onset spinal muscular atrophy (SMA), which could also give hope to ALS patients. Therefore, an effective gene and biomarker panel should be generated for potentially "at risk" individuals to provide timely interventions and better treatment outcomes for ALS patients as soon as possible.}, }
@article {pmid37565183, year = {2023}, author = {Sheers, NL and O'Sullivan, R and Howard, ME and Berlowitz, DJ}, title = {The role of lung volume recruitment therapy in neuromuscular disease: a narrative review.}, journal = {Frontiers in rehabilitation sciences}, volume = {4}, number = {}, pages = {1164628}, pmid = {37565183}, issn = {2673-6861}, abstract = {Respiratory muscle weakness results in substantial discomfort, disability, and ultimately death in many neuromuscular diseases. Respiratory system impairment manifests as shallow breathing, poor cough and associated difficulty clearing mucus, respiratory tract infections, hypoventilation, sleep-disordered breathing, and chronic ventilatory failure. Ventilatory support (i.e., non-invasive ventilation) is an established and key treatment for the latter. As survival outcomes improve for people living with many neuromuscular diseases, there is a shift towards more proactive and preventative chronic disease multidisciplinary care models that aim to manage symptoms, improve morbidity, and reduce mortality. Clinical care guidelines typically recommend therapies to improve cough effectiveness and mobilise mucus, with the aim of averting acute respiratory compromise or respiratory tract infections. Moreover, preventing recurrent infective episodes may prevent secondary parenchymal pathology and further lung function decline. Regular use of techniques that augment lung volume has similarly been recommended (volume recruitment). It has been speculated that enhancing lung inflation in people with respiratory muscle weakness when well may improve respiratory system "flexibility", mitigate restrictive chest wall disease, and slow lung volume decline. Unfortunately, clinical care guidelines are based largely on clinical rationale and consensus opinion rather than level A evidence. This narrative review outlines the physiological changes that occur in people with neuromuscular disease and how these changes impact on breathing, cough, and respiratory tract infections. The biological rationale for lung volume recruitment is provided, and the clinical trials that examine the immediate, short-term, and longer-term outcomes of lung volume recruitment in paediatric and adult neuromuscular diseases are presented and the results synthesised.}, }
@article {pmid37564648, year = {2023}, author = {Calafatti, M and Cocozza, G and Limatola, C and Garofalo, S}, title = {Microglial crosstalk with astrocytes and immune cells in amyotrophic lateral sclerosis.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1223096}, pmid = {37564648}, issn = {1664-3224}, mesh = {Mice ; Animals ; Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Microglia/pathology ; Astrocytes/pathology ; Motor Neurons/pathology ; }, abstract = {In recent years, biomedical research efforts aimed to unravel the mechanisms involved in motor neuron death that occurs in amyotrophic lateral sclerosis (ALS). While the main causes of disease progression were first sought in the motor neurons, more recent studies highlight the gliocentric theory demonstrating the pivotal role of microglia and astrocyte, but also of infiltrating immune cells, in the pathological processes that take place in the central nervous system microenvironment. From this point of view, microglia-astrocytes-lymphocytes crosstalk is fundamental to shape the microenvironment toward a pro-inflammatory one, enhancing neuronal damage. In this review, we dissect the current state-of-the-art knowledge of the microglial dialogue with other cell populations as one of the principal hallmarks of ALS progression. Particularly, we deeply investigate the microglia crosstalk with astrocytes and immune cells reporting in vitro and in vivo studies related to ALS mouse models and human patients. At last, we highlight the current experimental therapeutic approaches that aim to modulate microglial phenotype to revert the microenvironment, thus counteracting ALS progression.}, }
@article {pmid37563264, year = {2023}, author = {Nag, S and Schneider, JA}, title = {Limbic-predominant age-related TDP43 encephalopathy (LATE) neuropathological change in neurodegenerative diseases.}, journal = {Nature reviews. Neurology}, volume = {19}, number = {9}, pages = {525-541}, pmid = {37563264}, issn = {1759-4766}, support = {P30 AG072975/AG/NIA NIH HHS/United States ; R01 AG042210/AG/NIA NIH HHS/United States ; R01 AG067482/AG/NIA NIH HHS/United States ; R01 AG017917/AG/NIA NIH HHS/United States ; P30 AG010161/AG/NIA NIH HHS/United States ; RF1 AG022018/AG/NIA NIH HHS/United States ; }, mesh = {*Frontotemporal Lobar Degeneration/diagnosis ; *Alzheimer Disease/pathology ; *Neurodegenerative Diseases ; Dementia ; TDP-43 Proteinopathies ; Humans ; *Amyotrophic Lateral Sclerosis/complications ; Adult ; *Frontotemporal Dementia/pathology ; Aged, 80 and over ; DNA-Binding Proteins ; }, abstract = {TAR DNA-binding protein 43 (TDP43) is a focus of research in late-onset dementias. TDP43 pathology in the brain was initially identified in amyotrophic lateral sclerosis and frontotemporal lobar degeneration, and later in Alzheimer disease (AD), other neurodegenerative diseases and ageing. Limbic-predominant age-related TDP43 encephalopathy (LATE), recognized as a clinical entity in 2019, is characterized by amnestic dementia resembling AD dementia and occurring most commonly in adults over 80 years of age. Neuropathological findings in LATE, referred to as LATE neuropathological change (LATE-NC), consist of neuronal and glial cytoplasmic TDP43 localized predominantly in limbic areas with or without coexisting hippocampal sclerosis and/or AD neuropathological change and without frontotemporal lobar degeneration or amyotrophic lateral sclerosis pathology. LATE-NC is frequently associated with one or more coexisting pathologies, mainly AD neuropathological change. The focus of this Review is the pathology, genetic risk factors and nature of the cognitive impairments and dementia in pure LATE-NC and in LATE-NC associated with coexisting pathologies. As the clinical and cognitive profile of LATE is currently not easily distinguishable from AD dementia, it is important to develop biomarkers to aid in the diagnosis of this condition in the clinic. The pathogenesis of LATE-NC should be a focus of future research to form the basis for the development of preventive and therapeutic strategies.}, }
@article {pmid37562878, year = {2023}, author = {Weil, EL and Nakawah, MO and Masdeu, JC}, title = {Advances in the neuroimaging of motor disorders.}, journal = {Handbook of clinical neurology}, volume = {195}, number = {}, pages = {359-381}, doi = {10.1016/B978-0-323-98818-6.00039-X}, pmid = {37562878}, issn = {0072-9752}, mesh = {Humans ; Diffusion Tensor Imaging ; *Motor Disorders ; Neuroimaging/methods ; Magnetic Resonance Imaging/methods ; *Amyotrophic Lateral Sclerosis ; *Motor Neuron Disease/diagnostic imaging ; }, abstract = {Neuroimaging is a valuable adjunct to the history and examination in the evaluation of motor system disorders. Conventional imaging with computed tomography or magnetic resonance imaging depicts important anatomic information and helps to identify imaging patterns which may support diagnosis of a specific motor disorder. Advanced imaging techniques can provide further detail regarding volume, functional, or metabolic changes occurring in nervous system pathology. This chapter is an overview of the advances in neuroimaging with particular emphasis on both standard and less well-known advanced imaging techniques and findings, such as diffusion tensor imaging or volumetric studies, and their application to specific motor disorders. In addition, it provides reference to emerging imaging biomarkers in motor system disorders such as Parkinson disease, amyotrophic lateral sclerosis, and Huntington disease, and briefly reviews the neuroimaging findings in different causes of myelopathy and peripheral nerve disorders.}, }
@article {pmid37562867, year = {2023}, author = {Mahjoub, Y and Martino, D}, title = {Immunology and microbiome: Implications for motor systems.}, journal = {Handbook of clinical neurology}, volume = {195}, number = {}, pages = {135-157}, doi = {10.1016/B978-0-323-98818-6.00001-7}, pmid = {37562867}, issn = {0072-9752}, mesh = {Animals ; Humans ; *Gastrointestinal Microbiome/physiology ; Dysbiosis ; *Tourette Syndrome ; *Microbiota ; *Parkinson Disease ; }, abstract = {Immune-inflammatory mechanisms seem to play a relevant role in neurodegenerative disorders affecting motor systems, particularly Parkinson's disease, where activity changes in inflammatory cells and evidence of neuroinflammation in experimental models and patients is available. Amyotrophic lateral sclerosis is also characterized by neuroinflammatory changes that involve primarily glial cells, both microglia and astrocytes, as well as systemic immune dysregulation associated with more rapid progression. Similarly, the exploration of gut dysbiosis in these two prototypical neurodegenerative motor disorders is advancing rapidly. Altered composition of gut microbial constituents and related metabolic and putative functional pathways is supporting a pathophysiological link that is currently explored in preclinical, germ-free animal models. Less compelling, but still intriguing, evidence suggests that motor neurodevelopmental disorders, e.g., Tourette syndrome, are associated with abnormal trajectories of maturation that include also immune system development. Microglia has a key role also in these disorders, and new therapeutic avenues aiming at its modulation are exciting prospects. Preclinical and clinical research on the role of gut dysbiosis in Tourette syndrome and related behavioral disorders is still in its infancy, but early findings support the rationale to delve deeper into its contribution to neural and immune maturation abnormalities in its spectrum.}, }
@article {pmid37558576, year = {2023}, author = {Prado, MB and Pedro, KM and Adiao, KJB}, title = {Efficacy, safety and tolerability of high caloric diet in amyotrophic lateral sclerosis patients: A systematic review and meta-analysis.}, journal = {Revue neurologique}, volume = {179}, number = {9}, pages = {1008-1019}, doi = {10.1016/j.neurol.2023.01.731}, pmid = {37558576}, issn = {0035-3787}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy ; Prospective Studies ; *Motor Neuron Disease ; Diet ; Carbohydrates/therapeutic use ; }, abstract = {BACKGROUND: Several randomized clinical trials were done to determine whether supplementation with a high caloric diet, either through carbohydrate or lipid supplementation, is safe, tolerable and improves survival. However, most of these trials are small and the results are conflicting.<br><br>METHODS: Randomized prospective trials utilizing high caloric supplementation among patients with amyotrophic lateral sclerosis (ALS) were searched using the terms [("amyotrophic lateral sclerosis" or "motor neuron disease" or "ALS" or "MND") and ("high calorie" or "high fat" or "high protein" or "high carbohydrate" or "supplementation")] in Medline, Cochrane, Embase, Scopus, Prospero and Herdin by two independent neurologists. Journal articles deemed relevant were assessed for eligibility.<br><br>MAIN RESULTS: There were 57 articles obtained from databases, 49 of which were excluded. Four articles were further excluded since all of them had different interventions. Overall, there were 311 ALS patients included in the study, 176 of them were from the intervention group while 135 were used as controls. Overall, high caloric supplementation in ALS was deemed safe and tolerable, and also when adverse events, tolerability and mortality are combined using meta-analysis. Although in most publications the efficacy of giving high caloric supplementation has been generally beneficial, some of the outcome parameters are not statistically different from controls when studies are combined using meta-analysis.<br><br>CONCLUSIONS: Current evidence suggests that high calorie supplementation is generally safe and tolerable for patients with ALS. However, it has not been shown to be efficacious in improving weight and functional disability.}, }
@article {pmid37558082, year = {2024}, author = {Giannini, M and Porrua, O}, title = {Senataxin: A key actor in RNA metabolism, genome integrity and neurodegeneration.}, journal = {Biochimie}, volume = {217}, number = {}, pages = {10-19}, doi = {10.1016/j.biochi.2023.08.001}, pmid = {37558082}, issn = {1638-6183}, mesh = {Humans ; RNA Helicases/genetics/metabolism ; DNA Helicases/genetics/metabolism ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; *Neurodegenerative Diseases/genetics ; Transcription, Genetic ; Mutation ; Multifunctional Enzymes/genetics/metabolism ; RNA ; }, abstract = {The RNA/DNA helicase senataxin (SETX) has been involved in multiple crucial processes related to genome expression and integrity such us transcription termination, the regulation of transcription-replication conflicts and the resolution of R-loops. SETX has been the focus of numerous studies since the discovery that mutations in its coding gene are the root cause of two different neurodegenerative diseases: Ataxia with Oculomotor Apraxia type 2 (AOA2) and a juvenile form of Amyotrophic Lateral Sclerosis (ALS4). A plethora of cellular phenotypes have been described as the result of SETX deficiency, yet the precise molecular function of SETX as well as the molecular pathways leading from SETX mutations to AOA2 and ALS4 pathologies have remained unclear. However, recent data have shed light onto the biochemical activities and biological roles of SETX, thus providing new clues to understand the molecular consequences of SETX mutation. In this review we summarize near two decades of scientific effort to elucidate SETX function, we discuss strengths and limitations of the approaches and models used thus far to investigate SETX-associated diseases and suggest new possible research avenues for the study of AOA2 and ALS4 pathogenesis.}, }
@article {pmid37549725, year = {2023}, author = {Fan, H and Bai, Q and Yang, Y and Shi, X and Du, G and Yan, J and Shi, J and Wang, D}, title = {The key roles of reactive oxygen species in microglial inflammatory activation: Regulation by endogenous antioxidant system and exogenous sulfur-containing compounds.}, journal = {European journal of pharmacology}, volume = {956}, number = {}, pages = {175966}, doi = {10.1016/j.ejphar.2023.175966}, pmid = {37549725}, issn = {1879-0712}, mesh = {Humans ; *Antioxidants/pharmacology/metabolism ; Reactive Oxygen Species/metabolism ; *Microglia ; Sulfur Compounds/metabolism/pharmacology ; Neuroinflammatory Diseases ; Cysteine/pharmacology ; Sulfur/metabolism/pharmacology ; }, abstract = {Aberrant innate immunity in the brain has been implicated in the pathogenesis of several central nervous system (CNS) disorders, including Alzheimer's disease, Huntington's disease, Parkinson's disease, stroke, amyotrophic lateral sclerosis, and depression. Except for extraparenchymal CNS-associated macrophages, which predominantly afford protection against peripheral invading pathogens, it has been reported that microglia, a population of macrophage-like cells governing CNS immune defense in nearly all neurological diseases, are the main CNS resident immune cells. Although microglia have been recognized as the most important source of reactive oxygen species (ROS) in the CNS, ROS also may underlie microglial functions, especially M1 polarization, by modulating redox-sensitive signaling pathways. Recently, endogenous antioxidant systems, including glutathione, hydrogen sulfide, superoxide dismutase, and methionine sulfoxide reductase A, were found to be involved in regulating microglia-mediated neuroinflammation. A series of natural sulfur-containing compounds, including S-adenosyl methionine, S-methyl-L-cysteine, sulforaphane, DMS, and S-alk(enyl)-l-cysteine sulfoxide, modulating endogenous antioxidant systems have been discovered. We have summarized the current knowledge on the involvement of endogenous antioxidant systems in regulating microglial inflammatory activation and the effects of sulfur-containing compounds on endogenous antioxidant systems. Finally, we discuss the possibilities associated with compounds targeting the endogenous antioxidant system to treat neuroinflammation-associated diseases.}, }
@article {pmid37543480, year = {2023}, author = {Petrić Howe, M and Patani, R}, title = {Nonsense-mediated mRNA decay in neuronal physiology and neurodegeneration.}, journal = {Trends in neurosciences}, volume = {46}, number = {10}, pages = {879-892}, doi = {10.1016/j.tins.2023.07.001}, pmid = {37543480}, issn = {1878-108X}, support = {/CRUK_/Cancer Research UK/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; MR/S006591/1/MRC_/Medical Research Council/United Kingdom ; MR/S006591/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *Nonsense Mediated mRNA Decay ; *Protein Biosynthesis ; Neurons ; }, abstract = {The processes of mRNA export from the nucleus and subsequent mRNA translation in the cytoplasm are of particular relevance in eukaryotic cells. In highly polarised cells such as neurons, finely-tuned molecular regulation of these processes serves to safeguard the spatiotemporal fidelity of gene expression. Nonsense-mediated mRNA decay (NMD) is a cytoplasmic translation-dependent quality control process that regulates gene expression in a wide range of scenarios in the nervous system, including neurodevelopment, learning, and memory formation. Moreover, NMD dysregulation has been implicated in a broad range of neurodevelopmental and neurodegenerative disorders. We discuss how NMD and related aspects of mRNA translation regulate key neuronal functions and, in particular, we focus on evidence implicating these processes in the molecular pathogenesis of neurodegeneration. Finally, we discuss the therapeutic potential and challenges of targeting mRNA translation and NMD across the spectrum of largely untreatable neurological diseases.}, }
@article {pmid37535076, year = {2023}, author = {Yang, X and Zhang, Y and Luo, JX and Zhu, T and Ran, Z and Mu, BR and Lu, MH}, title = {Targeting mitophagy for neurological disorders treatment: advances in drugs and non-drug approaches.}, journal = {Naunyn-Schmiedeberg's archives of pharmacology}, volume = {396}, number = {12}, pages = {3503-3528}, pmid = {37535076}, issn = {1432-1912}, mesh = {Animals ; Humans ; Mitophagy/physiology ; Mitochondria/metabolism ; *Parkinson Disease/metabolism ; *Alzheimer Disease/metabolism ; }, abstract = {Mitochondria serve as a vital energy source for nerve cells. The mitochondrial network also acts as a defense mechanism against external stressors that can threaten the stability of the nervous system. However, excessive accumulation of damaged mitochondria can lead to neuronal death. Mitophagy is an essential pathway in the mitochondrial quality control system and can protect neurons by selectively removing damaged mitochondria. In most neurological disorders, dysfunctional mitochondria are a common feature, and drugs that target mitophagy can improve symptoms. Here, we reviewed the role of mitophagy in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, stroke, and traumatic brain injuries. We also summarized drug and non-drug approaches to promote mitophagy and described their therapeutic role in neurological disorders in order to provide valuable insight into the potential therapeutic agents available for neurological disease treatment. However, most studies on mitophagy regulation are based on preclinical research using cell and animal models, which may not accurately reflect the effects in humans. This poses a challenge to the clinical application of drugs targeting mitophagy. Additionally, these drugs may carry the risk of intolerable side effects and toxicity. Future research should focus on the development of safer and more targeted drugs for mitophagy.}, }
@article {pmid37529232, year = {2023}, author = {Wen, T and Zhang, Z}, title = {Cellular mechanisms of fibrin (ogen): insight from neurodegenerative diseases.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1197094}, pmid = {37529232}, issn = {1662-4548}, abstract = {Neurodegenerative diseases are prevalent and currently incurable conditions that progressively impair cognitive, behavioral, and psychiatric functions of the central or peripheral nervous system. Fibrinogen, a macromolecular glycoprotein, plays a crucial role in the inflammatory response and tissue repair in the human body and interacts with various nervous system cells due to its unique molecular structure. Accumulating evidence suggests that fibrinogen deposits in the brains of patients with neurodegenerative diseases. By regulating pathophysiological mechanisms and signaling pathways, fibrinogen can exacerbate the neuro-pathological features of neurodegenerative diseases, while depletion of fibrinogen contributes to the amelioration of cognitive function impairment in patients. This review comprehensively summarizes the molecular mechanisms and biological functions of fibrinogen in central nervous system cells and neurodegenerative diseases, including Alzheimer's disease, Multiple Sclerosis, Parkinson's disease, Vascular dementia, Huntington's disease, and Amyotrophic Lateral Sclerosis. Additionally, we discuss the potential of fibrinogen-related treatments in the management of neurodegenerative disorders.}, }
@article {pmid37525497, year = {2024}, author = {Chong, ZZ and Menkes, DL and Souayah, N}, title = {Pathogenesis underlying hexanucleotide repeat expansions in C9orf72 gene in amyotrophic lateral sclerosis.}, journal = {Reviews in the neurosciences}, volume = {35}, number = {1}, pages = {85-97}, pmid = {37525497}, issn = {2191-0200}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology ; C9orf72 Protein/genetics/metabolism ; Proteins/genetics/metabolism ; Dipeptides/genetics/metabolism ; RNA ; Arginine ; Alanine ; Glycine ; Proline ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and fatal neurodegenerative disorder. Mutations in C9orf72 and the resulting hexanucleotide repeat (GGGGCC) expansion (HRE) has been identified as a major cause of familial ALS, accounting for about 40 % of familial and 6 % of sporadic cases of ALS in Western patients. The pathological outcomes of HRE expansion in ALS have been recognized as the results of two mechanisms that include both the toxic gain-of-function and loss-of-function of C9ORF72. The gain of toxicity results from RNA and dipeptide repeats (DPRs). The HRE can be bidirectionally transcribed into RNA foci, which can bind to and disrupt RNA splicing, transport, and translation. The DPRs that include poly-glycine-alanine, poly-glycine-proline, poly-glycine- arginine, poly-proline-alanine, and poly-proline-arginine can induce toxicity by direct binding and sequestrating other proteins to interfere rRNA synthesis, ribosome biogenesis, translation, and nucleocytoplasmic transport. The C9ORF72 functions through binding to its partners-Smith-Magenis chromosome regions 8 (SMCR8) and WD repeat-containing protein (WDR41). Loss of C9ORF72 function results in impairment of autophagy, deregulation of autoimmunity, increased stress, and disruption of nucleocytoplasmic transport. Further insight into the mechanism in C9ORF72 HRE pathogenesis will facilitate identifying novel and effective therapeutic targets for ALS.}, }
@article {pmid37524128, year = {2023}, author = {Bernstein, HG and Smalla, KH and Keilhoff, G and Dobrowolny, H and Kreutz, MR and Steiner, J}, title = {The many "Neurofaces" of Prohibitins 1 and 2: Crucial for the healthy brain, dysregulated in numerous brain disorders.}, journal = {Journal of chemical neuroanatomy}, volume = {132}, number = {}, pages = {102321}, doi = {10.1016/j.jchemneu.2023.102321}, pmid = {37524128}, issn = {1873-6300}, mesh = {Humans ; *Prohibitins ; Endothelial Cells/metabolism ; Mitochondria/metabolism ; Brain/metabolism ; *Brain Diseases/metabolism ; }, abstract = {Prohibitin 1 (PHB1) and prohibitin 2 (PHB2) are proteins that are nearly ubiquitously expressed. They are localized in mitochondria, cytosol and cell nuclei. In the healthy CNS, they occur in neurons and non-neuronal cells (oligodendrocytes, astrocytes, microglia, and endothelial cells) and fulfill pivotal functions in brain development and aging, the regulation of brain metabolism, maintenance of structural integrity, synapse formation, aminoacidergic neurotransmission and, probably, regulation of brain action of certain hypothalamic-pituitary hormones.With regard to the diseased brain there is increasing evidence that prohibitins are prominently involved in numerous major diseases of the CNS, which are summarized and discussed in the present review (brain tumors, neurotropic viruses, Alzheimer disease, Down syndrome, Fronto-temporal and vascular dementia, dementia with Lewy bodies, Parkinson disease, Huntington disease, Multiple sclerosis, Amyotrophic lateral sclerosis, stroke, alcohol use disorder, schizophrenia and autism). Unfortunately, there is no PHB-targeted therapy available for any of these diseases.}, }
@article {pmid37522557, year = {2023}, author = {Kaur, K and Chen, PC and Ko, MW and Mei, A and Huerta-Yepez, S and Maharaj, D and Malarkannan, S and Jewett, A}, title = {Successes and Challenges in Taming the Beast: Cytotoxic Immune Effectors in Amyotrophic Lateral Sclerosis.}, journal = {Critical reviews in immunology}, volume = {43}, number = {1}, pages = {1-11}, doi = {10.1615/CritRevImmunol.2023047235}, pmid = {37522557}, issn = {1040-8401}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/therapy/metabolism ; Motor Neurons/metabolism/pathology ; Superoxide Dismutase-1/genetics/metabolism/pharmacology ; Cytokines/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurological disease characterized by the progressive loss of motor neurons in the brain and spinal cord. No effective therapeutic strategies have been established thus far, and therefore there is a significant unmet need for effective therapeutics to arrest the disease and reverse the pathologies induced by it. Although the cause of ALS is not well-defined, it appears to be heterogenous. Currently over 20 genes have been found to be associated with ALS. Family history can only be found in 10% of ALS patients, but in the remaining 90% no association with family history is found. The most common genetic causes are expansion in the C9orf72 gene and mutations in superoxide dismutase 1, TDP-43, and FUS. In our recent study, we also found mutations in TDP43 and FUS in ALS patients. To understand the pathogenesis of the disease, we set ourselves the task of analyzing the phenotype and function of all key immune effectors in ALS patients, comparing them with either a genetically healthy twin or healthy individuals. Our study demonstrated a significant increase in functional activation of NK and CD8+ T cytotoxic immune effectors and release of significant IFN-γ not only by the effector cells but also in the serum of ALS patients. Longitudinal analysis of CD8+ T cell-mediated IFN-γ secretion from ALS patients demonstrated continued and sustained increase in IFN-γ secretion with periods of decrease which coincided with certain treatments; however, the effects were largely short-lived. N-acetyl cysteine (NAC), one of the treatments used, is known to block cell death; however, even though such treatment was able to block most of the proinflammatory cytokines, chemokines, and growth factor release, it was not able to block IFN-γ and TNF-α, the two cytokines we had demonstrated previously to induce differentiation of the cells. In this review, we discuss the contribution of cytotoxic effector cells, especially primary NK cells, supercharged NK cells (sNK), and the contribution of sNK cells in expansion and functional activation of CD8+ T cells to memory/effector T cells in the pathogenesis of ALS. Potential new targeted therapeutic strategies are also discussed.}, }
@article {pmid37519177, year = {2023}, author = {Blagov, A and Borisov, E and Grechko, A and Popov, M and Sukhorukov, V and Orekhov, A}, title = {The Role of Impaired Mitochondrial Transport in the Development of Neurodegenerative Diseases.}, journal = {Journal of integrative neuroscience}, volume = {22}, number = {4}, pages = {86}, doi = {10.31083/j.jin2204086}, pmid = {37519177}, issn = {0219-6352}, support = {23-25-00237//Russian Science Foundation/ ; }, mesh = {Humans ; *Neurodegenerative Diseases ; Mitochondria ; *Alzheimer Disease ; *Parkinson Disease ; *Huntington Disease ; }, abstract = {The fight against neurodegenerative diseases is one of the key direction of modern medicine. Unfortunately, the difficulties in understanding the factors underlying the development of neurodegeneration hinder the development of breakthrough therapeutics that can stop or at least greatly slow down the progression of these diseases. In this review, it is considered the disruption of mitochondrial transport as one of the pathogenesis factors contributing to neurodegeneration using the examples of Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease. Here, the mechanism of mitochondrial transport under normal conditions and the mechanisms of disturbances for the indicated diseases will be considered.}, }
@article {pmid37516410, year = {2023}, author = {Ying, Z and Ye, N and Ma, Q and Chen, F and Li, N and Zhen, X}, title = {Targeted to neuronal organelles for CNS drug development.}, journal = {Advanced drug delivery reviews}, volume = {200}, number = {}, pages = {115025}, doi = {10.1016/j.addr.2023.115025}, pmid = {37516410}, issn = {1872-8294}, mesh = {Humans ; Mitochondria/metabolism/pathology ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Parkinson Disease ; Central Nervous System/metabolism/pathology ; Drug Development ; Central Nervous System Agents/pharmacology ; }, abstract = {Significant evidences indicate that sub-cellular organelle dynamics is critical for both physiological and pathological events and therefore may be attractive drug targets displaying great therapeutic potential. Although the basic biological mechanism underlying the dynamics of intracellular organelles has been extensively studied, relative drug development is still limited. In the present review, we show that due to the development of technical advanced imaging tools, especially live cell imaging methods, intracellular organelle dynamics (including mitochondrial dynamics and membrane contact sites) can be dissected at the molecular level. Based on these identified molecular targets, we review and discuss the potential of drug development to target organelle dynamics, especially mitochondria dynamics and ER-organelle membrane contact dynamics, in the central nervous system for treating human diseases, including neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis.}, }
@article {pmid37511491, year = {2023}, author = {Antonioni, A and Raho, EM and Lopriore, P and Pace, AP and Latino, RR and Assogna, M and Mancuso, M and Gragnaniello, D and Granieri, E and Pugliatti, M and Di Lorenzo, F and Koch, G}, title = {Frontotemporal Dementia, Where Do We Stand? A Narrative Review.}, journal = {International journal of molecular sciences}, volume = {24}, number = {14}, pages = {}, pmid = {37511491}, issn = {1422-0067}, mesh = {Middle Aged ; Humans ; *Frontotemporal Dementia/diagnosis/therapy/pathology ; *Neurodegenerative Diseases ; *Pick Disease of the Brain ; *Amyotrophic Lateral Sclerosis/pathology ; Temporal Lobe/pathology ; }, abstract = {Frontotemporal dementia (FTD) is a neurodegenerative disease of growing interest, since it accounts for up to 10% of middle-age-onset dementias and entails a social, economic, and emotional burden for the patients and caregivers. It is characterised by a (at least initially) selective degeneration of the frontal and/or temporal lobe, generally leading to behavioural alterations, speech disorders, and psychiatric symptoms. Despite the recent advances, given its extreme heterogeneity, an overview that can bring together all the data currently available is still lacking. Here, we aim to provide a state of the art on the pathogenesis of this disease, starting with established findings and integrating them with more recent ones. In particular, advances in the genetics field will be examined, assessing them in relation to both the clinical manifestations and histopathological findings, as well as considering the link with other diseases, such as amyotrophic lateral sclerosis (ALS). Furthermore, the current diagnostic criteria will be explored, including neuroimaging methods, nuclear medicine investigations, and biomarkers on biological fluids. Of note, the promising information provided by neurophysiological investigations, i.e., electroencephalography and non-invasive brain stimulation techniques, concerning the alterations in brain networks and neurotransmitter systems will be reviewed. Finally, current and experimental therapies will be considered.}, }
@article {pmid37511443, year = {2023}, author = {Kittipeerapat, N and Fabian, R and Bernsen, S and Weydt, P and Castro-Gomez, S}, title = {Creatine Kinase MB Isoenzyme Is a Complementary Biomarker in Amyotrophic Lateral Sclerosis.}, journal = {International journal of molecular sciences}, volume = {24}, number = {14}, pages = {}, pmid = {37511443}, issn = {1422-0067}, support = {390873048//Deutsche Forschungsgemeinschaft/ ; 21060//Alzheimer Forschung Initiative/ ; 0001//Alle-Lieben-Schmidt e.V/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; Isoenzymes ; *Neurodegenerative Diseases ; Creatine Kinase, MB Form ; Creatine Kinase ; Biomarkers ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is an invariably fatal neurodegenerative disease with limited therapeutic options. There is an urgent need for novel biomarkers to be used as surrogates for new therapeutic trials and disease monitoring. In this study, we sought to systematically study creatine kinase isoenzyme MB (CK-MB) in a real-world cohort of ALS patients, assess the diagnostic performance, and evaluate its association with other laboratory and clinical parameters. We reviewed data from 194 consecutive patients that included 130 ALS patients and 64 disease control patients (primary lateral sclerosis [PLS], benign fasciculations syndrome [BFS], Huntington's disease [HD] and Alzheimer's disease [AD]). CK-MB was elevated in the sera of more than half of all patients with ALS. In patients with spinal-onset ALS, CK-MB levels were significantly higher than in patients with other neurodegenerative diseases. Patients with slower rates of functional decline had a significantly higher baseline CK-MB. Furthermore, CK-MB elevations correlated with cardiac troponin T (cTnT) and with revised ALS Functional Rating Scale (ALSFRS-R) bulbar subcategory. We posit that measuring CK-MB in ALS patients in a complimentary fashion could potentially aid in the diagnostic workup of ALS and help discriminate the disease from some ALS mimics and other neurodegenerative diseases. CK-MB levels also may provide valuable prognostic information regarding disease aggressiveness as well as correlations with specific phenotypic presentations.}, }
@article {pmid37511056, year = {2023}, author = {Bettendorff, L}, title = {Synthetic Thioesters of Thiamine: Promising Tools for Slowing Progression of Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {24}, number = {14}, pages = {}, pmid = {37511056}, issn = {1422-0067}, mesh = {Animals ; Humans ; *Neurodegenerative Diseases/drug therapy ; Thiamine/pharmacology/therapeutic use ; Thiamine Pyrophosphate ; Coenzymes ; }, abstract = {Thiamine (vitamin B1) is essential for the brain. This is attributed to the coenzyme role of thiamine diphosphate (ThDP) in glucose and energy metabolism. The synthetic thiamine prodrug, the thioester benfotiamine (BFT), has been extensively studied and has beneficial effects both in rodent models of neurodegeneration and in human clinical studies. BFT has no known adverse effects and improves cognitive outcomes in patients with mild Alzheimer's disease. In cell culture and animal models, BFT has antioxidant and anti-inflammatory properties that seem to be mediated by a mechanism independent of the coenzyme function of ThDP. Recent in vitro studies show that another thiamine thioester, O,S-dibenzoylthiamine (DBT), is even more efficient than BFT, especially with respect to its anti-inflammatory potency, and is effective at lower concentrations. Thiamine thioesters have pleiotropic properties linked to an increase in circulating thiamine concentrations and possibly in hitherto unidentified open thiazole ring derivatives. The identification of the active neuroprotective metabolites and the clarification of their mechanism of action open extremely promising perspectives in the field of neurodegenerative, neurodevelopmental, and psychiatric conditions. The present review aims to summarize existing data on the neuroprotective effects of thiamine thioesters and give a comprehensive account.}, }
@article {pmid37511037, year = {2023}, author = {Xiang, L and Wang, Y and Liu, S and Liu, B and Jin, X and Cao, X}, title = {Targeting Protein Aggregates with Natural Products: An Optional Strategy for Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {24}, number = {14}, pages = {}, pmid = {37511037}, issn = {1422-0067}, support = {32000387//National Natural Science Foundation of China/ ; LY23C060001//Zhejiang Provincial Natural Science Foundation/ ; 2021LFR053//Scientific Research Foundation of Zhejiang A&amp;F University/ ; 19 0069//Swedish Cancer Society/ ; VR 2019-03604//Swedish Research Council/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/metabolism ; Protein Aggregates ; *Biological Products/pharmacology/therapeutic use ; *Parkinson Disease ; *Alzheimer Disease ; }, abstract = {Protein aggregation is one of the hallmarks of aging and aging-related diseases, especially for the neurodegenerative diseases (NDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Amyotrophic lateral sclerosis (ALS), and others. In these diseases, many pathogenic proteins, such as amyloid-β, tau, α-Syn, Htt, and FUS, form aggregates that disrupt the normal physiological function of cells and lead to associated neuronal lesions. Protein aggregates in NDs are widely recognized as one of the important targets for the treatment of these diseases. Natural products, with their diverse biological activities and rich medical history, represent a great treasure trove for the development of therapeutic strategies to combat disease. A number of in vitro and in vivo studies have shown that natural products, by virtue of their complex molecular scaffolds that specifically bind to pathogenic proteins and their aggregates, can inhibit the formation of aggregates, disrupt the structure of aggregates and destabilize them, thereby alleviating conditions associated with NDs. Here, we systematically reviewed studies using natural products to improve disease-related symptoms by reducing or inhibiting the formation of five pathogenic protein aggregates associated with NDs. This information should provide valuable insights into new directions and ideas for the treatment of neurodegenerative diseases.}, }
@article {pmid37511010, year = {2023}, author = {Carata, E and Muci, M and Di Giulio, S and Mariano, S and Panzarini, E}, title = {Looking to the Future of the Role of Macrophages and Extracellular Vesicles in Neuroinflammation in ALS.}, journal = {International journal of molecular sciences}, volume = {24}, number = {14}, pages = {}, pmid = {37511010}, issn = {1422-0067}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; Neuroinflammatory Diseases ; Macrophages/metabolism ; Inflammation/metabolism ; *Extracellular Vesicles/metabolism ; }, abstract = {Neuroinflammation is a common pathological feature of amyotrophic lateral sclerosis (ALS). Although scientific evidence to date does not allow defining neuroinflammation as an ALS trigger, its role in exacerbating motor neuron (MNs) degeneration and disease progression is attracting research interest. Activated CNS (Central Nervous System) glial cells, proinflammatory peripheral and infiltrated T lymphocytes and monocytes/macrophages, as well as the immunoreactive molecules they release, represent the active players for the role of immune dysregulation enhancing neuroinflammation. The crosstalk between the peripheral and CNS immune cells significantly correlates with the survival of ALS patients since the modification of peripheral macrophages can downregulate inflammation at the periphery along the nerves and in the CNS. As putative vehicles for misfolded protein and inflammatory mediators between cells, extracellular vesicles (EVs) have also drawn particular attention in the field of ALS. Both CNS and peripheral immune cells release EVs, which are able to modulate the behavior of neighboring recipient cells; unfortunately, the mechanisms involved in EVs-mediated communication in neuroinflammation remain unclear. This review aims to synthesize the current literature regarding EV-mediated cell-to-cell communication in the brain under ALS, with a particular point of view on the role of peripheral macrophages in responding to inflammation to understand the biological process and exploit it for ALS management.}, }
@article {pmid37508574, year = {2023}, author = {Malhotra, S and Miras, MCM and Pappolla, A and Montalban, X and Comabella, M}, title = {Liquid Biopsy in Neurological Diseases.}, journal = {Cells}, volume = {12}, number = {14}, pages = {}, pmid = {37508574}, issn = {2073-4409}, mesh = {Humans ; Liquid Biopsy/methods ; *Cell-Free Nucleic Acids ; *MicroRNAs ; *Central Nervous System Neoplasms ; Biomarkers ; }, abstract = {The most recent and non-invasive approach for studying early-stage biomarkers is liquid biopsy. This implies the extraction and analysis of non-solid biological tissues (serum, plasma, saliva, urine, and cerebrospinal fluid) without undergoing invasive procedures to determine disease prognosis. Liquid biopsy can be used for the screening of several components, such as extracellular vesicles, microRNAs, cell-free DNA, cell-free mitochondrial and nuclear DNA, circulating tumour cells, circulating tumour DNA, transfer RNA, and circular DNA or RNA derived from body fluids. Its application includes early disease diagnosis, the surveillance of disease activity, and treatment response monitoring, with growing evidence for validating this methodology in cancer, liver disease, and central nervous system (CNS) disorders. This review will provide an overview of mentioned liquid biopsy components, which could serve as valuable biomarkers for the evaluation of complex neurological conditions, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, epilepsy, stroke, traumatic brain injury, CNS tumours, and neuroinfectious diseases. Furthermore, this review highlights the future directions and potential limitations associated with liquid biopsy.}, }
@article {pmid37508558, year = {2023}, author = {Wu, LY and Song, YJ and Zhang, CL and Liu, J}, title = {KV Channel-Interacting Proteins in the Neurological and Cardiovascular Systems: An Updated Review.}, journal = {Cells}, volume = {12}, number = {14}, pages = {}, pmid = {37508558}, issn = {2073-4409}, mesh = {*Neurons/metabolism ; Carrier Proteins/metabolism ; Kv Channel-Interacting Proteins/genetics/metabolism ; Cell Membrane/metabolism ; *Cardiovascular System/metabolism ; }, abstract = {KV channel-interacting proteins (KChIP1-4) belong to a family of Ca[2+]-binding EF-hand proteins that are able to bind to the N-terminus of the KV4 channel α-subunits. KChIPs are predominantly expressed in the brain and heart, where they contribute to the maintenance of the excitability of neurons and cardiomyocytes by modulating the fast inactivating-KV4 currents. As the auxiliary subunit, KChIPs are critically involved in regulating the surface protein expression and gating properties of KV4 channels. Mechanistically, KChIP1, KChIP2, and KChIP3 promote the translocation of KV4 channels to the cell membrane, accelerate voltage-dependent activation, and slow the recovery rate of inactivation, which increases KV4 currents. By contrast, KChIP4 suppresses KV4 trafficking and eliminates the fast inactivation of KV4 currents. In the heart, IKs, ICa,L, and INa can also be regulated by KChIPs. ICa,L and INa are positively regulated by KChIP2, whereas IKs is negatively regulated by KChIP2. Interestingly, KChIP3 is also known as downstream regulatory element antagonist modulator (DREAM) because it can bind directly to the downstream regulatory element (DRE) on the promoters of target genes that are implicated in the regulation of pain, memory, endocrine, immune, and inflammatory reactions. In addition, all the KChIPs can act as transcription factors to repress the expression of genes involved in circadian regulation. Altered expression of KChIPs has been implicated in the pathogenesis of several neurological and cardiovascular diseases. For example, KChIP2 is decreased in failing hearts, while loss of KChIP2 leads to increased susceptibility to arrhythmias. KChIP3 is increased in Alzheimer's disease and amyotrophic lateral sclerosis, but decreased in epilepsy and Huntington's disease. In the present review, we summarize the progress of recent studies regarding the structural properties, physiological functions, and pathological roles of KChIPs in both health and disease. We also summarize the small-molecule compounds that regulate the function of KChIPs. This review will provide an overview and update of the regulatory mechanism of the KChIP family and the progress of targeted drug research as a reference for researchers in related fields.}, }
@article {pmid37505455, year = {2023}, author = {Dos Santos, MM and Ishida, K}, title = {We need to talk about Candida tropicalis: Virulence factors and survival mechanisms.}, journal = {Medical mycology}, volume = {61}, number = {8}, pages = {}, doi = {10.1093/mmy/myad075}, pmid = {37505455}, issn = {1460-2709}, support = {2022/08516-5//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado de S&#xe3;o Paulo/ ; 001 - 88887.663125/2022-00//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior/ ; 306041/2022-7//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; }, mesh = {Animals ; *Candida tropicalis/genetics ; *Antifungal Agents/therapeutic use ; Virulence Factors/genetics/metabolism ; Candida ; Candida albicans ; Drug Resistance, Fungal ; Microbial Sensitivity Tests/veterinary ; }, abstract = {Candida tropicalis is a notable species of the Candida genus representing an impressive epidemiology in tropical regions, especially in South America and Asia, where India already presents the species as the first in Candida epidemiology. Candida tropicalis has also shown a worrying antifungal resistance profile in recent years. It is essential to highlight that each pathogenic species of the Candida genus has a particular biology; however, Candida virulence factors are almost entirely based on studies with C. albicans. The intrinsic resistance of C. krusei to some azoles, the intrinsic osmotolerance of C. tropicalis, and the multidrug resistance of C. auris are just a few examples of how the biology of each Candida species is unique. Despite being a phylogenetically close species, C. tropicalis can support 15% NaCl, antagonistically metabolize and signal N-acetylglucosamine, encode 16 reported ALS genes, and other specificities discussed here compared to C. albicans. It is essential to clarify the details of the C. tropicalis infectious process, including identifying the participating secreted enzyme(s), the factors responsible for tissue damage, and the mechanisms underlying the morphogenesis and tolerance signaling pathways. In this review, we thoroughly assembled what is known about the main virulence factors of C. tropicalis, highlighting the missing pieces to stimulate further research with C. tropicalis and other non-Candida albicans species.}, }
@article {pmid37500993, year = {2023}, author = {Ludolph, A and Dupuis, L and Kasarskis, E and Steyn, F and Ngo, S and McDermott, C}, title = {Nutritional and metabolic factors in amyotrophic lateral sclerosis.}, journal = {Nature reviews. Neurology}, volume = {19}, number = {9}, pages = {511-524}, pmid = {37500993}, issn = {1759-4766}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; *Neurodegenerative Diseases ; Energy Metabolism ; Prognosis ; Disease Progression ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease that is classically thought to impact the motor system. Over the past 20 years, research has started to consider the contribution of non-motor symptoms and features of the disease, and how they might affect ALS prognosis. Of the non-motor features of the disease, nutritional status (for example, malnutrition) and metabolic balance (for example, weight loss and hypermetabolism) have been consistently shown to contribute to more rapid disease progression and/or earlier death. Several complex cellular changes observed in ALS, including mitochondrial dysfunction, are also starting to be shown to contribute to bioenergetic failure. The resulting energy depletion in high energy demanding neurons makes them sensitive to apoptosis. Given that nutritional and metabolic stressors at the whole-body and cellular level can impact the capacity to maintain optimal function, these factors present avenues through which we can identify novel targets for treatment in ALS. Several clinical trials are now underway evaluating the effectiveness of modifying energy balance in ALS, making this article timely in reviewing the evidence base for metabolic and nutritional interventions.}, }
@article {pmid37495165, year = {2023}, author = {Sammeta, SS and Banarase, TA and Rahangdale, SR and Wankhede, NL and Aglawe, MM and Taksande, BG and Mangrulkar, SV and Upaganlawar, AB and Koppula, S and Kopalli, SR and Umekar, MJ and Kale, MB}, title = {Molecular understanding of ER-MT communication dysfunction during neurodegeneration.}, journal = {Mitochondrion}, volume = {72}, number = {}, pages = {59-71}, doi = {10.1016/j.mito.2023.07.005}, pmid = {37495165}, issn = {1872-8278}, mesh = {Humans ; Endoplasmic Reticulum/metabolism ; Mitochondria/metabolism ; Mitochondrial Membranes/metabolism ; *Neurodegenerative Diseases/metabolism ; *Parkinson Disease/pathology ; }, abstract = {Biological researchers are seeing organelles in a new light. These cellular entities have been believed to be singular and distinctive structures that performed specialized purposes for a very long time. But in recentpast years, scientists have learned that organelles become dynamic and make physical contact. Additionally, Biological processes are regulated by organelles interactions and its alteration play an important role in cell malfunctioning and several pathologies, including neurodegenerative diseases. Mitochondrial-ER contact sites (MERCS) have received considerable attention in the domain of cell homeostasis and dysfunction, specifically in the area of neurodegeneration. This is largely due to the significant role of this subcellular compartment in a diverse array of vital cellular functions, including Ca[2+] homeostasis, transport, bioenergetics and turnover, mitochondrial dynamics, apoptotic signaling, ER stress, and inflammation. A significant number of disease-associated proteins were found to physically interact with the ER-Mitochondria (ER-MT) interface, causing structural and/or functional alterations in this compartment. In this review, we summarize current knowledge about the structure and functions of the ER-MT contact sites, as well as the possible repercussions of their alteration in notable neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and fronto-temporal dementia. The constraints and complexities in defining the nature and origin of the highlighted defects in ER-MT communication, as well as their concise contribution to the neurodegenerative process, are illustrated in particular. The possibility of using MERCS as a potential drug target to prevent neuronal damage and ultimately neurodegeneration is the topic of our final discussion.}, }
@article {pmid37494786, year = {2023}, author = {Jin, S and Zhang, L and Wang, L}, title = {Kaempferol, a potential neuroprotective agent in neurodegenerative diseases: From chemistry to medicine.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {165}, number = {}, pages = {115215}, doi = {10.1016/j.biopha.2023.115215}, pmid = {37494786}, issn = {1950-6007}, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/pathology ; *Neuroprotective Agents/pharmacology/therapeutic use/chemistry ; *Amyotrophic Lateral Sclerosis/drug therapy ; Kaempferols/pharmacology/therapeutic use ; *Alzheimer Disease/drug therapy ; *Parkinson Disease/drug therapy ; *Huntington Disease/drug therapy ; }, abstract = {Neurodegenerative diseases (NDDs) encompass a range of conditions that involve progressive deterioration and dysfunction of the nervous system. Some of the common NDDs include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). Although significant progress has been made in understanding the pathological mechanisms of NDDs in recent years, the development of targeted and effective drugs for their treatment remains challenging. Kaempferol is a flavonoid whose derivatives include kaempferol-O-rhamnoside, 3-O-β-rutinoside/6-hydroxykaempferol 3,6-di-O-β-d-glucoside, and kaempferide. Emerging studies have suggested that kaempferol and its derivatives possess neuroprotective properties and may have potential therapeutic benefits in NDDs. Here, we aimed to provide a theoretical basis for the use of kaempferol and its derivatives in the clinical treatment of NDDs. We systematically reviewed the literature in the PubMed, Web of Science, and Science Direct databases until June 2022 using the search terms "kaempferol," "kaempferol derivatives," "NDDs," "pharmacokinetics," and "biosynthesis" according to the reporting items for systematic review (PRISMA) standard. Based on combined results of in vivo and in vitro studies, we summarize the basic mechanisms and targets of kaempferol and its derivatives in the management of AD, PD, HD, and ALS. Kaempferol and its derivatives exert a neuroprotective role mainly by preventing the deposition of amyloid fibrils (such as Aβ, tau, and α-synuclein), inhibiting microglia activation, reducing the release of inflammatory factors, restoring the mitochondrial membrane to prevent oxidative stress, protecting the blood-brain barrier, and inhibiting specific enzyme activities (such as cholinesterase). Kaempferol and its derivatives are promising natural neuroprotective agents. By determining their pharmacological mechanism, kaempferol and its derivatives may be new candidate drugs for the treatment of NDDs.}, }
@article {pmid37493197, year = {2024}, author = {Sun, Y and Benatar, M and Mascías Cadavid, J and Ennist, D and Wicks, P and Staats, K and Beauchamp, M and Jhooty, S and Pattee, G and Brown, A and Bertorini, T and Barkhaus, P and Bromberg, M and Carter, G and Bedlack, R and Li, X}, title = {ALSUntangled #71: Nuedexta.}, journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration}, volume = {25}, number = {1-2}, pages = {218-222}, doi = {10.1080/21678421.2023.2239292}, pmid = {37493197}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Dextromethorphan/therapeutic use ; Drug Combinations ; *Quinidine/therapeutic use ; }, abstract = {Nuedexta is a combination of dextromethorphan hydrobromide and quinidine sulfate and was approved by the Food and Drug Administration (FDA) in 2010 to treat pseudobulbar affect (PBA). There have since been anecdotal case reports of bulbar function improvements after Nuedexta treatment. Here, we review the off-label use of Nuedexta for improving bulbar function in people with ALS. Nuedexta has plausible mechanisms for protecting brain stem motor neurons via its effects on S1R and glutamate excitotoxicity. Recent clinical trials support that Nuedexta can improve bulbar function in PALS, with or without PBA. Nuedexta causes mild to moderate side effects. Based on this information, we support considering Nuedexta treatment for bulbar dysfunction in ALS patients with or without PBA.}, }
@article {pmid37489441, year = {2023}, author = {Ramakrishna, K and Nalla, LV and Naresh, D and Venkateswarlu, K and Viswanadh, MK and Nalluri, BN and Chakravarthy, G and Duguluri, S and Singh, P and Rai, SN and Kumar, A and Singh, V and Singh, SK}, title = {WNT-β Catenin Signaling as a Potential Therapeutic Target for Neurodegenerative Diseases: Current Status and Future Perspective.}, journal = {Diseases (Basel, Switzerland)}, volume = {11}, number = {3}, pages = {}, pmid = {37489441}, issn = {2079-9721}, abstract = {Wnt/β-catenin (WβC) signaling pathway is an important signaling pathway for the maintenance of cellular homeostasis from the embryonic developmental stages to adulthood. The canonical pathway of WβC signaling is essential for neurogenesis, cell proliferation, and neurogenesis, whereas the noncanonical pathway (WNT/Ca[2+] and WNT/PCP) is responsible for cell polarity, calcium maintenance, and cell migration. Abnormal regulation of WβC signaling is involved in the pathogenesis of several neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and spinal muscular atrophy (SMA). Hence, the alteration of WβC signaling is considered a potential therapeutic target for the treatment of neurodegenerative disease. In the present review, we have used the bibliographical information from PubMed, Google Scholar, and Scopus to address the current prospects of WβC signaling role in the abovementioned neurodegenerative diseases.}, }
@article {pmid37488888, year = {2024}, author = {Zhou, M and Li, S and Huang, C}, title = {Physiological and pathological functions of circular RNAs in the nervous system.}, journal = {Neural regeneration research}, volume = {19}, number = {2}, pages = {342-349}, pmid = {37488888}, issn = {1673-5374}, abstract = {Circular RNAs (circRNAs) are a class of covalently closed single-stranded RNAs that are expressed during the development of specific cells and tissues. CircRNAs play crucial roles in physiological and pathological processes by sponging microRNAs, modulating gene transcription, controlling the activity of certain RNA-binding proteins, and producing functional peptides. A key focus of research at present is the functionality of circRNAs in the nervous system and several advances have emerged over the last 2 years. However, the precise role of circRNAs in the nervous system has yet to be comprehensively reviewed. In this review, we first summarize the recently described roles of circRNAs in brain development, maturity, and aging. Then, we focus on the involvement of circRNAs in various diseases of the central nervous system, such as brain cancer, chronic neurodegenerative diseases, acute injuries of the nervous system, and neuropathic pain. A better understanding of the functionality of circRNAs will help us to develop potential diagnostic, prognostic, and therapeutic strategies to treat diseases of the nervous system.}, }
@article {pmid37488879, year = {2024}, author = {Yu, Z and Teng, Y and Yang, J and Yang, L}, title = {The role of exosomes in adult neurogenesis: implications for neurodegenerative diseases.}, journal = {Neural regeneration research}, volume = {19}, number = {2}, pages = {282-288}, pmid = {37488879}, issn = {1673-5374}, abstract = {Exosomes are cup-shaped extracellular vesicles with a lipid bilayer that is approximately 30 to 200 nm in thickness. Exosomes are widely distributed in a range of body fluids, including urine, blood, milk, and saliva. Exosomes exert biological function by transporting factors between different cells and by regulating biological pathways in recipient cells. As an important form of intercellular communication, exosomes are increasingly being investigated due to their ability to transfer bioactive molecules such as lipids, proteins, mRNAs, and microRNAs between cells, and because they can regulate physiological and pathological processes in the central nervous system. Adult neurogenesis is a multistage process by which new neurons are generated and migrate to be integrated into existing neuronal circuits. In the adult brain, neurogenesis is mainly localized in two specialized niches: the subventricular zone adjacent to the lateral ventricles and the subgranular zone of the dentate gyrus. An increasing body of evidence indicates that adult neurogenesis is tightly controlled by environmental conditions with the niches. In recent studies, exosomes released from different sources of cells were shown to play an active role in regulating neurogenesis both in vitro and in vivo, thereby participating in the progression of neurodegenerative disorders in patients and in various disease models. Here, we provide a state-of-the-art synopsis of existing research that aimed to identify the diverse components of exosome cargoes and elucidate the therapeutic potential of exosomal contents in the regulation of neurogenesis in several neurodegenerative diseases. We emphasize that exosomal cargoes could serve as a potential biomarker to monitor functional neurogenesis in adults. In addition, exosomes can also be considered as a novel therapeutic approach to treat various neurodegenerative disorders by improving endogenous neurogenesis to mitigate neuronal loss in the central nervous system.}, }
@article {pmid37488847, year = {2024}, author = {Huber, CC and Wang, H}, title = {Pathogenic and therapeutic role of exosomes in neurodegenerative disorders.}, journal = {Neural regeneration research}, volume = {19}, number = {1}, pages = {75-79}, pmid = {37488847}, issn = {1673-5374}, support = {P20 GM103443/GM/NIGMS NIH HHS/United States ; P20 RR016479/RR/NCRR NIH HHS/United States ; RF1 AG072510/AG/NIA NIH HHS/United States ; T32 GM136503/GM/NIGMS NIH HHS/United States ; }, abstract = {Neurodegenerative disorders affect millions of people worldwide, and the prevalence of these disorders is only projected to rise as the number of people over 65 will drastically increase in the coming years. While therapies exist to aid in symptomatic relief, effective treatments that can stop or reverse the progress of each neurodegenerative disease are lacking. Recently, research on the role of extracellular vesicles as disease markers and therapeutics has been intensively studied. Exosomes, 30-150 nm in diameter, are one type of extracellular vesicles facilitating cell-to-cell communication. Exosomes are thought to play a role in disease propagation in a variety of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Accordingly, the exosomes derived from the patients are an invaluable source of disease biomarkers. On the other hand, exosomes, especially those derived from stem cells, could serve as a therapeutic for these disorders, as seen by a rapid increase in clinical trials investigating the therapeutic efficacy of exosomes in different neurological diseases. This review summarizes the pathological burden and therapeutic approach of exosomes in neurodegenerative disorders. We also highlight how heat shock increases the yield of exosomes while still maintaining their therapeutic efficacy. Finally, this review concludes with outstanding questions that remain to be addressed in exosomal research.}, }
@article {pmid37483353, year = {2023}, author = {Shi, Y and Zhao, Y and Lu, L and Gao, Q and Yu, D and Sun, M}, title = {CRISPR/Cas9: implication for modeling and therapy of amyotrophic lateral sclerosis.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1223777}, pmid = {37483353}, issn = {1662-4548}, abstract = {Amyotrophic lateral sclerosis (ALS) is a deadly neurological disease with a complicated and variable pathophysiology yet to be fully understood. There is currently no effective treatment available to either slow or terminate it. However, recent advances in ALS genomics have linked genes to phenotypes, encouraging the creation of novel therapeutic approaches and giving researchers more tools to create efficient animal models. Genetically engineered rodent models replicating ALS disease pathology have a high predictive value for translational research. This review addresses the history of the evolution of gene editing tools, the most recent ALS disease models, and the application of CRISPR/Cas9 against ALS disease.}, }
@article {pmid37481642, year = {2023}, author = {Yang, R and Yang, B and Liu, W and Tan, C and Chen, H and Wang, X}, title = {Emerging role of non-coding RNAs in neuroinflammation mediated by microglia and astrocytes.}, journal = {Journal of neuroinflammation}, volume = {20}, number = {1}, pages = {173}, pmid = {37481642}, issn = {1742-2094}, support = {32102749//National Natural Science Foundation of China/ ; 32122086//National Natural Science Foundation of China/ ; 2022M721277//China Postdoctoral Science Foundation/ ; 2021YFD1800800//National Key Research and Development Program of China/ ; 2021CFA016//Natural Science Foundation of Hubei Province/ ; 2662023PY005//Fundamental Research Funds for the Central Universities/ ; }, mesh = {Humans ; Astrocytes ; Microglia ; Neuroinflammatory Diseases ; *RNA, Long Noncoding/genetics ; *MicroRNAs ; }, abstract = {Neuroinflammation has been implicated in the initiation and progression of several central nervous system (CNS) disorders, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, ischemic stroke, traumatic brain injury, spinal cord injury, viral encephalitis, and bacterial encephalitis. Microglia and astrocytes are essential in neural development, maintenance of synaptic connections, and homeostasis in a healthy brain. The activation of astrocytes and microglia is a defense mechanism of the brain against damaged tissues and harmful pathogens. However, their activation triggers neuroinflammation, which can exacerbate or induce CNS injury. Non-coding RNAs (ncRNAs) are functional RNA molecules that lack coding capabilities but can actively regulate mRNA expression and function through various mechanisms. ncRNAs are highly expressed in astrocytes and microglia and are potential mediators of neuroinflammation. We reviewed the recent research progress on the role of miRNAs, lncRNAs, and circRNAs in regulating neuroinflammation in various CNS diseases. Understanding how these ncRNAs affect neuroinflammation will provide important therapeutic insights for preventing and managing CNS dysfunction.}, }
@article {pmid37475885, year = {2023}, author = {Acosta-Galeana, I and Hernández-Martínez, R and Reyes-Cruz, T and Chiquete, E and Aceves-Buendia, JJ}, title = {RNA-binding proteins as a common ground for neurodegeneration and inflammation in amyotrophic lateral sclerosis and multiple sclerosis.}, journal = {Frontiers in molecular neuroscience}, volume = {16}, number = {}, pages = {1193636}, pmid = {37475885}, issn = {1662-5099}, abstract = {The neurodegenerative and inflammatory illnesses of amyotrophic lateral sclerosis and multiple sclerosis were once thought to be completely distinct entities that did not share any remarkable features, but new research is beginning to reveal more information about their similarities and differences. Here, we review some of the pathophysiological features of both diseases and their experimental models: RNA-binding proteins, energy balance, protein transportation, and protein degradation at the molecular level. We make a thorough analysis on TDP-43 and hnRNP A1 dysfunction, as a possible common ground in both pathologies, establishing a potential link between neurodegeneration and pathological immunity. Furthermore, we highlight the putative variations that diverge from a common ground in an atemporal course that proposes three phases for all relevant molecular events.}, }
@article {pmid37475658, year = {2023}, author = {Roleston, C and Shaw, R and West, K}, title = {Compassionate communities interventions: a scoping review.}, journal = {Annals of palliative medicine}, volume = {12}, number = {5}, pages = {936-951}, doi = {10.21037/apm-22-867}, pmid = {37475658}, issn = {2224-5839}, mesh = {Humans ; *Palliative Care/methods ; Australia ; Europe ; }, abstract = {BACKGROUND: The compassionate communities (CC) movement is an emergent health promotion approach to palliative care that views illness, dying, death, and loss as universal experiences, and challenges the notion that disease precludes one from health care attention and interest. It seeks to normalise these phenomena and reorientate care to communities by activating naturally occurring networks and mobilising community resources. A surge of interventions aligned with the ethos of CC has been observed over the last decade. This scoping review seeks to synthesise what is currently known about the design, efficacy, and impact of CC interventions.<br><br>METHODS: Cochrane, PubMed, Scopus, and Web of Science were systematically searched. Hand searching was performed on three key journals, reference lists and citation lists of included articles, and relevant review articles. Two levels of analysis were conducted. First, a numerical presentation of the characteristics of CC interventions. Second, a thematically orientated narrative analysis of intervention efficacy.<br><br>RESULTS: A total of 1,882 records were screened; 62 papers were included. Most were implemented by palliative care organisations in Europe, North America, and Australia. Included studies were mapped against Clark et al.'s taxonomy of end-of-life interventions: educational (n=17); service (n=20); clinical (n=3); cultural (n=4); and multi-dimensional (n=18) interventions are discussed. While preliminary findings are positive, claims of efficacy are limited due to methodological paucity in the field.<br><br>CONCLUSIONS: We argue that the field would benefit from more transparent and theoretically driven CC interventions in order to explicate the mechanism(s) for successful intervention implementation.}, }
@article {pmid37475056, year = {2023}, author = {Yang, S and Park, JH and Lu, HC}, title = {Axonal energy metabolism, and the effects in aging and neurodegenerative diseases.}, journal = {Molecular neurodegeneration}, volume = {18}, number = {1}, pages = {49}, pmid = {37475056}, issn = {1750-1326}, support = {R01 NS086794/NS/NINDS NIH HHS/United States ; NS086794/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Humans ; *Neurodegenerative Diseases/metabolism ; NAD/metabolism ; Aging/metabolism ; Axons/metabolism ; Energy Metabolism ; Glucose/metabolism ; }, abstract = {Human studies consistently identify bioenergetic maladaptations in brains upon aging and neurodegenerative disorders of aging (NDAs), such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and Amyotrophic lateral sclerosis. Glucose is the major brain fuel and glucose hypometabolism has been observed in brain regions vulnerable to aging and NDAs. Many neurodegenerative susceptible regions are in the topological central hub of the brain connectome, linked by densely interconnected long-range axons. Axons, key components of the connectome, have high metabolic needs to support neurotransmission and other essential activities. Long-range axons are particularly vulnerable to injury, neurotoxin exposure, protein stress, lysosomal dysfunction, etc. Axonopathy is often an early sign of neurodegeneration. Recent studies ascribe axonal maintenance failures to local bioenergetic dysregulation. With this review, we aim to stimulate research in exploring metabolically oriented neuroprotection strategies to enhance or normalize bioenergetics in NDA models. Here we start by summarizing evidence from human patients and animal models to reveal the correlation between glucose hypometabolism and connectomic disintegration upon aging/NDAs. To encourage mechanistic investigations on how axonal bioenergetic dysregulation occurs during aging/NDAs, we first review the current literature on axonal bioenergetics in distinct axonal subdomains: axon initial segments, myelinated axonal segments, and axonal arbors harboring pre-synaptic boutons. In each subdomain, we focus on the organization, activity-dependent regulation of the bioenergetic system, and external glial support. Second, we review the mechanisms regulating axonal nicotinamide adenine dinucleotide (NAD[+]) homeostasis, an essential molecule for energy metabolism processes, including NAD[+] biosynthetic, recycling, and consuming pathways. Third, we highlight the innate metabolic vulnerability of the brain connectome and discuss its perturbation during aging and NDAs. As axonal bioenergetic deficits are developing into NDAs, especially in asymptomatic phase, they are likely exaggerated further by impaired NAD[+] homeostasis, the high energetic cost of neural network hyperactivity, and glial pathology. Future research in interrogating the causal relationship between metabolic vulnerability, axonopathy, amyloid/tau pathology, and cognitive decline will provide fundamental knowledge for developing therapeutic interventions.}, }
@article {pmid37470509, year = {2023}, author = {Strnad, P and San Martin, J}, title = {RNAi therapeutics for diseases involving protein aggregation: fazirsiran for alpha-1 antitrypsin deficiency-associated liver disease.}, journal = {Expert opinion on investigational drugs}, volume = {32}, number = {7}, pages = {571-581}, doi = {10.1080/13543784.2023.2239707}, pmid = {37470509}, issn = {1744-7658}, mesh = {Humans ; *Protein Aggregates ; RNA Interference ; RNAi Therapeutics ; *alpha 1-Antitrypsin Deficiency/complications/genetics/therapy ; RNA, Small Interfering ; }, abstract = {INTRODUCTION: Therapeutic agents that prevent protein misfolding or promote protein clearance are being studied to treat proteotoxic diseases. Among them, alpha-1 antitrypsin deficiency (AATD) is caused by mutations in the alpha-1 antitrypsin (SERPINA1) gene. Fazirsiran is a small interfering RNA (siRNA) that is intended to address the underlying cause of liver disease associated with AATD through the RNA interference (RNAi) mechanism.<br><br>AREAS COVERED: This article describes the role of misfolded proteins and protein aggregates in disease and options for therapeutic approaches. The RNAi mechanism is discussed, along with how the siRNA therapeutic fazirsiran for the treatment of AATD was developed. We also describe the implications of siRNA therapeutics in extrahepatic diseases.<br><br>EXPERT OPINION: Using RNAi as a therapeutic approach is well suited to treat disease in conditions where an excess of a protein or the effect of an abnormal mutated protein causes disease. The results observed for the first few siRNA therapeutics that were approved or are in development provide an important promise for the development of future drugs that can address such conditions in a specific and targeted way. Current developments should enable the use of RNAi therapeutics outside the liver, where there are many more possible diseases to address.}, }
@article {pmid37469832, year = {2023}, author = {Mora, S and Allodi, I}, title = {Neural circuit and synaptic dysfunctions in ALS-FTD pathology.}, journal = {Frontiers in neural circuits}, volume = {17}, number = {}, pages = {1208876}, pmid = {37469832}, issn = {1662-5110}, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; *Frontotemporal Dementia/complications/genetics/pathology ; Brain ; Cognition ; }, abstract = {Action selection is a capital feature of cognition that guides behavior in processes that range from motor patterns to executive functions. Here, the ongoing actions need to be monitored and adjusted in response to sensory stimuli to increase the chances of reaching the goal. As higher hierarchical processes, these functions rely on complex neural circuits, and connective loops found within the brain and the spinal cord. Successful execution of motor behaviors depends, first, on proper selection of actions, and second, on implementation of motor commands. Thus, pathological conditions crucially affecting the integrity and preservation of these circuits and their connectivity will heavily impact goal-oriented motor behaviors. Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) are two neurodegenerative disorders known to share disease etiology and pathophysiology. New evidence in the field of ALS-FTD has shown degeneration of specific neural circuits and alterations in synaptic connectivity, contributing to neuronal degeneration, which leads to the impairment of motor commands and executive functions. This evidence is based on studies performed on animal models of disease, post-mortem tissue, and patient derived stem cells. In the present work, we review the existing evidence supporting pathological loss of connectivity and selective impairment of neural circuits in ALS and FTD, two diseases which share strong genetic causes and impairment in motor and executive functions.}, }
@article {pmid37469125, year = {2023}, author = {Ghaderi, S and Fatehi, F and Kalra, S and Batouli, SAH}, title = {MRI biomarkers for memory-related impairment in amyotrophic lateral sclerosis: a systematic review.}, journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration}, volume = {}, number = {}, pages = {1-17}, doi = {10.1080/21678421.2023.2236651}, pmid = {37469125}, issn = {2167-9223}, abstract = {Introduction: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder associated with cognitive and behavioral impairments and motor symptoms. Magnetic resonance imaging (MRI) biomarkers have been investigated as potential tools for detecting and monitoring memory-related impairment in ALS. Our objective was to examine the importance of identifying MRI biomarkers for memory-related impairment in ALS, motor neuron disease (MND), and ALS frontotemporal dementia (FTD) (ALS-FTD) patients. Methods: PubMed and Scopus databases were searched. Keywords covering magnetic resonance imaging, ALS, MND, and memory impairments were searched. There were a total of 25 studies included in our work here. Results: The structural MRI (sMRI) studies reported gray matter (GM) atrophy in the regions associated with memory processing, such as the hippocampus and parahippocampal gyrus (PhG), in ALS patients. The diffusion tensor imaging (DTI) studies showed white matter (WM) alterations in the corticospinal tract (CST) and other tracts that are related to motor and extra-motor functions, and these alterations were associated with memory and executive function impairments in ALS. The functional MRI (fMRI) studies also demonstrated an altered activation in the prefrontal cortex, limbic system, and other brain regions involved in memory and emotional processing in ALS patients. Conclusion: MRI biomarkers show promise in uncovering the neural mechanisms of memory-related impairment in ALS. Nonetheless, addressing challenges such as sample sizes, imaging protocols, and longitudinal studies is crucial for future research. Ultimately, MRI biomarkers have the potential to be a tool for detecting and monitoring memory-related impairments in ALS.}, }
@article {pmid37467887, year = {2023}, author = {Troxell, DA and Bach, JR and Nilsestuen, JO}, title = {Mechanical Insufflation-Exsufflation Implementation and Management, Aided by Graphics Analysis.}, journal = {Chest}, volume = {164}, number = {6}, pages = {1505-1511}, doi = {10.1016/j.chest.2023.07.007}, pmid = {37467887}, issn = {1931-3543}, mesh = {Humans ; *Insufflation ; Respiration, Artificial ; Lung ; *Respiratory Insufficiency/therapy ; Cough ; }, abstract = {Mechanical insufflation-exsufflation (MIE) facilitates airway clearance to mitigate respiratory infection, decompensation, and ultimately the need for intubation and placement of a tracheostomy tube. Despite widespread adoption as a respiratory support intervention for motor neuron disease, muscular dystrophy, spinal cord injury, and other diseases associated with ventilatory pump failure and ineffective cough peak flow, there is debate in the clinical community about how to optimize settings when MIE is implemented. This article will demonstrate the clinical utility of MIE graphics in titrating the initial MIE settings, guiding upper airway and lung protective strategies and providing insight to clinicians for ongoing clinical management.}, }
@article {pmid37465321, year = {2023}, author = {Gnoni, V and Zoccolella, S and Giugno, A and Urso, D and Tamburrino, L and Filardi, M and Logroscino, G}, title = {Hypothalamus and amyotrophic lateral sclerosis: potential implications in sleep disorders.}, journal = {Frontiers in aging neuroscience}, volume = {15}, number = {}, pages = {1193483}, pmid = {37465321}, issn = {1663-4365}, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that affects both motor and non-motor functions, including sleep regulation. Emerging evidence suggests that the hypothalamus, a brain region that plays a critical role in sleep-wake regulation, may be involved in the pathogenesis of ALS-related sleep disturbances. In this review, we have summarized results of studies on sleep disorders in ALS published between 2000 and 2023. Thereafter, we examined possible mechanisms by which hypothalamic dysfunctions may contribute to ALS-related sleep disturbances. Achieving a deeper understanding of the relationship between hypothalamic dysfunction and sleep disturbances in ALS can help improve the overall management of ALS and reduce the burden on patients and their families.}, }
@article {pmid37463628, year = {2023}, author = {Soumya, BS and Shreenidhi, VP and Agarwal, A and Gandhirajan, RK and Dharmarajan, A and Warrier, S}, title = {Unwinding the role of Wnt signaling cascade and molecular triggers of motor neuron degeneration in amyotrophic lateral sclerosis (ALS).}, journal = {Cellular signalling}, volume = {110}, number = {}, pages = {110807}, doi = {10.1016/j.cellsig.2023.110807}, pmid = {37463628}, issn = {1873-3913}, mesh = {Humans ; Animals ; *Amyotrophic Lateral Sclerosis/metabolism ; Wnt Signaling Pathway ; Motor Neurons/metabolism ; Oxidative Stress ; Nerve Degeneration/metabolism/pathology ; Disease Models, Animal ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative condition, triggered by various factors causing the degeneration of upper and lower motor neurons, resulting in progressive muscle wasting, paralysis, and death. Multiple in vivo and in vitro models have been established to unravel the molecular events leading to the deterioration of motor neurons in ALS. The canonical and non-canonical Wnt signaling pathway has been implicated to play a crucial role in the progression of neurodegenerative disorders. This review discusses the role of Wnt signaling in the reported causes of ALS such as oxidative stress, mitochondrial dysfunction, autophagy, and apoptosis. Mutations in ALS-associated genes such as SOD1, C9orf72, TDP43, FUS, and OPTN cause an imbalance in neuronal integrity and homeostasis leading to motor neuron demise. Wnt signaling is also observed to play a crucial role in the muscle sparing of oculomotor neurons. The non-canonical Wnt/Ca[2+] pathway which regulates intrinsic electrophysiological properties and mobilizes calcium ions to maintain neuronal integrity has been found to be altered in the stem cell-derived ALS model. Thus, the interplay of dysregulated canonical and non-canonical Wnt pathways in multiple motor neuron disease models has shown that Wnt contributes to disease progression indicating it to be utilized as a potential target for ALS.}, }
@article {pmid37458987, year = {2023}, author = {Gupta, R and Advani, D and Yadav, D and Ambasta, RK and Kumar, P}, title = {Dissecting the Relationship Between Neuropsychiatric and Neurodegenerative Disorders.}, journal = {Molecular neurobiology}, volume = {60}, number = {11}, pages = {6476-6529}, pmid = {37458987}, issn = {1559-1182}, mesh = {Humans ; Aged ; *Alzheimer Disease/genetics ; *Parkinson Disease ; *Huntington Disease ; *Amyotrophic Lateral Sclerosis ; *Depressive Disorder, Major ; *Autism Spectrum Disorder ; *Neurodegenerative Diseases/metabolism ; }, abstract = {Neurodegenerative diseases (NDDs) and neuropsychiatric disorders (NPDs) are two common causes of death in elderly people, which includes progressive neuronal cell death and behavioral changes. NDDs include Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, and motor neuron disease, characterized by cognitive defects and memory impairment, whereas NPDs include depression, seizures, migraine headaches, eating disorders, addictions, palsies, major depressive disorders, anxiety, and schizophrenia, characterized by behavioral changes. Mounting evidence demonstrated that NDDs and NPDs share an overlapping mechanism, which includes post-translational modifications, the microbiota-gut-brain axis, and signaling events. Mounting evidence demonstrated that various drug molecules, namely, natural compounds, repurposed drugs, multitarget directed ligands, and RNAs, have been potentially implemented as therapeutic agents against NDDs and NPDs. Herein, we highlighted the overlapping mechanism, the role of anxiety/stress-releasing factors, cytosol-to-nucleus signaling, and the microbiota-gut-brain axis in the pathophysiology of NDDs and NPDs. We summarize the therapeutic application of natural compounds, repurposed drugs, and multitarget-directed ligands as therapeutic agents. Lastly, we briefly described the application of RNA interferences as therapeutic agents in the pathogenesis of NDDs and NPDs. Neurodegenerative diseases and neuropsychiatric diseases both share a common signaling molecule and molecular phenomenon, namely, pro-inflammatory cytokines, γCaMKII and MAPK/ERK, chemokine receptors, BBB permeability, and the gut-microbiota-brain axis. Studies have demonstrated that any alterations in the signaling mentioned above molecules and molecular phenomena lead to the pathophysiology of neurodegenerative diseases, namely, Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, and neuropsychiatric disorders, such as bipolar disorder, schizophrenia, depression, anxiety, autism spectrum disorder, and post-traumatic stress disorder.}, }
@article {pmid37457842, year = {2023}, author = {Mavridis, IN and Pyrgelis, ES}, title = {Nucleus accumbens changes in amyotrophic lateral sclerosis.}, journal = {American journal of neurodegenerative disease}, volume = {12}, number = {3}, pages = {85-88}, pmid = {37457842}, issn = {2165-591X}, abstract = {Amyotrophic lateral sclerosis (ALS), a representative example of motor neuron disease, is a progressive and fatal neurodegenerative disorder. The nucleus accumbens (NA) is the ventral striatum's main part and is considered as a modulator of the human brain's reward network. The purpose of this article is to review the current knowledge regarding NA changes in ALS patients. The NA involvement in ALS includes volumetric, cellular and molecular changes. There are recent imaging and pathological studies revealing NA atrophy in ALS, a finding which seems to be related to neuronal loss and protein deposition in this area. The clinical significance of NA atrophy in these patients is not currently fully understood. Perhaps it could be correlated with apathy, behavioral disturbances and cognitive impairment that ALS patients sometimes manifest.}, }
@article {pmid37456581, year = {2023}, author = {Giovannelli, L and Bari, E and Jommi, C and Tartara, F and Armocida, D and Garbossa, D and Cofano, F and Torre, ML and Segale, L}, title = {Mesenchymal stem cell secretome and extracellular vesicles for neurodegenerative diseases: Risk-benefit profile and next steps for the market access.}, journal = {Bioactive materials}, volume = {29}, number = {}, pages = {16-35}, pmid = {37456581}, issn = {2452-199X}, abstract = {Neurodegenerative diseases represent a growing burden on healthcare systems worldwide. Mesenchymal stem cells (MSCs) have shown promise as a potential therapy due to their neuroregenerative, neuroprotective, and immunomodulatory properties, which are, however, linked to the bioactive substances they release, collectively known as secretome. This paper provides an overview of the most recent research on the safety and efficacy of MSC-derived secretome and extracellular vesicles (EVs) in clinical (if available) and preclinical models of Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, Huntington's disease, acute ischemic stroke, and spinal cord injury. The article explores the biologically active substances within MSC-secretome/EVs, the mechanisms responsible for the observed therapeutic effects, and the strategies that may be used to optimize MSC-secretome/EVs production based on specific therapeutic needs. The review concludes with a critical discussion of current clinical trials and a perspective on potential future directions in translating MSC-secretome and EVs into the clinic, specifically regarding how to address the challenges associated with their pharmaceutical manufacturing, including scalability, batch-to-batch consistency, adherence to Good Manufacturing Practices (GMP) guidelines, formulation, and storage, along with quality controls, access to the market and relative costs, value for money and impact on total expenditure.}, }
@article {pmid37451615, year = {2023}, author = {Yen, H and Yen, H and Huang, CH and Huang, IH and Hung, WK and Su, HJ and Tai, CC and Haw, WWY and Flohr, C and Yiu, ZZN and Chi, CC}, title = {Systematic Review and Critical Appraisal of Urticaria Clinical Practice Guidelines: A Global Guidelines in Dermatology Mapping Project (GUIDEMAP).}, journal = {The journal of allergy and clinical immunology. In practice}, volume = {11}, number = {10}, pages = {3213-3220.e11}, doi = {10.1016/j.jaip.2023.07.002}, pmid = {37451615}, issn = {2213-2201}, mesh = {Humans ; Australia ; Databases, Factual ; *Dermatology ; Stakeholder Participation ; *Urticaria/diagnosis/therapy ; Practice Guidelines as Topic ; }, abstract = {BACKGROUND: Management of urticaria can be optimized with clinical practice guidelines (CPGs). However, the quality of recent urticaria CPGs remains unclear.<br><br>OBJECTIVE: To identify and appraise urticaria CPGs worldwide published in the last 5 years.<br><br>METHODS: A search for relevant urticaria CPGs was conducted between January 1, 2017, and May 31, 2022, using the following databases: MEDLINE, Embase, National Institute for Health and Care Excellence (NICE) Evidence Search, Guidelines International Network, ECRI Guidelines Trust, Australian Clinical Practice Guidelines, Trip Medical Database, and DynaMed. The included CPGs were critically appraised using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument, Lenzer et&#xa0;al's red flags, and the Institute of Medicine (IOM) criteria of trustworthiness.<br><br>RESULTS: We included 21 urticaria CPGs. Most guidelines reviewed treatment recommendations of chronic spontaneous urticaria. The majority of guidelines were from European and Asian countries with high and high-middle sociodemographic index, written in English, and openly accessible. Seventeen guidelines (81%) had at least 1 AGREE II domain rated poor quality. Applicability, rigor of development, and stakeholder involvement were the 3 AGREE II domains that scored the lowest across guidelines. Appraisal with Lenzer et&#xa0;al's red flags showed that 18 guidelines (86%) raised at least 1 red flag indicating potential bias. The top 3 domains raising red flags were: no inclusion of nonphysician experts/patient representative/community stakeholders, no or limited involvement of a methodologist in the evaluation of evidence, and lack of external review. Based on IOM's criteria of trustworthiness, 20 guidelines (95%) had 1 or more criteria that did not meet best practice standards. The 3 domains with the highest number of best practice standards not met were updating procedures, rating strength of recommendations, and external review. Guidelines scored highest for the AGREE II domains of defining scope and purpose and clarity of presentation, and had the most fully met IOM's best practice standard for articulation of recommendations. However, only 1 urticaria CPG by NICE was identified as rigorously developed across all 3 appraisal tools.<br><br>CONCLUSIONS: The quality of urticaria CPGs in the last 5 years varied widely. Only the NICE urticaria guideline consistently demonstrated excellent quality, high trustworthiness, and low risk of bias. Use of a rigorous framework to rate certainty of evidence and grade strength of recommendation, involvement of methodologists, stakeholder engagement with external review, and clear guidance for updating can help improve the quality of future CPGs.}, }
@article {pmid37450673, year = {2023}, author = {Mushtaq, U}, title = {EP1 receptor: Devil in emperors coat.}, journal = {Journal of cellular biochemistry}, volume = {124}, number = {8}, pages = {1105-1114}, doi = {10.1002/jcb.30436}, pmid = {37450673}, issn = {1097-4644}, mesh = {Receptors, Prostaglandin E, EP1 Subtype/genetics ; *Signal Transduction/physiology ; *Protein Kinase C/metabolism ; }, abstract = {EP1 receptor belongs to prostanoid receptors and is activated by prostaglandin E2. The receptor performs contrasting functions in central nervous system (CNS) and other tissues. Although the receptor is neurotoxic and proapoptotic in CNS, it has also been reported to act in an antiapoptotic manner by modulating cell survival, proliferation, invasion, and migration in different types of cancers. The receptor mediates its neurotoxic effects by increasing cytosolic Ca[2+] levels, leading to the activation of its downstream target, protein kinase C, in different neurological disorders including Alzheimer's disease, Parkinson's disease, stroke, amyotrophic lateral sclerosis, and epilepsy. Antagonists ONO-8713, SC51089, and SC51322 against EP1 receptor ameliorate the neurotoxic effect by attenuating the neuroinflammation. The receptor also shows increased expression in different types of cancers and has been found to activate different signaling pathways, which lead to the development, progression, and metastasis of different cancers. The receptor stimulates the cell survival pathway by phosphorylating the AKT and PTEN (phosphatase and tensin homolog deleted on chromosome 10) signaling pathways. Although there are limited studies about this receptor and not a single clinical trial has been targeting the EP1 receptor for different neurological disorders or cancer, the receptor is appearing as a potential candidate for therapeutic targets. The aim of this article is to review the recent progress in understanding the pathogenic roles of EP1 receptors in different pathological conditions.}, }
@article {pmid37450244, year = {2023}, author = {Dubowsky, M and Theunissen, F and Carr, JM and Rogers, ML}, title = {The Molecular Link Between TDP-43, Endogenous Retroviruses and Inflammatory Neurodegeneration in Amyotrophic Lateral Sclerosis: a Potential Target for Triumeq, an Antiretroviral Therapy.}, journal = {Molecular neurobiology}, volume = {60}, number = {11}, pages = {6330-6345}, pmid = {37450244}, issn = {1559-1182}, support = {1950//Motor Neurone Disease Australia/ ; 1950//Andrew Butcher Grant/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *Endogenous Retroviruses ; *Motor Neuron Disease/pathology ; Motor Neurons/metabolism ; DNA-Binding Proteins/metabolism ; *HIV Infections/pathology ; }, abstract = {Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND), is a progressive neurological disorder, characterised by the death of upper and lower motor neurons. The aetiology of ALS remains unknown, and treatment options are limited. Endogenous retroviruses (ERVs), specifically human endogenous retrovirus type K (HERV-K), have been proposed to be involved in the propagation of neurodegeneration in ALS. ERVs are genomic remnants of ancient viral infection events, with most being inactive and not retaining the capacity to encode a fully infectious virus. However, some ERVs retain the ability to be activated and transcribed, and ERV transcripts have been found to be elevated within the brain tissue of MND patients. A hallmark of ALS pathology is altered localisation of the transactive response (TAR) DNA binding protein 43 kDa (TDP-43), which is normally found within the nucleus of neuronal and glial cells and is involved in RNA regulation. In ALS, TDP-43 aggregates within the cytoplasm and facilitates neurodegeneration. The involvement of ERVs in ALS pathology is thought to occur through TDP-43 and neuroinflammatory mediators. In this review, the proposed involvement of TDP-43, HERV-K and immune regulators on the onset and progression of ALS will be discussed. Furthermore, the evidence supporting a therapy based on targeting ERVs in ALS will be reviewed.}, }
@article {pmid37445986, year = {2023}, author = {Ciurea, AV and Mohan, AG and Covache-Busuioc, RA and Costin, HP and Glavan, LA and Corlatescu, AD and Saceleanu, VM}, title = {Unraveling Molecular and Genetic Insights into Neurodegenerative Diseases: Advances in Understanding Alzheimer's, Parkinson's, and Huntington's Diseases and Amyotrophic Lateral Sclerosis.}, journal = {International journal of molecular sciences}, volume = {24}, number = {13}, pages = {}, pmid = {37445986}, issn = {1422-0067}, mesh = {Humans ; *Neurodegenerative Diseases/genetics ; *Huntington Disease/genetics ; *Alzheimer Disease/genetics ; *Parkinson Disease/genetics ; *Amyotrophic Lateral Sclerosis/genetics ; }, abstract = {Neurodegenerative diseases are, according to recent studies, one of the main causes of disability and death worldwide. Interest in molecular genetics has started to experience exponential growth thanks to numerous advancements in technology, shifts in the understanding of the disease as a phenomenon, and the change in the perspective regarding gene editing and the advantages of this action. The aim of this paper is to analyze the newest approaches in genetics and molecular sciences regarding four of the most important neurodegenerative disorders: Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. We intend through this review to focus on the newest treatment, diagnosis, and predictions regarding this large group of diseases, in order to obtain a more accurate analysis and to identify the emerging signs that could lead to a better outcome in order to increase both the quality and the life span of the patient. Moreover, this review could provide evidence of future possible novel therapies that target the specific genes and that could be useful to be taken into consideration when the classical approaches fail to shed light.}, }
@article {pmid37445890, year = {2023}, author = {Kousparou, C and Fyrilla, M and Stephanou, A and Patrikios, I}, title = {DHA/EPA (Omega-3) and LA/GLA (Omega-6) as Bioactive Molecules in Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {24}, number = {13}, pages = {}, pmid = {37445890}, issn = {1422-0067}, mesh = {Humans ; Eicosapentaenoic Acid/pharmacology ; Docosahexaenoic Acids/therapeutic use/metabolism ; *Neurodegenerative Diseases/drug therapy ; *Fatty Acids, Omega-3/therapeutic use ; Fatty Acids, Unsaturated/metabolism ; Arachidonic Acid/metabolism ; Linoleic Acids ; Inflammation/drug therapy ; }, abstract = {Neurodegenerative diseases are characterized by neuroinflammation, neuronal depletion and oxidative stress. They coincide with subtle chronic or flaring inflammation, sometimes escalating with infiltrations of the immune system cells in the inflamed parts causing mild to severe or even lethal damage. Thus, neurodegenerative diseases show all features of autoimmune diseases. Prevalence of neurodegenerative diseases has dramatically increased in recent decades and unfortunately, the therapeutic efficacy and safety profile of available drugs is moderate. The beneficial effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) polyunsaturated fatty acids (omega-3 PUFAs) are nowadays highlighted by a plethora of studies. They play a role in suppression of inflammation, gene expression, cellular membrane fluidity/permeability, immune functionality and intracellular/exocellular signaling. The role of omega-6 polyunsaturated fatty acids, such as linoleic acid (LA), gamma linolenic acid (GLA), and arachidonic acid (AA), on neuroprotection is controversial, as some of these agents, specifically AA, are proinflammatory, whilst current data suggest that they may have neuroprotective properties as well. This review provides an overview of the existing recent clinical studies with respect to the role of omega-3 and omega-6 PUFAs as therapeutic agents in chronic, inflammatory, autoimmune neurodegenerative diseases as well as the dosages and the period used for testing.}, }
@article {pmid37443797, year = {2023}, author = {Afonso, GJM and Cavaleiro, C and Valero, J and Mota, SI and Ferreiro, E}, title = {Recent Advances in Extracellular Vesicles in Amyotrophic Lateral Sclerosis and Emergent Perspectives.}, journal = {Cells}, volume = {12}, number = {13}, pages = {}, pmid = {37443797}, issn = {2073-4409}, support = {PTDC/BTM-ORG/0055/2021, UIDB/04539/2020, UIDP/04539/2020, LA/P/0058/2020, 2022.13281.BD, DL57/2016/CP1448/CT0027, CEECIND/00322/2017, 2022.00011.CEECIND.//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e Tecnologia/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; *Neurodegenerative Diseases ; *Extracellular Vesicles ; Motor Neurons ; *Exosomes ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a severe and incurable neurodegenerative disease characterized by the progressive death of motor neurons, leading to paralysis and death. It is a rare disease characterized by high patient-to-patient heterogeneity, which makes its study arduous and complex. Extracellular vesicles (EVs) have emerged as important players in the development of ALS. Thus, ALS phenotype-expressing cells can spread their abnormal bioactive cargo through the secretion of EVs, even in distant tissues. Importantly, owing to their nature and composition, EVs' formation and cargo can be exploited for better comprehension of this elusive disease and identification of novel biomarkers, as well as for potential therapeutic applications, such as those based on stem cell-derived exosomes. This review highlights recent advances in the identification of the role of EVs in ALS etiopathology and how EVs can be promising new therapeutic strategies.}, }
@article {pmid37443723, year = {2023}, author = {Spalloni, A and de Stefano, S and Gimenez, J and Greco, V and Mercuri, NB and Chiurchiù, V and Longone, P}, title = {The Ying and Yang of Hydrogen Sulfide as a Paracrine/Autocrine Agent in Neurodegeneration: Focus on Amyotrophic Lateral Sclerosis.}, journal = {Cells}, volume = {12}, number = {13}, pages = {}, pmid = {37443723}, issn = {2073-4409}, support = {RF-2018-12365509//Italian Ministry of Health/ ; Ricerca Corrente (Linea di Ricerca 2)//Governo Italiano/ ; }, mesh = {Humans ; *Hydrogen Sulfide ; *Neurodegenerative Diseases ; *Amyotrophic Lateral Sclerosis ; Central Nervous System ; Nitric Oxide ; }, abstract = {Ever since its presence was reported in the brain, the nature and role of hydrogen sulfide (H2S) in the Central Nervous System (CNS) have changed. Consequently, H2S has been elected as the third gas transmitter, along with carbon monoxide and nitric oxide, and a number of studies have focused on its neuromodulatory and protectant functions in physiological conditions. The research on H2S has highlighted its many facets in the periphery and in the CNS, and its role as a double-faced compound, switching from protective to toxic depending on its concentration. In this review, we will focus on the bell-shaped nature of H2S as an angiogenic factor and as a molecule released by glial cells (mainly astrocytes) and non-neuronal cells acting on the surrounding environment (paracrine) or on the releasing cells themselves (autocrine). Finally, we will discuss its role in Amyotrophic Lateral Sclerosis, a paradigm of a neurodegenerative disease.}, }
@article {pmid37440197, year = {2023}, author = {Yang, J and Li, H and Zhao, Y}, title = {Dessert or Poison? The Roles of Glycosylation in Alzheimer's, Parkinson's, Huntington's Disease, and Amyotrophic Lateral Sclerosis.}, journal = {Chembiochem : a European journal of chemical biology}, volume = {24}, number = {16}, pages = {e202300017}, doi = {10.1002/cbic.202300017}, pmid = {37440197}, issn = {1439-7633}, mesh = {Humans ; Aged ; *Huntington Disease ; *Neurodegenerative Diseases ; *Alzheimer Disease ; *Amyotrophic Lateral Sclerosis ; *Parkinson Disease ; Glycosylation ; *Poisons ; Quality of Life ; }, abstract = {Ministry of Education and Key Laboratory of Neurons and glial cells of the central nervous system (CNS) are modified by glycosylation and rely on glycosylation to achieve normal neural function. Neurodegenerative disease is a common disease of the elderly, affecting their healthy life span and quality of life, and no effective treatment is currently available. Recent research implies that various glycosylation traits are altered during neurodegenerative diseases, suggesting a potential implication of glycosylation in disease pathology. Herein, we summarized the current knowledge about glycosylation associated with Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic lateral sclerosis (ALS) pathogenesis, focusing on their promising functional avenues. Moreover, we collected research aimed at highlighting the need for such studies to provide a wealth of disease-related glycosylation information that will help us better understand the pathophysiological mechanisms and hopefully specific glycosylation information to provide further diagnostic and therapeutic directions for neurodegenerative diseases.}, }
@article {pmid37436254, year = {2023}, author = {Cunha-Correia, CD and Gama, MDP and Fontana, PN and Fantini, FGMM and Prado, GF and Dourado Júnior, MET and Schwingel, PA}, title = {Noninvasive mechanical ventilation assistance in amyotrophic lateral sclerosis: a systematic review.}, journal = {Sao Paulo medical journal = Revista paulista de medicina}, volume = {142}, number = {1}, pages = {e2022470}, pmid = {37436254}, issn = {1806-9460}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/complications ; *Noninvasive Ventilation/methods ; Quality of Life ; Respiration, Artificial/adverse effects ; *Respiratory Insufficiency/therapy/complications ; }, abstract = {BACKGROUND: Respiratory failure is the most common cause of death in patients with amyotrophic lateral sclerosis (ALS), and morbidity is related to poor quality of life (QOL). Non-invasive ventilation (NIV) may be associated with prolonged survival and QOL in patients with ALS.<br><br>OBJECTIVES: To assess whether NIV is effective and safe for patients with ALS in terms of survival and QOL, alerting the health system.<br><br>DESIGN AND SETTING: Systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting standards using population, intervention, comparison, and outcome strategies.<br><br>METHODS: The Cochrane Library, CENTRAL, MEDLINE, LILACS, EMBASE, and CRD databases were searched based on the eligibility criteria for all types of studies on NIV use in patients with ALS published up to January 2022. Data were extracted from the included studies, and the findings were presented using a narrative synthesis.<br><br>RESULTS: Of the 120 papers identified, only 14 were related to systematic reviews. After thorough reading, only one meta-analysis was considered eligible. In the second stage, 248 studies were included; however, only one systematic review was included. The results demonstrated that NIV provided relief from the symptoms of chronic hypoventilation, increased survival, and improved QOL compared to standard care. These results varied according to clinical phenotype.<br><br>CONCLUSIONS: NIV in patients with ALS improves the outcome and can delay the indication for tracheostomy, reducing expenditure on hospitalization and occupancy of intensive care unit beds.<br><br>PROSPERO database: CRD42021279910 - https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=279910.}, }
@article {pmid37433768, year = {2023}, author = {Zhang, W and Xiao, D and Mao, Q and Xia, H}, title = {Role of neuroinflammation in neurodegeneration development.}, journal = {Signal transduction and targeted therapy}, volume = {8}, number = {1}, pages = {267}, pmid = {37433768}, issn = {2059-3635}, support = {UL1 TR002538/TR/NCATS NIH HHS/United States ; }, mesh = {Animals ; *Alzheimer Disease/genetics ; *Amyotrophic Lateral Sclerosis/genetics ; Inflammation/genetics ; Neuroinflammatory Diseases ; *Parkinson Disease/genetics ; Protein Aggregates ; Humans ; Clinical Trials as Topic ; Disease Models, Animal ; }, abstract = {Studies in neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and Amyotrophic lateral sclerosis, Huntington's disease, and so on, have suggested that inflammation is not only a result of neurodegeneration but also a crucial player in this process. Protein aggregates which are very common pathological phenomenon in neurodegeneration can induce neuroinflammation which further aggravates protein aggregation and neurodegeneration. Actually, inflammation even happens earlier than protein aggregation. Neuroinflammation induced by genetic variations in CNS cells or by peripheral immune cells may induce protein deposition in some susceptible population. Numerous signaling pathways and a range of CNS cells have been suggested to be involved in the pathogenesis of neurodegeneration, although they are still far from being completely understood. Due to the limited success of traditional treatment methods, blocking or enhancing inflammatory signaling pathways involved in neurodegeneration are considered to be promising strategies for the therapy of neurodegenerative diseases, and many of them have got exciting results in animal models or clinical trials. Some of them, although very few, have been approved by FDA for clinical usage. Here we comprehensively review the factors affecting neuroinflammation and the major inflammatory signaling pathways involved in the pathogenicity of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and Amyotrophic lateral sclerosis. We also summarize the current strategies, both in animal models and in the clinic, for the treatment of neurodegenerative diseases.}, }
@article {pmid37432384, year = {2023}, author = {Renke, G and Almeida, VBP and Souza, EA and Lessa, S and Teixeira, RL and Rocha, L and Sousa, PL and Starling-Soares, B}, title = {Clinical Outcomes of the Deleterious Effects of Aluminum on Neuro-Cognition, Inflammation, and Health: A Review.}, journal = {Nutrients}, volume = {15}, number = {9}, pages = {}, pmid = {37432384}, issn = {2072-6643}, mesh = {Humans ; *Aluminum/toxicity ; *Inflammation ; Adjuvants, Immunologic ; Chelating Agents ; Cognition ; Food Additives ; }, abstract = {Introduction: In the scenario of metal toxicity, aluminum (Al) stands out as a ubiquitous type of metal that can be combined with other elements and form different compounds. Al is widely used daily as an adjuvant in vaccines, antacids, food additives (as components of AI-containing food additives), skin care products, cosmetics, and kitchenware, and can be an element or contaminant present in our daily life. Objective: To present a review of the main deleterious effects of Al on human health. Methods: The search was carried out from September 2022 to February 2023 in the Scopus, PubMed, Science Direct, Scielo, and Google Scholar databases, using scientific articles from 2012 to 2023. The quality of the studies was based on the GRADE instrument, and the risk of bias was analyzed according to the Cochrane instrument. Results and Conclusions: A total of 115 files were search returned. Further, 95 articles were evaluated, and 44 were included in this review. Based on the results, measuring Al's relevance to health is essential in medicine. Several studies have demonstrated clinical outcomes and metabolic alterations with Al exposure. The tolerable weekly intake established by the European Food Safety Authority (EFSA) of 1 mg Al/kg body weight can be achieved through dietary exposure alone. Proven neurotoxicity in humans is the critical adverse effect of Al. A carcinogenic effect of Al has not been proven so far. Preventive medicine advocates that exposure to Al should be kept as low as possible. Chelating agents, such as calcium disodium ethylene diamine tetraacetic acid and deferoxamine, are options for acute poisoning, and monomethysilanetriol supplementation may be a long-term strategy with chelation potential. Further studies are needed to assess the impacts of Al on human health.}, }
@article {pmid37429415, year = {2023}, author = {Asveda, T and Talwar, P and Ravanan, P}, title = {Exploring microglia and their phenomenal concatenation of stress responses in neurodegenerative disorders.}, journal = {Life sciences}, volume = {328}, number = {}, pages = {121920}, doi = {10.1016/j.lfs.2023.121920}, pmid = {37429415}, issn = {1879-0631}, mesh = {Humans ; Microglia/metabolism ; *Neurodegenerative Diseases/metabolism ; Central Nervous System/metabolism ; *Alzheimer Disease/metabolism ; *Parkinson Disease/metabolism ; }, abstract = {Neuronal cells are highly functioning but also extremely stress-sensitive cells. By defending the neuronal cells against pathogenic insults, microglial cells, a unique cell type, act as the frontline cavalry in the central nervous system (CNS). Their remarkable and unique ability to self-renew independently after their creation is crucial for maintaining normal brain function and neuroprotection. They have a wide range of molecular sensors that help maintain CNS homeostasis during development and adulthood. Despite being the protector of the CNS, studies have revealed that persistent microglial activation may be the root cause of innumerable neurodegenerative illnesses, including Alzheimer's disease (AD), Parkinson's disease (PD), and Amyotrophic Lateral Sclerosis (ALS). From our vigorous review, we state that there is a possible interlinking between pathways of Endoplasmic reticulum (ER) stress response, inflammation, and oxidative stress resulting in dysregulation of the microglial population, directly influencing the accumulation of pro-inflammatory cytokines, complement factors, free radicals, and nitric oxides leading to cell death via apoptosis. Recent research uses the suppression of these three pathways as a therapeutic approach to prevent neuronal death. Hence, in this review, we have spotlighted the advancement in microglial studies, which focus on their molecular defenses against multiple stresses, and current therapeutic strategies indirectly targeting glial cells for neurodevelopmental diseases.}, }
@article {pmid37428208, year = {2023}, author = {Johnston, B and Dönmez, CF and Julião, M}, title = {Effectiveness of dignity therapy in the context of culturally competent care in people with palliative care needs: a systematic review of systematic reviews.}, journal = {Current opinion in supportive and palliative care}, volume = {17}, number = {3}, pages = {186-192}, pmid = {37428208}, issn = {1751-4266}, mesh = {Humans ; *Culturally Competent Care ; *Palliative Care/psychology ; Quality of Life/psychology ; Respect ; Systematic Reviews as Topic ; }, abstract = {PURPOSE OF REVIEW: This review aims to synthesise the evidence from systematic reviews and meta-analyses on the efficacy of dignity therapy (DT) in relation to psychosocial and spiritual outcomes in the context of person-centred and culturally competent care for people with supportive and palliative care needs.<br><br>RECENT FINDINGS: Thirteen reviews were found, including seven conducted by nurses. Most reviews were of high quality, including various study populations such as cancer, motor neurone disease and non-malignant conditions. Six psychosocial and spiritual outcomes were identified: quality of life, anxiety, depression, hopefulness, meaning and purpose in life, and suffering based on the cultural variations in the implementation of DT.<br><br>SUMMARY: DT has a positive impact on anxiety, depression, suffering, and meaning and purpose in life for people with palliative care needs, but the evidence is somewhat conflicted as to whether DT is effective in improving hope, quality of life and spiritual outcomes in the context of culturally competent care. Nurse-led DT seems desirable given its pivotal role when caring for people with palliative care needs. More randomised controlled trials should be conducted for people with different cultural backgrounds to provide person-centred, culturally competent supportive and palliative care.}, }
@article {pmid37427325, year = {2023}, author = {Najafi, S and Najafi, P and Kaffash Farkhad, N and Hosseini Torshizi, G and Assaran Darban, R and Boroumand, AR and Sahab-Negah, S and Khodadoust, MA and Tavakol-Afshari, J}, title = {Mesenchymal stem cell therapy in amyotrophic lateral sclerosis (ALS) patients: A comprehensive review of disease information and future perspectives.}, journal = {Iranian journal of basic medical sciences}, volume = {26}, number = {8}, pages = {872-881}, pmid = {37427325}, issn = {2008-3866}, abstract = {Amyotrophic lateral sclerosis (ALS) is a rare deadly progressive neurological disease that primarily affects the upper and lower motor neurons with an annual incidence rate of 0.6 to 3.8 per 100,000 people. Weakening and gradual atrophy of the voluntary muscles are the first signs of the disease onset affecting all aspects of patients' lives, including eating, speaking, moving, and even breathing. Only 5-10% of patients have a familial type of the disease and show an autosomal dominant pattern, but the cause of the disease is unknown in the remaining 90% of patients (Sporadic ALS). However, in both types of disease, the patient's survival is 2 to 5 years from the disease onset. Some clinical and molecular biomarkers, magnetic resonance imaging (MRI), blood or urine test, muscle biopsy, and genetic testing are complementary methods for disease diagnosis. Unfortunately, with the exception of Riluzole, the only medically approved drug for the management of this disease, there is still no definitive cure for it. In this regard, the use of mesenchymal stem cells (MSCs) for the treatment or management of the disease has been common in preclinical and clinical studies for many years. MSCs are multipotent cells having immunoregulatory, anti-inflammatory, and differentiation ability that makes them a good candidate for this purpose. This review article aims to discuss multiple aspects of ALS disease and focus on MSCs' role in disease management based on performed clinical trials.}, }
@article {pmid37427010, year = {2023}, author = {Mballa Yene, BV and Lee, SY and Park, KS and Kang, YJ and Seo, SH and Yoo, JI}, title = {Prevalence of Sarcopenia in Africa: A Systematic Review.}, journal = {Clinical interventions in aging}, volume = {18}, number = {}, pages = {1021-1035}, pmid = {37427010}, issn = {1178-1998}, mesh = {Male ; Female ; Humans ; *Sarcopenia/epidemiology/diagnosis ; Prevalence ; Africa/epidemiology ; }, abstract = {OBJECTIVE: The world population gradually getting older, age-related sarcopenia is becoming more frequent. Known to be highly prevalent in high income countries, relative data in Africa are still scarce. This review aims to estimate the prevalence of sarcopenia in Africa and its characteristics.<br><br>STUDY DESIGN AND SETTING: A literature search in PubMed, Web of Science, Google Scholar, and Scopus was conducted in October 2022. All studies reporting the prevalence of sarcopenia in Africa within 15 years were included, and we did an assessment of bias with Hoy et al's risk bias assessment tool. The estimated prevalence of sarcopenia was the outcome and we performed secondary analyses by age, gender, and diagnostic criteria. The random effect model was used for the prevalence estimation. The prevalence of sarcopenia and 95% confidence interval (95% CI) were calculated using the inverse-variance method.<br><br>RESULTS: A total of 17 studies met our eligibility criteria, for a study population of 12,690 participants with 44.3% males and 55.7% females. The overall prevalence of sarcopenia was 25% (95% CI: 19-30%). The prevalence of sarcopenia among 50 years old and older was 23% (95% CI: 17-29%). We had a higher prevalence of sarcopenia among males (30%, %95 IC: 20-39%) than females (29%, %95 IC: 21-36%). The prevalence of sarcopenia was different depending on the diagnosis criteria used.<br><br>CONCLUSION: The prevalence of sarcopenia in Africa was relatively high. However, the fact that the majority of included studies were hospital-based studies shows the necessity of further community-based studies in order to have a more accurate representation of the situation in the general population.}, }
@article {pmid37408276, year = {2023}, author = {Hosaka, T and Tsuji, H and Kwak, S}, title = {Roles of Aging, Circular RNAs, and RNA Editing in the Pathogenesis of Amyotrophic Lateral Sclerosis: Potential Biomarkers and Therapeutic Targets.}, journal = {Cells}, volume = {12}, number = {10}, pages = {}, pmid = {37408276}, issn = {2073-4409}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/therapy/metabolism ; RNA, Circular/genetics/metabolism ; RNA Editing/genetics ; RNA/genetics/metabolism ; Aging/genetics ; Biomarkers/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is an incurable motor neuron disease caused by upper and lower motor neuron death. Despite advances in our understanding of ALS pathogenesis, effective treatment for this fatal disease remains elusive. As aging is a major risk factor for ALS, age-related molecular changes may provide clues for the development of new therapeutic strategies. Dysregulation of age-dependent RNA metabolism plays a pivotal role in the pathogenesis of ALS. In addition, failure of RNA editing at the glutamine/arginine (Q/R) site of GluA2 mRNA causes excitotoxicity due to excessive Ca[2+] influx through Ca[2+]-permeable α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors, which is recognized as an underlying mechanism of motor neuron death in ALS. Circular RNAs (circRNAs), a circular form of cognate RNA generated by back-splicing, are abundant in the brain and accumulate with age. Hence, they are assumed to play a role in neurodegeneration. Emerging evidence has demonstrated that age-related dysregulation of RNA editing and changes in circRNA expression are involved in ALS pathogenesis. Herein, we review the potential associations between age-dependent changes in circRNAs and RNA editing, and discuss the possibility of developing new therapies and biomarkers for ALS based on age-related changes in circRNAs and dysregulation of RNA editing.}, }
@article {pmid37407098, year = {2023}, author = {Kious, BM}, title = {Medical Assistance in Dying in Neurology.}, journal = {Neurologic clinics}, volume = {41}, number = {3}, pages = {443-454}, doi = {10.1016/j.ncl.2023.03.002}, pmid = {37407098}, issn = {1557-9875}, mesh = {Humans ; *Suicide, Assisted/psychology ; *Alzheimer Disease ; Medical Assistance ; *Neurology ; }, abstract = {An increasing number of jurisdictions have legalized medical assistance in dying (MAID) with significant variation in the procedures and eligibility criteria used. In the United States, MAID is available for persons with terminal illnesses but is frequently sought by persons with neurologic conditions. Persons with conditions that cause cognitive impairment, such as Alzheimer dementia, are often ineligible for MAID, as their illness is not considered terminal in its early stages, whereas in later stages, they may have impaired decision-making capacity.}, }
@article {pmid37395272, year = {2023}, author = {Hurtle, BT and Xie, L and Donnelly, CJ}, title = {Disrupting pathologic phase transitions in neurodegeneration.}, journal = {The Journal of clinical investigation}, volume = {133}, number = {13}, pages = {}, pmid = {37395272}, issn = {1558-8238}, support = {R01 NS127187/NS/NINDS NIH HHS/United States ; L30 AG048607/AG/NIA NIH HHS/United States ; R01 NS105756/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; Aged ; *TDP-43 Proteinopathies/pathology ; *Neurodegenerative Diseases/pathology ; *Frontotemporal Lobar Degeneration/metabolism/pathology ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; Proteins ; }, abstract = {Solid-like protein deposits found in aged and diseased human brains have revealed a relationship between insoluble protein accumulations and the resulting deficits in neurologic function. Clinically diverse neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, frontotemporal lobar degeneration, and amyotrophic lateral sclerosis, exhibit unique and disease-specific biochemical protein signatures and abnormal protein depositions that often correlate with disease pathogenesis. Recent evidence indicates that many pathologic proteins assemble into liquid-like protein phases through the highly coordinated process of liquid-liquid phase separation. Over the last decade, biomolecular phase transitions have emerged as a fundamental mechanism of cellular organization. Liquid-like condensates organize functionally related biomolecules within the cell, and many neuropathology-associated proteins reside within these dynamic structures. Thus, examining biomolecular phase transitions enhances our understanding of the molecular mechanisms mediating toxicity across diverse neurodegenerative diseases. This Review explores the known mechanisms contributing to aberrant protein phase transitions in neurodegenerative diseases, focusing on tau and TDP-43 proteinopathies and outlining potential therapeutic strategies to regulate these pathologic events.}, }
@article {pmid37394036, year = {2023}, author = {Arnold, FJ and Nguyen, AD and Bedlack, RS and Bennett, CL and La Spada, AR}, title = {Intercellular transmission of pathogenic proteins in ALS: Exploring the pathogenic wave.}, journal = {Neurobiology of disease}, volume = {184}, number = {}, pages = {106218}, doi = {10.1016/j.nbd.2023.106218}, pmid = {37394036}, issn = {1095-953X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; Superoxide Dismutase-1/metabolism ; Protein Aggregates ; C9orf72 Protein/genetics ; DNA-Binding Proteins/genetics/metabolism ; }, abstract = {In patients with amyotrophic lateral sclerosis (ALS), disease symptoms and pathology typically spread in a predictable spatiotemporal pattern beginning at a focal site of onset and progressing along defined neuroanatomical tracts. Like other neurodegenerative diseases, ALS is characterized by the presence of protein aggregates in postmortem patient tissue. Cytoplasmic, ubiquitin-positive aggregates of TDP-43 are observed in approximately 97% of sporadic and familial ALS patients, while SOD1 inclusions are likely specific to cases of SOD1-ALS. Additionally, the most common subtype of familial ALS, caused by a hexanucleotide repeat expansion in the first intron of the C9orf72 gene (C9-ALS), is further characterized by the presence of aggregated dipeptide repeat proteins (DPRs). As we will describe, cell-to-cell propagation of these pathological proteins tightly correlates with the contiguous spread of disease. While TDP-43 and SOD1 are capable of seeding protein misfolding and aggregation in a prion-like manner, C9orf72 DPRs appear to induce (and transmit) a 'disease state' more generally. Multiple mechanisms of intercellular transport have been described for all of these proteins, including anterograde and retrograde axonal transport, extracellular vesicle secretion, and macropinocytosis. In addition to neuron-to-neuron transmission, transmission of pathological proteins occurs between neurons and glia. Given that the spread of ALS disease pathology corresponds with the spread of symptoms in patients, the various mechanisms by which ALS-associated protein aggregates propagate through the central nervous system should be closely examined.}, }
@article {pmid37392160, year = {2023}, author = {Hivare, P and Mujmer, K and Swarup, G and Gupta, S and Bhatia, D}, title = {Endocytic pathways of pathogenic protein aggregates in neurodegenerative diseases.}, journal = {Traffic (Copenhagen, Denmark)}, volume = {24}, number = {10}, pages = {434-452}, doi = {10.1111/tra.12906}, pmid = {37392160}, issn = {1600-0854}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism ; Protein Aggregates ; *Alzheimer Disease/metabolism ; *Parkinson Disease/metabolism ; alpha-Synuclein/metabolism ; }, abstract = {Endocytosis is the fundamental uptake process through which cells internalize extracellular materials and species. Neurodegenerative diseases (NDs) are characterized by a progressive accumulation of intrinsically disordered protein species, leading to neuronal death. Misfolding in many proteins leads to various NDs such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS) and other disorders. Despite the significance of disordered protein species in neurodegeneration, their spread between cells and the cellular uptake of extracellular species is not entirely understood. This review discusses the major internalization mechanisms of the different conformer species of these proteins and their endocytic mechanisms. We briefly introduce the broad types of endocytic mechanisms found in cells and then summarize what is known about the endocytosis of monomeric, oligomeric and aggregated conformations of tau, Aβ, α-Syn, Huntingtin, Prions, SOD1, TDP-43 and other proteins associated with neurodegeneration. We also highlight the key players involved in internalizing these disordered proteins and the several techniques and approaches to identify their endocytic mechanisms. Finally, we discuss the obstacles involved in studying the endocytosis of these protein species and the need to develop better techniques to elucidate the uptake mechanisms of a particular disordered protein species.}, }
@article {pmid37391647, year = {2023}, author = {Karati, D and Mukherjee, S and Roy, S}, title = {Molecular and Structural Insight into Adenosine A2A Receptor in Neurodegenerative Disorders: A Significant Target for Efficient Treatment Approach.}, journal = {Molecular neurobiology}, volume = {60}, number = {10}, pages = {5987-6000}, pmid = {37391647}, issn = {1559-1182}, mesh = {Humans ; *Adenosine/pharmacology ; Receptor, Adenosine A2A/metabolism ; Ligands ; *Neurodegenerative Diseases/drug therapy ; Purinergic P1 Receptor Antagonists/therapeutic use ; Receptors, Purinergic P1 ; }, abstract = {All biological tissues and bodily fluids include the autacoid adenosine. The P1 class of purinergic receptors includes adenosine receptors. Four distinct G-protein-coupled receptors on the cellular membrane mediate the effects of adenosine, whose cytoplasmic content is regulated by producing/degrading enzymes and nucleoside transporters. A2A receptor has received a great deal of attention in recent years because it has a wide range of potential therapeutic uses. A2B and, more significantly, A2A receptors regulate numerous physiological mechanisms in the central nervous system (CNS). The inferior targetability of A2B receptors towards adenosine points that they might portray a promising medicinal target since they are triggered only under pharmacological circumstances (when adenosine levels rise up to micromolar concentrations). The accessibility of specific ligands for A2B receptors would permit the exploration of such a theory. A2A receptors mediate both potentially neurotoxic and neuroprotective actions. Hence, it is debatable to what extent they play a role in neurodegenerative illnesses. However, A2A receptor blockers have demonstrated clear antiparkinsonian consequences, and a significant attraction exists in the role of A2A receptors in other neurodegenerative disorders. Amyloid peptide extracellular accumulation and tau hyperphosphorylation are the pathogenic components of AD that lead to neuronal cell death, cognitive impairment, and memory loss. Interestingly, in vitro and in vivo research has shown that A2A adenosine receptor antagonists may block each of these clinical symptoms, offering a crucial new approach to combat a condition for which, regrettably, only symptomatic medications are currently available. At least two requirements must be met to determine whether such receptors are a target for diseases of the CNS: a complete understanding of the mechanisms governing A2A-dependent processes and the availability of ligands that can distinguish between the various receptor populations. This review concisely summarises the biological effects mediated by A2A adenosine receptors in neurodegenerative disorders and discusses the chemical characteristics of A2A adenosine receptor antagonists undergoing clinical trials. Selective A2A receptor blocker against neurodegenerative disorders.}, }
@article {pmid37391243, year = {2023}, author = {Gerecht, RB and Nable, JV}, title = {Out-of-Hospital Cardiac Arrest.}, journal = {Emergency medicine clinics of North America}, volume = {41}, number = {3}, pages = {433-453}, doi = {10.1016/j.emc.2023.03.002}, pmid = {37391243}, issn = {1558-0539}, mesh = {Humans ; *Out-of-Hospital Cardiac Arrest/diagnosis/therapy ; *Emergency Medical Services ; }, abstract = {Survival from out-of-hospital cardiac arrest (OHCA) is predicated on a community and system-wide approach that includes rapid recognition of cardiac arrest, capable bystander CPR, effective basic and advanced life support (BLS and ALS) by EMS providers, and coordinated postresuscitation care. Management of these critically ill patients continues to evolve. This article focuses on the management of OHCA by EMS providers.}, }
@article {pmid37390744, year = {2023}, author = {Eskandari, S and Rezayof, A and Asghari, SM and Hashemizadeh, S}, title = {Neurobiochemical characteristics of arginine-rich peptides explain their potential therapeutic efficacy in neurodegenerative diseases.}, journal = {Neuropeptides}, volume = {101}, number = {}, pages = {102356}, doi = {10.1016/j.npep.2023.102356}, pmid = {37390744}, issn = {1532-2785}, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy ; Arginine ; Oxidative Stress ; Peptides/metabolism ; *Nucleic Acids/metabolism/therapeutic use ; *Alzheimer Disease/metabolism ; }, abstract = {Neurodegenerative diseases, including Alzheimer̕ s disease (AD), Parkinson̕ s disease (PD), Huntington̕ s disease (HD), and Amyotrophic Lateral Sclerosis (ALS) require special attention to find new potential treatment methods. This review aims to summarize the current knowledge of the relationship between the biochemical properties of arginine-rich peptides (ARPs) and their neuroprotective effects to deal with the harmful effects of risk factors. It seems that ARPs have portrayed a promising and fantastic landscape for treating neurodegeneration-associated disorders. With multimodal mechanisms of action, ARPs play various unprecedented roles, including as the novel delivery platforms for entering the central nervous system (CNS), the potent antagonists for calcium influx, the invader molecules for targeting mitochondria, and the protein stabilizers. Interestingly, these peptides inhibit the proteolytic enzymes and block protein aggregation to induce pro-survival signaling pathways. ARPs also serve as the scavengers of toxic molecules and the reducers of oxidative stress agents. They also have anti-inflammatory, antimicrobial, and anti-cancer properties. Moreover, by providing an efficient nucleic acid delivery system, ARPs can play an essential role in developing various fields, including gene vaccines, gene therapy, gene editing, and imaging. ARP agents and ARP/cargo therapeutics can be raised as an emergent class of neurotherapeutics for neurodegeneration. Part of the aim of this review is to present recent advances in treating neurodegenerative diseases using ARPs as an emerging and powerful therapeutic tool. The applications and progress of ARPs-based nucleic acid delivery systems have also been discussed to highlight their usefulness as a broad-acting class of drugs.}, }
@article {pmid37387467, year = {2023}, author = {Timmins, HC and Vucic, S and Kiernan, MC}, title = {Cortical hyperexcitability in amyotrophic lateral sclerosis: from pathogenesis to diagnosis.}, journal = {Current opinion in neurology}, volume = {36}, number = {4}, pages = {353-359}, doi = {10.1097/WCO.0000000000001162}, pmid = {37387467}, issn = {1473-6551}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics/therapy ; Motor Neurons ; Transcranial Magnetic Stimulation/methods ; *Frontotemporal Dementia/diagnosis/genetics ; Biomarkers ; }, abstract = {PURPOSE OF REVIEW: Identification of upper motor neuron involvement remains a critical component of a diagnosis of amyotrophic lateral sclerosis (ALS), although supportive clinical signs are often not easily appreciated, particularly in the early symptomatic stages of the disease. Although diagnostic criteria have been developed to facilitate improved detection of lower motor neuron impairment through electrophysiological features that have improved diagnostic sensitivity, assessment of upper motor neuron involvement remains problematic.<br><br>RECENT FINDINGS: Recent evidence has emerged about pathophysiological processes, particularly glutamate-mediated excitotoxicity, which has resulted in the development of novel diagnostic investigations and uncovered potential therapeutic targets. Advances in genetics, including the C9orf72 gene, have changed concepts of ALS, from being classified as a neuromuscular disease to a disease that forms a continuum with other primary neurodegenerative disorders, particularly frontotemporal dementia. Transcranial magnetic stimulation has been utilized to provide pathophysiological insights, leading to the development of diagnostic and therapeutic biomarkers, which are now being introduced into the clinical setting.<br><br>SUMMARY: Specifically, the advent of cortical hyperexcitability has been consistently identified as an early and intrinsic feature of ALS. With greater accessibility of TMS techniques promoting clinical utilization, TMS measures of cortical function may develop as a diagnostic biomarker, with further potential utility in the clinical trial setting for monitoring of neuroprotective and genetic-based therapies.}, }
@article {pmid37385457, year = {2023}, author = {DuMont, M and Agostinis, A and Singh, K and Swan, E and Buttle, Y and Tropea, D}, title = {Sex representation in neurodegenerative and psychiatric disorders' preclinical and clinical studies.}, journal = {Neurobiology of disease}, volume = {184}, number = {}, pages = {106214}, doi = {10.1016/j.nbd.2023.106214}, pmid = {37385457}, issn = {1095-953X}, mesh = {Humans ; Male ; Female ; *Alzheimer Disease ; *Parkinson Disease ; *Amyotrophic Lateral Sclerosis/epidemiology/therapy ; *Attention Deficit Disorder with Hyperactivity ; }, abstract = {Many studies show the importance of biological sex for the onset, progression, and response to treatment in brain disorders. In line with these reports, health agencies have requested that all trials, both at the clinical and preclinical level, use a similar number of male and female subjects to correctly interpret the results. Despite these guidelines, many studies still tend to be unbalanced in the use of male and female subjects. In this review we consider three neurodegenerative disorders: Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis, and three psychiatric disorders: Depression, Attention Deficit Hyperactivity Disorder, and Schizophrenia. These disorders were chosen because of their prevalence and their recognized sex-specific differences in onset, progression, and response to treatment. Alzheimer's disease and Depression demonstrate higher prevalence in females, whereas Parkinson's Disease, Amyotrophic lateral sclerosis, Attention Deficit Hyperactivity Disorder, and schizophrenia show higher prevalence in males. Results from preclinical and clinical studies examining each of these disorders revealed sex-specific differences in risk factors, diagnostic biomarkers, and treatment response and efficacy, suggesting a role for sex-specific therapies in neurodegenerative and neuropsychiatric disorders. However, the qualitative analysis of the percentage of males and females enrolled in clinical trials in the last two decades shows that for most of the disorders, there is still a sex bias in the patients' enrolment.}, }
@article {pmid37383106, year = {2023}, author = {Wu, C and Feng, Y}, title = {Exploring the potential of mindfulness-based therapy in the prevention and treatment of neurodegenerative diseases based on molecular mechanism studies.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1097067}, pmid = {37383106}, issn = {1662-4548}, abstract = {Neurodegenerative diseases (ND) have received increasing attention due to their irreversibility, but there is still no means to completely cure ND in clinical practice. Mindfulness therapy (MT), including Qigong, Tai Chi, meditation, and yoga, etc., has become an effective complementary treatment modality in solving clinical and subclinical problems due to its advantages of low side effects, less pain, and easy acceptance by patients. MT is primarily used to treat mental and emotional disorders. In recent years, evidence has shown that MT has a certain therapeutic effect on ND with a potential molecular basis. In this review, we summarize the pathogenesis and risk factors of Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), relating to telomerase activity, epigenetics, stress, and the pro-inflammatory transcription factor nuclear factor kappa B (NF-κB) mediated inflammatory response, and analyze the molecular mechanism basis of MT to prevent and treat ND, to provide possible explanations for the potential of MT treatments for ND.}, }
@article {pmid37382103, year = {2023}, author = {Benatar, M and Turner, MR and Wuu, J}, title = {Presymptomatic amyotrophic lateral sclerosis: from characterization to prevention.}, journal = {Current opinion in neurology}, volume = {36}, number = {4}, pages = {360-364}, pmid = {37382103}, issn = {1473-6551}, support = {R01 NS105479/NS/NINDS NIH HHS/United States ; TURNER/OCT18/989-797/MNDA_/Motor Neurone Disease Association/United Kingdom ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics/prevention &amp; control ; *Frontotemporal Dementia/genetics ; Longitudinal Studies ; Biomarkers ; Asymptomatic Diseases ; }, abstract = {PURPOSE OF REVIEW: Significant progress in characterizing presymptomatic amyotrophic lateral sclerosis (ALS) is ushering in an era of potential disease prevention. Although these advances have largely been based on cohorts of deep-phenotyped mutation carriers at an elevated risk for ALS, there are increasing opportunities to apply principles and insights gleaned, to the broader population at risk for ALS [and frontotemporal dementia (FTD)].<br><br>RECENT FINDINGS: The discovery that blood neurofilament light chain (NfL) level increases presymptomatically and may serve as a susceptibility biomarker, predicting timing of phenoconversion in some mutation carriers, has empowered the first-ever prevention trial in SOD1 -ALS. Moreover, there is emerging evidence that presymptomatic disease is not uniformly clinically silent, with mild motor impairment (MMI), mild cognitive impairment (MCI), and/or mild behavioral impairment (MBI) representing a prodromal stage of disease. Structural and functional brain abnormalities, as well as systemic markers of metabolic dysfunction, have emerged as potentially even earlier markers of presymptomatic disease. Ongoing longitudinal studies will determine the extent to which these reflect an endophenotype of genetic risk.<br><br>SUMMARY: The discovery of presymptomatic biomarkers and the delineation of prodromal states is yielding unprecedented opportunities for earlier diagnosis, treatment, and perhaps even prevention of genetic and apparently sporadic forms of disease.}, }
@article {pmid37380145, year = {2023}, author = {Mercadante, S and Al-Husinat, L}, title = {Palliative Care in Amyotrophic Lateral Sclerosis.}, journal = {Journal of pain and symptom management}, volume = {66}, number = {4}, pages = {e485-e499}, doi = {10.1016/j.jpainsymman.2023.06.029}, pmid = {37380145}, issn = {1873-6513}, mesh = {Humans ; Palliative Care ; *Amyotrophic Lateral Sclerosis/therapy/diagnosis ; Quality of Life ; *Neurodegenerative Diseases ; *Hospice and Palliative Care Nursing ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease of the motor neurons. Given the evolutive characteristics of this disease, palliative care principles should be a foundation of ALS care. A multidisciplinary medical intervention is of paramount importance in the different phases of disease. The involvement of the palliative care team improves quality of life and symptoms, and prognosis. Early initiation is of paramount importance to ensuring patient-centered care, when the patient has still the capability to communicate effectively and participate in his medical care. Advance care planning supports patients and family members in understanding and sharing their preferences according to their personal values and life goals regarding future medical treatment. The principal problems which require intensive supportive care include cognitive disturbances, psychological distress, pain, sialorrhrea, nutrition, and ventilatory support. Communication skills of health-care professionals are mandatory to manage the inevitability of death. Palliative sedation has peculiar aspects in this population, particularly with the decision of withdrawing ventilatory support.}, }
@article {pmid37373667, year = {2023}, author = {Sipilä, JOT}, title = {Adult-Onset Neuroepidemiology in Finland: Lessons to Learn and Work to Do.}, journal = {Journal of clinical medicine}, volume = {12}, number = {12}, pages = {}, pmid = {37373667}, issn = {2077-0383}, abstract = {Finland is a relatively small genetic isolate with a genetically non-homogenous population. Available Finnish data on neuroepidemiology of adult-onset disorders are limited, and this paper describes the conclusions that can be drawn and their implications. Apparently, Finnish people have a (relatively) high risk of developing Unverricht-Lundborg disease (EPM1), Multiple Sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS), Spinal muscular atrophy, Jokela type (SMAJ) and adult-onset dystonia. On the other hand, some disorders, such as Friedreich's ataxia (FRDA) and Wilson's disease (WD), are almost absent or completely absent in the population. Valid and timely data concerning even many common disorders, such as stroke, migraine, neuropathy, Alzheimer's disease and Parkinson's disease, are unavailable, and there are virtually no data on many less-common neurological disorders, such as neurosarcoidosis or autoimmune encephalitides. There also appear to be marked regional differences in the incidence and prevalence of many diseases, suggesting that non-granular nationwide data may be misleading in many cases. Concentrated efforts to advance neuroepidemiological research in the country would be of clinical, administrative and scientific benefit, but currently, all progress is blocked by administrative and financial obstacles.}, }
@article {pmid37371694, year = {2023}, author = {De Marchi, F and Franjkic, T and Schito, P and Russo, T and Nimac, J and Chami, AA and Mele, A and Vidatic, L and Kriz, J and Julien, JP and Apic, G and Russell, RB and Rogelj, B and Cannon, JR and Baralle, M and Agosta, F and Hecimovic, S and Mazzini, L and Buratti, E and Munitic, I}, title = {Emerging Trends in the Field of Inflammation and Proteinopathy in ALS/FTD Spectrum Disorder.}, journal = {Biomedicines}, volume = {11}, number = {6}, pages = {}, pmid = {37371694}, issn = {2227-9059}, abstract = {Proteinopathy and neuroinflammation are two main hallmarks of neurodegenerative diseases. They also represent rare common events in an exceptionally broad landscape of genetic, environmental, neuropathologic, and clinical heterogeneity present in patients. Here, we aim to recount the emerging trends in amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD) spectrum disorder. Our review will predominantly focus on neuroinflammation and systemic immune imbalance in ALS and FTD, which have recently been highlighted as novel therapeutic targets. A common mechanism of most ALS and ~50% of FTD patients is dysregulation of TAR DNA-binding protein 43 (TDP-43), an RNA/DNA-binding protein, which becomes depleted from the nucleus and forms cytoplasmic aggregates in neurons and glia. This, in turn, via both gain and loss of function events, alters a variety of TDP-43-mediated cellular events. Experimental attempts to target TDP-43 aggregates or manipulate crosstalk in the context of inflammation will be discussed. Targeting inflammation, and the immune system in general, is of particular interest because of the high plasticity of immune cells compared to neurons.}, }
@article {pmid37371389, year = {2023}, author = {Górska, A and Markiewicz-Gospodarek, A and Markiewicz, R and Chilimoniuk, Z and Borowski, B and Trubalski, M and Czarnek, K}, title = {Distribution of Iron, Copper, Zinc and Cadmium in Glia, Their Influence on Glial Cells and Relationship with Neurodegenerative Diseases.}, journal = {Brain sciences}, volume = {13}, number = {6}, pages = {}, pmid = {37371389}, issn = {2076-3425}, abstract = {Recent data on the distribution and influence of copper, zinc and cadmium in glial cells are summarized. This review also examines the relationship between those metals and their role in neurodegenerative diseases like Alzheimer disease, multiple sclerosis, Parkinson disease and Amyotrophic lateral sclerosis, which have become a great challenge for today's physicians. The studies suggest that among glial cells, iron has the highest concentration in oligodendrocytes, copper in astrocytes and zinc in the glia of hippocampus and cortex. Previous studies have shown neurotoxic effects of copper, iron and manganese, while zinc can have a bidirectional effect, i.e., neurotoxic but also neuroprotective effects depending on the dose and disease state. Recent data point to the association of metals with neurodegeneration through their role in the modulation of protein aggregation. Metals can accumulate in the brain with aging and may be associated with age-related diseases.}, }
@article {pmid37369861, year = {2023}, author = {Zhu, Q and Xu, D and Huang, H and Li, D and Yang, D and Zhou, J and Zhao, Y}, title = {The safety and effectiveness of high-calorie therapy for treating amyotrophic lateral sclerosis: a systematic review and meta-analysis.}, journal = {Journal of neurology}, volume = {270}, number = {10}, pages = {4729-4743}, pmid = {37369861}, issn = {1432-1459}, support = {2022BCA055//Department of Science and Technology, Hubei Provincial People's Government/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; Lipids/therapeutic use ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting the upper and lower motor neurons, which can lead to death from respiratory failure within 3-5 years after the onset of this disease. Nowadays, no drug can effectively slow down the progression of this disease. High-calorie therapy, an emerging complementary alternative treatment, has been reported in studies to prolong the survival time of patients, prevent muscle atrophy and provide a better prognosis. However, no systematic review and meta-analysis were performed to summarize the evidence of this therapy. This meta-analysis comprehensively evaluates the effectiveness and safety of high-calorie therapy for treating ALS.<br><br>METHODS: We searched the electronic databases from inception to 1 April 2023: PubMed, Embase, Web of Science, Cochrane Library, Scopus, Ovid/Medline, and ProQuest. Randomized controlled trials (RCTs) that met the inclusion criteria were performed by meta-analysis. All statistical analyses were performed in STATA software.<br><br>RESULTS: A total of six eligible RCTs were included in this meta-analysis, involving 370 ALS patients. The meta-analyses showed that high-calorie therapy had superiority in improving body weight (SMD&#x2009;=&#x2009;1, 95% CI 0.36, 1.65) and BMI (SMD&#x2009;=&#x2009;0.83, 95% CI 0.02, 1.63). With respect to safety, there was no difference between the high-calorie therapy and the control group regarding the number of adverse events (RR&#x2009;=&#x2009;3.61, 95% CI 0.08, 162.49). However, ALSFRS-R scores (SMD&#x2009;=&#x2009;0.34, 95% CI -&#x2009;0.4, 1.08), survival rate (RR&#x2009;=&#x2009;1.23, 95% CI 0.98, 1.55), and lipid profile (LDL: SMD&#x2009;=&#x2009;0.21, 95% CI -&#x2009;0.33, 0.75; HDL: SMD&#x2009;=&#x2009;0.17, 95% CI -&#x2009;0.37, 0.71; TC: SMD&#x2009;=&#x2009;0.21, 95% CI -&#x2009;0.33, 0.75), CRP (SMD&#x2009;=&#x2009;0.85, 95% CI -&#x2009;1.37, 3.06) showed no significant difference compared to the control groups.<br><br>CONCLUSIONS: High-calorie therapy is effective in gaining weight and BMI with few side effects. However, no significant superiority was detected in ALSFRS-R scores, survival time, lipid profile, and CRP indicator. The overall quality of the included studies is high, and the results have some credibility, but future corroboration by high-quality RCTs is also expected.}, }
@article {pmid37366506, year = {2022}, author = {Erustes, AG and Guarache, GC and Guedes, EDC and Leão, AHFF and Pereira, GJDS and Smaili, SS}, title = {α-Synuclein Interactions in Mitochondria-ER Contacts: A Possible Role in Parkinson's Disease.}, journal = {Contact (Thousand Oaks (Ventura County, Calif.))}, volume = {5}, number = {}, pages = {25152564221119347}, pmid = {37366506}, issn = {2515-2564}, abstract = {Endoplasmic reticulum-mitochondria contact sites regulate various biological processes, such as mitochondrial dynamics, calcium homeostasis, autophagy and lipid metabolism. Notably, dysfunctions in these contact sites are closely related to neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis. However, details about the role of endoplasmic reticulum-mitochondria contact sites in neurodegenerative diseases remain unknown. In Parkinson's disease, interactions between α-synuclein in the contact sites and components of tether complexes that connect organelles can lead to various dysfunctions, especially with regards to calcium homeostasis. This review will summarize the main tether complexes present in endoplasmic reticulum-mitochondria contact sites, and their roles in calcium homeostasis and trafficking. We will discuss the impact of α-synuclein accumulation, its interaction with tethering complex components and the implications in Parkinson's disease pathology.}, }
@article {pmid37358003, year = {2024}, author = {Canever, JB and Queiroz, LY and Soares, ES and de Avelar, NCP and Cimarosti, HI}, title = {Circadian rhythm alterations affecting the pathology of neurodegenerative diseases.}, journal = {Journal of neurochemistry}, volume = {168}, number = {8}, pages = {1475-1489}, doi = {10.1111/jnc.15883}, pmid = {37358003}, issn = {1471-4159}, support = {//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; //Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/physiopathology/pathology/metabolism ; *Circadian Rhythm/physiology ; Animals ; }, abstract = {The circadian rhythm is a nearly 24-h oscillation found in various physiological processes in the human brain and body that is regulated by environmental and genetic factors. It is responsible for maintaining body homeostasis and it is critical for essential functions, such as metabolic regulation and memory consolidation. Dysregulation in the circadian rhythm can negatively impact human health, resulting in cardiovascular and metabolic diseases, psychiatric disorders, and premature death. Emerging evidence points to a relationship between the dysregulation circadian rhythm and neurodegenerative diseases, suggesting that the alterations in circadian function might play crucial roles in the pathogenesis and progression of neurodegenerative diseases. Better understanding this association is of paramount importance to expand the knowledge on the pathophysiology of neurodegenerative diseases, as well as, to provide potential targets for the development of new interventions based on the dysregulation of circadian rhythm. Here we review the latest findings on dysregulation of circadian rhythm alterations in Parkinson's disease, Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, spinocerebellar ataxia and multiple-system atrophy, focusing on research published in the last 3 years.}, }
@article {pmid37356043, year = {2023}, author = {Nguyen, QT and Thanh, LN and Hoang, VT and Phan, TTK and Heke, M and Hoang, DM}, title = {Bone Marrow-Derived Mononuclear Cells in the Treatment of Neurological Diseases: Knowns and Unknowns.}, journal = {Cellular and molecular neurobiology}, volume = {43}, number = {7}, pages = {3211-3250}, pmid = {37356043}, issn = {1573-6830}, mesh = {Humans ; *Autism Spectrum Disorder ; Bone Marrow ; *Stroke/therapy ; Bone Marrow Cells ; }, abstract = {Bone marrow-derived mononuclear cells (BMMNCs) have been used for decades in preclinical and clinical studies to treat various neurological diseases. However, there is still a knowledge gap in the understanding of the underlying mechanisms of BMMNCs in the treatment of neurological diseases. In addition, prerequisite factors for the efficacy of BMMNC administration, such as the optimal route, dose, and number of administrations, remain unclear. In this review, we discuss known and unknown aspects of BMMNCs, including the cell harvesting, administration route and dose; mechanisms of action; and their applications in neurological diseases, including stroke, cerebral palsy, spinal cord injury, traumatic brain injury, amyotrophic lateral sclerosis, autism spectrum disorder, and epilepsy. Furthermore, recommendations on indications for BMMNC administration and the advantages and limitations of BMMNC applications for neurological diseases are discussed. BMMNCs in the treatment of neurological diseases. BMMNCs have been applied in several neurological diseases. Proposed mechanisms for the action of BMMNCs include homing, differentiation and paracrine effects (angiogenesis, neuroprotection, and anti-inflammation). Further studies should be performed to determine the optimal cell dose and administration route, the roles of BMMNC subtypes, and the indications for the use of BMMNCs in neurological conditions with and without genetic abnormalities.}, }
@article {pmid37355220, year = {2023}, author = {Balog, BM and Sonti, A and Zigmond, RE}, title = {Neutrophil biology in injuries and diseases of the central and peripheral nervous systems.}, journal = {Progress in neurobiology}, volume = {228}, number = {}, pages = {102488}, pmid = {37355220}, issn = {1873-5118}, support = {F32 NS122918/NS/NINDS NIH HHS/United States ; R01 NS114891/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Neutrophils ; *Axons/physiology ; Nerve Regeneration/physiology ; Peripheral Nervous System ; Biology ; }, abstract = {The role of inflammation in nervous system injury and disease is attracting increased attention. Much of that research has focused on microglia in the central nervous system (CNS) and macrophages in the peripheral nervous system (PNS). Much less attention has been paid to the roles played by neutrophils. Neutrophils are part of the granulocyte subtype of myeloid cells. These cells, like macrophages, originate and differentiate in the bone marrow from which they enter the circulation. After tissue damage or infection, neutrophils are the first immune cells to infiltrate into tissues and are directed there by specific chemokines, which act on chemokine receptors on neutrophils. We have reviewed here the basic biology of these cells, including their differentiation, the types of granules they contain, the chemokines that act on them, the subpopulations of neutrophils that exist, and their functions. We also discuss tools available for identification and further study of neutrophils. We then turn to a review of what is known about the role of neutrophils in CNS and PNS diseases and injury, including stroke, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, spinal cord and traumatic brain injuries, CNS and PNS axon regeneration, and neuropathic pain. While in the past studies have focused on neutrophils deleterious effects, we will highlight new findings about their benefits. Studies on their actions should lead to identification of ways to modify neutrophil effects to improve health.}, }
@article {pmid37349906, year = {2023}, author = {Shojaie, A and Rota, S and Al Khleifat, A and Ray Chaudhuri, K and Al-Chalabi, A}, title = {Non-motor symptoms in amyotrophic lateral sclerosis: lessons from Parkinson's disease.}, journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration}, volume = {}, number = {}, pages = {1-10}, doi = {10.1080/21678421.2023.2220748}, pmid = {37349906}, issn = {2167-9223}, abstract = {Amyotrophic lateral sclerosis and Parkinson's disease are neurodegenerative diseases of the motor system which are now recognized also to affect non-motor pathways. Non-motor symptoms have been acknowledged as important determinants of quality of life in Parkinson's disease, and there is increasing interest in understanding the extent and role of non-motor symptoms in amyotrophic lateral sclerosis. We therefore reviewed what is known about non-motor symptoms in amyotrophic lateral sclerosis, using lessons from Parkinson's disease.}, }
@article {pmid37345437, year = {2023}, author = {Rush, CL and Lester, EG and Manglani, H and Woodworth, E and Vitolo, O and Fava, M and Berry, JD and Brizzi, K and Babu, S and Lindenberger, EC and Curtis, JR and Vranceanu, AM}, title = {Resilient together-ALS: leveraging the NDD transdiagnostic framework to develop an early dyadic intervention for people with amyotrophic lateral sclerosis and their informal care-partners.}, journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration}, volume = {}, number = {}, pages = {1-8}, doi = {10.1080/21678421.2023.2224400}, pmid = {37345437}, issn = {2167-9223}, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive weakness and eventual death, usually within 3-5 years. An ALS diagnosis is associated with substantial emotional distress for both the affected person and their family care-partners which impairs the ability to engage in important conversations about long term care planning, negatively impacts ALS symptoms for the patient, and quality of life for both patient and care-partner. Here we 1) discuss published works identified by the authors about psychosocial interventions for the ALS population, 2) identify a lack of early, dyadic interventions to support psychosocial needs of people with ALS and care-partners; 3) describe the Neurodegenerative Diseases (NDD) framework for early dyadic intervention development and 4) propose an adaptation of an evidence-based early dyadic psychosocial intervention, Recovering Together, for the unique needs of people with ALS and their care-partners (Resilient Together-ALS; RT-ALS) using the NDD framework. Future work will use stakeholder feedback to optimize the intervention for subsequent efficacy testing.}, }
@article {pmid37341302, year = {2023}, author = {Wang, Y and Wu, S and Li, Q and Sun, H and Wang, H}, title = {Pharmacological Inhibition of Ferroptosis as a Therapeutic Target for Neurodegenerative Diseases and Strokes.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {10}, number = {24}, pages = {e2300325}, pmid = {37341302}, issn = {2198-3844}, support = {81260196//National Natural Science Foundation of China/ ; 81450036//National Natural Science Foundation of China/ ; 2020YK02//Science Foundation of AMHT/ ; 2021YK05//Science Foundation of AMHT/ ; 2022YK01//Science Foundation of AMHT/ ; YN202104//Science Foundation of ASCH/ ; YN202305//Science Foundation of ASCH/ ; 2020MS08175//Natural Science Foundation of Inner Mongolia Autonomous Region/ ; 2021LHMS08024//Natural Science Foundation of Inner Mongolia Autonomous Region/ ; 2022MS08046//Natural Science Foundation of Inner Mongolia Autonomous Region/ ; YC202305//Science Foundation of Inner Mongolia Key Laboratory of human genetic diseases/ ; YC202304//Science Foundation of Inner Mongolia Key Laboratory of human genetic diseases/ ; }, mesh = {Humans ; *Ferroptosis ; *Neurodegenerative Diseases/drug therapy ; *Stroke/drug therapy ; Cell Death ; }, abstract = {Emerging evidence suggests that ferroptosis, a unique regulated cell death modality that is morphologically and mechanistically different from other forms of cell death, plays a vital role in the pathophysiological process of neurodegenerative diseases, and strokes. Accumulating evidence supports ferroptosis as a critical factor of neurodegenerative diseases and strokes, and pharmacological inhibition of ferroptosis as a therapeutic target for these diseases. In this review article, the core mechanisms of ferroptosis are overviewed and the roles of ferroptosis in neurodegenerative diseases and strokes are described. Finally, the emerging findings in treating neurodegenerative diseases and strokes through pharmacological inhibition of ferroptosis are described. This review demonstrates that pharmacological inhibition of ferroptosis by bioactive small-molecule compounds (ferroptosis inhibitors) could be effective for treatments of these diseases, and highlights a potential promising therapeutic avenue that could be used to prevent neurodegenerative diseases and strokes. This review article will shed light on developing novel therapeutic regimens by pharmacological inhibition of ferroptosis to slow down the progression of these diseases in the future.}, }
@article {pmid37338894, year = {2023}, author = {Burg, T and Van Den Bosch, L}, title = {Abnormal energy metabolism in ALS: a key player?.}, journal = {Current opinion in neurology}, volume = {36}, number = {4}, pages = {338-345}, pmid = {37338894}, issn = {1473-6551}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; *Neurodegenerative Diseases/pathology ; Motor Neurons/pathology ; Energy Metabolism ; Precision Medicine ; }, abstract = {PURPOSE OF THE REVIEW: Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease of the motor system due to the selective and progressive degeneration of both upper and lower motor neurons. Disturbances in energy homeostasis were repeatedly associated with the ALS pathogenesis and appear early during the disease process. In this review, we highlight recent work demonstrating the crucial role of energy metabolism in ALS and discuss its potential clinical relevance.<br><br>RECENT FINDINGS: The alteration of various metabolic pathways contributes to the heterogeneity of the clinical phenotype of ALS. Recent work showed that different ALS mutations selectively impact these pathways and translate to the disease phenotypes in patients and disease models. Strikingly, a growing number of studies point towards an early, even presymptomatic, contribution of abnormal energy homeostasis to the ALS pathogenesis. Advances in metabolomics generated valuable tools to study altered metabolic pathways, to test their therapeutic potential, and to develop personalized medicine. Importantly, recent preclinical studies and clinical trials demonstrated that targeting energy metabolism is a promising therapeutic approach.<br><br>SUMMARY: Abnormal energy metabolism is a key player in ALS pathogenesis, emerging as a source of potential disease biomarkers and therapeutic targets.}, }
@article {pmid37338820, year = {2023}, author = {Willemse, SW and van Es, MA}, title = {Susceptibility and disease modifier genes in amyotrophic lateral sclerosis: from genetic associations to therapeutic implications.}, journal = {Current opinion in neurology}, volume = {36}, number = {4}, pages = {365-370}, pmid = {37338820}, issn = {1473-6551}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/drug therapy ; Genes, Modifier ; Superoxide Dismutase-1/genetics/therapeutic use ; Motor Neurons ; Mutation ; }, abstract = {PURPOSE OF REVIEW: Amyotrophic lateral sclerosis (ALS) is a severe disease characterized by the degeneration of motor neurons. Large-scale genetic studies have now identified over 60 genes that are associated with ALS, which in large part have also been functionally characterized. The purpose of this review is to outline how these advances are being translated into novel therapeutic strategies.<br><br>RECENT FINDINGS: The emergence of techniques that allow the specific therapeutic targeting of a (mutant) gene, in particular antisense oligonucleotide therapy (ASOs), have led to the first successful gene therapy for SOD1-ALS and multiple other gene-targeted trials are underway. This includes genetic variants that modify the disease phenotype as well as causal mutations.<br><br>SUMMARY: Technological and methodological advances are enabling researchers to unravel the genetics of ALS. Both causal mutations and genetic modifiers are viable therapeutic targets. By performing natural history studies, the phenotype-genotype correlations can be characterized. In conjunction with biomarkers for target engagement and international collaboration, this makes performing gene-targeted trials ALS feasible. The first effective treatment has now been developed for SOD1-ALS and, with multiple studies underway, it seems realistic that more therapies will follow.}, }
@article {pmid37338307, year = {2023}, author = {Tripathi, SJ and Chakraborty, S and Miller, E and Pieper, AA and Paul, BD}, title = {Hydrogen sulfide signalling in neurodegenerative diseases.}, journal = {British journal of pharmacology}, volume = {}, number = {}, pages = {}, pmid = {37338307}, issn = {1476-5381}, support = {P30 AG062428/AG/NIA NIH HHS/United States ; R01 AG071512/AG/NIA NIH HHS/United States ; RO1AG066707/AG/NIA NIH HHS/United States ; 1 U01 AG073323/AG/NIA NIH HHS/United States ; RM1 GM142002/GM/NIGMS NIH HHS/United States ; U01 AG073323/AG/NIA NIH HHS/United States ; R01 AG066707/AG/NIA NIH HHS/United States ; T32 AG071474/AG/NIA NIH HHS/United States ; P50 DA044123/DA/NIDA NIH HHS/United States ; 1 P30 AGO62428-01/AG/NIA NIH HHS/United States ; R01AG071512/AG/NIA NIH HHS/United States ; I01 BX005976/BX/BLRD VA/United States ; 1R21AG073684-01/AG/NIA NIH HHS/United States ; DA044123/DA/NIDA NIH HHS/United States ; R21 AG073684/AG/NIA NIH HHS/United States ; }, abstract = {The gaseous neurotransmitter hydrogen sulfide (H2 S) exerts neuroprotective efficacy in the brain via post-translational modification of cysteine residues by sulfhydration, also known as persulfidation. This process is comparable in biological impact to phosphorylation and mediates a variety of signalling events. Unlike conventional neurotransmitters, H2 S cannot be stored in vesicles due to its gaseous nature. Instead, it is either locally synthesized or released from endogenous stores. Sulfhydration affords both specific and general neuroprotective effects and is critically diminished in several neurodegenerative disorders. Conversely, some forms of neurodegenerative disease are linked to excessive cellular H2 S. Here, we review the signalling roles of H2 S across the spectrum of neurodegenerative diseases, including Huntington's disease, Parkinson's disease, Alzheimer's disease, Down syndrome, traumatic brain injury, the ataxias, and amyotrophic lateral sclerosis, as well as neurodegeneration generally associated with ageing.}, }
@article {pmid37337289, year = {2023}, author = {Nango, H and Tsuruta, K and Miyagishi, H and Aono, Y and Saigusa, T and Kosuge, Y}, title = {Update on the pathological roles of prostaglandin E2 in neurodegeneration in amyotrophic lateral sclerosis.}, journal = {Translational neurodegeneration}, volume = {12}, number = {1}, pages = {32}, pmid = {37337289}, issn = {2047-9158}, mesh = {Mice ; Animals ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics/metabolism ; *Neurodegenerative Diseases/metabolism ; Motor Neurons/pathology ; Mice, Transgenic ; Dinoprostone/metabolism/pharmacology/therapeutic use ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by selective degeneration of upper and lower motor neurons. The pathogenesis of ALS remains largely unknown; however, inflammation of the spinal cord is a focus of ALS research and an important pathogenic process in ALS. Prostaglandin E2 (PGE2) is a major lipid mediator generated by the arachidonic-acid cascade and is abundant at inflammatory sites. PGE2 levels are increased in the postmortem spinal cords of ALS patients and in ALS model mice. Beneficial therapeutic effects have been obtained in ALS model mice using cyclooxygenase-2 inhibitors to inhibit the biosynthesis of PGE2, but the usefulness of this inhibitor has not yet been proven in clinical trials. In this review, we present current evidence on the involvement of PGE2 in the progression of ALS and discuss the potential of microsomal prostaglandin E synthase (mPGES) and the prostaglandin receptor E-prostanoid (EP) 2 as therapeutic targets for ALS. Signaling pathways involving prostaglandin receptors mediate toxic effects in the central nervous system. In some situations, however, the receptors mediate neuroprotective effects. Our recent studies demonstrated that levels of mPGES-1, which catalyzes the final step of PGE2 biosynthesis, are increased at the early-symptomatic stage in the spinal cords of transgenic ALS model mice carrying the G93A variant of superoxide dismutase-1. In addition, in an experimental motor-neuron model used in studies of ALS, PGE2 induces the production of reactive oxygen species and subsequent caspase-3-dependent cytotoxicity through activation of the EP2 receptor. Moreover, this PGE2-induced EP2 up-regulation in motor neurons plays a role in the death of motor neurons in ALS model mice. Further understanding of the pathophysiological role of PGE2 in neurodegeneration may provide new insights to guide the development of novel therapies for ALS.}, }
@article {pmid37336982, year = {2023}, author = {Nikom, D and Zheng, S}, title = {Alternative splicing in neurodegenerative disease and the promise of RNA therapies.}, journal = {Nature reviews. Neuroscience}, volume = {24}, number = {8}, pages = {457-473}, pmid = {37336982}, issn = {1471-0048}, support = {R01 NS125276/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; Alternative Splicing/genetics ; RNA/genetics/metabolism ; *Neurodegenerative Diseases/genetics/therapy/metabolism ; RNA Splicing ; Protein Isoforms/genetics/metabolism ; *Amyotrophic Lateral Sclerosis ; *Frontotemporal Dementia/genetics ; }, abstract = {Alternative splicing generates a myriad of RNA products and protein isoforms of different functions from a single gene. Dysregulated alternative splicing has emerged as a new mechanism broadly implicated in the pathogenesis of neurodegenerative diseases such as Alzheimer disease, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson disease and repeat expansion diseases. Understanding the mechanisms and functional outcomes of abnormal splicing in neurological disorders is vital in developing effective therapies to treat mis-splicing pathology. In this Review, we discuss emerging research and evidence of the roles of alternative splicing defects in major neurodegenerative diseases and summarize the latest advances in RNA-based therapeutic strategies to target these disorders.}, }
@article {pmid37333000, year = {2023}, author = {Boostani, R and Olfati, N and Shamshiri, H and Salimi, Z and Fatehi, F and Hedjazi, SA and Fakharian, A and Ghasemi, M and Okhovat, AA and Basiri, K and Haghi Ashtiani, B and Ansari, B and Raissi, GR and Khatoonabadi, SA and Sarraf, P and Movahed, S and Panahi, A and Ziaadini, B and Yazdchi, M and Bakhtiyari, J and Nafissi, S}, title = {Iranian clinical practice guideline for amyotrophic lateral sclerosis.}, journal = {Frontiers in neurology}, volume = {14}, number = {}, pages = {1154579}, pmid = {37333000}, issn = {1664-2295}, abstract = {Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegeneration involving motor neurons. The 3-5 years that patients have to live is marked by day-to-day loss of motor and sometimes cognitive abilities. Enormous amounts of healthcare services and resources are necessary to support patients and their caregivers during this relatively short but burdensome journey. Organization and management of these resources need to best meet patients' expectations and health system efficiency mandates. This can only occur in the setting of multidisciplinary ALS clinics which are known as the gold standard of ALS care worldwide. To introduce this standard to the care of Iranian ALS patients, which is an inevitable quality milestone, a national ALS clinical practice guideline is the necessary first step. The National ALS guideline will serve as the knowledge base for the development of local clinical pathways to guide patient journeys in multidisciplinary ALS clinics. To this end, we gathered a team of national neuromuscular experts as well as experts in related specialties necessary for delivering multidisciplinary care to ALS patients to develop the Iranian ALS clinical practice guideline. Clinical questions were prepared in the Patient, Intervention, Comparison, and Outcome (PICO) format to serve as a guide for the literature search. Considering the lack of adequate national/local studies at this time, a consensus-based approach was taken to evaluate the quality of the retrieved evidence and summarize recommendations.}, }
@article {pmid37332910, year = {2023}, author = {Rather, MA and Khan, A and Wang, L and Jahan, S and Rehman, MU and Makeen, HA and Mohan, S}, title = {TRP channels: Role in neurodegenerative diseases and therapeutic targets.}, journal = {Heliyon}, volume = {9}, number = {6}, pages = {e16910}, pmid = {37332910}, issn = {2405-8440}, abstract = {TRP (Transient receptor potential) channels are integral membrane proteins consisting of a superfamily of cation channels that allow permeability of both monovalent and divalent cations. TRP channels are subdivided into six subfamilies: TRPC, TRPV, TRPM, TRPP, TRPML, and TRPA, and are expressed in almost every cell and tissue. TRPs play an instrumental role in the regulation of various physiological processes. TRP channels are extensively represented in brain tissues and are present in both prokaryotes and eukaryotes, exhibiting responses to several mechanisms, including physical, chemical, and thermal stimuli. TRP channels are involved in the perturbation of Ca[2+] homeostasis in intracellular calcium stores, both in neuronal and non-neuronal cells, and its discrepancy leads to several neuronal disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic lateral sclerosis (ALS). TRPs participate in neurite outgrowth, receptor signaling, and excitotoxic cell death in the central nervous system. Understanding the mechanism of TRP channels in neurodegenerative diseases may extend to developing novel therapies. Thus, this review articulates TRP channels' physiological and pathological role in exploring new therapeutic interventions in neurodegenerative diseases.}, }
@article {pmid37331636, year = {2023}, author = {Zhang, H and Qi, G and Wang, K and Yang, J and Shen, Y and Yang, X and Chen, X and Yao, X and Gu, X and Qi, L and Zhou, C and Sun, H}, title = {Oxidative stress: Roles in skeletal muscle atrophy.}, journal = {Biochemical pharmacology}, volume = {214}, number = {}, pages = {115664}, doi = {10.1016/j.bcp.2023.115664}, pmid = {37331636}, issn = {1873-2968}, mesh = {Humans ; *Muscular Atrophy/metabolism ; Oxidative Stress ; Muscle, Skeletal/metabolism ; *Sarcopenia/drug therapy/metabolism/pathology ; Antioxidants/metabolism ; Chronic Disease ; }, abstract = {Oxidative stress, inflammation, mitochondrial dysfunction, reduced protein synthesis, and increased proteolysis are all critical factors in the process of muscle atrophy. In particular, oxidative stress is the key factor that triggers skeletal muscle atrophy. It is activated in the early stages of muscle atrophy and can be regulated by various factors. The mechanisms of oxidative stress in the development of muscle atrophy have not been completely elucidated. This review provides an overview of the sources of oxidative stress in skeletal muscle and the correlation of oxidative stress with inflammation, mitochondrial dysfunction, autophagy, protein synthesis, proteolysis, and muscle regeneration in muscle atrophy. Additionally, the role of oxidative stress in skeletal muscle atrophy caused by several pathological conditions, including denervation, unloading, chronic inflammatory diseases (diabetes mellitus, chronic kidney disease, chronic heart failure, and chronic obstructive pulmonary disease), sarcopenia, hereditary neuromuscular diseases (spinal muscular atrophy, amyotrophic lateral sclerosis, and Duchenne muscular dystrophy), and cancer cachexia, have been discussed. Finally, this review proposes the alleviation oxidative stress using antioxidants, Chinese herbal extracts, stem cell and extracellular vesicles as a promising therapeutic strategy for muscle atrophy. This review will aid in the development of novel therapeutic strategies and drugs for muscle atrophy.}, }
@article {pmid37327376, year = {2023}, author = {Shefner, JM and Musaro, A and Ngo, ST and Lunetta, C and Steyn, FJ and Robitaille, R and De Carvalho, M and Rutkove, S and Ludolph, AC and Dupuis, L}, title = {Skeletal muscle in amyotrophic lateral sclerosis.}, journal = {Brain : a journal of neurology}, volume = {146}, number = {11}, pages = {4425-4436}, pmid = {37327376}, issn = {1460-2156}, mesh = {Adult ; Humans ; *Amyotrophic Lateral Sclerosis/pathology ; Motor Neurons/pathology ; Muscle, Skeletal/pathology ; Neuromuscular Junction/pathology ; Muscle Weakness ; }, abstract = {Amyotrophic lateral sclerosis (ALS), the major adult-onset motor neuron disease, has been viewed almost exclusively as a disease of upper and lower motor neurons, with muscle changes interpreted as a consequence of the progressive loss of motor neurons and neuromuscular junctions. This has led to the prevailing view that the involvement of muscle in ALS is only secondary to motor neuron loss. Skeletal muscle and motor neurons reciprocally influence their respective development and constitute a single functional unit. In ALS, multiple studies indicate that skeletal muscle dysfunction might contribute to progressive muscle weakness, as well as to the final demise of neuromuscular junctions and motor neurons. Furthermore, skeletal muscle has been shown to participate in disease pathogenesis of several monogenic diseases closely related to ALS. Here, we move the narrative towards a better appreciation of muscle as a contributor of disease in ALS. We review the various potential roles of skeletal muscle cells in ALS, from passive bystanders to active players in ALS pathophysiology. We also compare ALS to other motor neuron diseases and draw perspectives for future research and treatment.}, }
@article {pmid37323141, year = {2023}, author = {Khatoon, S and Kalam, N and Rashid, S and Bano, G}, title = {Effects of gut microbiota on neurodegenerative diseases.}, journal = {Frontiers in aging neuroscience}, volume = {15}, number = {}, pages = {1145241}, pmid = {37323141}, issn = {1663-4365}, abstract = {A progressive degradation of the brain's structure and function, which results in a reduction in cognitive and motor skills, characterizes neurodegenerative diseases (NDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD). The morbidity linked to NDs is growing, which poses a severe threat to human being's mental and physical ability to live well. The gut-brain axis (GBA) is now known to have a crucial role in the emergence of NDs. The gut microbiota is a conduit for the GBA, a two-way communication system between the gut and the brain. The myriad microorganisms that make up the gut microbiota can affect brain physiology by transmitting numerous microbial chemicals from the gut to the brain via the GBA or neurological system. The synthesis of neurotransmitters, the immunological response, and the metabolism of lipids and glucose have all been demonstrated to be impacted by alterations in the gut microbiota, such as an imbalance of helpful and harmful bacteria. In order to develop innovative interventions and clinical therapies for NDs, it is crucial to comprehend the participation of the gut microbiota in these conditions. In addition to using antibiotics and other drugs to target particular bacterial species that may be a factor in NDs, this also includes using probiotics and other fecal microbiota transplantation to maintain a healthy gut microbiota. In conclusion, the examination of the GBA can aid in understanding the etiology and development of NDs, which may benefit the improvement of clinical treatments for these disorders and ND interventions. This review indicates existing knowledge about the involvement of microbiota present in the gut in NDs and potential treatment options.}, }
@article {pmid37322525, year = {2023}, author = {Karlsson, AW and Kragh-Sørensen, A and Børgesen, K and Behrens, KE and Andersen, T and Kidholm, ML and Rothmann, MJ and Ketelaar, M and Janssens, A}, title = {Roles, outcomes, and enablers within research partnerships: A rapid review of the literature on patient and public involvement and engagement in health research.}, journal = {Research involvement and engagement}, volume = {9}, number = {1}, pages = {43}, pmid = {37322525}, issn = {2056-7529}, abstract = {BACKGROUND: Recent studies mention a need to investigate partnership roles and dynamics within patient and public involvement and engagement (PPIE) in health research, and how impact and outcomes are achieved. Many labels exist to describe involvement processes, but it is unknown whether the label has implications on partnerships and outcomes. This rapid review investigates how roles between patients, relatives and researchers in a broad variety of PPIE activities in health research are described in peer reviewed papers and explores what enables these partnerships.<br><br>METHODS: Rapid review of articles published between 2012 and February 2022 describing, evaluating, or reflecting on experiences of PPIE in health research. All research disciplines and research areas were eligible. Four databases (Medline, Embase, PsychInfo and CINAHL) were searched between November 2021 and February 2022. We followed PRISMA guidelines and extracted descriptive factors: year, origin, research area and discipline, study focus, framework used and co-authorship. On a selection of articles, we performed a narrative analysis of partnership roles using Smits et al.'s. Involvement Matrix. Lastly, we performed a meta synthesis of reported enablers and outcomes of the partnerships. Patients and Relatives (PRs) have been involved in the whole rapid review process and are co-authors of this article.<br><br>RESULTS: Seventy articles from various research disciplines and areas were included. Forty articles were selected for a narrative analysis of the role description of PRs and researchers, and a meta synthesis of enablers and outcomes. Most articles described researchers as decision-makers throughout the research cycle. PRs most often were partners when they were included as co-authors; they were mostly partners in the design, analysis, write-up, and dissemination stages. Enablers of partnerships included: PR training, personality of PRs and communication skills, trust, remuneration and time.<br><br>CONCLUSIONS: Researchers' decision-making roles gives them control of where and when to include PRs in their projects. Co-authorship is a way of acknowledging patients' contributions which may lead to legitimation of their knowledge and the partnership. Authors describe common enablers, which can help future partnership formation.}, }
@article {pmid37316681, year = {2023}, author = {Blair, HA}, title = {Tofersen: First Approval.}, journal = {Drugs}, volume = {83}, number = {11}, pages = {1039-1043}, pmid = {37316681}, issn = {1179-1950}, mesh = {Adult ; Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics ; Superoxide Dismutase/genetics ; Oligonucleotides/pharmacology/therapeutic use ; Superoxide Dismutase-1/genetics ; Mutation ; }, abstract = {Tofersen (Qalsody[™]) is an antisense oligonucleotide being developed by Biogen for the treatment of amyotrophic lateral sclerosis (ALS). On 25 April 2023, tofersen was approved in the USA for the treatment of ALS in adults who have a mutation in the superoxide dismutase 1 (SOD1) gene. This article summarizes the milestones in the development of tofersen leading to this first approval for ALS.}, }
@article {pmid37316187, year = {2023}, author = {Iverson, GL and Castellani, RJ and Cassidy, JD and Schneider, GM and Schneider, KJ and Echemendia, RJ and Bailes, JE and Hayden, KA and Koerte, IK and Manley, GT and McNamee, M and Patricios, JS and Tator, CH and Cantu, RC and Dvorak, J}, title = {Examining later-in-life health risks associated with sport-related concussion and repetitive head impacts: a systematic review of case-control and cohort studies.}, journal = {British journal of sports medicine}, volume = {57}, number = {12}, pages = {810-821}, doi = {10.1136/bjsports-2023-106890}, pmid = {37316187}, issn = {1473-0480}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; *Sports ; *Brain Concussion/epidemiology/etiology ; Cohort Studies ; Case-Control Studies ; *Dementia ; }, abstract = {OBJECTIVE: Concern exists about possible problems with later-in-life brain health, such as cognitive impairment, mental health problems and neurological diseases, in former athletes. We examined the future risk for adverse health effects associated with sport-related concussion, or exposure to repetitive head impacts, in former athletes.<br><br>DESIGN: Systematic review.<br><br>DATA SOURCES: Search of MEDLINE, Embase, Cochrane, CINAHL Plus and SPORTDiscus in October 2019 and updated in March 2022.<br><br>ELIGIBILITY CRITERIA: Studies measuring future risk (cohort studies) or approximating that risk (case-control studies).<br><br>RESULTS: Ten studies of former amateur athletes and 18 studies of former professional athletes were included. No postmortem neuropathology studies or neuroimaging studies met criteria for inclusion. Depression was examined in five studies in former amateur athletes, none identifying an increased risk. Nine studies examined suicidality or suicide as a manner of death, and none found an association with increased risk. Some studies comparing professional athletes with the general population reported associations between sports participation and dementia or amyotrophic lateral sclerosis (ALS) as a cause of death. Most did not control for potential confounding factors (eg, genetic, demographic, health-related or environmental), were ecological in design and had high risk of bias.<br><br>CONCLUSION: Evidence does not support an increased risk of mental health or neurological diseases in former amateur athletes with exposure to repetitive head impacts. Some studies in former professional athletes suggest an increased risk of neurological disorders such as ALS and dementia; these findings need to be confirmed in higher quality studies with better control of confounding factors.<br><br>PROSPERO REGISTRATION NUMBER: CRD42022159486.}, }
@article {pmid37316101, year = {2023}, author = {Tavazzi, E and Longato, E and Vettoretti, M and Aidos, H and Trescato, I and Roversi, C and Martins, AS and Castanho, EN and Branco, R and Soares, DF and Guazzo, A and Birolo, G and Pala, D and Bosoni, P and Chiò, A and Manera, U and de Carvalho, M and Miranda, B and Gromicho, M and Alves, I and Bellazzi, R and Dagliati, A and Fariselli, P and Madeira, SC and Di Camillo, B}, title = {Artificial intelligence and statistical methods for stratification and prediction of progression in amyotrophic lateral sclerosis: A systematic review.}, journal = {Artificial intelligence in medicine}, volume = {142}, number = {}, pages = {102588}, doi = {10.1016/j.artmed.2023.102588}, pmid = {37316101}, issn = {1873-2860}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; Artificial Intelligence ; Brain ; Cluster Analysis ; Databases, Factual ; }, abstract = {BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disorder characterised by the progressive loss of motor neurons in the brain and spinal cord. The fact that ALS's disease course is highly heterogeneous, and its determinants not fully known, combined with ALS's relatively low prevalence, renders the successful application of artificial intelligence (AI) techniques particularly arduous.<br><br>OBJECTIVE: This systematic review aims at identifying areas of agreement and unanswered questions regarding two notable applications of AI in ALS, namely the automatic, data-driven stratification of patients according to their phenotype, and the prediction of ALS progression. Differently from previous works, this review is focused on the methodological landscape of AI in ALS.<br><br>METHODS: We conducted a systematic search of the Scopus and PubMed databases, looking for studies on data-driven stratification methods based on unsupervised techniques resulting in (A) automatic group discovery or (B) a transformation of the feature space allowing patient subgroups to be identified; and for studies on internally or externally validated methods for the prediction of ALS progression. We described the selected studies according to the following characteristics, when applicable: variables used, methodology, splitting criteria and number of groups, prediction outcomes, validation schemes, and metrics.<br><br>RESULTS: Of the starting 1604 unique reports (2837 combined hits between Scopus and PubMed), 239 were selected for thorough screening, leading to the inclusion of 15 studies on patient stratification, 28 on prediction of ALS progression, and 6 on both stratification and prediction. In terms of variables used, most stratification and prediction studies included demographics and features derived from the ALSFRS or ALSFRS-R scores, which were also the main prediction targets. The most represented stratification methods were K-means, and hierarchical and expectation-maximisation clustering; while random forests, logistic regression, the Cox proportional hazard model, and various flavours of deep learning were the most widely used prediction methods. Predictive model validation was, albeit unexpectedly, quite rarely performed in absolute terms (leading to the exclusion of 78 eligible studies), with the overwhelming majority of included studies resorting to internal validation only.<br><br>CONCLUSION: This systematic review highlighted a general agreement in terms of input variable selection for both stratification and prediction of ALS progression, and in terms of prediction targets. A striking lack of validated models emerged, as well as a general difficulty in reproducing many published studies, mainly due to the absence of the corresponding parameter lists. While deep learning seems promising for prediction applications, its superiority with respect to traditional methods has not been established; there is, instead, ample room for its application in the subfield of patient stratification. Finally, an open question remains on the role of new environmental and behavioural variables collected via novel, real-time sensors.}, }
@article {pmid37310359, year = {2023}, author = {Fang, J and Huang, Y and Wu, J and Shen, B and Yang, Y and Ju, M}, title = {Fluorogenic methodology for visualization of phase separation in chemical biology.}, journal = {Organic &amp; biomolecular chemistry}, volume = {21}, number = {25}, pages = {5140-5149}, doi = {10.1039/d3ob00660c}, pmid = {37310359}, issn = {1477-0539}, mesh = {Humans ; *Alzheimer Disease ; Biology ; }, abstract = {Phase separation is a common biological phenomenon in the liquid environment of organisms. Phase separation has been shown to be a key cause of many existing incurable diseases, such as the protein aggregates formed by phase separation of Alzheimer's Disease, Amyotrophic Lateral Sclerosis, Parkinson's disease, etc. Tracking the occurrence of phase separation in vivo is critical to many disease detection methods and solving many treatment problems. Its physicochemical properties and visual detection methods have flourished in the last few years in chemical biology, among which the fluorogenic toolbox has great application potential compared to the traditional detection methods that cannot visualize the phase separation process intuitively, but just show some parameters indirectly. This paper reviews the mechanism and disease correlation proven in recent years for phase separation and analyzes the detection methods for phase separation, including functional microscope imaging techniques, turbidity monitoring, macromolecule congestion sensing, in silico analysis, etc. It is worth mentioning that the qualitative and quantitative analysis of aggregates formed by phase separation using in vitro parameters has successfully provided basic physical and chemical properties for phase separation aggregates, and is an important cornerstone for researchers to carry forward the past and break through the existing technical shackles to create new in vivo monitoring methods such as fluorescence methodology. Crucially, fluorescence methods for cell microenvironment imaging based on different mechanisms are discussed, such as AIE-based probes, TICT-based probes and FRET-based probes, etc.}, }
@article {pmid37308302, year = {2023}, author = {Wolfson, C and Gauvin, DE and Ishola, F and Oskoui, M}, title = {Global Prevalence and Incidence of Amyotrophic Lateral Sclerosis: A Systematic Review.}, journal = {Neurology}, volume = {101}, number = {6}, pages = {e613-e623}, pmid = {37308302}, issn = {1526-632X}, mesh = {*Amyotrophic Lateral Sclerosis/epidemiology ; Incidence ; Prevalence ; Humans ; Africa/epidemiology ; Asia/epidemiology ; Europe/epidemiology ; North America/epidemiology ; South America/epidemiology ; Oceania/epidemiology ; }, abstract = {BACKGROUND AND OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disorder affecting upper and lower motor neurons. Due to its rarity and rapidly progressive nature, studying the epidemiology of ALS is challenging, and a comprehensive picture of the global burden of this disease is lacking. The objective of this systematic review was to describe the global incidence and prevalence of ALS.<br><br>METHODS: We searched MEDLINE, Embase, Global Health, PsycInfo, Cochrane Library, and CINAHL to identify articles published between January 1, 2010, and May 6, 2021. Studies that were population based and reported estimates of prevalence, incidence, and/or mortality of ALS were eligible for inclusion. This study focuses on the incidence and prevalence. Quality assessment was performed using a tool developed to evaluate methodology relevant to prevalence and incidence studies. This review was registered with PROSPERO, CRD42021250559.<br><br>RESULTS: This search generated 6,238 articles, of which 140 were selected for data extraction and quality assessment. Of these, 85 articles reported on the incidence and 61 on the prevalence of ALS. Incidence ranged from 0.26 per 100,000 person-years in Ecuador to 23.46 per 100,000 person-years in Japan. Point prevalence ranged from 1.57 per 100,000 in Iran to 11.80 per 100,000 in the United States. Many articles identified cases with ALS from multiple data sources.<br><br>DISCUSSION: There is variation in reported incidence and prevalence estimates of ALS across the world. While registries are an important and powerful tool to quantify disease burden, such resources are not available everywhere. This results in gaps in reporting of the global epidemiology of ALS, as highlighted by the degree of variation (and quality) in estimates of incidence and prevalence reported in this review.}, }
@article {pmid37307822, year = {2024}, author = {Chen, S and Cai, X and Lao, L and Wang, Y and Su, H and Sun, H}, title = {Brain-Gut-Microbiota Axis in Amyotrophic Lateral Sclerosis: A Historical Overview and Future Directions.}, journal = {Aging and disease}, volume = {15}, number = {1}, pages = {74-95}, pmid = {37307822}, issn = {2152-5250}, mesh = {Humans ; Aged ; Child, Preschool ; *Amyotrophic Lateral Sclerosis/epidemiology ; *Neurodegenerative Diseases/complications ; *Gastrointestinal Microbiome/physiology ; Brain-Gut Axis ; Brain ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease which is strongly associated with age. The incidence of ALS increases from the age of 40 and peaks between the ages of 65 and 70. Most patients die of respiratory muscle paralysis or lung infections within three to five years of the appearance of symptoms, dealing a huge blow to patients and their families. With aging populations, improved diagnostic methods and changes in reporting criteria, the incidence of ALS is likely to show an upward trend in the coming decades. Despite extensive researches have been done, the cause and pathogenesis of ALS remains unclear. In recent decades, large quantities of studies focusing on gut microbiota have shown that gut microbiota and its metabolites seem to change the evolvement of ALS through the brain-gut-microbiota axis, and in turn, the progression of ALS will exacerbate the imbalance of gut microbiota, thereby forming a vicious cycle. This suggests that further exploration and identification of the function of gut microbiota in ALS may be crucial to break the bottleneck in the diagnosis and treatment of this disease. Hence, the current review summarizes and discusses the latest research advancement and future directions of ALS and brain-gut-microbiota axis, so as to help relevant researchers gain correlative information instantly.}, }
@article {pmid37307819, year = {2024}, author = {He, D and Xu, Y and Liu, M and Cui, L}, title = {The Inflammatory Puzzle: Piecing together the Links between Neuroinflammation and Amyotrophic Lateral Sclerosis.}, journal = {Aging and disease}, volume = {15}, number = {1}, pages = {96-114}, pmid = {37307819}, issn = {2152-5250}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Neuroinflammatory Diseases ; *Neurodegenerative Diseases/complications ; Central Nervous System ; Signal Transduction/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that has a complex genetic basis. Through advancements in genetic screening, researchers have identified more than 40 mutant genes associated with ALS, some of which impact immune function. Neuroinflammation, with abnormal activation of immune cells and excessive production of inflammatory cytokines in the central nervous system, significantly contributes to the pathophysiology of ALS. In this review, we examine recent evidence on the involvement of ALS-associated mutant genes in immune dysregulation, with a specific focus on the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway and N6-methyladenosine (m[6]A)-mediated immune regulation in the context of neurodegeneration. We also discuss the perturbation of immune cell homeostasis in both the central nervous system and peripheral tissues in ALS. Furthermore, we explore the advancements made in the emerging genetic and cell-based therapies for ALS. This review underscores the complex relationship between ALS and neuroinflammation, highlighting the potential to identify modifiable factors for therapeutic intervention. A deeper understanding of the connection between neuroinflammation and the risk of ALS is crucial for advancing effective treatments for this debilitating disorder.}, }
@article {pmid37306196, year = {2023}, author = {Lloyd, EM and Pinniger, GJ and Murphy, RM and Grounds, MD}, title = {Slow or fast: Implications of myofibre type and associated differences for manifestation of neuromuscular disorders.}, journal = {Acta physiologica (Oxford, England)}, volume = {238}, number = {4}, pages = {e14012}, doi = {10.1111/apha.14012}, pmid = {37306196}, issn = {1748-1716}, mesh = {Male ; Animals ; Female ; *Muscle Fibers, Fast-Twitch ; *Muscle Fibers, Slow-Twitch ; Muscle, Skeletal/physiology ; Muscle Contraction/physiology ; Aging ; Mammals ; }, abstract = {Many neuromuscular disorders can have a differential impact on a specific myofibre type, forming the central premise of this review. The many different skeletal muscles in mammals contain a spectrum of slow- to fast-twitch myofibres with varying levels of protein isoforms that determine their distinctive contractile, metabolic, and other properties. The variations in functional properties across the range of classic 'slow' to 'fast' myofibres are outlined, combined with exemplars of the predominantly slow-twitch soleus and fast-twitch extensor digitorum longus muscles, species comparisons, and techniques used to study these properties. Other intrinsic and extrinsic differences are discussed in the context of slow and fast myofibres. These include inherent susceptibility to damage, myonecrosis, and regeneration, plus extrinsic nerves, extracellular matrix, and vasculature, examined in the context of growth, ageing, metabolic syndrome, and sexual dimorphism. These many differences emphasise the importance of carefully considering the influence of myofibre-type composition on manifestation of various neuromuscular disorders across the lifespan for both sexes. Equally, understanding the different responses of slow and fast myofibres due to intrinsic and extrinsic factors can provide deep insight into the precise molecular mechanisms that initiate and exacerbate various neuromuscular disorders. This focus on the influence of different myofibre types is of fundamental importance to enhance translation for clinical management and therapies for many skeletal muscle disorders.}, }
@article {pmid37304072, year = {2023}, author = {Santiago, JA and Potashkin, JA}, title = {Physical activity and lifestyle modifications in the treatment of neurodegenerative diseases.}, journal = {Frontiers in aging neuroscience}, volume = {15}, number = {}, pages = {1185671}, pmid = {37304072}, issn = {1663-4365}, support = {R01 AG062176/AG/NIA NIH HHS/United States ; }, abstract = {Neurodegenerative diseases have reached alarming numbers in the past decade. Unfortunately, clinical trials testing potential therapeutics have proven futile. In the absence of disease-modifying therapies, physical activity has emerged as the single most accessible lifestyle modification with the potential to fight off cognitive decline and neurodegeneration. In this review, we discuss findings from epidemiological, clinical, and molecular studies investigating the potential of lifestyle modifications in promoting brain health. We propose an evidence-based multidomain approach that includes physical activity, diet, cognitive training, and sleep hygiene to treat and prevent neurodegenerative diseases.}, }
@article {pmid37300059, year = {2023}, author = {Stateczny, A and Halicki, A and Specht, M and Specht, C and Lewicka, O}, title = {Review of Shoreline Extraction Methods from Aerial Laser Scanning.}, journal = {Sensors (Basel, Switzerland)}, volume = {23}, number = {11}, pages = {}, pmid = {37300059}, issn = {1424-8220}, support = {LIDER/10/0030/L-11/19/NCBR/2020//National Centre for Research and Development in Poland/ ; WN/2023/PZ/05//Gdynia Maritime University/ ; }, abstract = {Autonomous technologies are increasingly used in various areas of science. The use of unmanned vehicles for hydrographic surveys in shallow coastal areas requires accurate estimation of shoreline position. This is a nontrivial task, which can be performed using a wide range of sensors and methods. The aim of the publication is to review shoreline extraction methods based solely on data from aerial laser scanning (ALS). This narrative review discusses and critically analyses seven publications drawn up in the last ten years. The discussed papers employed nine different shoreline extraction methods based on aerial light detection and ranging (LiDAR) data. It should be noted that unambiguous evaluation of shoreline extraction methods is difficult or impossible. This is because not all of the methods reported achieved accuracy, the methods were assessed on different datasets, the measurements were conducted using different devices, the water areas differed in geometrical and optical properties, the shorelines had different geometries, and the extent of anthropogenic transformation. The methods proposed by the authors were compared with a wide range of reference methods.}, }
@article {pmid37298586, year = {2023}, author = {Cerasuolo, M and Di Meo, I and Auriemma, MC and Trojsi, F and Maiorino, MI and Cirillo, M and Esposito, F and Polito, R and Colangelo, AM and Paolisso, G and Papa, M and Rizzo, MR}, title = {Iron and Ferroptosis More than a Suspect: Beyond the Most Common Mechanisms of Neurodegeneration for New Therapeutic Approaches to Cognitive Decline and Dementia.}, journal = {International journal of molecular sciences}, volume = {24}, number = {11}, pages = {}, pmid = {37298586}, issn = {1422-0067}, mesh = {Humans ; Iron/metabolism ; *Alzheimer Disease/metabolism ; *Ferroptosis ; *Neurodegenerative Diseases/metabolism ; *Cognitive Dysfunction/drug therapy/etiology/metabolism ; }, abstract = {Neurodegeneration is a multifactorial process that involves multiple mechanisms. Examples of neurodegenerative diseases are Parkinson's disease, multiple sclerosis, Alzheimer's disease, prion diseases such as Creutzfeldt-Jakob's disease, and amyotrophic lateral sclerosis. These are progressive and irreversible pathologies, characterized by neuron vulnerability, loss of structure or function of neurons, and even neuron demise in the brain, leading to clinical, functional, and cognitive dysfunction and movement disorders. However, iron overload can cause neurodegeneration. Dysregulation of iron metabolism associated with cellular damage and oxidative stress is reported as a common event in several neurodegenerative diseases. Uncontrolled oxidation of membrane fatty acids triggers a programmed cell death involving iron, ROS, and ferroptosis, promoting cell death. In Alzheimer's disease, the iron content in the brain is significantly increased in vulnerable regions, resulting in a lack of antioxidant defenses and mitochondrial alterations. Iron interacts with glucose metabolism reciprocally. Overall, iron metabolism and accumulation and ferroptosis play a significant role, particularly in the context of diabetes-induced cognitive decline. Iron chelators improve cognitive performance, meaning that brain iron metabolism control reduces neuronal ferroptosis, promising a novel therapeutic approach to cognitive impairment.}, }
@article {pmid37298554, year = {2023}, author = {Michetti, F and Clementi, ME and Di Liddo, R and Valeriani, F and Ria, F and Rende, M and Di Sante, G and Romano Spica, V}, title = {The S100B Protein: A Multifaceted Pathogenic Factor More Than a Biomarker.}, journal = {International journal of molecular sciences}, volume = {24}, number = {11}, pages = {}, pmid = {37298554}, issn = {1422-0067}, mesh = {Humans ; Biomarkers/metabolism ; *Nervous System Diseases ; *Parkinson Disease/metabolism ; *S100 Calcium Binding Protein beta Subunit ; }, abstract = {S100B is a calcium-binding protein mainly concentrated in astrocytes in the nervous system. Its levels in biological fluids are recognized as a reliable biomarker of active neural distress, and more recently, mounting evidence points to S100B as a Damage-Associated Molecular Pattern molecule, which, at high concentration, triggers tissue reactions to damage. S100B levels and/or distribution in the nervous tissue of patients and/or experimental models of different neural disorders, for which the protein is used as a biomarker, are directly related to the progress of the disease. In addition, in experimental models of diseases such as Alzheimer's and Parkinson's diseases, amyotrophic lateral sclerosis, multiple sclerosis, traumatic and vascular acute neural injury, epilepsy, and inflammatory bowel disease, alteration of S100B levels correlates with the occurrence of clinical and/or toxic parameters. In general, overexpression/administration of S100B worsens the clinical presentation, whereas deletion/inactivation of the protein contributes to the amelioration of the symptoms. Thus, the S100B protein may be proposed as a common pathogenic factor in different disorders, sharing different symptoms and etiologies but appearing to share some common pathogenic processes reasonably attributable to neuroinflammation.}, }
@article {pmid37298512, year = {2023}, author = {Guo, Z}, title = {Ganglioside GM1 and the Central Nervous System.}, journal = {International journal of molecular sciences}, volume = {24}, number = {11}, pages = {}, pmid = {37298512}, issn = {1422-0067}, support = {R35 GM131686/GM/NIGMS NIH HHS/United States ; R35GM131686/NH/NIH HHS/United States ; }, mesh = {Humans ; *G(M1) Ganglioside/metabolism ; *Gangliosidosis, GM1 ; Central Nervous System/metabolism ; Brain/metabolism ; Glycosphingolipids/metabolism ; }, abstract = {GM1 is one of the major glycosphingolipids (GSLs) on the cell surface in the central nervous system (CNS). Its expression level, distribution pattern, and lipid composition are dependent upon cell and tissue type, developmental stage, and disease state, which suggests a potentially broad spectrum of functions of GM1 in various neurological and neuropathological processes. The major focus of this review is the roles that GM1 plays in the development and activities of brains, such as cell differentiation, neuritogenesis, neuroregeneration, signal transducing, memory, and cognition, as well as the molecular basis and mechanisms for these functions. Overall, GM1 is protective for the CNS. Additionally, this review has also examined the relationships between GM1 and neurological disorders, such as Alzheimer's disease, Parkinson's disease, GM1 gangliosidosis, Huntington's disease, epilepsy and seizure, amyotrophic lateral sclerosis, depression, alcohol dependence, etc., and the functional roles and therapeutic applications of GM1 in these disorders. Finally, current obstacles that hinder more in-depth investigations and understanding of GM1 and the future directions in this field are discussed.}, }
@article {pmid37298129, year = {2023}, author = {Molinaro, P and Sanguigno, L and Casamassa, A and Valsecchi, V and Sirabella, R and Pignataro, G and Annunziato, L and Formisano, L}, title = {Emerging Role of DREAM in Healthy Brain and Neurological Diseases.}, journal = {International journal of molecular sciences}, volume = {24}, number = {11}, pages = {}, pmid = {37298129}, issn = {1422-0067}, support = {PE0000006//Ministry of Education, Universities and Research/ ; PE0000012//Ministry of Education, Universities and Research/ ; CN00000041//Ministry of Education, Universities and Research/ ; 2017JL8SRX//Ministry of Education, Universities and Research/ ; 20173EAZ2Z//Ministry of Education, Universities and Research/ ; 2017WJZ9W9//Ministry of Education, Universities and Research/ ; }, mesh = {*Kv Channel-Interacting Proteins/metabolism ; *Repressor Proteins/genetics ; Brain/metabolism ; Dynorphins/metabolism ; Cell Nucleus/metabolism ; }, abstract = {The downstream regulatory element antagonist modulator (DREAM) is a multifunctional Ca[2+]-sensitive protein exerting a dual mechanism of action to regulate several Ca[2+]-dependent processes. Upon sumoylation, DREAM enters in nucleus where it downregulates the expression of several genes provided with a consensus sequence named dream regulatory element (DRE). On the other hand, DREAM could also directly modulate the activity or the localization of several cytosolic and plasma membrane proteins. In this review, we summarize recent advances in the knowledge of DREAM dysregulation and DREAM-dependent epigenetic remodeling as a central mechanism in the progression of several diseases affecting central nervous system, including stroke, Alzheimer's and Huntington's diseases, amyotrophic lateral sclerosis, and neuropathic pain. Interestingly, DREAM seems to exert a common detrimental role in these diseases by inhibiting the transcription of several neuroprotective genes, including the sodium/calcium exchanger isoform 3 (NCX3), brain-derived neurotrophic factor (BDNF), pro-dynorphin, and c-fos. These findings lead to the concept that DREAM might represent a pharmacological target to ameliorate symptoms and reduce neurodegenerative processes in several pathological conditions affecting central nervous system.}, }
@article {pmid37296644, year = {2023}, author = {Tzeplaeff, L and Wilfling, S and Requardt, MV and Herdick, M}, title = {Current State and Future Directions in the Therapy of ALS.}, journal = {Cells}, volume = {12}, number = {11}, pages = {}, pmid = {37296644}, issn = {2073-4409}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy ; Riluzole/therapeutic use ; Motor Neurons/pathology ; Biomarkers ; Disease Progression ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disorder affecting upper and lower motor neurons, with death resulting mainly from respiratory failure three to five years after symptom onset. As the exact underlying causative pathological pathway is unclear and potentially diverse, finding a suitable therapy to slow down or possibly stop disease progression remains challenging. Varying by country Riluzole, Edaravone, and Sodium phenylbutyrate/Taurursodiol are the only drugs currently approved in ALS treatment for their moderate effect on disease progression. Even though curative treatment options, able to prevent or stop disease progression, are still unknown, recent breakthroughs, especially in the field of targeting genetic disease forms, raise hope for improved care and therapy for ALS patients. In this review, we aim to summarize the current state of ALS therapy, including medication as well as supportive therapy, and discuss the ongoing developments and prospects in the field. Furthermore, we highlight the rationale behind the intense research on biomarkers and genetic testing as a feasible way to improve the classification of ALS patients towards personalized medicine.}, }
@article {pmid37296571, year = {2023}, author = {Valori, CF and Sulmona, C and Brambilla, L and Rossi, D}, title = {Astrocytes: Dissecting Their Diverse Roles in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia.}, journal = {Cells}, volume = {12}, number = {11}, pages = {}, pmid = {37296571}, issn = {2073-4409}, mesh = {Animals ; *Astrocytes ; *Frontotemporal Dementia ; *Amyotrophic Lateral Sclerosis ; }, abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are fatal neurodegenerative disorders often co-occurring in the same patient, a feature that suggests a common origin of the two diseases. Consistently, pathological inclusions of the same proteins as well as mutations in the same genes can be identified in both ALS/FTD. Although many studies have described several disrupted pathways within neurons, glial cells are also regarded as crucial pathogenetic contributors in ALS/FTD. Here, we focus our attention on astrocytes, a heterogenous population of glial cells that perform several functions for optimal central nervous system homeostasis. Firstly, we discuss how post-mortem material from ALS/FTD patients supports astrocyte dysfunction around three pillars: neuroinflammation, abnormal protein aggregation, and atrophy/degeneration. Furthermore, we summarize current attempts at monitoring astrocyte functions in living patients using either novel imaging strategies or soluble biomarkers. We then address how astrocyte pathology is recapitulated in animal and cellular models of ALS/FTD and how we used these models both to understand the molecular mechanisms driving glial dysfunction and as platforms for pre-clinical testing of therapeutics. Finally, we present the current clinical trials for ALS/FTD, restricting our discussion to treatments that modulate astrocyte functions, directly or indirectly.}, }
@article {pmid37291782, year = {2024}, author = {Dai, S and Qiu, L and Veeraraghavan, VP and Sheu, CL and Mony, U}, title = {Advances in iPSC Technology in Neural Disease Modeling, Drug Screening, and Therapy.}, journal = {Current stem cell research &amp; therapy}, volume = {19}, number = {6}, pages = {809-819}, doi = {10.2174/1574888X18666230608105703}, pmid = {37291782}, issn = {2212-3946}, mesh = {Humans ; *Induced Pluripotent Stem Cells/cytology ; *Drug Evaluation, Preclinical/methods ; Animals ; *Neurodegenerative Diseases/therapy ; Cell- and Tissue-Based Therapy/methods ; Cell Differentiation ; Disease Models, Animal ; }, abstract = {Neurodegenerative disorders (NDs) including Alzheimer's Disease, Parkinson's Disease, Amyotrophic Lateral Sclerosis (ALS), and Huntington's disease are all incurable and can only be managed with drugs for the associated symptoms. Animal models of human illnesses help to advance our understanding of the pathogenic processes of diseases. Understanding the pathogenesis as well as drug screening using appropriate disease models of neurodegenerative diseases (NDs) are vital for identifying novel therapies. Human-derived induced pluripotent stem cell (iPSC) models can be an efficient model to create disease in a dish and thereby can proceed with drug screening and identifying appropriate drugs. This technology has many benefits, including efficient reprogramming and regeneration potential, multidirectional differentiation, and the lack of ethical concerns, which open up new avenues for studying neurological illnesses in greater depth. The review mainly focuses on the use of iPSC technology in neuronal disease modeling, drug screening, and cell therapy.}, }
@article {pmid37288069, year = {2023}, author = {Corrigan, F and Wee, IC and Collins-Praino, LE}, title = {Chronic motor performance following different traumatic brain injury severity-A systematic review.}, journal = {Frontiers in neurology}, volume = {14}, number = {}, pages = {1180353}, pmid = {37288069}, issn = {1664-2295}, abstract = {INTRODUCTION: Traumatic brain injury (TBI) is now known to be a chronic disease, causing ongoing neurodegeneration and linked to increased risk of neurodegenerative motor diseases, such as Parkinson's disease and amyotrophic lateral sclerosis. While the presentation of motor deficits acutely following traumatic brain injury is well-documented, however, less is known about how these evolve in the long-term post-injury, or how the initial severity of injury affects these outcomes. The purpose of this review, therefore, was to examine objective assessment of chronic motor impairment across the spectrum of TBI in both preclinical and clinical models.<br><br>METHODS: PubMed, Embase, Scopus, and PsycINFO databases were searched with a search strategy containing key search terms for TBI and motor function. Original research articles reporting chronic motor outcomes with a clearly defined TBI severity (mild, repeated mild, moderate, moderate-severe, and severe) in an adult population were included.<br><br>RESULTS: A total of 97 studies met the inclusion criteria, incorporating 62 preclinical and 35 clinical studies. Motor domains examined included neuroscore, gait, fine-motor, balance, and locomotion for preclinical studies and neuroscore, fine-motor, posture, and gait for clinical studies. There was little consensus among the articles presented, with extensive differences both in assessment methodology of the tests and parameters reported. In general, an effect of severity was seen, with more severe injury leading to persistent motor deficits, although subtle fine motor deficits were also seen clinically following repeated injury. Only six clinical studies investigated motor outcomes beyond 10 years post-injury and two preclinical studies to 18-24 months post-injury, and, as such, the interaction between a previous TBI and aging on motor performance is yet to be comprehensively examined.<br><br>CONCLUSION: Further research is required to establish standardized motor assessment procedures to fully characterize chronic motor impairment across the spectrum of TBI with comprehensive outcomes and consistent protocols. Longitudinal studies investigating the same cohort over time are also a key for understanding the interaction between TBI and aging. This is particularly critical, given the risk of neurodegenerative motor disease development following TBI.}, }
@article {pmid37285737, year = {2023}, author = {Taheri, M and Askari, A and Hussen, BM and Eghbali, A and Ghafouri-Fard, S}, title = {A review on the role of MYC-induced long non-coding RNA in human disorders.}, journal = {Pathology, research and practice}, volume = {248}, number = {}, pages = {154568}, doi = {10.1016/j.prp.2023.154568}, pmid = {37285737}, issn = {1618-0631}, mesh = {Humans ; *Carcinoma, Hepatocellular/pathology ; Gene Expression Regulation, Neoplastic ; *Liver Neoplasms/pathology ; *MicroRNAs/genetics/metabolism ; *RNA, Long Noncoding/genetics/metabolism ; }, abstract = {MINCR (MYC-Induced Long Non-Coding RNA) is classified as an lncRNA. It has a significant correlation with MYC gene. MINCR has important roles in the carcinogenesis. It has been approved that this lncRNA can act as molecular sponge for miR-28-5p, miR-708-5p, miR-876-5p and miR-146a-5p. Dysregulated levels of MINCR has been observed in different types of cancer, especially hepatocellular carcinoma. In addition to malignant conditions, schizophrenia and neurodegenerative diseases such as Alzheimer's disease and amyotrophic lateral sclerosis are associated with dysregulation of expression patterns of MINCR. This review outlines MINCR molecular mechanisms of action in different disorders.}, }
@article {pmid37284659, year = {2023}, author = {Zhu, Q and Zhou, J and Zhang, Y and Huang, H and Han, J and Cao, B and Xu, D and Zhao, Y and Chen, G}, title = {Risk factors associated with amyotrophic lateral sclerosis based on the observational study: a systematic review and meta-analysis.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1196722}, pmid = {37284659}, issn = {1662-4548}, abstract = {OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder affecting the upper and lower motor neurons. Though the pathogenesis of ALS is still unclear, exploring the associations between risk factors and ALS can provide reliable evidence to find the pathogenesis. This meta-analysis aims to synthesize all related risk factors of ALS to understand this disease comprehensively.<br><br>METHODS: We searched the following databases: PubMed, EMBASE, Cochrane library, Web of Science, and Scopus. Moreover, observational studies, including cohort studies, and case-control studies, were included in this meta-analysis.<br><br>RESULTS: A total of 36 eligible observational studies were included, and 10 of them were cohort studies and the rest were case-control studies. We found six factors exacerbated the progression of disease: head trauma (OR = 1.26, 95% CI = 1.13, 1.40), physical activity (OR = 1.06, 95% CI = 1.04, 1.09), electric shock (OR = 2.72, 95% CI = 1.62, 4.56), military service (OR = 1.34, 95% CI = 1.11, 1.61), pesticides (OR = 1.96, 95% CI = 1.7, 2.26), and lead exposure (OR = 2.31, 95% CI = 1.44, 3.71). Of note, type 2 diabetes mellitus was a protective factor for ALS. However, cerebrovascular disease (OR = 0.99, 95% CI = 0.75, 1.29), agriculture (OR = 1.22, 95% CI = 0.74, 1.99), industry (OR = 1.24, 95% CI = 0.81, 1.91), service (OR = 0.47, 95% CI = 0.19, 1.17), smoking (OR = 1.25, 95% CI = 0.5, 3.09), chemicals (OR = 2.45, 95% CI = 0.89, 6.77), and heavy metal (OR = 1.5, 95% CI = 0.47, 4.84) were not risk factors for ALS based on meta-analyses.<br><br>CONCLUSIONS: Head trauma, physical activity, electric shock, military service, pesticides, and lead were risk factors for ALS onset and progression. But DM was a protective factor. This finding provides a better understanding of ALS risk factors with strong evidence for clinicians to rationalize clinical intervention strategies.<br><br>INPLSY REGISTRATION NUMBER: https://inplasy.com/inplasy-2022-9-0118/, INPLASY202290118.}, }
@article {pmid37277972, year = {2023}, author = {Mori, K and Gotoh, S and Ikeda, M}, title = {Aspects of degradation and translation of the expanded C9orf72 hexanucleotide repeat RNA.}, journal = {Journal of neurochemistry}, volume = {166}, number = {2}, pages = {156-171}, doi = {10.1111/jnc.15847}, pmid = {37277972}, issn = {1471-4159}, mesh = {Humans ; C9orf72 Protein/genetics ; Proteins/genetics/metabolism ; RNA/genetics/metabolism ; *Frontotemporal Dementia/genetics ; *Amyotrophic Lateral Sclerosis/genetics ; DNA Repeat Expansion/genetics ; }, abstract = {An hexanucleotide repeat expansion mutation in the non-coding region of C9orf72 gene causes frontotemporal dementia and amyotrophic lateral sclerosis. This mutation is estimated to be the most frequent genetic cause of these currently incurable diseases. Since the mutation causes autosomal dominantly inherited diseases, disease cascade essentially starts from the expanded DNA repeats. However, molecular disease mechanism is inevitably complex because possible toxic entity for the disease is not just functional loss of translated C9ORF72 protein, if any, but potentially includes bidirectionally transcribed expanded repeat containing RNA and their unconventional repeat-associated non-AUG translation products in all possible reading frames. Although the field learned so much about the disease since the identification of the mutation in 2011, how the expanded repeat causes a particular type of fronto-temporal lobe dominant neurodegeneration and/or motor neuron degeneration is not yet clear. In this review, we summarize and discuss the current understandings of molecular mechanism of this repeat expansion mutation with focuses on the degradation and translation of the repeat containing RNA transcripts.}, }
@article {pmid37274187, year = {2023}, author = {Santarelli, S and Londero, C and Soldano, A and Candelaresi, C and Todeschini, L and Vernizzi, L and Bellosta, P}, title = {Drosophila melanogaster as a model to study autophagy in neurodegenerative diseases induced by proteinopathies.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1082047}, pmid = {37274187}, issn = {1662-4548}, abstract = {Proteinopathies are a large group of neurodegenerative diseases caused by both genetic and sporadic mutations in particular genes which can lead to alterations of the protein structure and to the formation of aggregates, especially toxic for neurons. Autophagy is a key mechanism for clearing those aggregates and its function has been strongly associated with the ubiquitin-proteasome system (UPS), hence mutations in both pathways have been associated with the onset of neurodegenerative diseases, particularly those induced by protein misfolding and accumulation of aggregates. Many crucial discoveries regarding the molecular and cellular events underlying the role of autophagy in these diseases have come from studies using Drosophila models. Indeed, despite the physiological and morphological differences between the fly and the human brain, most of the biochemical and molecular aspects regulating protein homeostasis, including autophagy, are conserved between the two species.In this review, we will provide an overview of the most common neurodegenerative proteinopathies, which include PolyQ diseases (Huntington's disease, Spinocerebellar ataxia 1, 2, and 3), Amyotrophic Lateral Sclerosis (C9orf72, SOD1, TDP-43, FUS), Alzheimer's disease (APP, Tau) Parkinson's disease (a-syn, parkin and PINK1, LRRK2) and prion diseases, highlighting the studies using Drosophila that have contributed to understanding the conserved mechanisms and elucidating the role of autophagy in these diseases.}, }
@article {pmid37269968, year = {2023}, author = {Alqahtani, T and Deore, SL and Kide, AA and Shende, BA and Sharma, R and Dadarao Chakole, R and Nemade, LS and Kishor Kale, N and Borah, S and Shrikant Deokar, S and Behera, A and Dhawal Bhandari, D and Gaikwad, N and Kalam Azad, A and Ghosh, A}, title = {Mitochondrial dysfunction and oxidative stress in Alzheimer's disease, and Parkinson's disease, Huntington's disease and Amyotrophic Lateral Sclerosis -An updated review.}, journal = {Mitochondrion}, volume = {71}, number = {}, pages = {83-92}, doi = {10.1016/j.mito.2023.05.007}, pmid = {37269968}, issn = {1872-8278}, mesh = {Humans ; *Parkinson Disease/pathology ; *Alzheimer Disease/pathology ; *Huntington Disease/metabolism ; *Amyotrophic Lateral Sclerosis/pathology ; Oxidative Stress/physiology ; *Neurodegenerative Diseases/metabolism ; Mitochondria/metabolism ; }, abstract = {Misfolded proteins in the central nervous system can induce oxidative damage, which can contribute to neurodegenerative diseases in the mitochondria. Neurodegenerative patients face early mitochondrial dysfunction, impacting energy utilization. Amyloid-ß and tau problems both have an effect on mitochondria, which leads to mitochondrial malfunction and, ultimately, the onset of Alzheimer's disease. Cellular oxygen interaction yields reactive oxygen species within mitochondria, initiating oxidative damage to mitochondrial constituents. Parkinson's disease, linked to oxidative stress, α-synuclein aggregation, and inflammation, results from reduced brain mitochondria activity. Mitochondrial dynamics profoundly influence cellular apoptosis via distinct causative mechanisms. The condition known as Huntington's disease is characterized by an expansion of polyglutamine, primarily impactingthe cerebral cortex and striatum. Research has identified mitochondrial failure as an early pathogenic mechanism contributing to HD's selective neurodegeneration. The mitochondria are organelles that exhibit dynamism by undergoing fragmentation and fusion processes to attain optimal bioenergetic efficiency. They can also be transported along microtubules and regulateintracellular calcium homeostasis through their interaction with the endoplasmic reticulum. Additionally, the mitochondria produce free radicals. The functions of eukaryotic cells, particularly in neurons, have significantly deviated from the traditionally assigned role of cellular energy production. Most of them areimpaired in HD, which may lead to neuronal dysfunction before symptoms manifest. This article summarizes the most important changes in mitochondrial dynamics that come from neurodegenerative diseases including Alzheimer's, Parkinson's, Huntington's and Amyotrophic Lateral Sclerosis. Finally, we discussed about novel techniques that can potentially treat mitochondrial malfunction and oxidative stress in four most dominating neuro disorders.}, }
@article {pmid37269231, year = {2024}, author = {Alqallaf, A and Cates, DW and Render, KP and Patel, KA}, title = {Sodium Phenylbutyrate and Taurursodiol: A New Therapeutic Option for the Treatment of Amyotrophic Lateral Sclerosis.}, journal = {The Annals of pharmacotherapy}, volume = {58}, number = {2}, pages = {165-173}, doi = {10.1177/10600280231172802}, pmid = {37269231}, issn = {1542-6270}, mesh = {United States ; Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; Phenylbutyrates/adverse effects ; }, abstract = {OBJECTIVE: To review the safety and efficacy of sodium phenylbutyrate and taurursodiol (SP + T) in slowing progression of amyotrophic lateral sclerosis (ALS) compared with pre-existing therapies.<br><br>DATA SOURCES: A PubMed (from January 1, 2009, to April 13, 2023) and ClinicalTrials.gov search conducted using sodium phenylbutyrate, taurursodiol, AMX0035, riluzole, and edaravone. Additional articles were identified by hand from references.<br><br>This included English-language articles evaluating SP + T efficacy or safety in humans for decreasing neuronal death and slowing the progression of ALS.<br><br>DATA SYNTHESIS: In one phase II clinical trial that encompassed an open-label extension phase, disease severity, assessed by the rate of decline in overall score on the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised with higher scores indicating more functional ability, was -1.24 points per month with active drug and -1.66 points per month with placebo (difference, 0.42 points per month; 95% CI, 0.03-0.81; P = 0.03). Post hoc analysis found survival benefit of median 4.8 months with active medication compared with placebo.<br><br>SP + T is a new US Food and Drug Administration-approved oral suspension for the treatment of ALS. Patients who received active medication through the phase II trial showed decreased rates of disease progression. Overall, SP + T could be considered a potential agent for the treatment of ALS which has a high unmet need.<br><br>CONCLUSION: SP + T is an option for the treatment of ALS; however, additional data regarding efficacy in phase III trials with long-term safety profile considerations, as well as trials to compare current therapy with SP + T, are needed.}, }
@article {pmid37268555, year = {2024}, author = {Fakim, H and Vande Velde, C}, title = {The implications of physiological biomolecular condensates in amyotrophic lateral sclerosis.}, journal = {Seminars in cell &amp; developmental biology}, volume = {156}, number = {}, pages = {176-189}, doi = {10.1016/j.semcdb.2023.05.006}, pmid = {37268555}, issn = {1096-3634}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; Biomolecular Condensates ; DNA-Binding Proteins/genetics/metabolism ; *Neurodegenerative Diseases/metabolism ; Mutation/genetics ; RNA ; }, abstract = {In recent years, there has been an emphasis on the role of phase-separated biomolecular condensates, especially stress granules, in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). This is largely due to several ALS-associated mutations occurring in genes involved in stress granule assembly and observations that pathological inclusions detected in ALS patient neurons contain stress granule proteins, including the ALS-linked proteins TDP-43 and FUS. However, protein components of stress granules are also found in numerous other phase-separated biomolecular condensates under physiological conditions which are inadequately discussed in the context of ALS. In this review, we look beyond stress granules and describe the roles of TDP-43 and FUS in physiological condensates occurring in the nucleus and neurites, such as the nucleolus, Cajal bodies, paraspeckles and neuronal RNA transport granules. We also discuss the consequences of ALS-linked mutations in TDP-43 and FUS on their ability to phase separate into these stress-independent biomolecular condensates and perform their respective functions. Importantly, biomolecular condensates sequester multiple overlapping protein and RNA components, and their dysregulation could contribute to the observed pleiotropic effects of both sporadic and familial ALS on RNA metabolism.}, }
@article {pmid37266849, year = {2024}, author = {Ugale, V and Deshmukh, R and Lokwani, D and Narayana Reddy, P and Khadse, S and Chaudhari, P and Kulkarni, PP}, title = {GluN2B subunit selective N-methyl-D-aspartate receptor ligands: Democratizing recent progress to assist the development of novel neurotherapeutics.}, journal = {Molecular diversity}, volume = {28}, number = {3}, pages = {1765-1792}, pmid = {37266849}, issn = {1573-501X}, mesh = {*Receptors, N-Methyl-D-Aspartate/metabolism/antagonists &amp; inhibitors ; Humans ; Ligands ; Animals ; Structure-Activity Relationship ; Protein Subunits/metabolism/chemistry ; }, abstract = {N-methyl-D-aspartate receptors (NMDARs) play essential roles in vital aspects of brain functions. NMDARs mediate clinical features of neurological diseases and thus, represent a potential therapeutic target for their treatments. Many findings implicated the GluN2B subunit of NMDARs in various neurological disorders including epilepsy, ischemic brain damage, and neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease, Huntington's chorea, and amyotrophic lateral sclerosis. Although a large amount of information is growing consistently on the importance of GluN2B subunit, however, limited recent data is available on how subunit-selective ligands impact NMDAR functions, which blunts the ability to render the diagnosis or craft novel treatments tailored to patients. To bridge this gap, we have focused on and summarized recently reported GluN2B selective ligands as emerging subunit-selective antagonists and modulators of NMDAR. Herein, we have also presented an overview of the structure-function relationship for potential GluN2B/NMDAR ligands with their binding sites and connection to CNS functionalities. Understanding of design rules and roles of GluN2B selective compounds will provide the link to medicinal chemists and neuroscientists to explore novel neurotherapeutic strategies against dysfunctions of glutamatergic neurotransmission.}, }
@article {pmid37263278, year = {2025}, author = {Guler, Y}, title = {Clinical and pathological risk factors for tumour recurrence and upstaging in second TURBT for patients with NMIBC: a systematic review and meta-analysis.}, journal = {Aktuelle Urologie}, volume = {56}, number = {1}, pages = {30-40}, doi = {10.1055/a-2063-3144}, pmid = {37263278}, issn = {1438-8820}, mesh = {Humans ; *Neoplasm Recurrence, Local/pathology ; Risk Factors ; *Urinary Bladder Neoplasms/pathology/surgery ; Neoplasm Staging ; Non-Muscle Invasive Bladder Neoplasms ; }, abstract = {UNLABELLED: ZIEL: Offenlegung signifikanter Risikofaktoren durch Identifizierung gepoolter Effektschätzungsstatistiken in einer systemischen Überprüfung und Metaanalyse klinischer und pathologischer Risikofaktoren, die ein Tumorrezidiv und ein Upstaging auf eine zweite TURBT bei Patienten mit hochgradigem NMIBC vorhersagen.<br><br>MATERIAL-METHODE: Alle Datenquellen wurden umfassend bis Oktober 2022 untersucht. Die Daten wurden aus den relevanten Studien extrahiert und mit der Software RevMan analysiert. In einem inversen Varianzmodell mit zuf&#xe4;lligen und festen Effekten werden Odds Ratio (OR)-Werte mit 95%-Konfidenzintervallen [95%-KI] angegeben.<br><br>ERGEBNISSE: Der Review umfasste insgesamt 18 Studien und 4548 Patienten. Gem&#xe4;&#xdf; den gepoolten Effektsch&#xe4;tzern waren Carcinoma in situ (CIS), Tumorgrad, Multiplizit&#xe4;t und Chirurgenfaktoren signifikante Risikofaktoren. Die gepoolten Effektsch&#xe4;tzungen f&#xfc;r das Tumorstadium und die Tumormorphologie waren sehr nahe an der Signifikanz. F&#xfc;r CIS, Grad, Multiplizit&#xe4;t und Chirurgenfaktor, OR, IVR oder IVF [95%-KI] waren die p- und I2-Werte 1,8 [1,1, 3,0], 0,03, 75%; 2 [1,1, 3,4], 0,02, 53%; 1,3 [1,2, 1,6], <0,01, 40%; und 2 [1,4, 3], <0,01, 66%.<br><br>SCHLUSSFOLGERUNGEN: Als Ergebnis der ersten TURBT; Eine zweite TURBT sollte in den 2-6 Wochen der postoperativen Phase f&#xfc;r Patienten mit hochgradigem, begleitendem CIS, multipler, solider Morphologie, DM(-) im pathologischen Pr&#xe4;parat und NMIBC, das von Trainern/Juniorchirurgen operiert wird, geplant werden.}, }
@article {pmid37259916, year = {2023}, author = {Berth, SH and Lloyd, TE}, title = {Disruption of axonal transport in neurodegeneration.}, journal = {The Journal of clinical investigation}, volume = {133}, number = {11}, pages = {}, pmid = {37259916}, issn = {1558-8238}, support = {K08 NS118123/NS/NINDS NIH HHS/United States ; R01 NS082563/NS/NINDS NIH HHS/United States ; R01 NS094239/NS/NINDS NIH HHS/United States ; P30 NS050274/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; Axonal Transport/physiology ; *Neurodegenerative Diseases/metabolism ; Neurons/metabolism ; *Alzheimer Disease/metabolism ; *Parkinson Disease/metabolism ; }, abstract = {Neurons are markedly compartmentalized, which makes them reliant on axonal transport to maintain their health. Axonal transport is important for anterograde delivery of newly synthesized macromolecules and organelles from the cell body to the synapse and for the retrograde delivery of signaling endosomes and autophagosomes for degradation. Dysregulation of axonal transport occurs early in neurodegenerative diseases and plays a key role in axonal degeneration. Here, we provide an overview of mechanisms for regulation of axonal transport; discuss how these mechanisms are disrupted in neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, hereditary spastic paraplegia, amyotrophic lateral sclerosis, and Charcot-Marie-Tooth disease; and discuss therapeutic approaches targeting axonal transport.}, }
@article {pmid37259156, year = {2023}, author = {Ionescu, A and Altman, T and Perlson, E}, title = {Looking for answers far away from the soma-the (un)known axonal functions of TDP-43, and their contribution to early NMJ disruption in ALS.}, journal = {Molecular neurodegeneration}, volume = {18}, number = {1}, pages = {35}, pmid = {37259156}, issn = {1750-1326}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; Axons/metabolism ; *DNA-Binding Proteins/metabolism ; *Neurodegenerative Diseases/metabolism ; Neuromuscular Junction ; }, abstract = {Axon degeneration and Neuromuscular Junction (NMJ) disruption are key pathologies in the fatal neurodegenerative disease Amyotrophic Lateral Sclerosis (ALS). Despite accumulating evidence that axons and NMJs are impacted at a very early stage of the disease, current knowledge about the mechanisms leading to their degeneration remains elusive. Cytoplasmic mislocalization and accumulation of the protein TDP-43 are considered key pathological hallmarks of ALS, as they occur in ~ 97% of ALS patients, both sporadic and familial. Recent studies have identified pathological accumulation of TDP-43 in intramuscular nerves of muscle biopsies collected from pre-diagnosed, early symptomatic ALS patients. These findings suggest a gain of function for TDP-43 in axons, which might facilitate early NMJ disruption. In this review, we dissect the process leading to axonal TDP-43 accumulation and phosphorylation, discuss the known and hypothesized roles TDP-43 plays in healthy axons, and review possible mechanisms that connect TDP-43 pathology to the axon and NMJ degeneration in ALS.}, }
@article {pmid37258447, year = {2023}, author = {Liu, J and Duan, W and Deng, Y and Zhang, Q and Li, R and Long, J and Ahmed, W and Gu, C and Qiu, Y and Cai, H and Hu, Y and Chen, L}, title = {New Insights into Molecular Mechanisms Underlying Neurodegenerative Disorders.}, journal = {Journal of integrative neuroscience}, volume = {22}, number = {3}, pages = {58}, doi = {10.31083/j.jin2203058}, pmid = {37258447}, issn = {0219-6352}, support = {2022YFA1104900//National Key R&amp;D Program of China/ ; 2022YFA1104904//National Key R&amp;D Program of China/ ; 2021A1515010013//Natural Science Foundation of Guangdong Province/ ; 2021ZDZX2011//Department of Education of Guangdong Province/ ; 20221275//Traditional Chinese Medicine Bureau of Guangdong Province/ ; 202201011760//Guangzhou Municipal Science and Technology Project/ ; 1202101003//President Foundation of Integrated Hospital of Traditional Chinese Medicine of Southern Medical University/ ; 1202103007//President Foundation of Integrated Hospital of Traditional Chinese Medicine of Southern Medical University/ ; }, mesh = {Humans ; Quality of Life ; *Neurodegenerative Diseases/metabolism ; *Alzheimer Disease/metabolism ; *Parkinson Disease/etiology/therapy/metabolism ; Oxidative Stress ; }, abstract = {As a large and heterogeneous group of disorders, neurodegenerative diseases are characterized by the progressive loss of structure or function in neurons, finally leading to neuronal death. Neurodegenerative diseases cause serious threat to a patient's quality of life and the most common are Alzheimer's disease and Parkinson's disease. Currently, little is known of the detailed etiology of these disorders; as such, there are no effective treatments available. Furthermore, the lack of targeted, effective, and resolvable therapy for neurodegenerative diseases, represents an expanding research field for the discovery of new therapeutic strategies. Investigations of the potential pathogenesis of neurodegenerative diseases will become the basis of preventing the occurrence and development of neurodegenerative diseases and finding effective therapies. Existing theories and mechanisms, such as genetic and environmental factors, abnormal protein accumulation, and oxidative stress, are intricately associated with each other. However, there is no molecular theory that can entirely explain the pathological processes underlying neurodegenerative diseases. Due to the development of experimental technology and the support of multidisciplinary integration, it has been possible to perform more in-depth research on potential targets for neurodegenerative diseases and there have been many exciting discoveries in terms of original theories and underlying mechanisms. With this review, we intend to review the existing literature and provide new insights into the molecular mechanisms underlying neurodegenerative diseases.}, }
@article {pmid37257665, year = {2023}, author = {Lazo, PA and Morejón-García, P}, title = {VRK1 variants at the cross road of Cajal body neuropathogenic mechanisms in distal neuropathies and motor neuron diseases.}, journal = {Neurobiology of disease}, volume = {183}, number = {}, pages = {106172}, doi = {10.1016/j.nbd.2023.106172}, pmid = {37257665}, issn = {1095-953X}, mesh = {Humans ; Coiled Bodies/metabolism ; Syndrome ; Mutation ; *Motor Neuron Disease/metabolism ; Intracellular Signaling Peptides and Proteins/genetics ; *Charcot-Marie-Tooth Disease/genetics ; }, abstract = {Distal hereditary neuropathies and neuro motor diseases are complex neurological phenotypes associated with pathogenic variants in a large number of genes, but in some the origin is unknown. Recently, rare pathogenic variants of the human VRK1 gene have been associated with these neurological phenotypes. All VRK1 pathogenic variants are recessive, and their clinical presentation occurs in either homozygous or compound heterozygous patients. The pathogenic VRK1 gene pathogenic variants are located in three clusters within the protein sequence. The main, and initial, shared clinical phenotype among VRK1 pathogenic variants is a distal progressive loss of motor and/or sensory function, which includes diseases such as spinal muscular atrophy, Charcot-Marie-Tooth, amyotrophic lateral sclerosis and hereditary spastic paraplegia. In most cases, symptoms start early in infancy, or in utero, and are slowly progressive. Additional neurological symptoms vary among non-related patients, probably because of their different VRK1 variants and their genetic background. The underlying common pathogenic mechanism, by its functional impairment, is a likely consequence of the roles that the VRK1 protein plays in the regulation on the stability and assembly of Cajal bodies, which affect RNA maturation and processing, neuronal migration of RNPs along axons, and DNA-damage responses. Alterations of these processes are associated with several neuro sensory or motor syndromes. The clinical heterogeneity of the neurological phenotypes associated with VRK1 is a likely consequence of the protein complexes in which VRK1 is integrated, which include several proteins known to be associated with Cajal bodies and DNA damage responses. Several hereditary distal neurological diseases are a consequence of pathogenic variants in genes that alter these cellular functions. We conclude that VRK1-related distal hereditary neuropathies and motor neuron diseases represent a novel subgroup of Cajal body related neurological syndromes.}, }
@article {pmid37256332, year = {2023}, author = {Tayebi, H and Azadnajafabad, S and Maroufi, SF and Pour-Rashidi, A and Khorasanizadeh, M and Faramarzi, S and Slavin, KV}, title = {Applications of brain-computer interfaces in neurodegenerative diseases.}, journal = {Neurosurgical review}, volume = {46}, number = {1}, pages = {131}, pmid = {37256332}, issn = {1437-2320}, mesh = {Humans ; *Brain-Computer Interfaces ; Electroencephalography/methods ; *Neurodegenerative Diseases/therapy ; Brain ; Central Nervous System ; }, abstract = {Brain-computer interfaces (BCIs) provide the central nervous system with channels of direct communication to the outside world, without having to go through the peripheral nervous system. Neurodegenerative diseases (NDs) are notoriously incurable and burdensome medical conditions that will result in progressive deterioration of the nervous system. The applications of BCIs in NDs have been studied for decades now through different approaches, resulting in a considerable amount of literature in all related areas. In this study, we begin by introducing BCIs and proceed by explaining the principles of BCI-based neurorehabilitation. Then, we go through four specific types of NDs, including amyotrophic lateral sclerosis, Parkinson's disease, Alzheimer's disease, and spinal muscular atrophy, and review some of the applications of BCIs in the neural rehabilitation of these diseases. We conclude with a discussion of the characteristics, challenges, and future possibilities of research in the field. Going through the uses of BCIs in NDs, we can see that approaches and strategies employed to tackle the wide range of limitations caused by NDs are numerous and diverse. Furthermore, NDs can fall under different categories based on the target area of neurodegeneration and thus require different methods of BCI-based rehabilitation. In recent years, neurotechnology companies have substantially invested in research on BCIs, focusing on commercializing BCIs and bringing BCI-based technologies from bench to bedside. This can mean the beginning of a new era for BCI-based neurorehabilitation, with an anticipated spike in interest among researchers, practitioners, engineers, and entrepreneurs alike.}, }
@article {pmid37254833, year = {2023}, author = {White, S and O'Cathain, A and Halliday, V and Croot, L and McDermott, CJ}, title = {Factors influencing decisions people with motor neuron disease make about gastrostomy placement and ventilation: A qualitative evidence synthesis.}, journal = {Health expectations : an international journal of public participation in health care and health policy}, volume = {26}, number = {4}, pages = {1418-1435}, pmid = {37254833}, issn = {1369-7625}, support = {NIHR301592//National Institute for Health and Care Research/ ; }, mesh = {Humans ; *Gastrostomy/psychology ; Quality of Life ; *Motor Neuron Disease/therapy/complications/psychology ; Health Personnel ; Caregivers/psychology ; }, abstract = {BACKGROUND: People with motor neuron disease (pwMND) are routinely offered gastrostomy feeding tube placement and (non-invasive and invasive) ventilation to manage the functional decline associated with the disease. This study aimed to synthesise the findings from the qualitative literature to understand how individual, clinical team and organisational factors influence pwMND decisions about these interventions.<br><br>METHODS: The study design was guided by the enhancing transparency in reporting the synthesis of qualitative research (ENTREC) statement. The search of five bibliography databases and an extensive supplementary search strategy identified 27 papers that included qualitative accounts of pwMND, caregivers and healthcare professionals' (HCPs) experiences of making decisions about gastrostomy and ventilation. The findings from each study were included in a thematic synthesis.<br><br>FINDINGS: Making decisions about interventions is an emotional rather than simply a functional issue for pwMND. The interventions can signal an end to normality, and increasing dependence, where pwMND consider the balance between quality of life and extending survival. Interactions with multiple HCPs and caregivers can influence the process of decision-making and the decisions made. These interactions contribute to the autonomy pwMND are able to exert during decision-making. HCPs can both promote and threaten pwMND perceived agency over decisions through how they approach discussions about these interventions. Though there is uncertainty over the timing of interventions, pwMND who agree to interventions report reaching a tipping point where they accept the need for change.<br><br>CONCLUSION: Discussion of gastrostomy and ventilation options generate an emotional response in pwMND. Decisions are the consequence of interactions with multiple external agents, including HCPs treading a complex ethical path when trying to improve health outcomes while respecting pwMND right to autonomy. Future decision support interventions that address the emotional response and seek to support autonomy have the potential to enable pwMND to make informed and timely decisions about gastrostomy placement and ventilation.<br><br>The lead author collaborated with several patient and participant involvement (PPI) groups with regards to the conceptualisation and design of this project. Decisions that have been influenced by discussions with multiple PPI panels include widening the scope of decisions about ventilation in addition to gastrostomy placement and the perceptions of all stakeholders involved (i.e., pwMND, caregivers and HCPs).}, }
@article {pmid37253318, year = {2023}, author = {Liu, W and Ma, R and Sun, C and Xu, Y and Liu, Y and Hu, J and Ma, Y and Wang, D and Wen, D and Yu, Y}, title = {Implications from proteomic studies investigating circadian rhythm disorder-regulated neurodegenerative disease pathology.}, journal = {Sleep medicine reviews}, volume = {70}, number = {}, pages = {101789}, doi = {10.1016/j.smrv.2023.101789}, pmid = {37253318}, issn = {1532-2955}, mesh = {Humans ; *Neurodegenerative Diseases ; Proteomics ; *Parkinson Disease/metabolism ; *Alzheimer Disease ; *Chronobiology Disorders ; Circadian Rhythm/genetics ; }, abstract = {Neurodegenerative diseases (NDs) affect 15% of the world's population and are becoming an increasingly common cause of morbidity and mortality worldwide. Circadian rhythm disorders (CRDs) have been reported to be involved in the pathogenic regulation of various neurologic diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis and amyotrophic lateral sclerosis. Proteomic technology is helpful to explore treatment targets for CRDs in patients with NDs. Here, we review the key differentially expressed (DE) proteins identified in previous proteomic studies investigating NDs, CRDs and associated models and the related pathways identified by enrichment analysis. Furthermore, we summarize the advantages and disadvantages of the above studies and propose new proteomic technologies for the precise study of circadian disorder-mediated regulation of ND pathology. This review provides a theoretical and technical reference for the precise study of circadian disorder-mediated regulation of ND pathology.}, }
@article {pmid37250416, year = {2023}, author = {Wang, H and Guan, L and Deng, M}, title = {Recent progress of the genetics of amyotrophic lateral sclerosis and challenges of gene therapy.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1170996}, pmid = {37250416}, issn = {1662-4548}, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the degeneration of motor neurons in the brain and spinal cord. The causes of ALS are not fully understood. About 10% of ALS cases were associated with genetic factors. Since the discovery of the first familial ALS pathogenic gene SOD1 in 1993 and with the technology advancement, now over 40 ALS genes have been found. Recent studies have identified ALS related genes including ANXA11, ARPP21, CAV1, C21ORF2, CCNF, DNAJC7, GLT8D1, KIF5A, NEK1, SPTLC1, TIA1, and WDR7. These genetic discoveries contribute to a better understanding of ALS and show the potential to aid the development of better ALS treatments. Besides, several genes appear to be associated with other neurological disorders, such as CCNF and ANXA11 linked to FTD. With the deepening understanding of the classic ALS genes, rapid progress has been made in gene therapies. In this review, we summarize the latest progress on classical ALS genes and clinical trials for these gene therapies, as well as recent findings on newly discovered ALS genes.}, }
@article {pmid37249667, year = {2023}, author = {Nourelden, AZ and Kamal, I and Hagrass, AI and Tawfik, AG and Elhady, MM and Fathallah, AH and Eshag, MME and Zaazouee, MS}, title = {Safety and efficacy of edaravone in patients with amyotrophic lateral sclerosis: a systematic review and meta-analysis.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {44}, number = {10}, pages = {3429-3442}, pmid = {37249667}, issn = {1590-3478}, mesh = {United States ; Humans ; Edaravone/therapeutic use ; *Amyotrophic Lateral Sclerosis/drug therapy/chemically induced ; Prospective Studies ; Quality of Life ; Severity of Illness Index ; }, abstract = {AIM: The study aims to increase understanding of edaravone's efficacy and safety as an amyotrophic lateral sclerosis (ALS) treatment and provide significant insights regarding this field's future research.<br><br>METHODS: We conducted a comprehensive search of the Embase, PubMed, Cochrane Library, Web of Science, and Scopus databases for randomized controlled trials and observational studies up until September 2022. We evaluated the studies' quality using the Cochrane risk of bias tool and the National Institutes of Health tool.<br><br>RESULTS: We included 11 studies with 2845 ALS patients. We found that edaravone improved the survival rate at 18, 24, and 30&#xa0;months (risk ratio (RR)&#x2009;=&#x2009;1.03, 95% confidence interval (CI) [1.02 to 1.24], P&#x2009;=&#x2009;0.02), (RR&#x2009;=&#x2009;1.22, 95% CI [1.06 to 1.41], P&#x2009;=&#x2009;0.007), and (RR&#x2009;=&#x2009;1.17, 95% CI [1.01 to 1.34], P&#x2009;=&#x2009;0.03), respectively. However, the administration of edaravone did not result in any significant difference in adverse effects or efficacy outcomes between the two groups, as indicated by a P value greater than 0.05.<br><br>CONCLUSION: Edaravone improves survival rates of ALS patients at 18, 24, and 30&#xa0;months with no adverse effects. However, edaravone does not affect functional outcomes. In order to ensure the validity of our findings and assess the results in accordance with the disease stage, it is essential to carry out additional prospective, rigorous, and high-quality clinical trials. The current study offers preliminary indications regarding the effectiveness and safety of edaravone. However, further comprehensive research is required to establish the generalizability and sustainability of the findings.}, }
@article {pmid37248728, year = {2023}, author = {Young, HM and Kilaberia, TR and Whitney, R and Link, BM and Bell, JF and Tonkikh, O and Famula, J and Oskarsson, B}, title = {Needs of persons living with ALS at home and their family caregivers: A scoping review.}, journal = {Muscle &amp; nerve}, volume = {68}, number = {3}, pages = {240-249}, doi = {10.1002/mus.27849}, pmid = {37248728}, issn = {1097-4598}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/psychology ; Caregivers/psychology ; Cross-Sectional Studies ; *Home Care Services ; Emotions ; }, abstract = {INTRODUCTION/AIMS: Most persons with amyotrophic lateral sclerosis (ALS) live at home with support of family caregivers, with escalating complexity of care over the trajectory of the disease requiring resources and support to mitigate negative physical, social, and emotional outcomes.<br><br>METHODS: This scoping review identifies the home health/home care needs of persons with ALS and their caregivers as a basis for creating a home health medical standard. We used the PRISMA Extension for Scoping Reviews (PRISMA-ScR) to examine studies describing home care needs published between 2011 and 2021.<br><br>RESULTS: Our search yielded 481 articles, of which 44 were included with a total of 3592 (9-273) participants. Most studies used a cross-sectional design and 20 (45%) were rated as high quality. We grouped the needs identified as emotional/psychological, assistive devices and technology, information and education, and human resources and professional services. Most studies demonstrated persistent unmet needs and that available interventions were helpful while needs generally were not met proactively, despite the predictable trajectory.<br><br>DISCUSSION: This review describes biopsychosocial and equipment interventions over the trajectory of ALS with implications for anticipatory planning by clinicians, as well as policy for coverage of necessary services and supports. Interdisciplinary expert teams could develop consensus around needs across the trajectory and recommended services and supports. To make knowledge more accessible, encourage availability of services, and clarify the need for coverage of services, we aim to develop an expert consensus-based ALS home health medical standard guidance document in collaboration with the American Association of Neuromuscular and Electrodiagnostic Medicine.}, }
@article {pmid37247505, year = {2023}, author = {Moreno, R and Recio, J and Barber, S and Gil, C and Martinez, A}, title = {The emerging role of mixed lineage kinase 3 (MLK3) and its potential as a target for neurodegenerative diseases therapies.}, journal = {European journal of medicinal chemistry}, volume = {257}, number = {}, pages = {115511}, doi = {10.1016/j.ejmech.2023.115511}, pmid = {37247505}, issn = {1768-3254}, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy ; *Parkinson Disease/drug therapy ; MAP Kinase Kinase Kinases ; Cell Death ; Mitogen-Activated Protein Kinase Kinase Kinase 11 ; }, abstract = {Selective and brain-permeable protein kinase inhibitors are in preclinical development for treating neurodegenerative diseases. Among them, MLK3 inhibitors, with a potent neuroprotective biological action have emerged as valuable agents for the treatment of pathologies such as Alzheimer's, Parkinson's disease and amyotrophic lateral sclerosis. In fact, one MLK3 inhibitor, CEP-1347, reached clinical trials for Parkinson's disease. Additionally, another compound called prostetin/12k, a potent and rather selective MLK3 inhibitor has started clinical development for ALS based on its motor neuron protection in both in vitro and in vivo models. In this review, we will focus on the role of MLK3 in neuron-related cell death processes, neurodegenerative diseases, and the potential advantages of targeting this kinase through pharmacological modulation for neuroprotective treatment.}, }
@article {pmid37245265, year = {2023}, author = {Biglari, N and Mehdizadeh, A and Vafaei Mastanabad, M and Gharaeikhezri, MH and Gol Mohammad Pour Afrakoti, L and Pourbala, H and Yousefi, M and Soltani-Zangbar, MS}, title = {Application of mesenchymal stem cells (MSCs) in neurodegenerative disorders: History, findings, and prospective challenges.}, journal = {Pathology, research and practice}, volume = {247}, number = {}, pages = {154541}, doi = {10.1016/j.prp.2023.154541}, pmid = {37245265}, issn = {1618-0631}, mesh = {Humans ; Prospective Studies ; *Neurodegenerative Diseases/metabolism/therapy ; *Mesenchymal Stem Cells/metabolism ; *Parkinson Disease ; *Alzheimer Disease/metabolism ; }, abstract = {Over the past few decades, the application of mesenchymal stem cells has captured the attention of researchers and practitioners worldwide. These cells can be obtained from practically every tissue in the body and are used to treat a broad variety of conditions, most notably neurological diseases such as Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer's disease. Studies are still being conducted, and the results of these studies have led to the identification of several different molecular pathways involved in the neuroglial speciation process. These molecular systems are closely regulated and interconnected due to the coordinated efforts of many components that make up the machinery responsible for cell signaling. Within the scope of this study, we compared and contrasted the numerous mesenchymal cell sources and their cellular features. These many sources of mesenchymal cells included adipocyte cells, fetal umbilical cord tissue, and bone marrow. In addition, we investigated whether these cells can potentially treat and modify neurodegenerative illnesses.}, }
@article {pmid37243319, year = {2023}, author = {Elmansy, MF and Reidl, CT and Rahaman, M and Özdinler, PH and Silverman, RB}, title = {Small molecules targeting different cellular pathologies for the treatment of amyotrophic lateral sclerosis.}, journal = {Medicinal research reviews}, volume = {43}, number = {6}, pages = {2260-2302}, pmid = {37243319}, issn = {1098-1128}, support = {R01 AG061708/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics ; *Neurodegenerative Diseases/metabolism ; Disease Models, Animal ; Motor Neurons/metabolism/pathology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease in which the motor neuron circuitry displays progressive degeneration, affecting mostly the motor neurons in the brain and in the spinal cord. There are no effective cures, albeit three drugs, riluzole, edaravone, and AMX0035 (a combination of sodium phenylbutyrate and taurursodiol), have been approved by the Food and Drug Administration, with limited improvement in patients. There is an urgent need to build better and more effective treatment strategies for ALS. Since the disease is very heterogenous, numerous approaches have been explored, such as targeting genetic mutations, decreasing oxidative stress and excitotoxicity, enhancing mitochondrial function and protein degradation mechanisms, and inhibiting neuroinflammation. In addition, various chemical libraries or previously identified drugs have been screened for potential repurposing in the treatment of ALS. Here, we review previous drug discovery efforts targeting a variety of cellular pathologies that occur from genetic mutations that cause ALS, such as mutations in SOD1, C9orf72, FUS, and TARDP-43 genes. These mutations result in protein aggregation, which causes neuronal degeneration. Compounds used to target cellular pathologies that stem from these mutations are discussed and comparisons among different preclinical models are presented. Because the drug discovery landscape for ALS and other motor neuron diseases is changing rapidly, we also offer recommendations for a novel, more effective, direction in ALS drug discovery that could accelerate translation of effective compounds from animals to patients.}, }
@article {pmid37240836, year = {2023}, author = {Barbieri, R and Nizzari, M and Zanardi, I and Pusch, M and Gavazzo, P}, title = {Voltage-Gated Sodium Channel Dysfunctions in Neurological Disorders.}, journal = {Life (Basel, Switzerland)}, volume = {13}, number = {5}, pages = {}, pmid = {37240836}, issn = {2075-1729}, abstract = {The pore-forming subunits (α subunits) of voltage-gated sodium channels (VGSC) are encoded in humans by a family of nine highly conserved genes. Among them, SCN1A, SCN2A, SCN3A, and SCN8A are primarily expressed in the central nervous system. The encoded proteins Nav1.1, Nav1.2, Nav1.3, and Nav1.6, respectively, are important players in the initiation and propagation of action potentials and in turn of the neural network activity. In the context of neurological diseases, mutations in the genes encoding Nav1.1, 1.2, 1.3 and 1.6 are responsible for many forms of genetic epilepsy and for Nav1.1 also of hemiplegic migraine. Several pharmacological therapeutic approaches targeting these channels are used or are under study. Mutations of genes encoding VGSCs are also involved in autism and in different types of even severe intellectual disability (ID). It is conceivable that in these conditions their dysfunction could indirectly cause a certain level of neurodegenerative processes; however, so far, these mechanisms have not been deeply investigated. Conversely, VGSCs seem to have a modulatory role in the most common neurodegenerative diseases such as Alzheimer's, where SCN8A expression has been shown to be negatively correlated with disease severity.}, }
@article {pmid37240459, year = {2023}, author = {Carlucci, A and Fusar Poli, B}, title = {Getting It Right in Restrictive Lung Disease.}, journal = {Journal of clinical medicine}, volume = {12}, number = {10}, pages = {}, pmid = {37240459}, issn = {2077-0383}, abstract = {Restrictive lung disease (predominantly in patients with neuromuscular disease (NMD) and ribcage deformity) may induce chronic hypercapnic respiratory failure, which represents an absolute indication to start home NIV (HNIV). However, in the early phases of NMD, patients may present only diurnal symptoms or orthopnoea and sleep disturbances with normal diurnal gas exchange. The evaluation of respiratory function decline may predict the presence of sleep disturbances (SD) and nocturnal hypoventilation that can be respectively diagnosed with polygraphy and PCO2 transcutaneous monitoring. If nocturnal hypoventilation and/or apnoea/hypopnea syndrome are detected, HNIV should be introduced. Once HNIV has been started, adequate follow-up is mandatory. The ventilator's built-in software provides important information about patient adherence and eventual leaks to correct. Detailed data about pressure and flow curves may suggest the presence of upper airway obstruction (UAO) during NIV that may occur with or without decrease in respiratory drive. Etiology and treatment of these two different forms of UAO are different. For this reason, in some circumstances, it might be useful to perform a polygraph. PtCO2 monitoring, together with pulse-oximetry, seem to be very important tools to optimize HNIV. The role of HNIV in neuromuscular disease is to correct diurnal and nocturnal hypoventilation with the consequence of improving quality of life, symptoms, and survival.}, }
@article {pmid37240368, year = {2023}, author = {Singh, J and Goodman-Vincent, E and Santosh, P}, title = {Evidence Synthesis of Gene Therapy and Gene Editing from Different Disorders-Implications for Individuals with Rett Syndrome: A Systematic Review.}, journal = {International journal of molecular sciences}, volume = {24}, number = {10}, pages = {}, pmid = {37240368}, issn = {1422-0067}, support = {RE16403//Reverse Rett/ ; RE16403//Reverse Rett/ ; }, mesh = {Humans ; *Rett Syndrome/therapy/drug therapy ; Gene Editing ; Tissue Distribution ; Methyl-CpG-Binding Protein 2/genetics/metabolism ; Brain/metabolism ; Genetic Therapy ; }, abstract = {This systematic review and thematic analysis critically evaluated gene therapy trials in amyotrophic lateral sclerosis, haemoglobinopathies, immunodeficiencies, leukodystrophies, lysosomal storage disorders and retinal dystrophies and extrapolated the key clinical findings to individuals with Rett syndrome (RTT). The PRISMA guidelines were used to search six databases during the last decade, followed by a thematic analysis to identify the emerging themes. Thematic analysis across the different disorders revealed four themes: (I) Therapeutic time window of gene therapy; (II) Administration and dosing strategies for gene therapy; (III) Methods of gene therapeutics and (IV) Future areas of clinical interest. Our synthesis of information has further enriched the current clinical evidence base and can assist in optimising gene therapy and gene editing studies in individuals with RTT, but it would also benefit when applied to other disorders. The findings suggest that gene therapies have better outcomes when the brain is not the primary target. Across different disorders, early intervention appears to be more critical, and targeting the pre-symptomatic stage might prevent symptom pathology. Intervention at later stages of disease progression may benefit by helping to clinically stabilise patients and preventing disease-related symptoms from worsening. If gene therapy or editing has the desired outcome, older patients would need concerted rehabilitation efforts to reverse their impairments. The timing of intervention and the administration route would be critical parameters for successful outcomes of gene therapy/editing trials in individuals with RTT. Current approaches also need to overcome the challenges of MeCP2 dosing, genotoxicity, transduction efficiencies and biodistribution.}, }
@article {pmid37240018, year = {2023}, author = {Pardo-Moreno, T and Mohamed-Mohamed, H and Suleiman-Martos, S and Ramos-Rodriguez, JJ and Rivas-Dominguez, A and Melguizo-Rodríguez, L and Gómez-Urquiza, JL and Bermudez-Pulgarin, B and Garcia-Morales, V}, title = {Amyotrophic Lateral Sclerosis and Serum Lipid Level Association: A Systematic Review and Meta-Analytic Study.}, journal = {International journal of molecular sciences}, volume = {24}, number = {10}, pages = {}, pmid = {37240018}, issn = {1422-0067}, support = {P18-RT-3324//Regional Government of Andalusia/ ; 20-01293 and PECART-0096-2020//Regional Government of Andalusia/ ; P20-01061//Regional Government of Andalusia/ ; PID2019-110960GB-I00//Ministry of Science and Innovation, Spain/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; *Neurodegenerative Diseases ; Triglycerides ; Cholesterol, HDL ; Cholesterol, LDL ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with unknown etiology. Many metabolic alterations occur during ALS progress and can be used as a method of pre-diagnostic and early diagnosis. Dyslipidemia is one of the physiological changes observed in numerous ALS patients. The aim of this study is to analyze the possible relationship between the rate of disease progression (functional rating scale (ALS-FRS)) and the plasma lipid levels at the early stage of ALS. A systematic review was carried out in July 2022. The search equation was "Triglycerides AND amyotrophic lateral sclerosis" and its variants. Four meta-analyses were performed. Four studies were included in the meta-analysis. No significant differences were observed between the lipid levels (total cholesterol, triglycerides, HDL cholesterol, and LDL cholesterol) and the ALS-FRS score at the onset of the disease. Although the number of studies included in this research was low, the results of this meta-analytic study suggest that there is no clear relationship between the symptoms observed in ALS patients and the plasma lipid levels. An increase in research, as well as an expansion of the geographical area, would be of interest.}, }
@article {pmid37238732, year = {2023}, author = {Maksimovic, K and Youssef, M and You, J and Sung, HK and Park, J}, title = {Evidence of Metabolic Dysfunction in Amyotrophic Lateral Sclerosis (ALS) Patients and Animal Models.}, journal = {Biomolecules}, volume = {13}, number = {5}, pages = {}, pmid = {37238732}, issn = {2218-273X}, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/metabolism ; *Neurodegenerative Diseases/metabolism ; Motor Neurons/metabolism ; Models, Animal ; Glucose/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects motor neurons, leading to muscle weakness, paralysis, and eventual death. Research from the past few decades has appreciated that ALS is not only a disease of the motor neurons but also a disease that involves systemic metabolic dysfunction. This review will examine the foundational research of understanding metabolic dysfunction in ALS and provide an overview of past and current studies in ALS patients and animal models, spanning from full systems to various metabolic organs. While ALS-affected muscle tissue exhibits elevated energy demand and a fuel preference switch from glycolysis to fatty acid oxidation, adipose tissue in ALS undergoes increased lipolysis. Dysfunctions in the liver and pancreas contribute to impaired glucose homeostasis and insulin secretion. The central nervous system (CNS) displays abnormal glucose regulation, mitochondrial dysfunction, and increased oxidative stress. Importantly, the hypothalamus, a brain region that controls whole-body metabolism, undergoes atrophy associated with pathological aggregates of TDP-43. This review will also cover past and present treatment options that target metabolic dysfunction in ALS and provide insights into the future of metabolism research in ALS.}, }
@article {pmid37238605, year = {2023}, author = {Zhang, H and Dai, S and Yang, Y and Wei, J and Li, X and Luo, P and Jiang, X}, title = {Role of Sirtuin 3 in Degenerative Diseases of the Central Nervous System.}, journal = {Biomolecules}, volume = {13}, number = {5}, pages = {}, pmid = {37238605}, issn = {2218-273X}, mesh = {Humans ; Central Nervous System/metabolism ; Mitochondria/metabolism ; *Neurodegenerative Diseases/metabolism ; *Parkinson Disease/metabolism ; *Sirtuin 3/metabolism ; }, abstract = {An NAD[+]-dependent deacetylase called Sirtuin 3 (Sirt3) is involved in the metabolic processes of the mitochondria, including energy generation, the tricarboxylic acid cycle, and oxidative stress. Sirt3 activation can slow down or prevent mitochondrial dysfunction in response to neurodegenerative disorders, demonstrating a strong neuroprotective impact. The mechanism of Sirt3 in neurodegenerative illnesses has been elucidated over time; it is essential for neuron, astrocyte, and microglial function, and its primary regulatory factors include antiapoptosis, oxidative stress, and the maintenance of metabolic homeostasis. Neurodegenerative disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS), may benefit from a thorough and in-depth investigation of Sirt3. In this review, we primarily cover Sirt3's role and its regulation in the nerve cells and the connection between Sirt3 and neurodegenerative disorders.}, }
@article {pmid37231108, year = {2023}, author = {Berriat, F and Lobsiger, CS and Boillée, S}, title = {The contribution of the peripheral immune system to neurodegeneration.}, journal = {Nature neuroscience}, volume = {26}, number = {6}, pages = {942-954}, pmid = {37231108}, issn = {1546-1726}, mesh = {Humans ; Central Nervous System ; *Alzheimer Disease/metabolism ; *Neurodegenerative Diseases/pathology ; *Amyotrophic Lateral Sclerosis/pathology ; Leukocytes/metabolism ; }, abstract = {Microglial cells are the major immune cells of the central nervous system (CNS), and directly react to neurodegeneration, but other immune cell types are also able to react to pathology and can modify the course of neurodegenerative processes. These mainly include monocytes/macrophages and lymphocytes. While these peripheral immune cells were initially considered to act only after infiltrating the CNS, recent evidence suggests that some of them can also act directly from the periphery. We will review the existing and emerging evidence for a role of peripheral immune cells in neurodegenerative diseases, both with and without CNS infiltration. Our focus will be on amyotrophic lateral sclerosis, but we will also compare to Alzheimer's disease and Parkinson's disease to highlight similarities or differences. Peripheral immune cells are easily accessible, and therefore may be an attractive therapeutic target for neurodegenerative diseases. Thus, understanding how these peripheral immune cells communicate with the CNS deserves deeper investigation.}, }
@article {pmid37219417, year = {2023}, author = {Sales de Campos, P and Olsen, WL and Wymer, JP and Smith, BK}, title = {Respiratory therapies for Amyotrophic Lateral Sclerosis: A state of the art review.}, journal = {Chronic respiratory disease}, volume = {20}, number = {}, pages = {14799731231175915}, pmid = {37219417}, issn = {1479-9731}, support = {T32 HL134621/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; Respiration, Artificial ; Cough ; Hypoxia ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition noteworthy for upper and lower motor neuron death. Involvement of respiratory motor neuron pools leads to progressive pathology. These impairments include decreases in neural activation and muscle coordination, progressive airway obstruction, weakened airway defenses, restrictive lung disease, increased risk of pulmonary infections, and weakness and atrophy of respiratory muscles. These neural, airway, pulmonary, and neuromuscular changes deteriorate integrated respiratory-related functions including sleep, cough, swallowing, and breathing. Ultimately, respiratory complications account for a large portion of morbidity and mortality in ALS. This state-of-the-art review highlights applications of respiratory therapies for ALS, including lung volume recruitment, mechanical insufflation-exsufflation, non-invasive ventilation, and respiratory strength training. Therapeutic acute intermittent hypoxia, an emerging therapeutic tool for inducing respiratory plasticity will also be introduced. A focus on emerging evidence and future work underscores the common goal to continue to improve survival for patients living with ALS.}, }
@article {pmid37217723, year = {2023}, author = {Nguyen, TT and Nguyen-Thi, PT and Nguyen, THA and Ho, TT and Tran, NM and Van Vo, T and Van Vo, G}, title = {Recent Advancements in Nanomaterials: A Promising Way to Manage Neurodegenerative Disorders.}, journal = {Molecular diagnosis &amp; therapy}, volume = {27}, number = {4}, pages = {457-473}, pmid = {37217723}, issn = {1179-2000}, mesh = {Humans ; *Neurodegenerative Diseases/diagnosis/drug therapy ; *Alzheimer Disease/diagnosis/drug therapy ; Brain/metabolism ; Blood-Brain Barrier/metabolism ; *Nanoparticles/therapeutic use/chemistry ; }, abstract = {Neurodegenerative diseases (NDs) such as dementia, Alzheimer's disease, Parkinson's disease, frontotemporal dementia, and amyotrophic lateral sclerosis are some of the most prevalent disorders currently afflicting healthcare systems. Many of these diseases share similar pathological hallmarks, including elevated oxidative stress, mitochondrial dysfunction, protein misfolding, excitotoxicity, and neuroinflammation, all of which contribute to the deterioration of the nervous system's structure and function. The development of diagnostic and therapeutic materials in the monitoring and treatment of these diseases remains challenging. One of the biggest challenges facing therapeutic and diagnostic materials is the blood-brain barrier (BBB). The BBB is a multifunctional membrane possessing a plethora of biochemical, cellular, and immunological features that ensure brain homeostasis by preventing the entry and accumulation of unwanted compounds. With regards to neurodegenerative diseases, the recent application of tailored nanomaterials (nanocarriers and nanoparticles) has led to advances in diagnostics and therapeutics. In this review, we provide an overview of commonly used nanoparticles and their applications in NDs, which may offer new therapeutic strategies for the prevention and treatment of neurodegenerative diseases.}, }
@article {pmid37210484, year = {2023}, author = {Jandhyala, R}, title = {Neutral theory: applicability and neutrality of clinical study endpoints where a disease-specific instrument is available.}, journal = {BMC medical research methodology}, volume = {23}, number = {1}, pages = {121}, pmid = {37210484}, issn = {1471-2288}, mesh = {Humans ; *Rare Diseases/diagnosis/epidemiology ; *Endpoint Determination ; Clinical Studies as Topic ; }, abstract = {BACKGROUND: There is a pressing need to improve the accuracy of rare disease clinical study endpoints. Neutral theory, first described here, can be used to assess the accuracy of endpoints and improve their selection in rare disease clinical studies, reducing the risk of patient misclassification.<br><br>METHODS: Neutral theory was used to assess the accuracy of rare disease clinical study endpoints and the resulting probability of false positive and false negative classifications at different disease prevalence rates. Search strings were extracted from the Orphanet Register of Rare Diseases using a proprietary algorithm to conduct a systematic review of studies published until January 2021. Overall, 11 rare diseases with one disease-specific disease severity scale (133 studies) and 12 rare diseases with more than one disease-specific disease severity scale (483 studies) were included. All indicators from clinical studies were extracted, and Neutral theory was used to calculate their match to disease-specific disease severity scales, which were used as surrogates for the disease phenotype. For those with more than one disease-severity scale, endpoints were compared with the first disease-specific disease severity scale and a composite of all later scales. A Neutrality score of&#x2009;>&#x2009;1.50 was considered acceptable.<br><br>RESULTS: Around half the clinical studies for half the rare diseases with one disease-specific disease severity score (palmoplantar psoriasis, achalasia, systemic lupus erythematosus, systemic sclerosis and Fournier's gangrene) met the threshold for an acceptable match to the disease phenotype, one rare disease (Guillain-Barr&#xe9; syndrome) had one study with an acceptable match, and four diseases (Behcet's syndrome, Creutzfeldt-Jakob disease, atypical hemolytic uremic syndrome and Prader-Willi syndrome) had no studies. Clinical study endpoints in almost half the rare diseases with more than one disease-specific DSS (acromegaly, amyotrophic lateral sclerosis, cystic fibrosis, Fabry disease and juvenile rheumatoid arthritis) were a better match to the composite, while endpoints in the remaining rare diseases (Charcot Marie Tooth disease, Gaucher disease Type I, Huntington's disease, Sjogren's syndrome and Tourette syndrome) were a worse match. Misclassifications varied with increasing disease prevalence.<br><br>CONCLUSIONS: Neutral theory confirmed that disease-severity measurement needs improvement in rare disease clinical studies, especially for some diseases, and suggested that the potential for accuracy increases as the body of knowledge on a disease increases. Using Neutral theory to benchmark disease-severity measurement in rare disease clinical studies may reduce the risk of misclassification, ensuring that recruitment and treatment effect assessment optimise medicine adoption and benefit patients.}, }
@article {pmid37209406, year = {2023}, author = {Gwathmey, KG and Corcia, P and McDermott, CJ and Genge, A and Sennfält, S and de Carvalho, M and Ingre, C}, title = {Diagnostic delay in amyotrophic lateral sclerosis.}, journal = {European journal of neurology}, volume = {30}, number = {9}, pages = {2595-2601}, doi = {10.1111/ene.15874}, pmid = {37209406}, issn = {1468-1331}, support = {/DH_/Department of Health/United Kingdom ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; Delayed Diagnosis ; *Neurodegenerative Diseases ; Retrospective Studies ; *General Practitioners ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disease, and the time from symptom onset to diagnosis remains long. With the advent of disease-modifying treatments, the need to identify and diagnose ALS in a timely fashion has never been greater.<br><br>METHODS: We reviewed the literature to define the severity of ALS diagnostic delay, the various factors that contribute to this delay (including patient and physician factors), and the role that site of symptom onset plays in a patient's diagnostic journey.<br><br>RESULTS: Diagnostic delay is influenced by general practitioners' lack of recognition of ALS due to disease rarity and heterogenous presentations. As a result, patients are referred to non-neurologists, have unnecessary diagnostic testing, and may ultimately be misdiagnosed. Patient factors include their illness behavior-which impacts diagnostic delay-and their site of symptom onset. Limb-onset patients have the greatest diagnostic delay because they are frequently misdiagnosed with degenerative spine disease or peripheral neuropathy.<br><br>CONCLUSION: Prompt ALS diagnosis results in more effective clinical management, with earlier access to disease-modifying therapies, multidisciplinary care, and, if desired, clinical trial involvement. Due to lack of commercially available ALS biomarkers, alternative strategies to identify and triage patients who likely have ALS must be employed. Several diagnostic tools have been developed to encourage general practitioners to consider ALS and make an urgent referral to ALS specialists, bypassing unnecessary referrals to non-neurologists and unnecessary diagnostic workup.}, }
@article {pmid37207075, year = {2023}, author = {Sato, K and Takayama, KI and Inoue, S}, title = {Role of piRNA biogenesis and its neuronal function in the development of neurodegenerative diseases.}, journal = {Frontiers in aging neuroscience}, volume = {15}, number = {}, pages = {1157818}, pmid = {37207075}, issn = {1663-4365}, abstract = {Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), are caused by neuronal loss and dysfunction. Despite remarkable improvements in our understanding of these pathogeneses, serious worldwide problems with significant public health burdens are remained. Therefore, new efficient diagnostic and therapeutic strategies are urgently required. PIWI-interacting RNAs (piRNAs) are a major class of small non-coding RNAs that silence gene expression through transcriptional and post-transcriptional processes. Recent studies have demonstrated that piRNAs, originally found in the germ line, are also produced in non-gonadal somatic cells, including neurons, and further revealed the emerging roles of piRNAs, including their roles in neurodevelopment, aging, and neurodegenerative diseases. In this review, we aimed to summarize the current knowledge regarding the piRNA roles in the pathophysiology of neurodegenerative diseases. In this context, we first reviewed on recent updates on neuronal piRNA functions, including biogenesis, axon regeneration, behavior, and memory formation, in humans and mice. We also discuss the aberrant expression and dysregulation of neuronal piRNAs in neurodegenerative diseases, such as AD, PD, and ALS. Moreover, we review pioneering preclinical studies on piRNAs as biomarkers and therapeutic targets. Elucidation of the mechanisms underlying piRNA biogenesis and their functions in the brain would provide new perspectives for the clinical diagnosis and treatment of AD and various neurodegenerative diseases.}, }
@article {pmid37205225, year = {2023}, author = {Cannon, AE and Zürrer, WE and Zejlon, C and Kulcsar, Z and Lewandowski, S and Piehl, F and Granberg, T and Ineichen, BV}, title = {Neuroimaging findings in preclinical amyotrophic lateral sclerosis models-How well do they mimic the clinical phenotype? A systematic review.}, journal = {Frontiers in veterinary science}, volume = {10}, number = {}, pages = {1135282}, pmid = {37205225}, issn = {2297-1769}, abstract = {BACKGROUND AND OBJECTIVES: Animal models for motor neuron diseases (MND) such as amyotrophic lateral sclerosis (ALS) are commonly used in preclinical research. However, it is insufficiently understood how much findings from these model systems can be translated to humans. Thus, we aimed at systematically assessing the translational value of MND animal models to probe their external validity with regards to magnetic resonance imaging (MRI) features.<br><br>METHODS: In a comprehensive literature search in PubMed and Embase, we retrieved 201 unique publications of which 34 were deemed eligible for qualitative synthesis including risk of bias assessment.<br><br>RESULTS: ALS animal models can indeed present with human ALS neuroimaging features: Similar to the human paradigm, (regional) brain and spinal cord atrophy as well as signal changes in motor systems are commonly observed in ALS animal models. Blood-brain barrier breakdown seems to be more specific to ALS models, at least in the imaging domain. It is noteworthy that the G93A-SOD1 model, mimicking a rare clinical genotype, was the most frequently used ALS proxy.<br><br>CONCLUSIONS: Our systematic review provides high-grade evidence that preclinical ALS models indeed show imaging features highly reminiscent of human ALS assigning them a high external validity in this domain. This opposes the high attrition of drugs during bench-to-bedside translation and thus raises concerns that phenotypic reproducibility does not necessarily render an animal model appropriate for drug development. These findings emphasize a careful application of these model systems for ALS therapy development thereby benefiting refinement of animal experiments.<br><br>https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022373146.}, }
@article {pmid37196683, year = {2023}, author = {Prasad Panda, S and Kesharwani, A and Prasanna Mallick, S and Prasanth, D and Kumar Pasala, P and Bharadwaj Tatipamula, V}, title = {Viral-induced neuronal necroptosis: Detrimental to brain function and regulation by necroptosis inhibitors.}, journal = {Biochemical pharmacology}, volume = {213}, number = {}, pages = {115591}, doi = {10.1016/j.bcp.2023.115591}, pmid = {37196683}, issn = {1873-2968}, mesh = {Humans ; *Protein Kinases/metabolism ; Inflammasomes/metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Necroptosis ; Neuroinflammatory Diseases ; Apoptosis ; Necrosis ; Caspase 1/metabolism ; Receptors, Death Domain/metabolism ; Interleukin-1/metabolism ; Receptor-Interacting Protein Serine-Threonine Kinases/genetics/metabolism ; *MicroRNAs ; }, abstract = {Neuronal necroptosis (programmed necrosis) in the CNS naturally occurs through a caspase-independent way and, especially in neurodegenerative diseases (NDDs) such as Alzheimer's disease (AD), Parknson's disease (PD), Amyotrophic Lateral Sclerosis (ALS) and viral infections. Understanding necroptosis pathways (death receptor-dependent and independent), and its connections with other cell death pathways could lead to new insights into treatment. Receptor-interacting protein kinase (RIPK) mediates necroptosis via mixed-lineage kinase-like (MLKL) proteins. RIPK/MLKL necrosome contains FADD, procaspase-8-cellular FLICE-inhibitory proteins (cFLIPs), RIPK1/RIPK3, and MLKL. The necrotic stimuli cause phosphorylation of MLKL and translocate to the plasma membrane, causing an influx of Ca[2+] and Na[+] ions and, the immediate opening of mitochondrial permeability transition pore (mPTP) with the release of inflammatory cell damage-associated molecular patterns (DAMPs) like mitochondrial DNA (mtDNA), high-mobility group box1 (HMGB1), and interleukin1 (IL-1). The MLKL translocates to the nucleus to induce transcription of the NLRP3 inflammasome complex elements. MLKL-induced NLRP3 activity causes caspase-1 cleavage and, IL-1 activation which promotes neuroinflammation. RIPK1-dependent transcription increases illness-associated microglial and lysosomal abnormalities to facilitate amyloid plaque (Aβ) aggregation in AD. Recent research has linked neuroinflammation and mitochondrial fission with necroptosis. MicroRNAs (miRs) such as miR512-3p, miR874, miR499, miR155, and miR128a regulate neuronal necroptosis by targeting key components of necroptotic pathways. Necroptosis inhibitors act by inhibiting the membrane translocation of MLKL and RIPK1 activity. This review insights into the RIPK/MLKL necrosome-NLRP3 inflammasome interactions during death receptor-dependent and independent neuronal necroptosis, and clinical intervention by miRs to protect the brain from NDDs.}, }
@article {pmid37193974, year = {2023}, author = {Lawes-Wickwar, S and Lovat, E and Alao, A and Hamer-Hunt, J and Yurtoglu, N and Jensen, C and Clarke, N and Roberts, N and Park, S}, title = {Digital undergraduate medical education and patient and carer involvement: a rapid systematic review of current practice.}, journal = {BMC medical education}, volume = {23}, number = {1}, pages = {335}, pmid = {37193974}, issn = {1472-6920}, mesh = {Humans ; Caregivers ; *Education, Medical, Undergraduate ; Health Personnel/education ; Learning ; *Students, Medical ; }, abstract = {BACKGROUND: Involving patients and carers in medical students' learning aims to centralise the perspective of healthcare users and supports our future medical workforce in the development of key skills. Medical schools are increasingly using digital technology for teaching and it is timely to understand how to maintain patient and carer involvement in this context.<br><br>METHODS: Ovid MEDLINE, Ovid EMBASE and medRxiv were searched in October 2020 and reference lists of key articles were hand searched. Eligible studies reported authentic patient or carer involvement in undergraduate medical education where technology was also used. Study quality was assessed by the Mixed Methods Appraisal Tool (MMAT). Levels of patient or carer involvement were assessed using Towle et al.'s (2010) taxonomy, from Level 1 (lowest level) to Level 6 (highest level).<br><br>RESULTS: Twenty studies were included in this systematic review. In 70% of studies, patients and carers featured in video or web-based case scenarios with no interaction between healthcare users and students. The remaining 30% of studies reported real-time interactions between students and patients via remote clinical encounters. Digital teaching sessions involving patients or carers were perceived to be valuable by students and educators, and increased student engagement, patient-centred attitudes, clinical knowledge, and communication skills. No studies reported the perspective of patients or carers.<br><br>DISCUSSION: Digital technology has not yet driven higher levels of patient and carer involvement in medical training. "Live" interactions between students and patients are becoming more common but challenges need addressing to ensure positive experiences for all involved. Future teaching should enhance the role of patients and carers in medical education and support them to overcome any potential barriers to doing so remotely.}, }
@article {pmid37191604, year = {2023}, author = {Thomson, CG and Hutchinson, PR and Stern, PJ}, title = {Misdiagnosis in Amyotrophic Lateral Sclerosis.}, journal = {The Journal of hand surgery}, volume = {48}, number = {8}, pages = {822-826}, doi = {10.1016/j.jhsa.2023.03.023}, pmid = {37191604}, issn = {1531-6564}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/surgery ; Referral and Consultation ; *Cubital Tunnel Syndrome ; Diagnostic Errors ; Neurosurgical Procedures ; }, abstract = {The symptoms of amyotrophic lateral sclerosis (ALS) can mimic those of compressive neuropathies, such as carpal and cubital tunnel syndromes, especially early in a patient's clinical course. We surveyed members of the American Society for Surgery of the Hand and found that 11% of active and retired members have performed nerve decompression surgeries on patients later diagnosed with ALS. Hand surgeons are commonly the first providers to evaluate patients with undiagnosed ALS. As such, it is important to be aware of the history, signs, and symptoms of ALS to provide an accurate diagnosis and prevent unnecessary morbidities, such as nerve decompression surgery, which invariably results in poor outcomes. The major "red flag" symptoms warranting further work-up include weakness without sensory symptoms, profound weakness and atrophy in multiple nerve distributions, progressively bilateral and global symptoms, presence of bulbar symptoms (such as tongue fasciculations and speech/swallowing difficulties), and, if surgery is performed, failure to improve. If any of these red flags are present, we recommend neurodiagnostic testing and prompt referral to a neurologist for further work-up and treatment.}, }
@article {pmid37191427, year = {2023}, author = {Huang, Y and Zhao, M and Chen, X and Zhang, R and Le, A and Hong, M and Zhang, Y and Jia, L and Zang, W and Jiang, C and Wang, J and Fan, X and Wang, J}, title = {Tryptophan Metabolism in Central Nervous System Diseases: Pathophysiology and Potential Therapeutic Strategies.}, journal = {Aging and disease}, volume = {14}, number = {3}, pages = {858-878}, pmid = {37191427}, issn = {2152-5250}, abstract = {The metabolism of L-tryptophan (TRP) regulates homeostasis, immunity, and neuronal function. Altered TRP metabolism has been implicated in the pathophysiology of various diseases of the central nervous system. TRP is metabolized through two main pathways, the kynurenine pathway and the methoxyindole pathway. First, TRP is metabolized to kynurenine, then kynurenic acid, quinolinic acid, anthranilic acid, 3-hydroxykynurenine, and finally 3-hydroxyanthranilic acid along the kynurenine pathway. Second, TRP is metabolized to serotonin and melatonin along the methoxyindole pathway. In this review, we summarize the biological properties of key metabolites and their pathogenic functions in 12 disorders of the central nervous system: schizophrenia, bipolar disorder, major depressive disorder, spinal cord injury, traumatic brain injury, ischemic stroke, intracerebral hemorrhage, multiple sclerosis, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease. Furthermore, we summarize preclinical and clinical studies, mainly since 2015, that investigated the metabolic pathway of TRP, focusing on changes in biomarkers of these neurologic disorders, their pathogenic implications, and potential therapeutic strategies targeting this metabolic pathway. This critical, comprehensive, and up-to-date review helps identify promising directions for future preclinical, clinical, and translational research on neuropsychiatric disorders.}, }
@article {pmid37190097, year = {2023}, author = {Dorn, GW}, title = {Reversing Dysdynamism to Interrupt Mitochondrial Degeneration in Amyotrophic Lateral Sclerosis.}, journal = {Cells}, volume = {12}, number = {8}, pages = {}, pmid = {37190097}, issn = {2073-4409}, support = {R35 HL135736/HL/NHLBI NIH HHS/United States ; R35 HL135736/NH/NIH HHS/United States ; R42 NS115184/NH/NIH HHS/United States ; R42 NS113642/NH/NIH HHS/United States ; }, mesh = {Animals ; Mice ; *Amyotrophic Lateral Sclerosis/metabolism ; Apoptosis ; Mitochondria/metabolism ; Mitochondrial Dynamics/physiology ; *Neurodegenerative Diseases/metabolism ; Humans ; Disease Models, Animal ; }, abstract = {Amyotrophic lateral sclerosis is one of several chronic neurodegenerative conditions in which mitochondrial abnormalities are posited to contribute to disease progression. Therapeutic options targeting mitochondria include enhancing metabolism, suppressing reactive oxygen production and disrupting mitochondria-mediated programmed cell death pathways. Herein is reviewed mechanistic evidence supporting a meaningful pathophysiological role for the constellation of abnormal mitochondrial fusion, fission and transport, collectively designated mitochondrial dysdynamism, in ALS. Following this is a discussion on preclinical studies in ALS mice that seemingly validate the idea that normalizing mitochondrial dynamism can delay ALS by interrupting a vicious cycle of mitochondrial degeneration, leading to neuronal die-back and death. Finally, the relative benefits of suppressing mitochondrial fusion vs. enhancing mitochondrial fusion in ALS are speculated upon, and the paper concludes with the prediction that the two approaches could be additive or synergistic, although a side-by-side comparative trial may be challenging to perform.}, }
@article {pmid37190090, year = {2023}, author = {Sanchez-Tejerina, D and Llaurado, A and Sotoca, J and Lopez-Diego, V and Vidal Taboada, JM and Salvado, M and Juntas-Morales, R}, title = {Biofluid Biomarkers in the Prognosis of Amyotrophic Lateral Sclerosis: Recent Developments and Therapeutic Applications.}, journal = {Cells}, volume = {12}, number = {8}, pages = {}, pmid = {37190090}, issn = {2073-4409}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics/therapy ; *Neurodegenerative Diseases ; Prospective Studies ; Biomarkers/metabolism ; Motor Neurons/metabolism ; }, abstract = {Amyotrophic lateral sclerosis is a neurodegenerative disease characterized by the degeneration of motor neurons for which effective therapies are lacking. One of the most explored areas of research in ALS is the discovery and validation of biomarkers that can be applied to clinical practice and incorporated into the development of innovative therapies. The study of biomarkers requires an adequate theoretical and operational framework, highlighting the "fit-for-purpose" concept and distinguishing different types of biomarkers based on common terminology. In this review, we aim to discuss the current status of fluid-based prognostic and predictive biomarkers in ALS, with particular emphasis on those that are the most promising ones for clinical trial design and routine clinical practice. Neurofilaments in cerebrospinal fluid and blood are the main prognostic and pharmacodynamic biomarkers. Furthermore, several candidates exist covering various pathological aspects of the disease, such as immune, metabolic and muscle damage markers. Urine has been studied less often and should be explored for its possible advantages. New advances in the knowledge of cryptic exons introduce the possibility of discovering new biomarkers. Collaborative efforts, prospective studies and standardized procedures are needed to validate candidate biomarkers. A combined biomarkers panel can provide a more detailed disease status.}, }
@article {pmid37189772, year = {2023}, author = {Barker, S and Paul, BD and Pieper, AA}, title = {Increased Risk of Aging-Related Neurodegenerative Disease after Traumatic Brain Injury.}, journal = {Biomedicines}, volume = {11}, number = {4}, pages = {}, pmid = {37189772}, issn = {2227-9059}, support = {P30 AG062428/AG/NIA NIH HHS/United States ; R01 AG071512/AG/NIA NIH HHS/United States ; U01 AG073323/AG/NIA NIH HHS/United States ; R01 AG066707/AG/NIA NIH HHS/United States ; R01 AG065240/AG/NIA NIH HHS/United States ; T32 AG071474/AG/NIA NIH HHS/United States ; P50 DA044123/DA/NIDA NIH HHS/United States ; T32 GM007250/GM/NIGMS NIH HHS/United States ; R21 AG073684/AG/NIA NIH HHS/United States ; RF1 AG074346/AG/NIA NIH HHS/United States ; RM1 GM142002/GM/NIGMS NIH HHS/United States ; I01 BX005976/BX/BLRD VA/United States ; P30 AG072959/AG/NIA NIH HHS/United States ; }, abstract = {Traumatic brain injury (TBI) survivors frequently suffer from chronically progressive complications, including significantly increased risk of developing aging-related neurodegenerative disease. As advances in neurocritical care increase the number of TBI survivors, the impact and awareness of this problem are growing. The mechanisms by which TBI increases the risk of developing aging-related neurodegenerative disease, however, are not completely understood. As a result, there are no protective treatments for patients. Here, we review the current literature surrounding the epidemiology and potential mechanistic relationships between brain injury and aging-related neurodegenerative disease. In addition to increasing the risk for developing all forms of dementia, the most prominent aging-related neurodegenerative conditions that are accelerated by TBI are amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Parkinson's disease (PD), and Alzheimer's disease (AD), with ALS and FTD being the least well-established. Mechanistic links between TBI and all forms of dementia that are reviewed include oxidative stress, dysregulated proteostasis, and neuroinflammation. Disease-specific mechanistic links with TBI that are reviewed include TAR DNA binding protein 43 and motor cortex lesions in ALS and FTD; alpha-synuclein, dopaminergic cell death, and synergistic toxin exposure in PD; and brain insulin resistance, amyloid beta pathology, and tau pathology in AD. While compelling mechanistic links have been identified, significantly expanded investigation in the field is needed to develop therapies to protect TBI survivors from the increased risk of aging-related neurodegenerative disease.}, }
@article {pmid37189749, year = {2023}, author = {Reddy, VP and Aryal, P and Soni, P}, title = {RAGE Inhibitors in Neurodegenerative Diseases.}, journal = {Biomedicines}, volume = {11}, number = {4}, pages = {}, pmid = {37189749}, issn = {2227-9059}, abstract = {Nonenzymatic reactions of reducing sugars with primary amino groups of amino acids, proteins, and nucleic acids, followed by oxidative degradations would lead to the formation of advanced glycation endproducts (AGEs). The AGEs exert multifactorial effects on cell damage leading to the onset of neurological disorders. The interaction of AGEs with the receptors for advanced glycation endproducts (RAGE) contribute to the activation of intracellular signaling and the expression of the pro-inflammatory transcription factors and various inflammatory cytokines. This inflammatory signaling cascade is associated with various neurological diseases, including Alzheimer's disease (AD), secondary effects of traumatic brain injury (TBI), amyotrophic lateral sclerosis (ALS), and diabetic neuropathy, and other AGE-related diseases, including diabetes and atherosclerosis. Furthermore, the imbalance of gut microbiota and intestinal inflammation are also associated with endothelial dysfunction, disrupted blood-brain barrier (BBB) and thereby the onset and progression of AD and other neurological diseases. AGEs and RAGE play an important role in altering the gut microbiota composition and thereby increase the gut permeability and affect the modulation of the immune-related cytokines. The inhibition of the AGE-RAGE interactions, through small molecule-based therapeutics, prevents the inflammatory cascade of events associated with AGE-RAGE interactions, and thereby attenuates the disease progression. Some of the RAGE antagonists, such as Azeliragon, are currently in clinical development for treating neurological diseases, including AD, although currently there have been no FDA-approved therapeutics based on the RAGE antagonists. This review outlines the AGE-RAGE interactions as a leading cause of the onset of neurological diseases and the current efforts on developing therapeutics for neurological diseases based on the RAGE antagonists.}, }
@article {pmid37189617, year = {2023}, author = {Chiarini, A and Gui, L and Viviani, C and Armato, U and Dal Prà, I}, title = {NLRP3 Inflammasome's Activation in Acute and Chronic Brain Diseases-An Update on Pathogenetic Mechanisms and Therapeutic Perspectives with Respect to Other Inflammasomes.}, journal = {Biomedicines}, volume = {11}, number = {4}, pages = {}, pmid = {37189617}, issn = {2227-9059}, support = {FUR 2020//Italian Ministry of University &amp; Research/ ; }, abstract = {Increasingly prevalent acute and chronic human brain diseases are scourges for the elderly. Besides the lack of therapies, these ailments share a neuroinflammation that is triggered/sustained by different innate immunity-related protein oligomers called inflammasomes. Relevant neuroinflammation players such as microglia/monocytes typically exhibit a strong NLRP3 inflammasome activation. Hence the idea that NLRP3 suppression might solve neurodegenerative ailments. Here we review the recent Literature about this topic. First, we update conditions and mechanisms, including RNAs, extracellular vesicles/exosomes, endogenous compounds, and ethnic/pharmacological agents/extracts regulating NLRP3 function. Second, we pinpoint NLRP3-activating mechanisms and known NLRP3 inhibition effects in acute (ischemia, stroke, hemorrhage), chronic (Alzheimer's disease, Parkinson's disease, Huntington's disease, MS, ALS), and virus-induced (Zika, SARS-CoV-2, and others) human brain diseases. The available data show that (i) disease-specific divergent mechanisms activate the (mainly animal) brains NLRP3; (ii) no evidence proves that NLRP3 inhibition modifies human brain diseases (yet ad hoc trials are ongoing); and (iii) no findings exclude that concurrently activated other-than-NLRP3 inflammasomes might functionally replace the inhibited NLRP3. Finally, we highlight that among the causes of the persistent lack of therapies are the species difference problem in disease models and a preference for symptomatic over etiologic therapeutic approaches. Therefore, we posit that human neural cell-based disease models could drive etiological, pathogenetic, and therapeutic advances, including NLRP3's and other inflammasomes' regulation, while minimizing failure risks in candidate drug trials.}, }
@article {pmid37186678, year = {2024}, author = {Samanta, S and Chakraborty, S and Bagchi, D}, title = {Pathogenesis of Neurodegenerative Diseases and the Protective Role of Natural Bioactive Components.}, journal = {Journal of the American Nutrition Association}, volume = {43}, number = {1}, pages = {20-32}, doi = {10.1080/27697061.2023.2203235}, pmid = {37186678}, issn = {2769-707X}, mesh = {Humans ; *Neurodegenerative Diseases/prevention &amp; control ; Antioxidants/therapeutic use ; Reactive Oxygen Species/metabolism ; Neuroinflammatory Diseases ; Vitamins ; Flavonoids/pharmacology ; }, abstract = {Neurodegenerative diseases are a serious problem throughout the world. There are several causes of neurodegenerative diseases; these include genetic predisposition, accumulation of misfolded proteins, oxidative stress, neuroinflammation, and excitotoxicity. Oxidative stress increases the production of reactive oxygen species (ROS) that advance lipid peroxidation, DNA damage, and neuroinflammation. The cellular antioxidant system (superoxide dismutase, catalase, peroxidase, and reduced glutathione) plays a crucial role in scavenging free radicals. An imbalance in the defensive actions of antioxidants and overproduction of ROS intensify neurodegeneration. The formation of misfolded proteins, glutamate toxicity, oxidative stress, and cytokine imbalance promote the pathogenesis of Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. Antioxidants are now attractive molecules to fight against neurodegeneration. Certain vitamins (A, E, C) and polyphenolic compounds (flavonoids) show excellent antioxidant properties. Diet is the major source of antioxidants. However, diet medicinal herbs are also rich sources of numerous flavonoids. Antioxidants prevent ROS-mediated neuronal degeneration in post-oxidative stress conditions. The present review is focused on the pathogenesis of neurodegenerative diseases and the protective role of antioxidants. KEY TEACHING POINTSThis review shows that multiple factors are directly or indirectly associated with the pathogenesis of neurodegenerative diseases.Failure to cellular antioxidant capacity increases oxidative stress that intensifies neuroinflammation and disease progression.Different vitamins, carotenoids, and flavonoids, having antioxidant capacity, can be considered protective agents.}, }
@article {pmid37185741, year = {2023}, author = {López-Pingarrón, L and Almeida, H and Soria-Aznar, M and Reyes-Gonzales, MC and Terrón, MP and García, JJ}, title = {Role of Oxidative Stress on the Etiology and Pathophysiology of Amyotrophic Lateral Sclerosis (ALS) and Its Relation with the Enteric Nervous System.}, journal = {Current issues in molecular biology}, volume = {45}, number = {4}, pages = {3315-3332}, pmid = {37185741}, issn = {1467-3045}, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting motor neurons in the spinal cord, cerebral cortex, and medulla oblongata. Most patients present a clinical phenotype of classic ALS-with predominant atrophy, muscle weakness, and fasciculations-and survival of 3 to 5 years following diagnosis. In the present review, we performed a literature search to provide an update on the etiology and pathophysiological mechanisms involved in ALS. There are two types of ALS: the familial form with genetic involvement, and the sporadic form with a multifactorial origin. ALS pathophysiology is characterized by involvement of multiple processes, including oxidative stress, glutamate excitotoxicity, and neuroinflammation. Moreover, it is proposed that conditioning risk factors affect ALS development, such as susceptibility to neurodegeneration in motor neurons, the intensity of performed physical activity, and intestinal dysbiosis with involvement of the enteric nervous system, which supports the existing theories of disease generation. To improve patients' prognosis and survival, it is necessary to further deepen our understanding of the etiopathogenesis of ALS.}, }
@article {pmid37182892, year = {2023}, author = {Lim, WF and Rinaldi, C}, title = {RNA Transcript Diversity in Neuromuscular Research.}, journal = {Journal of neuromuscular diseases}, volume = {10}, number = {4}, pages = {473-482}, pmid = {37182892}, issn = {2214-3602}, mesh = {Humans ; *RNA Splice Sites ; *Alternative Splicing ; RNA Splicing/genetics ; Exons ; Introns ; }, abstract = {Three decades since the Human Genome Project began, scientists have now identified more then 25,000 protein coding genes in the human genome. The vast majority of the protein coding genes (> 90%) are multi-exonic, with the coding DNA being interrupted by intronic sequences, which are removed from the pre-mRNA transcripts before being translated into proteins, a process called splicing maturation. Variations in this process, i.e. by exon skipping, intron retention, alternative 5' splice site (5'ss), 3' splice site (3'ss), or polyadenylation usage, lead to remarkable transcriptome and proteome diversity in human tissues. Given its critical biological importance, alternative splicing is tightly regulated in a tissue- and developmental stage-specific manner. The central nervous system and skeletal muscle are amongst the tissues with the highest number of differentially expressed alternative exons, revealing a remarkable degree of transcriptome complexity. It is therefore not surprising that splicing mis-regulation is causally associated with a myriad of neuromuscular diseases, including but not limited to amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), Duchenne muscular dystrophy (DMD), and myotonic dystrophy type 1 and 2 (DM1, DM2). A gene's transcript diversity has since become an integral and an important consideration for drug design, development and therapy. In this review, we will discuss transcript diversity in the context of neuromuscular diseases and current approaches to address splicing mis-regulation.}, }
@article {pmid37179826, year = {2023}, author = {Casanova, A and Wevers, A and Navarro-Ledesma, S and Pruimboom, L}, title = {Mitochondria: It is all about energy.}, journal = {Frontiers in physiology}, volume = {14}, number = {}, pages = {1114231}, pmid = {37179826}, issn = {1664-042X}, abstract = {Mitochondria play a key role in both health and disease. Their function is not limited to energy production but serves multiple mechanisms varying from iron and calcium homeostasis to the production of hormones and neurotransmitters, such as melatonin. They enable and influence communication at all physical levels through interaction with other organelles, the nucleus, and the outside environment. The literature suggests crosstalk mechanisms between mitochondria and circadian clocks, the gut microbiota, and the immune system. They might even be the hub supporting and integrating activity across all these domains. Hence, they might be the (missing) link in both health and disease. Mitochondrial dysfunction is related to metabolic syndrome, neuronal diseases, cancer, cardiovascular and infectious diseases, and inflammatory disorders. In this regard, diseases such as cancer, Alzheimer's, Parkinson's, amyotrophic lateral sclerosis (ALS), chronic fatigue syndrome (CFS), and chronic pain are discussed. This review focuses on understanding the mitochondrial mechanisms of action that allow for the maintenance of mitochondrial health and the pathways toward dysregulated mechanisms. Although mitochondria have allowed us to adapt to changes over the course of evolution, in turn, evolution has shaped mitochondria. Each evolution-based intervention influences mitochondria in its own way. The use of physiological stress triggers tolerance to the stressor, achieving adaptability and resistance. This review describes strategies that could recover mitochondrial functioning in multiple diseases, providing a comprehensive, root-cause-focused, integrative approach to recovering health and treating people suffering from chronic diseases.}, }
@article {pmid37178447, year = {2024}, author = {Gutiérrez-Tiznado, P and López-Lázaro, S and Fonseca, GM}, title = {Age estimation by evaluation of obliteration of the palatine sutures: a scoping review.}, journal = {Forensic science, medicine, and pathology}, volume = {20}, number = {2}, pages = {716-723}, pmid = {37178447}, issn = {1556-2891}, mesh = {Humans ; *Age Determination by Skeleton/methods ; *Cranial Sutures ; Palate, Hard/pathology ; Forensic Anthropology/methods ; Palate/pathology ; }, abstract = {The age estimation (AE) of human remains is a challenging task since it is dependent on the state in which these remains are found. Since the macroscopic evaluation of palatal sutures has been proposed as a method for AE, the aim of this study was to review the literature on this method, considering that the cases of edentulous elderly are among the greatest challenges in anthropological and forensic contexts. A scoping review was performed using a specific search strategy in PubMed, Web of Science, SciELO, LILACS, and Google Scholar. The search identified 13 articles, among which the USA yielded the most information with 3 articles. Only 1 study was identified in Latin America (Peru). There was great diversity regarding the origin of samples, and the studies were carried out on both historical and modern populations. Only 6 articles exceeded the average sample size (168.08) and 4 articles studied samples of fewer than 100 individuals. Although 6 different methods were identified, Mann et al.'s revised method was the most used. The selection of appropriate methods for AE depends on what skeletal elements are present and the general age of the specimens. Although evaluation of the obliteration of the palatal sutures has been found to be simple and promising for AE in individuals over 60 years of age, this method has been reported to have less precision than other more complex methods, which makes the use of a combination of methods necessary to increase the level of confidence and the percentage of success. Further research could resolve this weakness, and methodological refinement (perhaps the digitization and automation of processes, or the application of Bayesian methodology) could provide the necessary solidity to comply with international standards in the forensic scenario.}, }
@article {pmid37176144, year = {2023}, author = {Valles, SL and Singh, SK and Campos-Campos, J and Colmena, C and Campo-Palacio, I and Alvarez-Gamez, K and Caballero, O and Jorda, A}, title = {Functions of Astrocytes under Normal Conditions and after a Brain Disease.}, journal = {International journal of molecular sciences}, volume = {24}, number = {9}, pages = {}, pmid = {37176144}, issn = {1422-0067}, mesh = {Humans ; Rats ; Animals ; *Astrocytes/pathology ; Neuroglia/pathology ; Neurons/pathology ; Microglia/physiology ; *Alzheimer Disease/pathology ; }, abstract = {In the central nervous system (CNS) there are a greater number of glial cells than neurons (between five and ten times more). Furthermore, they have a greater number of functions (more than eight functions). Glia comprises different types of cells, those of neural origin (astrocytes, radial glia, and oligodendroglia) and differentiated blood monocytes (microglia). During ontogeny, neurons develop earlier (at fetal day 15 in the rat) and astrocytes develop later (at fetal day 21 in the rat), which could indicate their important and crucial role in the CNS. Analysis of the phylogeny reveals that reptiles have a lower number of astrocytes compared to neurons and in humans this is reversed, as there have a greater number of astrocytes compared to neurons. These data perhaps imply that astrocytes are important and special cells, involved in many vital functions, including memory, and learning processes. In addition, astrocytes are involved in different mechanisms that protect the CNS through the production of antioxidant and anti-inflammatory proteins and they clean the extracellular environment and help neurons to communicate correctly with each other. The production of inflammatory mediators is important to prevent changes in brain homeostasis. On the contrary, excessive, or continued production appears as a characteristic element in many diseases, such as Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and in neurodevelopmental diseases, such as bipolar disorder, schizophrenia, and autism. Furthermore, different drugs and techniques have been developed to reverse oxidative stress and/or excess of inflammation that occurs in many CNS diseases, but much remains to be investigated. This review attempts to highlight the functional relevance of astrocytes in normal and neuropathological conditions by showing the molecular and cellular mechanisms of their role in the CNS.}, }
@article {pmid37175665, year = {2023}, author = {Khan, AW and Farooq, M and Hwang, MJ and Haseeb, M and Choi, S}, title = {Autoimmune Neuroinflammatory Diseases: Role of Interleukins.}, journal = {International journal of molecular sciences}, volume = {24}, number = {9}, pages = {}, pmid = {37175665}, issn = {1422-0067}, support = {HN21C1058//Korea Drug Development Fund funded by the Ministry of Science and ICT; Ministry of Trade, Industry, and Energy; and Ministry of Health and Welfare/ ; 2022M3A9G1014520, 2023R1A2C2003034, 2019M3D1A1078940, and 2019R1A6A1A11051471//National Research Foundation of Korea/ ; }, mesh = {Humans ; *Neuroinflammatory Diseases ; Interleukin-17 ; Interleukin-6 ; Interleukins ; Inflammation/drug therapy ; Cytokines ; Th17 Cells ; Interleukin-1/therapeutic use ; *Autoimmune Diseases ; }, abstract = {Autoimmune neuroinflammatory diseases are a group of disorders resulting from abnormal immune responses in the nervous system, causing inflammation and tissue damage. The interleukin (IL) family of cytokines, especially IL-1, IL-6, and IL-17, plays a critical role in the pathogenesis of these diseases. IL-1 is involved in the activation of immune cells, production of pro-inflammatory cytokines, and promotion of blood-brain barrier breakdown. IL-6 is essential for the differentiation of T cells into Th17 cells and has been implicated in the initiation and progression of neuroinflammation. IL-17 is a potent pro-inflammatory cytokine produced by Th17 cells that plays a crucial role in recruiting immune cells to sites of inflammation. This review summarizes the current understanding of the roles of different interleukins in autoimmune neuroinflammatory diseases, including multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's disease, neuromyelitis optica, and autoimmune encephalitis, and discusses the potential of targeting ILs as a therapeutic strategy against these diseases. We also highlight the need for further research to better understand the roles of ILs in autoimmune neuroinflammatory diseases and to identify new targets for treating these debilitating diseases.}, }
@article {pmid37174703, year = {2023}, author = {Kinger, S and Dubey, AR and Kumar, P and Jagtap, YA and Choudhary, A and Kumar, A and Prajapati, VK and Dhiman, R and Mishra, A}, title = {Molecular Chaperones' Potential against Defective Proteostasis of Amyotrophic Lateral Sclerosis.}, journal = {Cells}, volume = {12}, number = {9}, pages = {}, pmid = {37174703}, issn = {2073-4409}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; Proteostasis ; Molecular Chaperones/metabolism ; HSP40 Heat-Shock Proteins ; Mutant Proteins/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neuronal degenerative condition identified via a build-up of mutant aberrantly folded proteins. The native folding of polypeptides is mediated by molecular chaperones, preventing their pathogenic aggregation. The mutant protein expression in ALS is linked with the entrapment and depletion of chaperone capacity. The lack of a thorough understanding of chaperones' involvement in ALS pathogenesis presents a significant challenge in its treatment. Here, we review how the accumulation of the ALS-linked mutant FUS, TDP-43, SOD1, and C9orf72 proteins damage cellular homeostasis mechanisms leading to neuronal loss. Further, we discuss how the HSP70 and DNAJ family co-chaperones can act as potential targets for reducing misfolded protein accumulation in ALS. Moreover, small HSPB1 and HSPB8 chaperones can facilitate neuroprotection and prevent stress-associated misfolded protein apoptosis. Designing therapeutic strategies by pharmacologically enhancing cellular chaperone capacity to reduce mutant protein proteotoxic effects on ALS pathomechanisms can be a considerable advancement. Chaperones, apart from directly interacting with misfolded proteins for protein quality control, can also filter their toxicity by initiating strong stress-response pathways, modulating transcriptional expression profiles, and promoting anti-apoptotic functions. Overall, these properties of chaperones make them an attractive target for gaining fundamental insights into misfolded protein disorders and designing more effective therapies against ALS.}, }
@article {pmid37171705, year = {2023}, author = {Poonai, N and Creene, C and Dobrowlanski, A and Geda, R and Hartling, L and Ali, S and Bhatt, M and Trottier, ED and Sabhaney, V and O'Hearn, K and Jain, R and Osmond, MH}, title = {Inhaled nitrous oxide for painful procedures in children and youth: a systematic review and meta-analysis.}, journal = {CJEM}, volume = {25}, number = {6}, pages = {508-528}, pmid = {37171705}, issn = {1481-8043}, mesh = {Child ; Adolescent ; Humans ; Nitrous Oxide/adverse effects ; Midazolam ; *Ketamine ; *Lacerations ; Pain ; Anesthetics, Local ; Lidocaine, Prilocaine Drug Combination ; Oxygen ; }, abstract = {OBJECTIVES: The objective of this study was to synthesize indication-based evidence for N2O for distress and pain in children.<br><br>STUDY DESIGN: We included trials of N2O in participants 0-21&#xa0;years, reporting distress or pain for emergency department procedures. The primary outcome was procedural distress. Where meta-analysis was not possible, we used Tricco et al.'s classification of "neutral" (p&#x2009;&#x2265;&#x2009;0.05), "favorable," or "unfavorable" (p&#x2009;<&#x2009;0.05, supporting N2O or comparator, respectively). We used the Cochrane Collaboration's Risk of Bias tool and the Grading of Recommendations Assessment, Development, and Evaluation system to evaluate risk of bias and quality of evidence, respectively.<br><br>RESULTS: We included 30 trials. For pain using the Visual Analog Scale (0-100&#xa0;mm) during IV insertion, 70% N2O (delta:-16.5; 95%CI:-28.6 to -4.4; p&#x2009;=&#x2009;0.008; three trials; I[2]&#x2009;=&#x2009;0%) and 50% N2O plus eutectic mixture of local anesthetics (EMLA) (delta:-1.2; 95%CI:-2.1 to -0.3; p&#x2009;=&#x2009;0.007; two trials; I[2]&#x2009;=&#x2009;43%) were superior to EMLA. 50% N2O was not superior to EMLA (delta:-0.4; 95%CI:-1.2 to 0.3; p&#x2009;=&#x2009;0.26; two trials; I[2]&#x2009;=&#x2009;15%). For distress and pain during laceration repair, N2O was "favorable" versus each of SC lidocaine, oxygen, and oral midazolam but "neutral" versus IV ketamine (five trials). For distress and pain during fracture reduction (three trials), N2O was "neutral" versus each of IM meperidine plus promethazine, regional anesthesia, and IV ketamine plus midazolam. For distress and pain during lumbar puncture (one trial), N2O was "favorable" versus oxygen. For distress and pain during urethral catheterization (one trial), N2O was "neutral" versus oral midazolam. For pain during intramuscular injection (one trial), N2O plus EMLA was "favorable" versus N2O and EMLA alone. Common adverse effects of N2O included nausea (4.4%), agitation (3.7%), and vomiting (3.6%) AEs were less frequent with N2O alone (278/1147 (24.2%)) versus N2O plus midazolam (48/52 (92.3%)) and N2O plus fentanyl (123/201 (61.2%)).<br><br>CONCLUSIONS: There is sufficient evidence to recommend N2O plus topical anesthetic for IV insertion and laceration repair. Adverse effects are greater when combined with other sedating agents.}, }
@article {pmid37168926, year = {2023}, author = {Duan, QQ and Jiang, Z and Su, WM and Gu, XJ and Wang, H and Cheng, YF and Cao, B and Gao, X and Wang, Y and Chen, YP}, title = {Risk factors of amyotrophic lateral sclerosis: a global meta-summary.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1177431}, pmid = {37168926}, issn = {1662-4548}, abstract = {BACKGROUND: The etiology of amyotrophic lateral sclerosis (ALS) remains largely unknown. This study aimed to summarize the relationship between ALS and its genetic and non-genetic risk factors.<br><br>METHOD: A search of relevant literature from PubMed, Embase, and Cochrane Database from inception to December 2022 was performed. Random-effects or fixed-effects models were performed by Stata MP 15.0 to pool multivariate or adjusted ratios (OR). PROSPERO registration number: CRD42022301549.<br><br>RESULTS: 230 eligible studies were included, of which 67 involved 22 non-genetic factors, and 163 involved genetic factors. Four aspects of non-genetic factors, including lifestyle, environmental and occupational exposures, pre-existing diseases/comorbidity and medical exposures, and others, were analyzed. Exposure to heavy metals (OR = 1.79), pesticides (OR = 1.46), solvents (OR = 1.37), previous head trauma (OR = 1.37), military service (OR = 1.29), stroke (OR = 1.26), magnetic field (OR = 1.22) and hypertension (OR = 1.04) are significant risk factors, but use of antidiabetics (OR = 0.52), high BMI (OR = 0.60 for obese and overweight vs. normal and underweight), living in urban (OR = 0.70), diabetes mellitus (OR = 0.83), and kidney disease (OR = 0.84) decrease the risk for ALS. In addition, eight common ALS-related genes were evaluated, the mutation frequencies of these genes were ranked from highest to lowest as SOD1 (2.2%), C9orf72 (2.1%), ATXN2 (1.7%), FUS (1.7%), TARDBP (0.8%), VCP (0.6%), UBQLN2(0.6%) and SQSTM1 (0.6%) in all the ALS patients.<br><br>CONCLUSIONS: Our findings suggested that effective intervention for risk exposure and timely modification of lifestyle might prevent the occurrence of ALS. Genetic mutations are important risk factors for ALS and it is essential to detect genetic mutations correctly and scientifically.<br><br>https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=301549, identifier: CRD42022301549.}, }
@article {pmid37168679, year = {2023}, author = {Yang, X and Ma, Z and Lian, P and Xu, Y and Cao, X}, title = {Common mechanisms underlying axonal transport deficits in neurodegenerative diseases: a mini review.}, journal = {Frontiers in molecular neuroscience}, volume = {16}, number = {}, pages = {1172197}, pmid = {37168679}, issn = {1662-5099}, abstract = {Many neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis are characterized by the accumulation of pathogenic proteins and abnormal localization of organelles. These pathological features may be related to axonal transport deficits in neurons, which lead to failures in pathological protein targeting to specific sites for degradation and organelle transportation to designated areas needed for normal physiological functioning. Axonal transport deficits are most likely early pathological events in such diseases and gradually lead to the loss of axonal integrity and other degenerative changes. In this review, we investigated reports of mechanisms underlying the development of axonal transport deficits in a variety of common neurodegenerative diseases, such as Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease and Huntington's disease to provide new ideas for therapeutic targets that may be used early in the disease process. The mechanisms can be summarized as follows: (1) motor protein changes including expression levels and post-translational modification alteration; (2) changes in microtubules including reducing stability and disrupting tracks; (3) changes in cargoes including diminished binding to motor proteins. Future studies should determine which axonal transport defects are disease-specific and whether they are suitable therapeutic targets in neurodegenerative diseases.}, }
@article {pmid37167080, year = {2023}, author = {Gold, ND and Mallard, AJ and Hermann, JC and Zeifman, RJ and Pagni, BA and Bogenschutz, MP and Ross, S}, title = {Exploring the Potential Utility of Psychedelic Therapy for Patients With Amyotrophic Lateral Sclerosis.}, journal = {Journal of palliative medicine}, volume = {26}, number = {10}, pages = {1408-1418}, doi = {10.1089/jpm.2022.0604}, pmid = {37167080}, issn = {1557-7740}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Hallucinogens/therapeutic use ; *Neurodegenerative Diseases ; *Motor Neuron Disease ; *Ketamine ; }, abstract = {Background: Amyotrophic lateral sclerosis (ALS) is an aggressive, terminal neurodegenerative disease that causes death of motor neurons and has an average survival time of 3-4 years. ALS is the most common motor neuron degenerative disease and is increasing in prevalence. There is a pressing need for more effective ALS treatments as available pharmacotherapies do not reverse disease progression or provide substantial clinical benefit. Furthermore, despite psychological distress being highly prevalent in ALS patients, psychological treatments remain understudied. Psychedelics (i.e., serotonergic psychedelics and related compounds like ketamine) have seen a resurgence of research into therapeutic applications for treating a multitude of neuropsychiatric conditions, including psychiatric and existential distress in life-threatening illnesses. Methods: We conducted a narrative review to examine the potential of psychedelic assisted-psychotherapy (PAP) to alleviate psychiatric and psychospiritual distress in ALS. We also discussed the safety of using psychedelics in this population and proposed putative neurobiological mechanisms that may therapeutically intervene on ALS neuropathology. Results: PAP has the potential to treat psychological dimensions and may also intervene on neuropathological dimensions of ALS. Robust improvements in psychiatric and psychospiritual distress from PAP in other populations provide a strong rationale for utilizing this therapy to treat ALS-related psychiatric and existential distress. Furthermore, relevant neuroprotective properties of psychedelics warrant future preclinical trials to investigate this area in ALS models. Conclusion: PAP has the potential to serve as an effective treatment in ALS. Given the lack of effective treatment options, researchers should rigorously explore this therapy for ALS in future trials.}, }
@article {pmid37166702, year = {2023}, author = {Malar, DS and Thitilertdecha, P and Ruckvongacheep, KS and Brimson, S and Tencomnao, T and Brimson, JM}, title = {Targeting Sigma Receptors for the Treatment of Neurodegenerative and Neurodevelopmental Disorders.}, journal = {CNS drugs}, volume = {37}, number = {5}, pages = {399-440}, pmid = {37166702}, issn = {1179-1934}, mesh = {Humans ; *Receptors, sigma/metabolism/therapeutic use ; *Amyotrophic Lateral Sclerosis ; Neurons/metabolism ; *Huntington Disease ; *Neurodevelopmental Disorders/drug therapy/metabolism ; }, abstract = {The sigma-1 receptor is a 223 amino acid-long protein with a recently identified structure. The sigma-2 receptor is a genetically unrelated protein with a similarly shaped binding pocket and acts to influence cellular activities similar to the sigma-1 receptor. Both proteins are highly expressed in neuronal tissues. As such, they have become targets for treating neurological diseases, including Alzheimer's disease (AD), Huntington's disease (HD), Parkinson's disease (PD), multiple sclerosis (MS), Rett syndrome (RS), developmental and epileptic encephalopathies (DEE), and motor neuron disease/amyotrophic lateral sclerosis (MND/ALS). In recent years, there have been many pre-clinical and clinical studies of sigma receptor (1 and 2) ligands for treating neurological disease. Drugs such as blarcamesine, dextromethorphan and pridopidine, which have sigma-1 receptor activity as part of their pharmacological profile, are effective in treating multiple aspects of several neurological diseases. Furthermore, several sigma-2 receptor ligands are under investigation, including CT1812, rivastigmine and SAS0132. This review aims to provide a current and up-to-date analysis of the current clinical and pre-clinical data of drugs with sigma receptor activities for treating neurological disease.}, }
@article {pmid37163838, year = {2023}, author = {Zhang, Y and Ren, R and Yang, L and Nie, Y and Zhang, H and Shi, Y and Sanford, LD and Vitiello, MV and Tang, X}, title = {Sleep in amyotrophic lateral sclerosis: A systematic review and meta-analysis of polysomnographic findings.}, journal = {Sleep medicine}, volume = {107}, number = {}, pages = {116-125}, doi = {10.1016/j.sleep.2023.04.014}, pmid = {37163838}, issn = {1878-5506}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; Polysomnography ; Sleep ; Sleep, REM ; Sleep Latency ; }, abstract = {BACKGROUND: This study explores the polysomnographic differences between amyotrophic lateral sclerosis (ALS) patients and healthy controls.<br><br>METHODS: An electronic literature search was conducted in MEDLINE, EMBASE, All EBM databases, Web of Science, and CNKI from inception to Oct 2022.<br><br>RESULTS: Meta-analyses revealed significant reductions in sleep efficiency, total sleep time, N2%, slow wave sleep percentage, minimum SpO2, and mean SpO2, and increases in wake time after sleep onset and N1%, sleep latency, rapid eye movement sleep latency, time spent with SpO2 < 90%, oxygen desaturation index, and apnea hypopnea index in ALS patients compared with controls. Sensitivity analyses showed that some heterogeneity was explained by excluding patients taking medications impacting sleep, whether studies employed an adaptation night, and the use of different PSG scoring rules.<br><br>CONCLUSIONS: Significant polysomnographic abnormalities are present in ALS. Our findings underscore the need for a comprehensive PSG assessment of sleep changes in ALS patients. When performing PSG examinations in ALS, whether the patients are taking medication impacting sleep and the scoring system used should be considered.}, }
@article {pmid37162686, year = {2023}, author = {Mangrulkar, SV and Wankhede, NL and Kale, MB and Upaganlawar, AB and Taksande, BG and Umekar, MJ and Anwer, MK and Dailah, HG and Mohan, S and Behl, T}, title = {Mitochondrial Dysfunction as a Signaling Target for Therapeutic Intervention in Major Neurodegenerative Disease.}, journal = {Neurotoxicity research}, volume = {41}, number = {6}, pages = {708-729}, pmid = {37162686}, issn = {1476-3524}, mesh = {Humans ; Aged ; *Neurodegenerative Diseases/metabolism ; Mitochondria/metabolism ; DNA, Mitochondrial/genetics/metabolism/therapeutic use ; Oxidative Stress ; Aging ; }, abstract = {Neurodegenerative diseases (NDD) are incurable and the most prevalent cognitive and motor disorders of elderly. Mitochondria are essential for a wide range of cellular processes playing a pivotal role in a number of cellular functions like metabolism, intracellular signaling, apoptosis, and immunity. A plethora of evidence indicates the central role of mitochondrial functions in pathogenesis of many aging related NDD. Considering how mitochondria function in neurodegenerative diseases, oxidative stress, and mutations in mtDNA both contribute to aging. Many substantial reports suggested the involvement of numerous contributing factors including, mitochondrial dysfunction, oxidative stress, mitophagy, accumulation of somatic mtDNA mutations, compromised mitochondrial dynamics, and transport within axons in neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, Huntington's disease, and Amyotrophic Lateral Sclerosis. Therapies therefore target fundamental mitochondrial processes such as energy metabolism, free-radical generation, mitochondrial biogenesis, mitochondrial redox state, mitochondrial dynamics, mitochondrial protein synthesis, mitochondrial quality control, and metabolism hold great promise to develop pharmacological based therapies in NDD. By emphasizing the most efficient pharmacological strategies to target dysfunction of mitochondria in the treatment of neurodegenerative diseases, this review serves the scientific community engaged in translational medical science by focusing on the establishment of novel, mitochondria-targeted treatment strategies.}, }
@article {pmid37153665, year = {2023}, author = {Hong, D and Zhang, C and Wu, W and Lu, X and Zhang, L}, title = {Modulation of the gut-brain axis via the gut microbiota: a new era in treatment of amyotrophic lateral sclerosis.}, journal = {Frontiers in neurology}, volume = {14}, number = {}, pages = {1133546}, pmid = {37153665}, issn = {1664-2295}, abstract = {There are trillions of different microorganisms in the human digestive system. These gut microbes are involved in the digestion of food and its conversion into the nutrients required by the body. In addition, the gut microbiota communicates with other parts of the body to maintain overall health. The connection between the gut microbiota and the brain is known as the gut-brain axis (GBA), and involves connections via the central nervous system (CNS), the enteric nervous system (ENS), and endocrine and immune pathways. The gut microbiota regulates the central nervous system bottom-up through the GBA, which has prompted researchers to pay considerable attention to the potential pathways by which the gut microbiota might play a role in the prevention and treatment of amyotrophic lateral sclerosis (ALS). Studies with animal models of ALS have shown that dysregulation of the gut ecology leads to dysregulation of brain-gut signaling. This, in turn, induces changes in the intestinal barrier, endotoxemia, and systemic inflammation, which contribute to the development of ALS. Through the use of antibiotics, probiotic supplementation, phage therapy, and other methods of inducing changes in the intestinal microbiota that can inhibit inflammation and delay neuronal degeneration, the clinical symptoms of ALS can be alleviated, and the progression of the disease can be delayed. Therefore, the gut microbiota may be a key target for effective management and treatment of ALS.}, }
@article {pmid37150307, year = {2023}, author = {Westi, EW and Andersen, JV and Aldana, BI}, title = {Using stable isotope tracing to unravel the metabolic components of neurodegeneration: Focus on neuron-glia metabolic interactions.}, journal = {Neurobiology of disease}, volume = {182}, number = {}, pages = {106145}, doi = {10.1016/j.nbd.2023.106145}, pmid = {37150307}, issn = {1095-953X}, mesh = {*Neuroglia ; *Neurons/metabolism ; Astrocytes/metabolism ; Synaptic Transmission ; Isotopes/metabolism ; }, abstract = {Disrupted brain metabolism is a critical component of several neurodegenerative diseases. Energy metabolism of both neurons and astrocytes is closely connected to neurotransmitter recycling via the glutamate/GABA-glutamine cycle. Neurons and astrocytes hereby work in close metabolic collaboration which is essential to sustain neurotransmission. Elucidating the mechanistic involvement of altered brain metabolism in disease progression has been aided by the advance of techniques to monitor cellular metabolism, in particular by mapping metabolism of substrates containing stable isotopes, a technique known as isotope tracing. Here we review key aspects of isotope tracing including advantages, drawbacks and applications to different cerebral preparations. In addition, we narrate how isotope tracing has facilitated the discovery of central metabolic features in neurodegeneration with a focus on the metabolic cooperation between neurons and astrocytes.}, }
@article {pmid37143267, year = {2024}, author = {Forouzanfar, F and Pourbagher-Shahri, AM and Vafaee, F and Sathyapalan, T and Sahebkar, A}, title = {Phytochemicals as Substances that Affect Astrogliosis and their Implications for the Management of Neurodegenerative Diseases.}, journal = {Current medicinal chemistry}, volume = {31}, number = {34}, pages = {5550-5566}, pmid = {37143267}, issn = {1875-533X}, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/pathology ; *Phytochemicals/pharmacology/chemistry/therapeutic use ; *Astrocytes/drug effects/pathology/metabolism ; Animals ; Neuroprotective Agents/pharmacology/chemistry/therapeutic use ; Gliosis/drug therapy/pathology ; }, abstract = {Astrocytes are a multifunctional subset of glial cells that are important in maintaining the health and function of the central nervous system (CNS). Reactive astrocytes may release inflammatory mediators, chemokines, and cytokines, as well as neurotrophic factors. There may be neuroprotective (e.g., cytokines, like IL-6 and TGF-b) and neurotoxic effects (e.g., IL-1β and TNF-a) associated with these molecules. In response to CNS pathologies, astrocytes go to a state called astrogliosis which produces diverse and heterogenic functions specific to the pathology. Astrogliosis has been linked to the progression of many neurodegenerative disorders. Phytochemicals are a large group of compounds derived from natural herbs with health benefits. This review will summarize how several phytochemicals affect neurodegenerative diseases (e.g., Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis, and Parkinson's disease) in basic medical and clinical studies and how they might affect astrogliosis in the process.}, }
@article {pmid37143081, year = {2023}, author = {Fisher, EMC and Greensmith, L and Malaspina, A and Fratta, P and Hanna, MG and Schiavo, G and Isaacs, AM and Orrell, RW and Cunningham, TJ and Arozena, AA}, title = {Opinion: more mouse models and more translation needed for ALS.}, journal = {Molecular neurodegeneration}, volume = {18}, number = {1}, pages = {30}, pmid = {37143081}, issn = {1750-1326}, support = {223022/Z/21//WT_/Wellcome Trust/United Kingdom ; FISHER/OCT14/876-792/MNDA_/Motor Neurone Disease Association/United Kingdom ; MC_EX_MR/N501931/1/MRC_/Medical Research Council/United Kingdom ; MR/S005021/1/MRC_/Medical Research Council/United Kingdom ; MR/R005184/1/MRC_/Medical Research Council/United Kingdom ; 107116/Z/15/Z/WT_/Wellcome Trust/United Kingdom ; MR/L021056/1/MRC_/Medical Research Council/United Kingdom ; FISHER/APR14/874-792/MNDA_/Motor Neurone Disease Association/United Kingdom ; MR/K018523/1/MRC_/Medical Research Council/United Kingdom ; MALASPINA/APR13/817-791/MNDA_/Motor Neurone Disease Association/United Kingdom ; G0801110/MRC_/Medical Research Council/United Kingdom ; TURNER/OCT15/972-797/MNDA_/Motor Neurone Disease Association/United Kingdom ; }, mesh = {Mice ; Animals ; Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; Disease Models, Animal ; Mutation ; Phenotype ; }, abstract = {Amyotrophic lateral sclerosis is a complex disorder most of which is 'sporadic' of unknown origin but approximately 10% is familial, arising from single mutations in any of more than 30 genes. Thus, there are more than 30 familial ALS subtypes, with different, often unknown, molecular pathologies leading to a complex constellation of clinical phenotypes. We have mouse models for many genetic forms of the disorder, but these do not, on their own, necessarily show us the key pathological pathways at work in human patients. To date, we have no models for the 90% of ALS that is 'sporadic'. Potential therapies have been developed mainly using a limited set of mouse models, and through lack of alternatives, in the past these have been tested on patients regardless of aetiology. Cancer researchers have undertaken therapy development with similar challenges; they have responded by producing complex mouse models that have transformed understanding of pathological processes, and they have implemented patient stratification in multi-centre trials, leading to the effective translation of basic research findings to the clinic. ALS researchers have successfully adopted this combined approach, and now to increase our understanding of key disease pathologies, and our rate of progress for moving from mouse models to mechanism to ALS therapies we need more, innovative, complex mouse models to address specific questions.}, }
@article {pmid37138438, year = {2024}, author = {Barbero Mazzucca, C and Cappellano, G and Chiocchetti, A}, title = {Nutrition, Immunity and Aging: Current Scenario and Future Perspectives in Neurodegenerative Diseases.}, journal = {CNS &amp; neurological disorders drug targets}, volume = {23}, number = {5}, pages = {573-587}, pmid = {37138438}, issn = {1996-3181}, support = {//Fondazione Cariplo/ ; }, mesh = {Humans ; *Aging/immunology/physiology ; *Neurodegenerative Diseases/immunology ; Inflammation ; Alzheimer Disease/immunology ; Nutritional Status ; Amyotrophic Lateral Sclerosis/immunology ; Parkinson Disease/immunology ; Animals ; Immunity/physiology ; }, abstract = {Aging is a gradual decline of physiological function and tissue homeostasis and, in many instances, is related to increased (neuro)-degeneration, together with inflammation, becoming one of the most important risks for developing neurodegenerative diseases. Certain individual nutrients or foods in combination may counteract aging and associated neurodegenerative diseases by promoting a balance between the pro- and anti-inflammatory responses. Thus, nutrition could represent a powerful modulator of this fine balance, other than a modifiable risk factor to contrast inflammaging. This narrative review explores from a broad perspective the impact of nutrition on the hallmarks of aging and inflammation in Alzheimer's disease (AD), Parkinson's disease (PD) and Amyotrophic Lateral Sclerosis Syndrome (ALS), starting from nutrients up to single foods and complex dietary patterns.}, }
@article {pmid37137507, year = {2023}, author = {D'Cruz, RF and Kaltsakas, G and Suh, ES and Hart, N}, title = {Quality of life in patients with chronic respiratory failure on home mechanical ventilation.}, journal = {European respiratory review : an official journal of the European Respiratory Society}, volume = {32}, number = {168}, pages = {}, pmid = {37137507}, issn = {1600-0617}, mesh = {Humans ; Respiration, Artificial/adverse effects ; Quality of Life ; *Respiratory Insufficiency/diagnosis/etiology/therapy ; *Neuromuscular Diseases/complications/diagnosis/therapy ; *Pulmonary Disease, Chronic Obstructive/diagnosis/therapy ; *Home Care Services ; }, abstract = {Home mechanical ventilation (HMV) is a treatment for chronic respiratory failure that has shown clinical and cost effectiveness in patients with underlying COPD, obesity-related respiratory failure and neuromuscular disease (NMD). By treating chronic respiratory failure with adequate adherence to HMV, improvement in patient-reported outcomes including health-related quality of life (HRQoL) have been evaluated using general and disease-specific quantitative, semi-qualitative and qualitative methods. However, the treatment response in terms of trajectory of change in HRQoL is not uniform across the restrictive and obstructive disease groups. In this review, the effect of HMV on HRQoL across the domains of symptom perception, physical wellbeing, mental wellbeing, anxiety, depression, self-efficacy and sleep quality in stable and post-acute COPD, rapidly progressive NMD (such as amyotrophic lateral sclerosis), inherited NMD (including Duchenne muscular dystrophy) and obesity-related respiratory failure will be discussed.}, }
@article {pmid37132030, year = {2023}, author = {Pearce, L and Costa, N and Sherrington, C and Hassett, L}, title = {Implementation of digital health interventions in rehabilitation: A scoping review.}, journal = {Clinical rehabilitation}, volume = {37}, number = {11}, pages = {1533-1551}, doi = {10.1177/02692155231172299}, pmid = {37132030}, issn = {1477-0873}, mesh = {Humans ; *Rehabilitation ; *Telemedicine ; }, abstract = {OBJECTIVE: Digital health interventions have potential to enhance rehabilitation services by increasing accessibility, affordability and scalability. However, implementation of digital interventions in rehabilitation is poorly understood. This scoping review aims to map current strategies, research designs, frameworks, outcomes and determinants used to support and evaluate the implementation of digital interventions in rehabilitation.<br><br>DATA SOURCES: Comprehensive searches from inception until October 2022 of MEDLINE, CINAHL, PsycINFO, PEDro, SpeechBITE, NeuroBITE, REHABDATA, WHO International Clinical Trial Registry and the Cochrane Library.<br><br>METHODS: Two reviewers screened studies against the eligibility criteria. Implementation science taxonomies and methods, including Powell et al.'s compilation of implementation strategies, were used to guide analysis and synthesis of findings.<br><br>RESULTS: The search retrieved 13,833 papers and 23 studies were included. Only 4 studies were randomised controlled trials and 9 studies (39%) were feasibility studies. Thirty-seven discrete implementation strategies were reported across studies. Strategies related to training and educating clinicians (91%), providing interactive assistance (61%), and developing stakeholder interrelationships (43%) were most frequently reported. Few studies adequately described implementation strategies and methods for selecting strategies. Almost all studies measured implementation outcomes and determinants; most commonly, acceptability, compatibility and dose delivered of digital interventions.<br><br>CONCLUSION: The rigour of implementation methods in the field is currently poor. Digital interventions require carefully planned and tailored implementation to facilitate successful adoption into rehabilitation practice. To keep pace with rapidly advancing technology, future rehabilitation research should prioritise using implementation science methods to explore and evaluate implementation while testing effectiveness of digital interventions.}, }
@article {pmid37127082, year = {2023}, author = {Nicoletti, A and Baschi, R and Cicero, CE and Iacono, S and Re, VL and Luca, A and Schirò, G and Monastero, R and , }, title = {Sex and gender differences in Alzheimer's disease, Parkinson's disease, and Amyotrophic Lateral Sclerosis: A narrative review.}, journal = {Mechanisms of ageing and development}, volume = {212}, number = {}, pages = {111821}, doi = {10.1016/j.mad.2023.111821}, pmid = {37127082}, issn = {1872-6216}, mesh = {Male ; Female ; Humans ; *Alzheimer Disease/diagnosis/epidemiology ; *Parkinson Disease/diagnosis/epidemiology/genetics ; *Amyotrophic Lateral Sclerosis/diagnosis/epidemiology/genetics ; Sex Factors ; Biomarkers ; }, abstract = {Neurodegenerative diseases (NDs), including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), exhibit high phenotypic variability and they are very common in the general population. These diseases are associated with poor prognosis and a significant burden on patients and their caregivers. Although increasing evidence suggests that biological sex is an important factor for the development and phenotypical expression of some NDs, the role of sex and gender in the diagnosis and prognosis of NDs has been poorly explored. Current knowledge relating to sex- and gender-related differences in the epidemiology, clinical features, biomarkers, and treatment of AD, PD, and ALS will be summarized in this narrative review. The cumulative evidence hitherto collected suggests that sex and gender are factors to be considered in explaining the heterogeneity of these NDs. Clarifying the role of sex and gender in AD, PD, and ALS is a key topic in precision medicine, which will facilitate sex-specific prevention and treatment strategies to be implemented in the near future.}, }
@article {pmid37125006, year = {2023}, author = {Patocka, C and Lockey, A and Lauridsen, KG and Greif, R}, title = {Impact of accredited advanced life support course participation on in-hospital cardiac arrest patient outcomes: A systematic review.}, journal = {Resuscitation plus}, volume = {14}, number = {}, pages = {100389}, pmid = {37125006}, issn = {2666-5204}, abstract = {AIM: Advanced life support courses have a clear educational impact; however, it is important to determine whether participation of one or more members of the resuscitation team in an accredited advanced life support course improves in-hospital cardiac arrest patient survival outcomes.<br><br>METHODS: We searched EMBASE.com, Medline, Cochrane and CINAHL from inception to 1 November 2022. Included studies were randomised or non-randomised interventional studies assessing the impact of attendance at accredited life support courses on patient outcomes. Accredited life support courses were classified into 3 contexts: Advanced Life Support (ALS), Neonatal Resuscitation Training (NRT), and Helping Babies Breathe (HBB). Existing systematic reviews were identified for each of the contexts and an adolopment process was pursued. Appropriate risk of bias assessment tools were used across all outcomes. When meta-analysis was appropriate a random-effects model was used to produce a summary of effect sizes for each outcome.<br><br>RESULTS: Of 2714 citations screened, 19 studies (1 ALS; 7 NRT; 11 HBB) were eligible for inclusion. Three systematic reviews which satisfied AMSTAR-2 criteria for methodological quality, included 16 of the studies we identified in our search. Among adult patients all outcomes including return of spontaneous circulation, survival to discharge and survival to 30&#xa0;days were consistently better with accredited ALS training. Among neonatal patients there were reductions in stillbirths and early neonatal mortality.<br><br>CONCLUSION: These results support the recommendation that accredited advanced life support courses, specifically Advanced Life Support, Neonatal Resuscitation Training, and Helping Babies Breathe improve patient outcomes.}, }
@article {pmid37124925, year = {2023}, author = {Banarase, TA and Sammeta, SS and Wankhede, NL and Mangrulkar, SV and Rahangdale, SR and Aglawe, MM and Taksande, BG and Upaganlawar, AB and Umekar, MJ and Kale, MB}, title = {Mitophagy regulation in aging and neurodegenerative disease.}, journal = {Biophysical reviews}, volume = {15}, number = {2}, pages = {239-255}, pmid = {37124925}, issn = {1867-2450}, abstract = {Mitochondria are the primary cellular energy generators, supplying the majority of adenosine triphosphate through oxidative phosphorylation, which is necessary for neuron function and survival. Mitophagy is the metabolic process of eliminating dysfunctional or redundant mitochondria. It is a type of autophagy and it is crucial for maintaining mitochondrial and neuronal health. Impaired mitophagy leads to an accumulation of damaged mitochondria and proteins leading to the dysregulation of mitochondrial quality control processes. Recent research shows the vital role of mitophagy in neurons and the pathogenesis of major neurodegenerative diseases. Mitophagy also plays a major role in the process of aging. This review describes the alterations that are being caused in the mitophagy process at the molecular level in aging and in neurodegenerative diseases, particularly Alzheimer's, Parkinson's, and Huntington's diseases and amyotrophic lateral sclerosis, also looks at how mitophagy can be exploited as a therapeutic target for these diseases.}, }
@article {pmid37123415, year = {2023}, author = {Davidson, K and Pickering, AM}, title = {The proteasome: A key modulator of nervous system function, brain aging, and neurodegenerative disease.}, journal = {Frontiers in cell and developmental biology}, volume = {11}, number = {}, pages = {1124907}, pmid = {37123415}, issn = {2296-634X}, support = {RF1 AG065301/AG/NIA NIH HHS/United States ; }, abstract = {The proteasome is a large multi-subunit protease responsible for the degradation and removal of oxidized, misfolded, and polyubiquitinated proteins. The proteasome plays critical roles in nervous system processes. This includes maintenance of cellular homeostasis in neurons. It also includes roles in long-term potentiation via modulation of CREB signaling. The proteasome also possesses roles in promoting dendritic spine growth driven by proteasome localization to the dendritic spines in an NMDA/CaMKIIα dependent manner. Proteasome inhibition experiments in varied organisms has been shown to impact memory, consolidation, recollection and extinction. The proteasome has been further shown to impact circadian rhythm through modulation of a range of 'clock' genes, and glial function. Proteasome function is impaired as a consequence both of aging and neurodegenerative diseases. Many studies have demonstrated an impairment in 26S proteasome function in the brain and other tissues as a consequence of age, driven by a disassembly of 26S proteasome in favor of 20S proteasome. Some studies also show proteasome augmentation to correct age-related deficits. In amyotrophic lateral sclerosis Alzheimer's, Parkinson's and Huntington's disease proteasome function is impaired through distinct mechanisms with impacts on disease susceptibility and progression. Age and neurodegenerative-related deficits in the function of the constitutive proteasome are often also accompanied by an increase in an alternative form of proteasome called the immunoproteasome. This article discusses the critical role of the proteasome in the nervous system. We then describe how proteasome dysfunction contributes to brain aging and neurodegenerative disease.}, }
@article {pmid37122628, year = {2023}, author = {Sánchez-Vidaña, DI and Li, J and Abokyi, S and Chan, JN and Ngai, SP and Lau, BW}, title = {In vitro methods in autophagy research: Applications in neurodegenerative diseases and mood disorders.}, journal = {Frontiers in molecular neuroscience}, volume = {16}, number = {}, pages = {1168948}, pmid = {37122628}, issn = {1662-5099}, abstract = {BACKGROUND: Autophagy is a conserved physiological intracellular mechanism responsible for the degradation and recycling of cytoplasmic constituents (e.g., damaged organelles, and protein aggregates) to maintain cell homeostasis. Aberrant autophagy has been observed in neurodegenerative diseases, including Alzheimer's Disease (AD), Parkinson's Disease (PD), Amyotrophic Lateral Sclerosis (ALS), and Huntington's Disease (HD), and recently aberrant autophagy has been associated with mood disorders, such as depression. Several in vitro methods have been developed to study the complex and tightly regulated mechanisms of autophagy. In vitro methods applied to autophagy research are used to identify molecular key players involved in dysfunctional autophagy and to screen autophagy regulators with therapeutic applications in neurological diseases and mood disorders. Therefore, the aims of this narrative review are (1) to compile information on the cell-based methods used in autophagy research, (2) to discuss their application, and (3) to create a catalog of traditional and novel in vitro methods applied in neurodegenerative diseases and depression.<br><br>METHODS: Pubmed and Google Scholar were used to retrieve relevant in vitro studies on autophagy mechanisms in neurological diseases and depression using a combination of search terms per mechanism and disease (e.g., "macroautophagy" and "Alzheimer's disease"). A total of 37 studies were included (14 in PD, 8 in AD, 5 in ALS, 5 in %, and 5 in depression).<br><br>RESULTS: A repertoire of traditional and novel approaches and techniques was compiled and discussed. The methods used in autophagy research focused on the mechanisms of macroautophagy, microautophagy, and chaperone-mediated autophagy. The in vitro tools presented in this review can be applied to explore pathophysiological mechanisms at a molecular level and to screen for potential therapeutic agents and their mechanism of action, which can be of great importance to understanding disease biology and potential therapeutic options in the context of neurodegenerative disorders and depression.<br><br>CONCLUSION: This is the first review to compile, discuss, and provide a catalog of traditional and novel in vitro models applied to neurodegenerative disorders and depression.}, }
@article {pmid37121991, year = {2023}, author = {Gangfuß, A and Kohl, Z}, title = {[Amyotrophic lateral sclerosis-Motor neuron disease with a wide clinical and genetic spectrum].}, journal = {Der Nervenarzt}, volume = {94}, number = {6}, pages = {494-500}, pmid = {37121991}, issn = {1433-0407}, mesh = {Young Adult ; Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics/therapy ; *Motor Neuron Disease/diagnosis/genetics/therapy ; Diagnosis, Differential ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is the most frequent motor neuron disease. Besides a timely diagnosis, precise knowledge of the clinical manifestations and differential diagnoses is essential. While most patients develop the disease at an older age, hereditary causes play a more frequent role in the juvenile forms.<br><br>OBJECTIVE: What is the current state of ALS diagnostics, which new treatment options exist?<br><br>MATERIAL AND METHOD: Literature search using Pubmed.gov.<br><br>RESULTS: The main focus is on an individualized symptomatic treatment as no curative treatment approaches exist. However, new insights into the genetic and pathophysiological principles of the different forms of ALS open the way for future disease-modifying treatment options.<br><br>CONCLUSION: In cases of a clinical suspicion of ALS molecular genetic diagnostics should be considered, particularly in juvenile and young adult patients, to exclude differential diagnoses and to enable patients access to new treatment approaches.}, }
@article {pmid37119957, year = {2023}, author = {Kalu, ME and Bello-Haas, VD and Griffin, M and Boamah, S and Harris, J and Zaide, M and Rayner, D and Khattab, N and Abrahim, S}, title = {A Scoping Review of Personal, Financial, and Environmental Determinants of Mobility Among Older Adults.}, journal = {Archives of physical medicine and rehabilitation}, volume = {104}, number = {12}, pages = {2147-2168}, doi = {10.1016/j.apmr.2023.04.007}, pmid = {37119957}, issn = {1532-821X}, mesh = {Humans ; Aged ; *Research Design ; Sample Size ; }, abstract = {OBJECTIVE: To synthesize available evidence of factors comprising the personal, financial, and environmental mobility determinants and their association with older adults' self-reported and performance-based mobility outcomes.<br><br>DATA SOURCES: PubMed, EMBASE, PsychINFO, Web of Science, AgeLine, Sociological Abstract, Allied and Complementary Medicine Database, and Cumulative Index to Nursing and Allied Health Literature databases search for articles published from January 2000 to December 2021.<br><br>STUDY SECTION: Using predefined inclusion and exclusion criteria, multiple reviewers independently screened 27,293 retrieved citations from databases, of which 422 articles underwent full-text screening, and 300 articles were extracted.<br><br>DATA EXTRACTION: The 300 articles' information, including study design, sample characteristics including sample size, mean age and sex, factors within each determinant, and their associations with mobility outcomes, were extracted.<br><br>DATA SYNTHESIS: Because of the heterogeneity of the reported associations, we followed Barnett et al's study protocol and reported associations between factors and mobility outcomes by analyses rather than by article to account for multiple associations generated in 1 article. Qualitative data were synthesized using content analysis. A total of 300 articles were included with 269 quantitative, 22 qualitative, and 9 mixed-method articles representing personal (n=80), and financial (n=1), environmental (n=98), more than 1 factor (n=121). The 278 quantitative and mixed-method articles reported 1270 analyses; 596 (46.9%) were positively and 220 (17.3%) were negatively associated with mobility outcomes among older adults. Personal (65.2%), financial (64.6%), and environmental factors (62.9%) were associated with mobility outcomes, mainly in the expected direction with few exceptions in environmental factors.<br><br>CONCLUSIONS: Gaps exist in understanding the effect of some environmental factors (eg, number and type of street connections) and the role of gender on older adults' walking outcomes. We have provided a comprehensive list of factors with each determinant, allowing the creation of core outcome set for a specific context, population, or other forms of mobility, for example, driving.}, }
@article {pmid37116688, year = {2024}, author = {Moreno-Jiménez, L and Benito-Martín, MS and Sanclemente-Alamán, I and Matías-Guiu, JA and Sancho-Bielsa, F and Canales-Aguirre, A and Mateos-Díaz, JC and Matías-Guiu, J and Aguilar, J and Gómez-Pinedo, U}, title = {Murine experimental models of amyotrophic lateral sclerosis: an update.}, journal = {Neurologia}, volume = {39}, number = {3}, pages = {282-291}, doi = {10.1016/j.nrleng.2021.07.004}, pmid = {37116688}, issn = {2173-5808}, mesh = {Humans ; Animals ; Mice ; *Amyotrophic Lateral Sclerosis/pathology ; *Neurodegenerative Diseases ; DNA-Binding Proteins/genetics ; Mutation ; }, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease whose aetiology is unknown. It is characterised by upper and lower motor neuron degeneration. Approximately 90% of cases of ALS are sporadic, whereas the other 10% are familial. Regardless of whether the case is familial o sporadic, patients will develop progressive weakness, muscle atrophy with spasticity, and muscle contractures. Life expectancy of these patients is generally 2 to 5 years after diagnosis.<br><br>DEVELOPMENT: In vivo models have helped to clarify the aetiology and pathogenesis of ALS, as well as the mechanisms of the disease. However, as these mechanisms are not yet fully understood, experimental models are essential to the continued study of the pathogenesis of ALS, as well as in the search for possible therapeutic targets. Although 90% of cases are sporadic, most of the models used to study ALS pathogenesis are based on genetic mutations associated with the familial form of the disease; the pathogenesis of sporadic ALS remains unknown. Therefore, it would be critical to establish models based on the sporadic form.<br><br>CONCLUSIONS: This article reviews the main genetic and sporadic experimental models used in the study of this disease, focusing on those that have been developed using rodents.}, }
@article {pmid37115318, year = {2023}, author = {Holloway, K and Neherin, K and Dam, KU and Zhang, H}, title = {Cellular senescence and neurodegeneration.}, journal = {Human genetics}, volume = {142}, number = {8}, pages = {1247-1262}, pmid = {37115318}, issn = {1432-1203}, mesh = {Mice ; Animals ; *Amyloid beta-Peptides ; Cellular Senescence/genetics ; *Alzheimer Disease/genetics ; Aging/physiology ; }, abstract = {Advancing age is a major risk factor of Alzheimer's disease (AD). The worldwide prevalence of AD is approximately 50 million people, and this number is projected to increase substantially. The molecular mechanisms underlying the aging-associated susceptibility to cognitive impairment in AD are largely unknown. As a hallmark of aging, cellular senescence is a significant contributor to aging and age-related diseases including AD. Senescent neurons and glial cells have been detected to accumulate in the brains of AD patients and mouse models. Importantly, selective elimination of senescent cells ameliorates amyloid beta and tau pathologies and improves cognition in AD mouse models, indicating a critical role of cellular senescence in AD pathogenesis. Nonetheless, the mechanisms underlying when and how cellular senescence contributes to AD pathogenesis remain unclear. This review provides an overview of cellular senescence and discusses recent advances in the understanding of the impact of cellular senescence on AD pathogenesis, with brief discussions of the possible role of cellular senescence in other neurodegenerative diseases including Down syndrome, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis.}, }
@article {pmid37115110, year = {2023}, author = {Rhine, K and Odeh, HM and Shorter, J and Myong, S}, title = {Regulation of Biomolecular Condensates by Poly(ADP-ribose).}, journal = {Chemical reviews}, volume = {123}, number = {14}, pages = {9065-9093}, pmid = {37115110}, issn = {1520-6890}, support = {F31 NS113439/NS/NINDS NIH HHS/United States ; RF1 AG071326/AG/NIA NIH HHS/United States ; R21 AG079609/AG/NIA NIH HHS/United States ; R01 GM138690/GM/NIGMS NIH HHS/United States ; RF1 NS113636/NS/NINDS NIH HHS/United States ; R01 GM099836/GM/NIGMS NIH HHS/United States ; R21 AG065854/AG/NIA NIH HHS/United States ; }, mesh = {*Poly Adenosine Diphosphate Ribose/metabolism ; *Poly(ADP-ribose) Polymerases/chemistry/metabolism ; Biomolecular Condensates ; Poly ADP Ribosylation ; Protein Processing, Post-Translational ; }, abstract = {Biomolecular condensates are reversible compartments that form through a process called phase separation. Post-translational modifications like ADP-ribosylation can nucleate the formation of these condensates by accelerating the self-association of proteins. Poly(ADP-ribose) (PAR) chains are remarkably transient modifications with turnover rates on the order of minutes, yet they can be required for the formation of granules in response to oxidative stress, DNA damage, and other stimuli. Moreover, accumulation of PAR is linked with adverse phase transitions in neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. In this review, we provide a primer on how PAR is synthesized and regulated, the diverse structures and chemistries of ADP-ribosylation modifications, and protein-PAR interactions. We review substantial progress in recent efforts to determine the molecular mechanism of PAR-mediated phase separation, and we further delineate how inhibitors of PAR polymerases may be effective treatments for neurodegenerative pathologies. Finally, we highlight the need for rigorous biochemical interrogation of ADP-ribosylation in vivo and in vitro to clarify the exact pathway from PARylation to condensate formation.}, }
@article {pmid37108873, year = {2023}, author = {Lipke, PN and Ragonis-Bachar, P}, title = {Sticking to the Subject: Multifunctionality in Microbial Adhesins.}, journal = {Journal of fungi (Basel, Switzerland)}, volume = {9}, number = {4}, pages = {}, pmid = {37108873}, issn = {2309-608X}, abstract = {Bacterial and fungal adhesins mediate microbial aggregation, biofilm formation, and adhesion to host. We divide these proteins into two major classes: professional adhesins and moonlighting adhesins that have a non-adhesive activity that is evolutionarily conserved. A fundamental difference between the two classes is the dissociation rate. Whereas moonlighters, including cytoplasmic enzymes and chaperones, can bind with high affinity, they usually dissociate quickly. Professional adhesins often have unusually long dissociation rates: minutes or hours. Each adhesin has at least three activities: cell surface association, binding to a ligand or adhesive partner protein, and as a microbial surface pattern for host recognition. We briefly discuss Bacillus subtilis TasA, pilin adhesins, gram positive MSCRAMMs, and yeast mating adhesins, lectins and flocculins, and Candida Awp and Als families. For these professional adhesins, multiple activities include binding to diverse ligands and binding partners, assembly into molecular complexes, maintenance of cell wall integrity, signaling for cellular differentiation in biofilms and in mating, surface amyloid formation, and anchorage of moonlighting adhesins. We summarize the structural features that lead to these diverse activities. We conclude that adhesins resemble other proteins with multiple activities, but they have unique structural features to facilitate multifunctionality.}, }
@article {pmid37108835, year = {2023}, author = {Sandrelli, F and Bisaglia, M}, title = {Molecular and Physiological Determinants of Amyotrophic Lateral Sclerosis: What the DJ-1 Protein Teaches Us.}, journal = {International journal of molecular sciences}, volume = {24}, number = {8}, pages = {}, pmid = {37108835}, issn = {1422-0067}, mesh = {Humans ; Adult ; *Amyotrophic Lateral Sclerosis/metabolism ; Protein Deglycase DJ-1/genetics/metabolism ; Motor Neurons/metabolism ; Mutation ; Oxidative Stress/physiology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is an adult-onset disease which causes the progressive degeneration of cortical and spinal motoneurons, leading to death a few years after the first symptom onset. ALS is mainly a sporadic disorder, and its causative mechanisms are mostly unclear. About 5-10% of cases have a genetic inheritance, and the study of ALS-associated genes has been fundamental in defining the pathological pathways likely also involved in the sporadic forms of the disease. Mutations affecting the DJ-1 gene appear to explain a subset of familial ALS forms. DJ-1 is involved in multiple molecular mechanisms, acting primarily as a protective agent against oxidative stress. Here, we focus on the involvement of DJ-1 in interconnected cellular functions related to mitochondrial homeostasis, reactive oxygen species (ROS) levels, energy metabolism, and hypoxia response, in both physiological and pathological conditions. We discuss the possibility that impairments in one of these pathways may affect the others, contributing to a pathological background in which additional environmental or genetic factors may act in favor of the onset and/or progression of ALS. These pathways may represent potential therapeutic targets to reduce the likelihood of developing ALS and/or slow disease progression.}, }
@article {pmid37108335, year = {2023}, author = {Teruel-Peña, B and Gómez-Urquiza, JL and Suleiman-Martos, N and Prieto, I and García-Cózar, FJ and Ramírez-Sánchez, M and Fernández-Martos, C and Domínguez-Vías, G}, title = {Systematic Review and Meta-Analyses of Aminopeptidases as Prognostic Biomarkers in Amyotrophic Lateral Sclerosis.}, journal = {International journal of molecular sciences}, volume = {24}, number = {8}, pages = {}, pmid = {37108335}, issn = {1422-0067}, support = {PPJIA2022.09//University of Granada/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics ; Aminopeptidases ; Genome-Wide Association Study ; *Neurodegenerative Diseases ; Prognosis ; Biomarkers ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons in the spinal cord, brain stem, and cerebral cortex. Biomarkers for ALS are essential for disease detection and to provide information on potential therapeutic targets. Aminopeptidases catalyze the cleavage of amino acids from the amino terminus of protein or substrates such as neuropeptides. Since certain aminopeptidases are known to increase the risk of neurodegeneration, such mechanisms may reveal new targets to determine their association with ALS risk and their interest as a diagnostic biomarker. The authors performed a systematic review and meta-analyses of genome-wide association studies (GWASs) to identify reported aminopeptidases genetic loci associated with the risk of ALS. PubMed, Scopus, CINAHL, ISI Web of Science, ProQuest, LILACS, and Cochrane databases were searched to retrieve eligible studies in English or Spanish, published up to 27 January 2023. A total of 16 studies were included in this systematic review, where a series of aminopeptidases could be related to ALS and could be promising biomarkers (DPP1, DPP2, DPP4, LeuAP, pGluAP, and PSA/NPEPPS). The literature reported the association of single-nucleotide polymorphisms (SNPs: rs10260404 and rs17174381) with the risk of ALS. The genetic variation rs10260404 in the DPP6 gene was identified to be highly associated with ALS susceptibility, but meta-analyses of genotypes in five studies in a matched cohort of different ancestry (1873 cases and 1861 control subjects) showed no ALS risk association. Meta-analyses of eight studies for minor allele frequency (MAF) also found no ALS association for the "C" allele. The systematic review identified aminopeptidases as possible biomarkers. However, the meta-analyses for rs1060404 of DPP6 do not show a risk associated with ALS.}, }
@article {pmid37107340, year = {2023}, author = {Rey, F and Berardo, C and Maghraby, E and Mauri, A and Messa, L and Esposito, L and Casili, G and Ottolenghi, S and Bonaventura, E and Cuzzocrea, S and Zuccotti, G and Tonduti, D and Esposito, E and Paterniti, I and Cereda, C and Carelli, S}, title = {Redox Imbalance in Neurological Disorders in Adults and Children.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {12}, number = {4}, pages = {}, pmid = {37107340}, issn = {2076-3921}, abstract = {Oxygen is a central molecule for numerous metabolic and cytophysiological processes, and, indeed, its imbalance can lead to numerous pathological consequences. In the human body, the brain is an aerobic organ and for this reason, it is very sensitive to oxygen equilibrium. The consequences of oxygen imbalance are especially devastating when occurring in this organ. Indeed, oxygen imbalance can lead to hypoxia, hyperoxia, protein misfolding, mitochondria dysfunction, alterations in heme metabolism and neuroinflammation. Consequently, these dysfunctions can cause numerous neurological alterations, both in the pediatric life and in the adult ages. These disorders share numerous common pathways, most of which are consequent to redox imbalance. In this review, we will focus on the dysfunctions present in neurodegenerative disorders (specifically Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis) and pediatric neurological disorders (X-adrenoleukodystrophies, spinal muscular atrophy, mucopolysaccharidoses and Pelizaeus-Merzbacher Disease), highlighting their underlining dysfunction in redox and identifying potential therapeutic strategies.}, }
@article {pmid37102648, year = {2023}, author = {Dabi, YT and Ajagbe, AO and Degechisa, ST}, title = {Toll-like receptors in pathogenesis of neurodegenerative diseases and their therapeutic potential.}, journal = {Immunity, inflammation and disease}, volume = {11}, number = {4}, pages = {e839}, pmid = {37102648}, issn = {2050-4527}, mesh = {Humans ; *Neurodegenerative Diseases/therapy/drug therapy ; Toll-Like Receptors/metabolism ; Inflammation/metabolism ; Microglia/metabolism/pathology ; Neurons/metabolism/pathology ; }, abstract = {Toll-like receptors (TLRs) are a family of pattern-recognition receptors triggered by pathogen-derived and tissue-damage-related ligands. TLRs were previously believed to only be expressed in immune cells. However, it is now confirmed that they are ubiquitously expressed in cells within the body including neurons, astrocytes, and microglia of the central nervous system (CNS). Activation of TLRs is capable of inducing immunologic and inflammatory responses to injury or infection of CNS. This response is self-limiting that usually resolves once the infection has been eradicated or the tissue damage has been repaired. However, the persistence of inflammation-inducing insults or a failure in normal resolution mechanisms may result in overwhelming inflammation which may induce neurodegeneration. This implies that TLRs may play a role in mediating the link between inflammation and neurodegenerative diseases namely Alzheimer's disease, Parkinson's disease, Huntington's disease, stroke, and amyotrophic lateral sclerosis. So, new therapeutic approaches that specifically target TLRs may be developed by better understanding TLR expression mechanisms in the CNS and their connections to particular neurodegenerative disorders. Therefore, this review paper discussed the role of TLRs in neurodegenerative diseases.}, }
@article {pmid37100932, year = {2023}, author = {Guo, C and Chen, L and Wang, Y}, title = {Substance abuse and neurodegenerative diseases: focus on ferroptosis.}, journal = {Archives of toxicology}, volume = {97}, number = {6}, pages = {1519-1528}, pmid = {37100932}, issn = {1432-0738}, support = {81973404//National Natural Science Foundation of China/ ; 2022-MS-224//Natural Science Foundation of Liaoning Province/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/chemically induced ; *Ferroptosis ; Oxidative Stress/physiology ; *Parkinson Disease ; *Alzheimer Disease/drug therapy ; Lipid Peroxidation ; }, abstract = {Psychostimulants and alcohol are widely abused substances with the adverse effects on global public health. Substance abuse seriously harms people's health and causes various diseases, especially neurodegenerative diseases. Neurodegenerative diseases include Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). The pathogenesis of neurodegenerative diseases is complex and diverse, usually involving oxidative stress, mitochondrial dysfunction, metal homeostasis disorder, and neuro-inflammation. The precise molecular mechanisms underlying neurodegeneration remain unclear, which is a major obstacle to therapeutic approaches. Therefore, it is urgent to improve the understanding of the molecular mechanisms of neurodegenerative processes and to identify the therapeutic targets for treatment and prevention. Ferroptosis is a regulatory cell necrosis caused by iron ion catalysis and lipid peroxidation induced by reactive oxygen species (ROS), which is thought to be associated with nervous system diseases, particularly neurodegenerative diseases. This review overviewed the ferroptosis process and explored the relationship of ferroptosis with substance abuse and neurodegenerative diseases, which provides a new way to study the molecular mechanisms of neurodegenerative diseases induced by alcohol, cocaine, and methamphetamine (MA), and also provides the potential therapeutic targets for substance abuse-induced neurodegenerative diseases.}, }
@article {pmid37090799, year = {2023}, author = {Castelnovo, V and Canu, E and De Mattei, F and Filippi, M and Agosta, F}, title = {Basal ganglia alterations in amyotrophic lateral sclerosis.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1133758}, pmid = {37090799}, issn = {1662-4548}, abstract = {Amyotrophic lateral sclerosis (ALS) has traditionally been associated with brain damage involving the primary motor cortices and corticospinal tracts. In the recent decades, most of the research studies in ALS have focused on extra-motor and subcortical brain regions. The aim of these studies was to detect additional biomarkers able to support the diagnosis and to predict disease progression. The involvement of the frontal cortices, mainly in ALS cases who develop cognitive and/or behavioral impairment, is amply recognized in the field. A potential involvement of fronto-temporal and fronto-striatal connectivity changes in the disease evolution has also been reported. On this latter regard, there is still a shortage of studies which investigated basal ganglia (BG) alterations and their role in ALS clinical manifestation and progression. The present review aims to provide an overview on the magnetic resonance imaging studies reporting structural and/or functional BG alterations in patients with ALS, to clarify the role of BG damage in the disease clinical evolution and to propose potential future developments in this field.}, }
@article {pmid37090492, year = {2023}, author = {Pingle, SC and Lin, F and Anekoji, MS and Patro, CPK and Datta, S and Jones, LD and Kesari, S and Ashili, S}, title = {Exploring the role of cerebrospinal fluid as analyte in neurologic disorders.}, journal = {Future science OA}, volume = {9}, number = {4}, pages = {FSO851}, pmid = {37090492}, issn = {2056-5623}, abstract = {The cerebrospinal fluid (CSF) is a clear ultrafiltrate of blood that envelopes and protects the central nervous system while regulating neuronal function through the maintenance of interstitial fluid homeostasis in the brain. Due to its anatomic location and physiological functions, the CSF can provide a reliable source of biomarkers for the diagnosis and treatment monitoring of different neurological diseases, including neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and primary and secondary brain malignancies. The incorporation of CSF biomarkers into the drug discovery and development can improve the efficiency of drug development and increase the chances of success. This review aims to consolidate the current use of CSF biomarkers in clinical practice and explore future perspectives for the field.}, }
@article {pmid37089709, year = {2023}, author = {Wijeweera, G and Wijekoon, N and Gonawala, L and Imran, Y and Mohan, C and De Silva, KRD}, title = {Therapeutic Implications of Some Natural Products for Neuroimmune Diseases: A Narrative of Clinical Studies Review.}, journal = {Evidence-based complementary and alternative medicine : eCAM}, volume = {2023}, number = {}, pages = {5583996}, pmid = {37089709}, issn = {1741-427X}, abstract = {Neuroimmune diseases are a group of disorders that occur due to the dysregulation of both the nervous and immune systems, and these illnesses impact tens of millions of people worldwide. However, patients who suffer from these debilitating conditions have very few FDA-approved treatment options. Neuroimmune crosstalk is important for controlling the immune system both centrally and peripherally to maintain tissue homeostasis. This review aims to provide readers with information on how natural products modulate neuroimmune crosstalk and the therapeutic implications of natural products, including curcumin, epigallocatechin-3-gallate (EGCG), ginkgo special extract, ashwagandha, Centella asiatica, Bacopa monnieri, ginseng, and cannabis to mitigate the progression of neuroimmune diseases, such as Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease, depression, and anxiety disorders. The majority of the natural products based clinical studies mentioned in this study have yielded positive results. To achieve the expected results from natural products based clinical studies, researchers should focus on enhancing bioavailability and determining the synergistic mechanisms of herbal compounds and extracts, which will lead to the discovery of more effective phytomedicines while averting the probable negative effects of natural product extracts. Therefore, future studies developing nutraceuticals to mitigate neuroimmune diseases that incorporate phytochemicals to produce synergistic effects must analyse efficacy, bioavailability, gut-brain axis function safety, chemical modifications, and encapsulation with nanoparticles.}, }
@article {pmid37087974, year = {2023}, author = {Casale, M and Somefun, O and Haupt Ronnie, G and Desmond, C and Sherr, L and Cluver, L}, title = {A conceptual framework and exploratory model for health and social intervention acceptability among African adolescents and youth.}, journal = {Social science &amp; medicine (1982)}, volume = {326}, number = {}, pages = {115899}, doi = {10.1016/j.socscimed.2023.115899}, pmid = {37087974}, issn = {1873-5347}, mesh = {Adolescent ; Humans ; Africa ; *Black People ; Interdisciplinary Studies ; *Social Work ; *Health Promotion ; }, abstract = {Intervention acceptability has become an increasingly key consideration in the development, evaluation and implementation of health and social interventions. However, to date this area of investigation has been constrained by the absence of a consistent definition of acceptability, comprehensive conceptual frameworks disaggregating its components, and few reliable assessment measures. This paper aims to contribute to this gap, by proposing a conceptual framework and exploratory model for acceptability with a specific priority population for health and developmental interventions: adolescents and youth in Africa. We document our multi-staged approach to model development, comprising both inductive and deductive components, and both systematic and interpretative review methods. This included thematic analyses of respective acceptability definitions and findings, from 55 studies assessing acceptability of 60 interventions conducted with young people aged 10-24 in (mainly Southern and Eastern) Africa over a decade; a consideration of these findings in relation to Sekhon et al.'s Theoretical Framework of Acceptability (TFA); a cross-disciplinary review of acceptability definitions and models; a review of key health behavioural change models; and expert consultation with interdisciplinary researchers. Our proposed framework incorporates nine component constructs: affective attitude, intervention understanding, perceived positive effects, relevance, perceived social acceptability, burden, ethicality, perceived negative effects and self-efficacy. We discuss the rationale for the inclusion and definition of each component, highlighting key behavioural models that adopt similar constructs. We then extend this framework to develop an exploratory model for acceptability with young people, that links the framework components to each other and to intervention engagement. Acceptability is represented as an emergent property of a complex, adaptive system of interacting components, which can influence user engagement directly and indirectly, and in turn be influenced by user engagement. We discuss opportunities for applying and further refining or developing these models, and their value as a point of reference for the development of acceptability assessment tools.}, }
@article {pmid37084987, year = {2023}, author = {Ma, Y and Farny, NG}, title = {Connecting the dots: Neuronal senescence, stress granules, and neurodegeneration.}, journal = {Gene}, volume = {871}, number = {}, pages = {147437}, pmid = {37084987}, issn = {1879-0038}, support = {R03 AG077140/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Stress Granules ; Cytoplasmic Granules/genetics/metabolism/pathology ; Neurons/metabolism ; Proteins/metabolism ; *Neurodegenerative Diseases/metabolism ; }, abstract = {Cellular senescence increases with aging. While senescence is associated with an exit of the cell cycle, there is ample evidence that post-mitotic cells including neurons can undergo senescence as the brain ages, and that senescence likely contributes significantly to the progression of neurodegenerative diseases (ND) such as Alzheimer's Disease (AD) and Amyotrophic Lateral Sclerosis (ALS). Stress granules (SGs) are stress-induced cytoplasmic biomolecular condensates of RNA and proteins, which have been linked to the development of AD and ALS. The SG seeding hypothesis of NDs proposes that chronic stress in aging neurons results in static SGs that progress into pathological aggregates Alterations in SG dynamics have also been linked to senescence, though studies that link SGs and senescence in the context of NDs and the aging brain have not yet been performed. In this Review, we summarize the literature on senescence, and explore the contribution of senescence to the aging brain. We describe senescence phenotypes in aging neurons and glia, and their links to neuroinflammation and the development of AD and ALS. We further examine the relationships of SGs to senescence and to ND. We propose a new hypothesis that neuronal senescence may contribute to the mechanism of SG seeding in ND by altering SG dynamics in aged cells, thereby providing additional aggregation opportunities within aged neurons.}, }
@article {pmid37084148, year = {2023}, author = {Wuerch, E and Urgoiti, GR and Yong, VW}, title = {The Promise of Niacin in Neurology.}, journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics}, volume = {20}, number = {4}, pages = {1037-1054}, pmid = {37084148}, issn = {1878-7479}, mesh = {Humans ; *Niacin/therapeutic use/metabolism ; Amyloid beta-Peptides ; *Pellagra/metabolism ; *Nervous System Diseases ; *Alzheimer Disease ; *Neurology ; }, abstract = {Niacin (vitamin B3) is an essential nutrient that treats pellagra, and prior to the advent of statins, niacin was commonly used to counter dyslipidemia. Recent evidence has posited niacin as a promising therapeutic for several neurological disorders. In this review, we discuss the biochemistry of niacin, including its homeostatic roles in NAD[+] supplementation and metabolism. Niacin also has roles outside of metabolism, largely through engaging hydroxycarboxylic acid receptor 2 (Hcar2). These receptor-mediated activities of niacin include regulation of immune responses, phagocytosis of myelin debris after demyelination or of amyloid beta in models of Alzheimer's disease, and cholesterol efflux from cells. We describe the neurological disorders in which niacin has been investigated or has been proposed as a candidate medication. These are multiple sclerosis, Alzheimer's disease, Parkinson's disease, glioblastoma and amyotrophic lateral sclerosis. Finally, we explore the proposed mechanisms through which niacin may ameliorate neuropathology. While several questions remain, the prospect of niacin as a therapeutic to alleviate neurological impairment is promising.}, }
@article {pmid37069469, year = {2023}, author = {Hamad, AA and Attia, AN and Al-Dardery, NM and Mohamed, SF and Meshref, M}, title = {Safety and efficacy of lithium in patients with amyotrophic lateral sclerosis: a systematic review and meta-analysis of randomized controlled trials.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {44}, number = {9}, pages = {3029-3036}, pmid = {37069469}, issn = {1590-3478}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy ; Lithium/adverse effects ; Valproic Acid/adverse effects ; Randomized Controlled Trials as Topic ; Vital Capacity ; }, abstract = {OBJECTIVES: This study provides a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating the safety and efficacy of lithium in amyotrophic lateral sclerosis (ALS) patients.<br><br>METHODS: PubMed, Web of Science, Cochrane CENTRAL, Scopus, and Your Journals@Ovid were searched up to 9 December 2022. RCTs investigating lithium, either alone or with any supplement, in ALS patients were included. Meta-analysis was performed using RevMan and results are presented in forest plot.<br><br>RESULTS: Four RCTs with 469 patients met the inclusion criteria and were included in our study. Lithium doses varied among the included studies and one study used a combined therapy of lithium with valproate. Meta-analysis showed no difference between lithium and placebo regarding severe adverse events (odds ratio&#x2009;=&#x2009;1.13, 95% confidence interval: 0.73 to 1.75, P&#x2009;=&#x2009;0.58). No significant differences were observed with regard to survival rate between the two groups (hazard ratio&#x2009;=&#x2009;0.95, 95% confidence interval: 0.65 to 1.37, P&#x2009;=&#x2009;0.77). There were also no significant differences between the two groups with regard to average changes of revised amyotrophic lateral sclerosis functional rating scale (P&#x2009;=&#x2009;0.35) and forced vital capacity percentage predicted (P&#x2009;=&#x2009;0.73). Subgroup analysis showed no significant differences regarding all investigated outcomes either for lithium alone or lithium with valproate.<br><br>CONCLUSION: Current evidence suggests a safety profile with no benefit of lithium for ALS. However, given the limited number of RCTs and the safety findings, we recommend further well-designed RCTs to investigate lithium and valproate in ALS patients.}, }
@article {pmid37068329, year = {2023}, author = {Vucic, S and Stanley Chen, KH and Kiernan, MC and Hallett, M and Benninger, DH and Di Lazzaro, V and Rossini, PM and Benussi, A and Berardelli, A and Currà, A and Krieg, SM and Lefaucheur, JP and Long Lo, Y and Macdonell, RA and Massimini, M and Rosanova, M and Picht, T and Stinear, CM and Paulus, W and Ugawa, Y and Ziemann, U and Chen, R}, title = {Clinical diagnostic utility of transcranial magnetic stimulation in neurological disorders. Updated report of an IFCN committee.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {150}, number = {}, pages = {131-175}, pmid = {37068329}, issn = {1872-8952}, support = {Z99 NS999999/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Humans ; Transcranial Magnetic Stimulation/methods ; *Nervous System Diseases ; *Amyotrophic Lateral Sclerosis ; *Alzheimer Disease ; Evoked Potentials, Motor/physiology ; }, abstract = {The review provides a comprehensive update (previous report: Chen R, Cros D, Curra A, Di Lazzaro V, Lefaucheur JP, Magistris MR, et al. The clinical diagnostic utility of transcranial magnetic stimulation: report of an IFCN committee. Clin Neurophysiol 2008;119(3):504-32) on clinical diagnostic utility of transcranial magnetic stimulation (TMS) in neurological diseases. Most TMS measures rely on stimulation of motor cortex and recording of motor evoked potentials. Paired-pulse TMS techniques, incorporating conventional amplitude-based and threshold tracking, have established clinical utility in neurodegenerative, movement, episodic (epilepsy, migraines), chronic pain and functional diseases. Cortical hyperexcitability has emerged as a diagnostic aid in amyotrophic lateral sclerosis. Single-pulse TMS measures are of utility in stroke, and myelopathy even in the absence of radiological changes. Short-latency afferent inhibition, related to central cholinergic transmission, is reduced in Alzheimer's disease. The triple stimulation technique (TST) may enhance diagnostic utility of conventional TMS measures to detect upper motor neuron involvement. The recording of motor evoked potentials can be used to perform functional mapping of the motor cortex or in preoperative assessment of eloquent brain regions before surgical resection of brain tumors. TMS exhibits utility in assessing lumbosacral/cervical nerve root function, especially in demyelinating neuropathies, and may be of utility in localizing the site of facial nerve palsies. TMS measures also have high sensitivity in detecting subclinical corticospinal lesions in multiple sclerosis. Abnormalities in central motor conduction time or TST correlate with motor impairment and disability in MS. Cerebellar stimulation may detect lesions in the cerebellum or cerebello-dentato-thalamo-motor cortical pathways. Combining TMS with electroencephalography, provides a novel method to measure parameters altered in neurological disorders, including cortical excitability, effective connectivity, and response complexity.}, }
@article {pmid37063844, year = {2023}, author = {Yu, X and Liu, MM and Zheng, CY and Liu, YT and Wang, Z and Wang, ZY}, title = {Telomerase reverse transcriptase and neurodegenerative diseases.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1165632}, pmid = {37063844}, issn = {1664-3224}, mesh = {Humans ; Cellular Senescence ; *Neurodegenerative Diseases/therapy ; *Telomerase/genetics ; Telomere Shortening ; T-Lymphocytes ; }, abstract = {Neurodegenerative diseases (NDs) are chronic conditions that result in progressive damage to the nervous system, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic lateral sclerosis (ALS). Age is a major risk factor for NDs. Telomere shortening is a biological marker of cellular aging, and telomerase reverse transcriptase (TERT) has been shown to slow down this process by maintaining telomere length. The blood-brain barrier (BBB) makes the brain a unique immune organ, and while the number of T cells present in the central nervous system is limited, they play an important role in NDs. Research suggests that NDs can be influenced by modulating peripheral T cell immune responses, and that TERT may play a significant role in T cell senescence and NDs. This review focuses on the current state of research on TERT in NDs and explores the potential connections between TERT, T cells, and NDs. Further studies on aging and telomeres may provide valuable insights for developing therapeutic strategies for age-related diseases.}, }
@article {pmid37062503, year = {2023}, author = {Alavi, MS and Karimi, G and Ghanimi, HA and Roohbakhsh, A}, title = {The potential of CYP46A1 as a novel therapeutic target for neurological disorders: An updated review of mechanisms.}, journal = {European journal of pharmacology}, volume = {949}, number = {}, pages = {175726}, doi = {10.1016/j.ejphar.2023.175726}, pmid = {37062503}, issn = {1879-0712}, mesh = {Humans ; Cholesterol 24-Hydroxylase/metabolism ; *Cholesterol/metabolism ; *Alzheimer Disease/metabolism ; Brain/metabolism ; }, abstract = {Cholesterol is a key component of the cell membrane that impacts the permeability, fluidity, and functions of membrane-bound proteins. It also participates in synaptogenesis, synaptic function, axonal growth, dendrite outgrowth, and microtubule stability. Cholesterol biosynthesis and metabolism are in balance in the brain. Its metabolism in the brain is mediated mainly by CYP46A1 or cholesterol 24-hydroxylase. It is responsible for eliminating about 80% of the cholesterol excess from the human brain. CYP46A1 converts cholesterol to 24S-hydroxycholesterol (24HC) that readily crosses the blood-brain barrier and reaches the liver for the final elimination process. Studies show that cholesterol and 24HC levels change during neurological diseases and conditions. So, it was hypothesized that inhibition or activation of CYP46A1 would be an effective therapeutic strategy. Accordingly, preclinical studies, using genetic and pharmacological interventions, assessed the role of CYP46A1 in main neurodegenerative disorders such as Parkinson's disease, Huntington's disease, Alzheimer's disease, multiple sclerosis, spinocerebellar ataxias, and amyotrophic lateral sclerosis. In addition, its role in seizures and brain injury was evaluated. The recent development of soticlestat, as a selective and potent CYP46A1 inhibitor, with significant anti-seizure effects in preclinical and clinical studies, suggests the importance of this target for future drug developments. Previous studies have shown that both activation and inhibition of CYP46A1 are of therapeutic value. This article, using recent studies, highlights the role of CYP46A1 in various brain diseases and insults.}, }
@article {pmid37061287, year = {2023}, author = {Yoshimura, A and Ohyagi, M and Ito, M}, title = {T cells in the brain inflammation.}, journal = {Advances in immunology}, volume = {157}, number = {}, pages = {29-58}, doi = {10.1016/bs.ai.2022.10.001}, pmid = {37061287}, issn = {1557-8445}, mesh = {Humans ; CD8-Positive T-Lymphocytes ; *Alzheimer Disease ; *Neurodegenerative Diseases ; *Infectious Encephalitis ; *Encephalitis ; Cerebral Infarction ; Inflammation ; }, abstract = {The immune system is deeply involved in autoimmune diseases of the central nervous system (CNS), such as multiple sclerosis, N-methyl-d-aspartate (NMDA) receptor encephalitis, and narcolepsy. Additionally, the immune system is involved in various brain diseases including cerebral infarction and neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). In particular, reports related to T cells are increasing. T cells may also play important roles in brain deterioration and dementia that occur with aging. Our understanding of the role of immune cells in the context of the brain has been greatly improved by the use of acute ischemic brain injury models. Additionally, similar neural damage and repair events are shown to occur in more chronic brain neurodegenerative brain diseases. In this review, we focus on the role of T cells, including CD4[+] T cells, CD8[+] T cells and regulatory T cells (Tregs) in cerebral infarction and neurodegenerative diseases.}, }
@article {pmid37055865, year = {2023}, author = {Shadfar, S and Parakh, S and Jamali, MS and Atkin, JD}, title = {Redox dysregulation as a driver for DNA damage and its relationship to neurodegenerative diseases.}, journal = {Translational neurodegeneration}, volume = {12}, number = {1}, pages = {18}, pmid = {37055865}, issn = {2047-9158}, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy ; Oxidative Stress/genetics ; Oxidation-Reduction ; Reactive Oxygen Species/therapeutic use ; Antioxidants/therapeutic use ; DNA Damage/genetics ; }, abstract = {Redox homeostasis refers to the balance between the production of reactive oxygen species (ROS) as well as reactive nitrogen species (RNS), and their elimination by antioxidants. It is linked to all important cellular activities and oxidative stress is a result of imbalance between pro-oxidants and antioxidant species. Oxidative stress perturbs many cellular activities, including processes that maintain the integrity of DNA. Nucleic acids are highly reactive and therefore particularly susceptible to damage. The DNA damage response detects and repairs these DNA lesions. Efficient DNA repair processes are therefore essential for maintaining cellular viability, but they decline considerably during aging. DNA damage and deficiencies in DNA repair are increasingly described in age-related neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and Huntington's disease. Furthermore, oxidative stress has long been associated with these conditions. Moreover, both redox dysregulation and DNA damage increase significantly during aging, which is the biggest risk factor for neurodegenerative diseases. However, the links between redox dysfunction and DNA damage, and their joint contributions to pathophysiology in these conditions, are only just emerging. This review will discuss these associations and address the increasing evidence for redox dysregulation as an important and major source of DNA damage in neurodegenerative disorders. Understanding these connections may facilitate a better understanding of disease mechanisms, and ultimately lead to the design of better therapeutic strategies based on preventing both redox dysregulation and DNA damage.}, }
@article {pmid37053133, year = {2023}, author = {Hung, J and Chen, J and Chen, O}, title = {Are the relationships between mental health issues and being left-behind gendered in China: A systematic review and meta-analysis.}, journal = {PloS one}, volume = {18}, number = {4}, pages = {e0279278}, pmid = {37053133}, issn = {1932-6203}, mesh = {Male ; Child ; Female ; Humans ; *Mental Health ; *Suicide, Attempted ; Parents ; Suicidal Ideation ; China/epidemiology ; Randomized Controlled Trials as Topic ; }, abstract = {BACKGROUND: While most existing studies reveal left-behind children (LBC) are prone to suffering from mental health issues, some other literature fails to develop a statistical significance between being left-behind and facing mental health dilemmas. In further detail, it is noteworthy that suicide ideation is a gendered issue. Here girls, relative to their male counterparts, are more likely to experience emotional and affective challenges, alongside a higher risk of suicide ideation. Aside from suicide ideation, the rate of suicide attempts is also higher among Chinese female than among male LBC. However, Chang et al. counter-argue that, within the LBC cohorts, it is not statistically significant to state that girls were more likely for suicide attempts than boys.<br><br>METHODS: In this paper, a systematic review of relevant literature and a meta-analysis of all qualified randomised controlled trial (RCT) studies were conducted. The authors aim to examine all relevant studies with similar methodologies to observe the nuanced relationships between being left-behind and mental health issues in Chinese contexts. Specifically, the authors will, grounded on the findings from the systematic review and meta-analysis, assess whether the relationship between mental health issues and being left-behind is gendered in Chinese contexts by analysing all relevant findings derived from similar methodologies and the same method (i.e., RCT).<br><br>RESULTS: Aside from Wanjie et al.'s studies, it is noticeable that the rest of the studies share similar point estimates and their CIs overlapped to a large extent. As per the I2, given the presence of Wanjie et al.'s studies that demonstrate an observably higher degree of heterogeneity than the rest of the studies, the I2 values, each for the measurement of anxiety and depression, are 74.8 percent and 34.7 percent respectively. This shows that there is a considerable heterogeneity level for anxiety, while the heterogeneity level for depression is moderate. However, both p-values for the I2 statistics are larger than 0.05. Therefore, at the 0.05 significance level, it is statistically insignificant to reject the null hypothesis that there is no heterogeneity between individual studies in both the subgroups of anxiety and depression. Therefore, the concern of the potentially substantial heterogeneity should be irrelevant in this meta-analysis. Beyond the discussion from the forest plot, when looking at the single study addressing the relationship between being left-behind and having suicide attempts (note: LBC-OR is 1.22; 95 percent CI is 1.22 -and NLBC-OR is 1.42; 95 percent CI is 1.09-1.86 -at the p-value of 0.34), the findings demonstrate that such a relationship per se is not gendered at the 0.05 statistical significance level. However, when examining the relationship between being resilient and left-behind, such an association is gendered where the OR of female left-behind university students being resilient, relative to male left-behind university students, is slightly higher than that of female non-left-behind university students being resilient, relative to their male non-left-behind university student counterparts. It is noteworthy that this study focuses on studying left-behind and non-left-behind samples who entered universities. Since a raft of LBC are socially, educationally disadvantaged, they lack the opportunities to receive higher education. Therefore, the findings of this study might not be indicative of the LBC population at large.<br><br>CONCLUSIONS: While the findings of this meta-analysis project fail to reflect any gendered issues statistically, the authors are aware of the fact that the data included in this project were collected based on perception. Here samples, or their parents and teachers, were responsible for answering the questions with respect to samples' mental health status and demographic details. In China, especially in less developed rural regions, the discourse on mental health challenges might continue to be seen as taboo, so individuals giving responses might, consciously or not, tend to give socially desirable answers to avoid any potential social stigmatisation. Therefore, there is some extent of reservation regarding the validity of the included studies' data.}, }
@article {pmid37047320, year = {2023}, author = {Bianco, A and Antonacci, Y and Liguori, M}, title = {Sex and Gender Differences in Neurodegenerative Diseases: Challenges for Therapeutic Opportunities.}, journal = {International journal of molecular sciences}, volume = {24}, number = {7}, pages = {}, pmid = {37047320}, issn = {1422-0067}, mesh = {Male ; Female ; Humans ; *Neurodegenerative Diseases/therapy/pathology ; Sex Factors ; Sex Characteristics ; *Parkinson Disease/pathology ; Neurons/pathology ; }, abstract = {The term "neurodegenerative diseases" (NDs) identifies a group of heterogeneous diseases characterized by progressive loss of selectively vulnerable populations of neurons, which progressively deteriorates over time, leading to neuronal dysfunction. Protein aggregation and neuronal loss have been considered the most characteristic hallmarks of NDs, but growing evidence confirms that significant dysregulation of innate immune pathways plays a crucial role as well. NDs vary from multiple sclerosis, in which the autoimmune inflammatory component is predominant, to more "classical" NDs, such as Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, and spinal muscular atrophy. Of interest, many of the clinical differences reported in NDs seem to be closely linked to sex, which may be justified by the significant changes in immune mechanisms between affected females and males. In this review, we examined some of the most studied NDs by looking at their pathogenic and phenotypical features to highlight sex-related discrepancies, if any, with particular interest in the individuals' responses to treatment. We believe that pointing out these differences in clinical practice may help achieve more successful precision and personalized care.}, }
@article {pmid37047273, year = {2023}, author = {Russo, C and Valle, MS and Casabona, A and Malaguarnera, L}, title = {Chitinase Signature in the Plasticity of Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {24}, number = {7}, pages = {}, pmid = {37047273}, issn = {1422-0067}, support = {E63C22002080006//This research was founded by PNRR: "Health Extended ALliance for Innovative Therapies, Advanced Lab-research, and Integrated Approaches of Precision"/ ; }, mesh = {Humans ; *Neurodegenerative Diseases ; *Chitinases/genetics ; Neuroinflammatory Diseases ; Biomarkers ; *Multiple Sclerosis ; }, abstract = {Several reports have pointed out that Chitinases are expressed and secreted by various cell types of central nervous system (CNS), including activated microglia and astrocytes. These cells play a key role in neuroinflammation and in the pathogenesis of many neurodegenerative disorders. Increased levels of Chitinases, in particular Chitotriosidase (CHIT-1) and chitinase-3-like protein 1 (CHI3L1), have been found increased in several neurodegenerative disorders. Although having important biological roles in inflammation, to date, the molecular mechanisms of Chitinase involvement in the pathogenesis of neurodegenerative disorders is not well-elucidated. Several studies showed that some Chitinases could be assumed as markers for diagnosis, prognosis, activity, and severity of a disease and therefore can be helpful in the choice of treatment. However, some studies showed controversial results. This review will discuss the potential of Chitinases in the pathogenesis of some neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis, to understand their role as distinctive biomarkers of neuronal cell activity during neuroinflammatory processes. Knowledge of the role of Chitinases in neuronal cell activation could allow for the development of new methodologies for downregulating neuroinflammation and consequently for diminishing negative neurological disease outcomes.}, }
@article {pmid37044239, year = {2023}, author = {Bernal, AF and Mota, N and Pamplona, R and Area-Gomez, E and Portero-Otin, M}, title = {Hakuna MAM-Tata: Investigating the role of mitochondrial-associated membranes in ALS.}, journal = {Biochimica et biophysica acta. Molecular basis of disease}, volume = {1869}, number = {6}, pages = {166716}, doi = {10.1016/j.bbadis.2023.166716}, pmid = {37044239}, issn = {1879-260X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; *Neurodegenerative Diseases/pathology ; Mitochondrial Membranes/metabolism ; Mitochondria/metabolism ; Endoplasmic Reticulum/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease leading to selective and progressive motor neuron (MN) death. Despite significant heterogeneity in pathogenic and clinical terms, MN demise ultimately unifies patients. Across the many disturbances in neuronal biology present in the disease and its models, two common trends are loss of calcium homeostasis and dysregulations in lipid metabolism. Since both mitochondria and endoplasmic reticulum (ER) are essential in these functions, their intertwin through the so-called mitochondrial-associated membranes (MAMs) should be relevant in this disease. In this review, we present a short overview of MAMs functional aspects and how its dysfunction could explain a substantial part of the cellular disarrangements in ALS's natural history. MAMs are hubs for lipid synthesis, integrating glycerophospholipids, sphingolipids, and cholesteryl ester metabolism. These lipids are essential for membrane biology, so there should be a close coupling to cellular energy demands, a role that MAMs may partially fulfill. Not surprisingly, MAMs are also host part of calcium signaling to mitochondria, so their impairment could lead to mitochondrial dysfunction, affecting oxidative phosphorylation and enhancing the vulnerability of MNs. We present data supporting that MAMs' maladaptation could be essential to MNs' vulnerability in ALS.}, }
@article {pmid37038031, year = {2023}, author = {Newman, PM and Qi, Y and Mou, W and McNamara, TP}, title = {Statistically Optimal Cue Integration During Human Spatial Navigation.}, journal = {Psychonomic bulletin &amp; review}, volume = {30}, number = {5}, pages = {1621-1642}, pmid = {37038031}, issn = {1531-5320}, mesh = {Humans ; *Cues ; *Spatial Navigation ; Bayes Theorem ; }, abstract = {In 2007, Cheng and colleagues published their influential review wherein they analyzed the literature on spatial cue interaction during navigation through a Bayesian lens, and concluded that models of optimal cue integration often applied in psychophysical studies could explain cue interaction during navigation. Since then, numerous empirical investigations have been conducted to assess the degree to which human navigators are optimal when integrating multiple spatial cues during a variety of navigation-related tasks. In the current review, we discuss the literature on human cue integration during navigation that has been published since Cheng et al.'s original review. Evidence from most studies demonstrate optimal navigation behavior when humans are presented with multiple spatial cues. However, applications of optimal cue integration models vary in their underlying assumptions (e.g., uninformative priors and decision rules). Furthermore, cue integration behavior depends in part on the nature of the cues being integrated and the navigational task (e.g., homing versus non-home goal localization). We discuss the implications of these models and suggest directions for future research.}, }
@article {pmid37037874, year = {2023}, author = {Qian, K and Jiang, X and Liu, ZQ and Zhang, J and Fu, P and Su, Y and Brazhe, NA and Liu, D and Zhu, LQ}, title = {Revisiting the critical roles of reactive astrocytes in neurodegeneration.}, journal = {Molecular psychiatry}, volume = {28}, number = {7}, pages = {2697-2706}, pmid = {37037874}, issn = {1476-5578}, mesh = {Humans ; Astrocytes/metabolism ; *Neurodegenerative Diseases ; *Huntington Disease ; Blood-Brain Barrier/metabolism ; *Alzheimer Disease/pathology ; }, abstract = {Astrocytes, an integral component of the central nervous system (CNS), contribute to the maintenance of physiological homeostasis through their roles in synaptic function, K[+] buffering, blood-brain barrier (BBB) maintenance, and neuronal metabolism. Reactive astrocytes refer to astrocytes undergoing morphological, molecular and functional remodelling in response to pathological stimuli. The activation and differentiation of astrocytes are implicated in the pathogenesis of multiple neurodegenerative diseases. However, there are still controversies regarding their subset identification, function and nomenclature in neurodegeneration. In this review, we revisit the multidimensional roles of reactive astrocytes in Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). Furthermore, we propose a precise linkage between astrocyte subsets and their functions based on single-cell sequencing analyses.}, }
@article {pmid37037728, year = {2023}, author = {Shaw, AV and Verma, Y and Tucker, S and Jain, A and Furniss, D}, title = {Relative motion orthoses for early active motion after finger extensor and flexor tendon repairs: A systematic review.}, journal = {Journal of hand therapy : official journal of the American Society of Hand Therapists}, volume = {36}, number = {2}, pages = {332-346}, doi = {10.1016/j.jht.2023.02.011}, pmid = {37037728}, issn = {1545-004X}, mesh = {Humans ; Retrospective Studies ; Orthotic Devices ; *Tendon Injuries/surgery/rehabilitation ; Tendons ; Fingers ; *Finger Injuries/surgery/rehabilitation ; Range of Motion, Articular ; }, abstract = {BACKGROUND: The relative motion (RM) orthosis was introduced over 40 years ago for extensor tendon rehabilitation and more recently applied to flexor tendon repairs.<br><br>PURPOSE: We systematically reviewed the evidence for RM orthoses following surgical repair of finger extensor and flexor tendon injuries including indications for use, configuration and schedule of orthosis wear, and clinical outcomes.<br><br>STUDY DESIGN: Systematic review.<br><br>METHODS: A PRISMA-compliant systematic review searched eight databases and five trial registries, from database inception to January 7, 2022. The protocol was registered prospectively (CRD42020211579). We identified studies describing patients undergoing rehabilitation using RM orthoses after surgical repair of acute tendon injuries of the finger and hand.<br><br>RESULTS: For extensor tendon repairs, ten studies, one trial registry and five conference abstracts met inclusion criteria, reporting outcomes of 521 patients with injuries in zones IV-VII. Miller's criteria were predominantly used to report range of motion; with 89.6% and 86.9% reporting good or excellent outcomes for extension lag and flexion deficit, respectively. For flexor tendon repairs, one retrospective case series was included reporting outcomes in eight patients following zones I-II repairs. Mean total active motion was 86%. No tendon ruptures were reported due to the orthosis not protecting the repair for either the RME or RMF approaches.<br><br>DISCUSSION: Variation was seen in use of RME plus or only, use of night orthoses and orthotic wear schedules, which may be the result of evolution of the RM approach. Since Hirth et&#xa0;al's 2016 scoping review, there are five additional studies, including two RCTs reporting the use of the RM orthosis in extensor tendon rehabilitation.<br><br>CONCLUSIONS: There is now good evidence that the RM approach is safe in zones V-VI extensor tendon repairs. Limited evidence currently exists for zones IV and VII extensor and for flexor tendon repairs. Further high-quality clinical studies are needed to demonstrate its safety and efficacy.}, }
@article {pmid37032500, year = {2024}, author = {Qi, W and Guan, W}, title = {A Comprehensive Review on the Importance of MiRNA-206 in the Animal Model and Human Diseases.}, journal = {Current neuropharmacology}, volume = {22}, number = {6}, pages = {1064-1079}, pmid = {37032500}, issn = {1875-6190}, support = {81900551//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Humans ; *MicroRNAs/genetics/metabolism ; *Neoplasms/genetics ; Biomarkers ; Models, Animal ; *Osteoarthritis/genetics ; Gene Expression Regulation, Neoplastic ; }, abstract = {MicroRNA-206 (miR-206) is a microRNA that is involved in many human diseases, such as myasthenia gravis, osteoarthritis, depression, cancers, etc. Both inhibition effects and progression roles of miR-206 have been reported for the past few years. High expression of miR-206 was observed in patients with osteoarthritis, gastric cancer and epithelial ovarian cancer compared to normal people. The study also showed that miR-206 promotes cancer progression in breast cancer patients and avascular necrosis of the femoral head. Meanwhile, several studies have shown that expression levels of miR-206 were down-regulated in laryngeal carcinoma cell multiplication, as well as in hepatocellular carcinoma, non-small lung cancer and infantile hemangioma. Moreover, miR-206 was up-regulated in the mild stage of amyotrophic lateral sclerosis patients and then down-regulated in the moderate and severe stages, indicating that miR-206 has the double effects of starting and aggravating the disease. In neuropsychiatric disorders, such as depression, miR-206 also plays an important role in the progression of the disease; the level of miR-206 is most highly expressed in the brains of patients with depression. In the current review, we summarize the role of miR-206 in various diseases, and miR-206 may be developed as a new biomarker for diagnosing diseases in the near future.}, }
@article {pmid37031723, year = {2023}, author = {Zhang, YY and Li, XS and Ren, KD and Peng, J and Luo, XJ}, title = {Restoration of metal homeostasis: a potential strategy against neurodegenerative diseases.}, journal = {Ageing research reviews}, volume = {87}, number = {}, pages = {101931}, doi = {10.1016/j.arr.2023.101931}, pmid = {37031723}, issn = {1872-9649}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism ; *Alzheimer Disease/metabolism ; *Parkinson Disease/metabolism ; Ion Channels/metabolism/therapeutic use ; Homeostasis ; }, abstract = {Metal homeostasis is critical to normal neurophysiological activity. Metal ions are involved in the development, metabolism, redox and neurotransmitter transmission of the central nervous system (CNS). Thus, disturbance of homeostasis (such as metal deficiency or excess) can result in serious consequences, including neurooxidative stress, excitotoxicity, neuroinflammation, and nerve cell death. The uptake, transport and metabolism of metal ions are highly regulated by ion channels. There is growing evidence that metal ion disorders and/or the dysfunction of ion channels contribute to the progression of neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). Therefore, metal homeostasis-related signaling pathways are emerging as promising therapeutic targets for diverse neurological diseases. This review summarizes recent advances in the studies regarding the physiological and pathophysiological functions of metal ions and their channels, as well as their role in neurodegenerative diseases. In addition, currently available metal ion modulators and in vivo quantitative metal ion imaging methods are also discussed. Current work provides certain recommendations based on literatures and in-depth reflections to improve neurodegenerative diseases. Future studies should turn to crosstalk and interactions between different metal ions and their channels. Concomitant pharmacological interventions for two or more metal signaling pathways may offer clinical advantages in treating the neurodegenerative diseases.}, }
@article {pmid37031050, year = {2023}, author = {Alberini, CM}, title = {IGF2 in memory, neurodevelopmental disorders, and neurodegenerative diseases.}, journal = {Trends in neurosciences}, volume = {46}, number = {6}, pages = {488-502}, pmid = {37031050}, issn = {1878-108X}, support = {R01 MH065635/MH/NIMH NIH HHS/United States ; R37 MH065635/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; *Alzheimer Disease ; Brain/metabolism ; *Neurodegenerative Diseases/metabolism ; *Neurodevelopmental Disorders ; *Parkinson Disease ; Humans ; }, abstract = {Insulin-like growth factor 2 (IGF2) emerged as a critical mechanism of synaptic plasticity and learning and memory. Deficits in IGF2 in the brain, serum, or cerebrospinal fluid (CSF) are associated with brain diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). Increasing IGF2 levels enhances memory in healthy animals and reverses numerous symptoms in laboratory models of aging, neurodevelopmental disorders, and neurodegenerative diseases. These effects occur via the IGF2 receptor (IGF2R) - a receptor that is highly expressed in neurons and regulates protein trafficking, synthesis, and degradation. Here, I summarize the current knowledge regarding IGF2 expression and functions in the brain, particularly in memory, and propose a novel conceptual model for IGF2/IGF2R mechanisms of action in brain health and diseases.}, }
@article {pmid37027074, year = {2023}, author = {Cecerska-Heryć, E and Pękała, M and Serwin, N and Gliźniewicz, M and Grygorcewicz, B and Michalczyk, A and Heryć, R and Budkowska, M and Dołęgowska, B}, title = {The Use of Stem Cells as a Potential Treatment Method for Selected Neurodegenerative Diseases: Review.}, journal = {Cellular and molecular neurobiology}, volume = {43}, number = {6}, pages = {2643-2673}, pmid = {37027074}, issn = {1573-6830}, mesh = {Animals ; Humans ; *Neurodegenerative Diseases/therapy ; *Amyotrophic Lateral Sclerosis/therapy ; Stem Cells ; *Huntington Disease/pathology/therapy ; *Alzheimer Disease ; *Parkinson Disease/therapy ; }, abstract = {Stem cells have been the subject of research for years due to their enormous therapeutic potential. Most neurological diseases such as multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD) are incurable or very difficult to treat. Therefore new therapies are sought in which autologous stem cells are used. They are often the patient's only hope for recovery or slowing down the progress of the disease symptoms. The most important conclusions arise after analyzing the literature on the use of stem cells in neurodegenerative diseases. The effectiveness of MSC cell therapy has been confirmed in ALS and HD therapy. MSC cells slow down ALS progression and show early promising signs of efficacy. In HD, they reduced huntingtin (Htt) aggregation and stimulation of endogenous neurogenesis. MS therapy with hematopoietic stem cells (HSCs) inducted significant recalibration of pro-inflammatory and immunoregulatory components of the immune system. iPSC cells allow for accurate PD modeling. They are patient-specific and therefore minimize the risk of immune rejection and, in long-term observation, did not form any tumors in the brain. Extracellular vesicles derived from bone marrow mesenchymal stromal cells (BM-MSC-EVs) and Human adipose-derived stromal/stem cells (hASCs) cells are widely used to treat AD. Due to the reduction of Aβ42 deposits and increasing the survival of neurons, they improve memory and learning abilities. Despite many animal models and clinical trial studies, cell therapy still needs to be refined to increase its effectiveness in the human body.}, }
@article {pmid37026513, year = {2023}, author = {Li, F and Liu, A and Zhao, M and Luo, L}, title = {Astrocytic Chitinase-3-like protein 1 in neurological diseases: Potential roles and future perspectives.}, journal = {Journal of neurochemistry}, volume = {165}, number = {6}, pages = {772-790}, doi = {10.1111/jnc.15824}, pmid = {37026513}, issn = {1471-4159}, support = {2021-ZZ-JC030//Project of Shaanxi Provincial Administration of Traditional Chinese Medicine/ ; 82204425//National Natural Science Foundation of China/ ; 32241007//National Natural Science Foundation of China/ ; }, mesh = {Humans ; Chitinase-3-Like Protein 1/metabolism ; Astrocytes/metabolism ; *Chitinases/metabolism ; *Neurodegenerative Diseases/metabolism ; Synapsins/metabolism ; *Brain Neoplasms/metabolism ; }, abstract = {Chitinase-3-like protein 1 (CHI3L1) is a secreted glycoprotein characterized by its ability to regulate multiple biological processes, such as the inflammatory response and gene transcriptional signaling activation. Abnormal CHI3L1 expression has been associated with multiple neurological disorders and serves as a biomarker for the early detection of several neurodegenerative diseases. Aberrant CHI3L1 expression is also reportedly associated with brain tumor migration and metastasis, as well as contributions to immune escape, playing important roles in brain tumor progression. CHI3L1 is synthesized and secreted mainly by reactive astrocytes in the central nervous system. Thus, targeting astrocytic CHI3L1 could be a promising approach for the treatment of neurological diseases, such as traumatic brain injury, ischemic stroke, Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, and glioma. Based on current knowledge of CHI3L1, we assume that it acts as a molecule mediating several signaling pathways driving the initiation and progression of neurological disorders. This narrative review is the first to introduce the potential roles of astrocytic CHI3L1 in neurological disorders. We also equally explore astrocytic CHI3L1 mRNA expression under physiological and pathological conditions. Inhibiting CHI3L1 and disrupting its interaction with its receptors through multiple mechanisms of action are briefly discussed. These endeavors highlight the pivotal roles of astrocytic CHI3L1 in neurological disorders and could contribute to the development of effective inhibitors based on the strategy of structure-based drug discovery, which could be an attractive therapeutic approach for neurological disease treatment.}, }
@article {pmid37024676, year = {2023}, author = {Akçimen, F and Lopez, ER and Landers, JE and Nath, A and Chiò, A and Chia, R and Traynor, BJ}, title = {Amyotrophic lateral sclerosis: translating genetic discoveries into therapies.}, journal = {Nature reviews. Genetics}, volume = {24}, number = {9}, pages = {642-658}, pmid = {37024676}, issn = {1471-0064}, support = {Z01 AG000949/ImNIH/Intramural NIH HHS/United States ; Z99 AG999999/ImNIH/Intramural NIH HHS/United States ; ZIA AG000933/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/therapy ; Mutation ; Gene-Environment Interaction ; }, abstract = {Recent advances in sequencing technologies and collaborative efforts have led to substantial progress in identifying the genetic causes of amyotrophic lateral sclerosis (ALS). This momentum has, in turn, fostered the development of putative molecular therapies. In this Review, we outline the current genetic knowledge, emphasizing recent discoveries and emerging concepts such as the implication of distinct types of mutation, variability in mutated genes in diverse genetic ancestries and gene-environment interactions. We also propose a high-level model to synthesize the interdependent effects of genetics, environmental and lifestyle factors, and ageing into a unified theory of ALS. Furthermore, we summarize the current status of therapies developed on the basis of genetic knowledge established for ALS over the past 30 years, and we discuss how developing treatments for ALS will advance our understanding of targeting other neurological diseases.}, }
@article {pmid37021679, year = {2023}, author = {Shammas, MK and Huang, TH and Narendra, DP}, title = {CHCHD2 and CHCHD10-related neurodegeneration: molecular pathogenesis and the path to precision therapy.}, journal = {Biochemical Society transactions}, volume = {51}, number = {2}, pages = {797-809}, doi = {10.1042/BST20221365}, pmid = {37021679}, issn = {1470-8752}, support = {ZIA NS003169/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; DNA-Binding Proteins/genetics/metabolism ; Transcription Factors/genetics/metabolism ; Mitochondria/metabolism ; Mutation ; *Parkinson Disease/metabolism ; Mitochondrial Proteins/genetics/metabolism ; }, abstract = {In the last decade, dominant mutations in the mitochondrial protein CHCHD10 (p.R15L and p.S59L) and its paralog CHCHD2 (p.T61I) were shown to cause familial amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD), respectively, with phenotypes that often resemble the idiopathic forms of the diseases. Different mutations in CHCHD10 cause additional neuromuscular disorders, including the lower motor neuron disease Spinal Muscular Atrophy Jokela type (SMAJ) (p.G66V) and autosomal dominant isolated mitochondrial myopathy (IMMD) (p.G58R). Modeling these disorders is revealing how mitochondrial dysfunction may drive ALS and PD pathogenesis by a gain of function mechanism, driven by protein misfolding of CHCHD2 and CHCHD10 into toxic species. It is also laying the groundwork for precision therapy of CHCHD2/CHCHD10-related neurodegeneration. In this review, we address the normal function of CHCHD2 and CHCHD10, the mechanisms of their disease pathogenesis, the strong genotype-phenotype correlations that have emerged for CHCHD10, and potential therapeutic strategies for these disorders.}, }
@article {pmid37018859, year = {2023}, author = {Kamalian, A and Foroughmand, I and Koski, L and Darvish, M and Saghazadeh, A and Kamalian, A and Razavi, SZE and Abdi, S and Dehgolan, SR and Fotouhi, A and Roos, PM}, title = {Metal concentrations in cerebrospinal fluid, blood, serum, plasma, hair, and nails in amyotrophic lateral sclerosis: A systematic review and meta-analysis.}, journal = {Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)}, volume = {78}, number = {}, pages = {127165}, doi = {10.1016/j.jtemb.2023.127165}, pmid = {37018859}, issn = {1878-3252}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/cerebrospinal fluid ; Lead ; *Selenium ; Serum ; *Neurodegenerative Diseases ; Nails ; Cross-Sectional Studies ; Plasma ; Hair ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with progressive muscle wasting, paralysis, and respiratory failure. Whereas approximately 10-15 % of ALS cases are familial, the etiology of the remaining, sporadic ALS cases remains largely unknown. Environmental exposures have been suggested as causative factors for decades, and previous studies have found elevated concentrations of metals in ALS patients.<br><br>PURPOSE: This meta-analysis aims to assess metal concentrations in body fluids and tissues of ALS patients.<br><br>METHODS: We searched the MEDLINE and EMBASE databases on December 7th, 2022 for cross-sectional, case-control, and cohort studies which measure metal concentrations in whole blood, blood plasma, blood serum, cerebrospinal fluid (CSF), urine, erythrocytes, nail, and hair samples of ALS patients. Meta-analysis was then performed when three or more articles existed for a comparison.<br><br>FINDINGS: Twenty-nine studies measuring 23 metals were included and 13 meta-analyses were performed from 4234 screened entries. The meta-analysis results showed elevated concentrations of lead and selenium. Lead, measured in whole blood in 6 studies, was significantly elevated by 2.88&#xa0;&#xb5;g/L (95 % CI: 0.83-4.93, p&#xa0;=&#xa0;0.006) and lead, measured in CSF in 4 studies, was significantly elevated by 0.21&#xa0;&#xb5;g/L (95 % CI: 0.01 - 0.41, p&#xa0;=&#xa0;0.04) in ALS patients when compared to controls. Selenium, measured in serum/plasma in 4 studies, was significantly elevated by 4.26&#xa0;&#xb5;g/L (95% CI: 0.73 - 7.79, p&#xa0;=&#xa0;0.02) when compared to controls.Analyses of other metal concentrations showed no statistically significant difference between the groups.<br><br>CONCLUSION: Lead has been discussed as a possible causative agent in ALS since 1850. Lead has been found in the spinal cord of ALS patients, and occupational exposure to lead is more common in ALS patients than in controls. Selenium in the form of neurotoxic selenite has been shown to geochemically correlate to ALS occurrence in Italy. Although no causal relationship can be established from the results of this meta-analysis, the findings suggest an involvement of lead and selenium in the pathophysiology of ALS. After a thorough meta-analysis of published studies on metal concentrations in ALS it can only be concluded that lead and selenium are elevated in ALS.}, }
@article {pmid37016529, year = {2024}, author = {Adam, H and Gopinath, SCB and Arshad, MKM and Adam, T and Subramaniam, S and Hashim, U}, title = {An Update on Parkinson's Disease and its Neurodegenerative Counterparts.}, journal = {Current medicinal chemistry}, volume = {31}, number = {19}, pages = {2770-2787}, pmid = {37016529}, issn = {1875-533X}, mesh = {Humans ; *Parkinson Disease/metabolism/pathology/diagnosis ; Neurodegenerative Diseases/metabolism/pathology ; alpha-Synuclein/metabolism ; Multiple System Atrophy/metabolism/diagnosis/pathology ; Animals ; }, abstract = {INTRODUCTION: Neurodegenerative disorders are a group of diseases that cause nerve cell degeneration in the brain, resulting in a variety of symptoms and are not treatable with drugs. Parkinson's disease (PD), prion disease, motor neuron disease (MND), Huntington's disease (HD), spinal cerebral dyskinesia (SCA), spinal muscle atrophy (SMA), multiple system atrophy, Alzheimer's disease (AD), spinocerebellar ataxia (SCA) (ALS), pantothenate kinase-related neurodegeneration, and TDP-43 protein disorder are examples of neurodegenerative diseases. Dementia is caused by the loss of brain and spinal cord nerve cells in neurodegenerative diseases.<br><br>BACKGROUND: Even though environmental and genetic predispositions have also been involved in the process, redox metal abuse plays a crucial role in neurodegeneration since the preponderance of symptoms originates from abnormal metal metabolism.<br><br>METHOD: Hence, this review investigates several neurodegenerative diseases that may occur symptoms similar to Parkinson's disease to understand the differences and similarities between Parkinson's disease and other neurodegenerative disorders based on reviewing previously published papers.<br><br>RESULTS: Based on the findings, the aggregation of alpha-synuclein occurs in Parkinson's disease, multiple system atrophy, and dementia with Lewy bodies. Other neurodegenerative diseases occur with different protein aggregation or mutations.<br><br>CONCLUSION: We can conclude that Parkinson's disease, Multiple system atrophy, and Dementia with Lewy bodies are closely related. Therefore, researchers must distinguish among the three diseases to avoid misdiagnosis of Multiple System Atrophy and Dementia with Lewy bodies with Parkinson's disease symptoms.}, }
@article {pmid37015866, year = {2023}, author = {Favron-Godbout, C and Racine, E}, title = {[Not Available].}, journal = {Journal international de bioethique et d'ethique des sciences}, volume = {33}, number = {3}, pages = {95-128}, doi = {10.3917/jibes.333.0095}, pmid = {37015866}, issn = {2608-1008}, mesh = {Humans ; *Suicide, Assisted ; *Amyotrophic Lateral Sclerosis ; *Neurodegenerative Diseases ; Morals ; Medical Assistance ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease that leads some people with the disease to consider medical assistance in dying (MAiD). In this article, we describe how a variety of moral problems can emerge from this particular context and affect the well-being of people with ALS, their loved ones, and their caregivers. As MAiD is framed by specific eligibility criteria, broadening its eligibility is often proposed to address these issues. This critical review of the literature aims to identify moral issues relating to ALS that may persist or arise in the event of such widening. The MEDLINE, EMBASE CINAHL and Web of Science databases were searched using 4 search combinations to capture insights from existing literature on ethics, MAiD and ALS (N=41). A thematic content analysis highlighted 3 contextual categories where moral issues emerge (the experience of the disease, the choice of how to die, and the implementation of MAiD). Two important observations are discussed: 1) there are differences in perspective between stakeholders, which can lead to disagreement, but some similarities of perspective also exist; 2) the widening of MAiD eligibility mainly concerns moral issues related to the choice of how to die, and thus constitutes a partial solution to the problems identified.}, }
@article {pmid37014255, year = {2023}, author = {Ravaria, P and Saxena, P and Laksmi Bs, S and Ranjan, V and Abidi, SWF and Saha, P and Ramamoorthy, S and Ahmad, F and Rana, SS}, title = {Molecular mechanisms of neuroprotective offerings by rosmarinic acid against neurodegenerative and other CNS pathologies.}, journal = {Phytotherapy research : PTR}, volume = {37}, number = {5}, pages = {2119-2143}, doi = {10.1002/ptr.7825}, pmid = {37014255}, issn = {1099-1573}, support = {VIT SEED Grant - RGEMS Fund (Sanction Order No. SG20220054)//Vellore Institute of Technology, Vellore/ ; }, mesh = {Animals ; *Neurodegenerative Diseases/drug therapy ; *Alzheimer Disease/drug therapy ; Neuroprotection ; Cinnamates/pharmacology/therapeutic use/metabolism ; *Neuroprotective Agents/pharmacology/therapeutic use ; Rosmarinic Acid ; }, abstract = {Rosmarinic acid (RA) is a natural phenolic compound present in culinary herbs of the Boraginaceae, Lamiaceae/Labiatae, and Nepetoideae families. While the medicinal applications of these plants have been known for ages, RA has only been relatively recently established as an effective ameliorative agent against various disorders including cardiac diseases, cancer, and neuropathologies. In particular, several studies have confirmed the neuroprotective potential of RA in multiple cellular and animal models, as well as in clinical studies. The neuroprotective effects mediated by RA stem from its multimodal actions on a plethora of cellular and molecular pathways; including oxidative, bioenergetic, neuroinflammatory, and synaptic signaling. In recent years, RA has garnered tremendous interest as an ideal therapeutic candidate for treating neurodegenerative diseases. This review first briefly discusses the pharmacokinetics of RA and then proceeds to detail the neuroprotective mechanisms of RA at the molecular levels. Finally, the authors focus on the ameliorative potential of RA against several central nervous system (CNS) disorders, ranging from neuropsychological stress and epilepsy to neurodegenerative diseases such as Alzheimer's disease, Huntington's disease, Parkinson's disease, Lewy body dementia, and amyotrophic lateral sclerosis.}, }
@article {pmid37009800, year = {2023}, author = {Choi, HJ and Lee, JY and Kim, K}, title = {Glutathionylation on RNA-binding proteins: a regulator of liquid‒liquid phase separation in the pathogenesis of amyotrophic lateral sclerosis.}, journal = {Experimental &amp; molecular medicine}, volume = {55}, number = {4}, pages = {735-744}, pmid = {37009800}, issn = {2092-6413}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; RNA-Binding Proteins/genetics/metabolism ; Protein Processing, Post-Translational ; *Neurodegenerative Diseases ; Protein Aggregates ; }, abstract = {RNA-binding proteins (RBPs) containing low-sequence complexity domains mediate the formation of cellular condensates and membrane-less organelles with biological functions via liquid‒liquid phase separation (LLPS). However, the abnormal phase transition of these proteins induces the formation of insoluble aggregates. Aggregates are pathological hallmarks of neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS). The molecular mechanisms underlying aggregate formation by ALS-associated RPBs remain largely unknown. This review highlights emerging studies on various posttranslational modifications (PTMs) related to protein aggregation. We begin with the introduction of several ALS-associated RBPs that form aggregates induced by phase separation. In addition, we highlight our recent discovery of a new PTM involved in the phase transition during the pathogenesis of fused-in-sarcoma (FUS)-associated ALS. We suggest a molecular mechanism through which LLPS mediates glutathionylation in FUS-linked ALS. This review aims to provide a detailed overview of the key molecular mechanisms of LLPS-mediated aggregate formation by PTMs, which will help further the understanding of the pathogenesis and development of ALS therapeutics.}, }
@article {pmid37006471, year = {2023}, author = {Diab, R and Pilotto, F and Saxena, S}, title = {Autophagy and neurodegeneration: Unraveling the role of C9ORF72 in the regulation of autophagy and its relationship to ALS-FTD pathology.}, journal = {Frontiers in cellular neuroscience}, volume = {17}, number = {}, pages = {1086895}, pmid = {37006471}, issn = {1662-5102}, abstract = {The proper functioning of the cell clearance machinery is critical for neuronal health within the central nervous system (CNS). In normal physiological conditions, the cell clearance machinery is actively involved in the elimination of misfolded and toxic proteins throughout the lifetime of an organism. The highly conserved and regulated pathway of autophagy is one of the important processes involved in preventing and neutralizing pathogenic buildup of toxic proteins that could eventually lead to the development of neurodegenerative diseases (NDs) such as Alzheimer's disease or Amyotrophic lateral sclerosis (ALS). The most common genetic cause of ALS and frontotemporal dementia (FTD) is a hexanucleotide expansion consisting of GGGGCC (G4C2) repeats in the chromosome 9 open reading frame 72 gene (C9ORF72). These abnormally expanded repeats have been implicated in leading to three main modes of disease pathology: loss of function of the C9ORF72 protein, the generation of RNA foci, and the production of dipeptide repeat proteins (DPRs). In this review, we discuss the normal physiological role of C9ORF72 in the autophagy-lysosome pathway (ALP), and present recent research deciphering how dysfunction of the ALP synergizes with C9ORF72 haploinsufficiency, which together with the gain of toxic mechanisms involving hexanucleotide repeat expansions and DPRs, drive the disease process. This review delves further into the interactions of C9ORF72 with RAB proteins involved in endosomal/lysosomal trafficking, and their role in regulating various steps in autophagy and lysosomal pathways. Lastly, the review aims to provide a framework for further investigations of neuronal autophagy in C9ORF72-linked ALS-FTD as well as other neurodegenerative diseases.}, }
@article {pmid37005761, year = {2023}, author = {Dahlmanns, M and Dahlmanns, JK and Savaskan, N and Steiner, HH and Yakubov, E}, title = {Glial Glutamate Transporter-Mediated Plasticity: System xc[-]/xCT/SLC7A11 and EAAT1/2 in Brain Diseases.}, journal = {Frontiers in bioscience (Landmark edition)}, volume = {28}, number = {3}, pages = {57}, doi = {10.31083/j.fbl2803057}, pmid = {37005761}, issn = {2768-6698}, mesh = {Humans ; Amino Acid Transport System X-AG ; *Amyotrophic Lateral Sclerosis ; Cystine/metabolism ; *Parkinson Disease ; *Alzheimer Disease ; Antioxidants ; Glutamic Acid/metabolism ; Microglia/metabolism ; *Multiple Sclerosis ; *Glioma ; Amino Acid Transport System y+/genetics/metabolism ; }, abstract = {Glial cells play an essential role in the complex function of the nervous system. In particular, astrocytes provide nutritive support for neuronal cells and are involved in regulating synaptic transmission. Oligodendrocytes ensheath axons and support information transfer over long distances. Microglial cells constitute part of the innate immune system in the brain. Glial cells are equipped with the glutamate-cystine-exchanger xCT (SLC7A11), the catalytic subunit of system xc-, and the excitatory amino acid transporter 1 (EAAT1, GLAST) and EAAT2 (GLT-1). Thereby, glial cells maintain balanced extracellular glutamate levels that enable synaptic transmission and prevent excitotoxic states. Expression levels of these transporters, however, are not fixed. Instead, expression of glial glutamate transporters are highly regulated in reaction to the external situations. Interestingly, such regulation and homeostasis is lost in diseases such as glioma, (tumor-associated) epilepsy, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis or multiple sclerosis. Upregulation of system xc- (xCT or SLC7A11) increases glutamate export from the cell, while a downregulation of EAATs decreases intracellular glutamate import. Occurring simultaneously, these reactions entail excitotoxicity and thus harm neuronal function. The release of glutamate via the antiporter system xc- is accompanied by the import of cystine-an amino acid essential in the antioxidant glutathione. This homeostasis between excitotoxicity and intracellular antioxidant response is plastic and off-balance in central nervous system (CNS) diseases. System xc- is highly expressed on glioma cells and sensitizes them to ferroptotic cell death. Hence, system xc- is a potential target for chemotherapeutic add-on therapy. Recent research reveals a pivotal role of system xc- and EAAT1/2 in tumor-associated and other types of epilepsy. Numerous studies show that in Alzheimer's disease, amyotrophic lateral sclerosis and Parkinson's disease, these glutamate transporters are dysregulated-and disease mechanisms could be interposed by targeting system xc- and EAAT1/2. Interestingly, in neuroinflammatory diseases such as multiple sclerosis, there is growing evidence for glutamate transporter involvement. Here, we propose that the current knowledge strongly suggest a benefit from rebalancing glial transporters during treatment.}, }
@article {pmid37004595, year = {2023}, author = {Liu, Y}, title = {Zebrafish as a Model Organism for Studying Pathologic Mechanisms of Neurodegenerative Diseases and other Neural Disorders.}, journal = {Cellular and molecular neurobiology}, volume = {43}, number = {6}, pages = {2603-2620}, pmid = {37004595}, issn = {1573-6830}, support = {ZR2022MC192//Shandong Provincial Natural Science Foundation/ ; 2021boshi01//the Doctoral Research Startup Funding from Qingdao Huanghai University , China/ ; hhxyjg2021//the School Teaching Reform Project of Qingdao Huanghai University, China/ ; }, mesh = {Animals ; Humans ; *Neurodegenerative Diseases/genetics/pathology ; Zebrafish/genetics ; }, abstract = {Zebrafish are widely considered an excellent vertebrate model for studying the pathogenesis of human diseases because of their transparency of embryonic development, easy breeding, high similarity with human genes, and easy gene manipulation. Previous studies have shown that zebrafish as a model organism provides an ideal operating platform for clarifying the pathological and molecular mechanisms of neurodegenerative diseases and related human diseases. This review mainly summarizes the achievements and prospects of zebrafish used as model organisms in the research of neurodegenerative diseases and other human diseases related to the nervous system in recent years. In the future study of human disease mechanisms, the application of the zebrafish model will continue to provide a valuable operating platform and technical support for investigating and finding better prevention and treatment of these diseases, which has broad application prospects and practical significance. Zebrafish models used in neurodegenerative diseases and other diseases related to the nervous system.}, }
@article {pmid37004330, year = {2023}, author = {Wei, X and Huang, G and Liu, J and Ge, J and Zhang, W and Mei, Z}, title = {An update on the role of Hippo signaling pathway in ischemia-associated central nervous system diseases.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {162}, number = {}, pages = {114619}, doi = {10.1016/j.biopha.2023.114619}, pmid = {37004330}, issn = {1950-6007}, mesh = {Humans ; Hippo Signaling Pathway ; *Brain Ischemia/metabolism ; Blood-Brain Barrier/metabolism ; *Parkinson Disease ; *Alzheimer Disease ; Ischemia ; *Ischemic Stroke ; }, abstract = {The most frequent reason of morbidity and mortality in the world, cerebral ischemia sets off a chain of molecular and cellular pathologies that associated with some central nervous system (CNS) disorders mainly including ischemic stroke, Alzheimer's disease (AD), Parkinson's disease (PD), epilepsy and other CNS diseases. In recent times, despite significant advancements in the treatment of the pathological processes underlying various neurological illnesses, effective therapeutic approaches that are specifically targeted to minimizing the damage of such diseases remain absent. Hippo signaling pathway, characterized by enzyme linked reactions between MSTI/2, LAST1/2, and YAP or TAZ proteins, controls cell division, survival, and differentiation, as well as being engaged in a variety of biological activities, such as the development and transformation of the nervous system. Recently, accumulating studies demonstrated that Hippo pathway takes part in the processes of ischemic stroke, AD, PD, etc., including but not limited to oxidative stress, inflammatory response, blood-brain barrier damage, mitochondrial disorders, and neural cells death. Thus, it's crucial to understand the molecular basis of the Hippo signaling pathway for determining potential new therapeutic targets against ischemia-associated CNS diseases. Here, we discuss latest advances in the deciphering of the Hippo signaling pathway and highlight the therapeutic potential of targeting the pathway in treating ischemia-associated CNS diseases.}, }
@article {pmid37002507, year = {2023}, author = {Arora, S and Brakey, HR and Jones, JL and Hood, N and Fuentes, JE and Cirolia, L}, title = {Project ECHO for Cancer Care: a Scoping Review of Provider Outcome Evaluations.}, journal = {Journal of cancer education : the official journal of the American Association for Cancer Education}, volume = {38}, number = {5}, pages = {1509-1521}, pmid = {37002507}, issn = {1543-0154}, support = {UL1 TR001449/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; *Outcome Assessment, Health Care ; Education, Medical, Continuing ; Data Collection ; *Neoplasms/diagnostic imaging/therapy ; }, abstract = {The Project ECHO model of telementoring has been used for the past 10 years to expand access to specialized cancer care. This scoping review identifies evidence for the model's ability to improve provider outcomes, synthesizing findings from existing studies within Moore et al.'s (2009) framework for continuing medical education outcomes. We search two large research databases and a collection maintained by Project ECHO staff for articles that focus on cancer ECHO programs, involve primary data collection, and were published between December 1, 2016, and November 30, 2021. We identified 25 articles for inclusion in our scoping review. Most articles reported results for outcomes related to program participation: attendance, satisfaction, and learning. Yet, just under half reported changes in provider practices. Results demonstrate widespread participation and improved learning resulting from ECHO programs focused on cancer care. There is also evidence of improved practices related to HCV vaccination and palliative care. We highlight examples of best practices as well as opportunities to improve provider outcome evaluations for cancer ECHO programs.}, }
@article {pmid36998129, year = {2023}, author = {Khaafi, F and Javadi, B}, title = {Molecular Targets Underlying the Neuroprotective Effects of Boswellic Acid: A Systematic Review.}, journal = {Mini reviews in medicinal chemistry}, volume = {23}, number = {19}, pages = {1912-1925}, doi = {10.2174/1389557523666230330113611}, pmid = {36998129}, issn = {1875-5607}, mesh = {Humans ; *Neuroprotective Agents/pharmacology/therapeutic use ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Alzheimer Disease/drug therapy ; *Parkinson Disease/drug therapy ; }, abstract = {BACKGROUND: Neurodegenerative procedures include a large spectrum of disorders with diverse pathological features and clinical manifestations, such as Alzheimer's Disease (AD), Parkinson's disease (PD), Multiple sclerosis, and Amyotrophic lateral sclerosis (ALS). Neurodegenerative diseases (NDs) are indicated by progressive loss of neurons and cognitive function, which is associated with free radical formation, extra and intercellular accumulation of misfolded proteins, oxidative stress, mitochondrial and neurotrophins dysfunction, bioenergetic impairment, inflammation, and apoptotic cell death. Boswellic acid is a pentacyclic triterpene molecule of plant origin that has been applied for treating several inflammatory disorders. Numerous studies have also investigated its' therapeutic potential against multiple NDs.<br><br>OBJECTIVE: In this article, we aim to review the neuroprotective effects of boswellic acid on NDs and the related mechanisms of action.<br><br>METHODS: The databases of PubMed, Google Scholar, Web of Sciences, and Scopus were searched to find studies that reported the effects of boswellic acid on NDs without time limits. Review articles, letters, editorials, unpublished data, and articles not published in the English language were not included in the study.<br><br>RESULTS: Overall, 17 studies were included in the present study (8 NDs in general, 5 AD, 3 PD, and 1 ALS). According to the reports, boswellic acid exerts anti-inflammatory, antioxidant, antiapoptotic, and neuromodulatory effects against NDs. Boswellic acid decreases Tau phosphorylation and amyloid-&#x3b2; (A&#x3b2;) generation in AD. This substance also protects nigrostriatal dopaminergic neurons and improves motor impairments in PD and modulates neurotransmitters, decreases the demyelination region, and improves behavioral functions in ALS.<br><br>CONCLUSION: Due to the significant effects of boswellic acid in NDs, more clinical studies are necessary to evaluate the pharmacokinetics of this substance because it seems that boswellic acid can be used as a complementary or alternative treatment in patients with NDs.}, }
@article {pmid36998125, year = {2024}, author = {De Marchi, F and Venkatesan, S and Saraceno, M and Mazzini, L and Grossini, E}, title = {Acetyl-L-carnitine and Amyotrophic Lateral Sclerosis: Current Evidence and Potential use.}, journal = {CNS &amp; neurological disorders drug targets}, volume = {23}, number = {5}, pages = {588-601}, pmid = {36998125}, issn = {1996-3181}, support = {//Universit&#xe0; degli Studi del Piemonte Orientale/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/metabolism ; *Acetylcarnitine/therapeutic use/pharmacology ; *Oxidative Stress/drug effects ; Mitochondria/drug effects/metabolism ; Animals ; }, abstract = {BACKGROUND: The management of neurodegenerative diseases can be frustrating for clinicians, given the limited progress of conventional medicine in this context.<br><br>AIM: For this reason, a more comprehensive, integrative approach is urgently needed. Among various emerging focuses for intervention, the modulation of central nervous system energetics, oxidative stress, and inflammation is becoming more and more promising.<br><br>METHODS: In particular, electrons leakage involved in the mitochondrial energetics can generate reactive oxygen-free radical-related mitochondrial dysfunction that would contribute to the etiopathology of many disorders, such as Alzheimer's and other dementias, Parkinson's disease, multiple sclerosis, stroke, and amyotrophic lateral sclerosis (ALS).<br><br>RESULTS: In this context, using agents, like acetyl L-carnitine (ALCAR), provides mitochondrial support, reduces oxidative stress, and improves synaptic transmission.<br><br>CONCLUSION: This narrative review aims to update the existing literature on ALCAR molecular profile, tolerability, and translational clinical potential use in neurodegeneration, focusing on ALS.}, }
@article {pmid36997360, year = {2023}, author = {Favron-Godbout, C and Racine, E}, title = {[Not Available].}, journal = {Journal international de bioethique et d'ethique des sciences}, volume = {33}, number = {3}, pages = {95-128}, doi = {10.54695/jibes.333.0095}, pmid = {36997360}, issn = {2608-1008}, mesh = {Humans ; *Suicide, Assisted ; *Amyotrophic Lateral Sclerosis ; *Neurodegenerative Diseases ; Morals ; Medical Assistance ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease that leads some people with the disease to consider medical assistance in dying (MAiD). In this article, we describe how a variety of moral problems can emerge from this particular context and affect the well-being of people with ALS, their loved ones, and their caregivers. As MAiD is framed by specific eligibility criteria, broadening its eligibility is often proposed to address these issues. This critical review of the literature aims to identify moral issues relating to ALS that may persist or arise in the event of such widening. The MEDLINE, EMBASE CINAHL and Web of Science databases were searched using 4 search combinations to capture insights from existing literature on ethics, MAiD and ALS (N=41). A thematic content analysis highlighted 3 contextual categories where moral issues emerge (the experience of the disease, the choice of how to die, and the implementation of MAiD). Two important observations are discussed: 1) there are differences in perspective between stakeholders, which can lead to disagreement, but some similarities of perspective also exist; 2) the widening of MAiD eligibility mainly concerns moral issues related to the choice of how to die, and thus constitutes a partial solution to the problems identified.}, }
@article {pmid36991279, year = {2023}, author = {Mueller, S and Decker, L and Menge, S and Ludolph, AC and Freischmidt, A}, title = {The Fragile X Protein Family in Amyotrophic Lateral Sclerosis.}, journal = {Molecular neurobiology}, volume = {60}, number = {7}, pages = {3898-3910}, pmid = {36991279}, issn = {1559-1182}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; *Neurodegenerative Diseases/genetics ; RNA-Binding Proteins/genetics ; Motor Neurons/metabolism ; DNA Damage ; RNA-Binding Protein FUS/genetics ; Fragile X Mental Retardation Protein/genetics ; }, abstract = {The fragile X protein (FXP) family comprises the multifunctional RNA-binding proteins FMR1, FXR1, and FXR2 that play an important role in RNA metabolism and regulation of translation, but also in DNA damage and cellular stress responses, mitochondrial organization, and more. FMR1 is well known for its implication in neurodevelopmental diseases. Recent evidence suggests substantial contribution of this protein family to amyotrophic lateral sclerosis (ALS) pathogenesis. ALS is a highly heterogeneous neurodegenerative disease with multiple genetic and unclear environmental causes and very limited treatment options. The loss of motoneurons in ALS is still poorly understood, especially because pathogenic mechanisms are often restricted to patients with mutations in specific causative genes. Identification of converging disease mechanisms evident in most patients and suitable for therapeutic intervention is therefore of high importance. Recently, deregulation of the FXPs has been linked to pathogenic processes in different types of ALS. Strikingly, in many cases, available data points towards loss of expression and/or function of the FXPs early in the disease, or even at the presymptomatic state. In this review, we briefly introduce the FXPs and summarize available data about these proteins in ALS. This includes their relation to TDP-43, FUS, and ALS-related miRNAs, as well as their possible contribution to pathogenic protein aggregation and defective RNA editing. Furthermore, open questions that need to be addressed before definitively judging suitability of these proteins as novel therapeutic targets are discussed.}, }
@article {pmid36990317, year = {2023}, author = {Heo, AJ and Kim, SB and Kwon, YT and Ji, CH}, title = {The N-degron pathway: From basic science to therapeutic applications.}, journal = {Biochimica et biophysica acta. Gene regulatory mechanisms}, volume = {1866}, number = {2}, pages = {194934}, doi = {10.1016/j.bbagrm.2023.194934}, pmid = {36990317}, issn = {1876-4320}, mesh = {Humans ; *Amino Acids/metabolism ; Autophagy ; Proteasome Endopeptidase Complex/metabolism ; *Proteolysis ; Ubiquitin/metabolism ; }, abstract = {The N-degron pathway is a degradative system in which single N-terminal (Nt) amino acids regulate the half-lives of proteins and other biological materials. These determinants, called N-degrons, are recognized by N-recognins that link them to the ubiquitin (Ub)-proteasome system (UPS) or autophagy-lysosome system (ALS). In the UPS, the Arg/N-degron pathway targets the Nt-arginine (Nt-Arg) and other N-degrons to assemble Lys48 (K48)-linked Ub chains by UBR box N-recognins for proteasomal proteolysis. In the ALS, Arg/N-degrons are recognized by the N-recognin p62/SQSTSM-1/Sequestosome-1 to induce cis-degradation of substrates and trans-degradation of various cargoes such as protein aggregates and subcellular organelles. This crosstalk between the UPS and ALP involves reprogramming of the Ub code. Eukaryotic cells developed diverse ways to target all 20 principal amino acids for degradation. Here we discuss the components, regulation, and functions of the N-degron pathways, with an emphasis on the basic mechanisms and therapeutic applications of Arg/N-degrons and N-recognins.}, }
@article {pmid36982324, year = {2023}, author = {Panizzutti, B and Skvarc, D and Lin, S and Croce, S and Meehan, A and Bortolasci, CC and Marx, W and Walker, AJ and Hasebe, K and Kavanagh, BE and Morris, MJ and Mohebbi, M and Turner, A and Gray, L and Berk, L and Walder, K and Berk, M and Dean, OM}, title = {Minocycline as Treatment for Psychiatric and Neurological Conditions: A Systematic Review and Meta-Analysis.}, journal = {International journal of molecular sciences}, volume = {24}, number = {6}, pages = {}, pmid = {36982324}, issn = {1422-0067}, mesh = {Humans ; Minocycline/therapeutic use ; *Schizophrenia/drug therapy ; *Bipolar Disorder/drug therapy ; *Obsessive-Compulsive Disorder ; Anti-Inflammatory Agents/therapeutic use ; }, abstract = {Minocycline has anti-inflammatory, antioxidant, and anti-apoptotic properties that explain the renewed interest in its use as an adjunctive treatment for psychiatric and neurological conditions. Following the completion of several new clinical trials using minocycline, we proposed an up-to-date systematic review and meta-analysis of the data available. The PICO (patient/population, intervention, comparison and outcomes) framework was used to search 5 databases aiming to identify randomized controlled trials that used minocycline as an adjunctive treatment for psychiatric and neurological conditions. Search results, data extraction, and risk of bias were performed by two independent authors for each publication. Quantitative meta-analysis was performed using RevMan software. Literature search and review resulted in 32 studies being included in this review: 10 in schizophrenia, 3 studies in depression, and 7 in stroke, with the benefit of minocycline being used in some of the core symptoms evaluated; 2 in bipolar disorder and 2 in substance use, without demonstrating a benefit for using minocycline; 1 in obsessive-compulsive disorder, 2 in brain and spinal injuries, 2 in amyotrophic lateral sclerosis, 1 in Alzheimer's disease, 1 in multiple systems atrophy, and 1 in pain, with mixes results. For most of the conditions included in this review the data is still limited and difficult to interpret, warranting more well-designed and powered studies. On the other hand, the studies available for schizophrenia seem to suggest an overall benefit favoring the use of minocycline as an adjunctive treatment.}, }
@article {pmid36982315, year = {2023}, author = {Balbi, M and Bonanno, G and Bonifacino, T and Milanese, M}, title = {The Physio-Pathological Role of Group I Metabotropic Glutamate Receptors Expressed by Microglia in Health and Disease with a Focus on Amyotrophic Lateral Sclerosis.}, journal = {International journal of molecular sciences}, volume = {24}, number = {6}, pages = {}, pmid = {36982315}, issn = {1422-0067}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; Microglia/metabolism ; Neurons/metabolism ; *Receptors, Metabotropic Glutamate/metabolism ; }, abstract = {Microglia cells are the resident immune cells of the central nervous system. They act as the first-line immune guardians of nervous tissue and central drivers of neuroinflammation. Any homeostatic alteration that can compromise neuron and tissue integrity could activate microglia. Once activated, microglia exhibit highly diverse phenotypes and functions related to either beneficial or harmful consequences. Microglia activation is associated with the release of protective or deleterious cytokines, chemokines, and growth factors that can in turn determine defensive or pathological outcomes. This scenario is complicated by the pathology-related specific phenotypes that microglia can assume, thus leading to the so-called disease-associated microglia phenotypes. Microglia express several receptors that regulate the balance between pro- and anti-inflammatory features, sometimes exerting opposite actions on microglial functions according to specific conditions. In this context, group I metabotropic glutamate receptors (mGluRs) are molecular structures that may contribute to the modulation of the reactive phenotype of microglia cells, and this is worthy of exploration. Here, we summarize the role of group I mGluRs in shaping microglia cells' phenotype in specific physio-pathological conditions, including some neurodegenerative disorders. A significant section of the review is specifically focused on amyotrophic lateral sclerosis (ALS) since it represents an entirely unexplored topic of research in the field.}, }
@article {pmid36980310, year = {2023}, author = {Du, H and Huo, Z and Chen, Y and Zhao, Z and Meng, F and Wang, X and Liu, S and Zhang, H and Zhou, F and Liu, J and Zhang, L and Zhou, S and Guan, Y and Wang, X}, title = {Induced Pluripotent Stem Cells and Their Applications in Amyotrophic Lateral Sclerosis.}, journal = {Cells}, volume = {12}, number = {6}, pages = {}, pmid = {36980310}, issn = {2073-4409}, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/genetics/therapy/metabolism ; *Induced Pluripotent Stem Cells/metabolism ; *Neurodegenerative Diseases/metabolism ; Neurons/metabolism ; Cell- and Tissue-Based Therapy ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that results in the loss of motor function in the central nervous system (CNS) and ultimately death. The mechanisms underlying ALS pathogenesis have not yet been fully elucidated, and ALS cannot be treated effectively. Most studies have applied animal or single-gene intervention cell lines as ALS disease models, but they cannot accurately reflect the pathological characteristics of ALS. Induced pluripotent stem cells (iPSCs) can be reprogrammed from somatic cells, possessing the ability to self-renew and differentiate into a variety of cells. iPSCs can be obtained from ALS patients with different genotypes and phenotypes, and the genetic background of the donor cells remains unchanged during reprogramming. iPSCs can differentiate into neurons and glial cells related to ALS. Therefore, iPSCs provide an excellent method to evaluate the impact of diseases on ALS patients. Moreover, patient-derived iPSCs are obtained from their own somatic cells, avoiding ethical concerns and posing only a low risk of immune rejection. The iPSC technology creates new hope for ALS treatment. Here, we review recent studies on iPSCs and their applications in disease modeling, drug screening and cell therapy in ALS, with a particular focus on the potential for ALS treatment.}, }
@article {pmid36980297, year = {2023}, author = {Schreiber, S and Bernal, J and Arndt, P and Schreiber, F and Müller, P and Morton, L and Braun-Dullaeus, RC and Valdés-Hernández, MDC and Duarte, R and Wardlaw, JM and Meuth, SG and Mietzner, G and Vielhaber, S and Dunay, IR and Dityatev, A and Jandke, S and Mattern, H}, title = {Brain Vascular Health in ALS Is Mediated through Motor Cortex Microvascular Integrity.}, journal = {Cells}, volume = {12}, number = {6}, pages = {}, pmid = {36980297}, issn = {2073-4409}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; *Motor Cortex/metabolism ; Vascular Endothelial Growth Factor A/metabolism ; Motor Neurons/pathology ; Blood-Brain Barrier/pathology ; }, abstract = {Brain vascular health appears to be critical for preventing the development of amyotrophic lateral sclerosis (ALS) and slowing its progression. ALS patients often demonstrate cardiovascular risk factors and commonly suffer from cerebrovascular disease, with evidence of pathological alterations in their small cerebral blood vessels. Impaired vascular brain health has detrimental effects on motor neurons: vascular endothelial growth factor levels are lowered in ALS, which can compromise endothelial cell formation and the integrity of the blood-brain barrier. Increased turnover of neurovascular unit cells precedes their senescence, which, together with pericyte alterations, further fosters the failure of toxic metabolite removal. We here provide a comprehensive overview of the pathogenesis of impaired brain vascular health in ALS and how novel magnetic resonance imaging techniques can aid its detection. In particular, we discuss vascular patterns of blood supply to the motor cortex with the number of branches from the anterior and middle cerebral arteries acting as a novel marker of resistance and resilience against downstream effects of vascular risk and events in ALS. We outline how certain interventions adapted to patient needs and capabilities have the potential to mechanistically target the brain microvasculature towards favorable motor cortex blood supply patterns. Through this strategy, we aim to guide novel approaches to ALS management and a better understanding of ALS pathophysiology.}, }
@article {pmid36980167, year = {2023}, author = {Figueiredo, AS and Loureiro, JR and Macedo-Ribeiro, S and Silveira, I}, title = {Advances in Nucleotide Repeat Expansion Diseases: Transcription Gets in Phase.}, journal = {Cells}, volume = {12}, number = {6}, pages = {}, pmid = {36980167}, issn = {2073-4409}, mesh = {Humans ; *DNA Repeat Expansion/genetics ; Mutation ; Proteins/genetics ; *Neuromuscular Diseases/genetics ; RNA/genetics ; Nucleotides ; }, abstract = {Unstable DNA repeat expansions and insertions have been found to cause more than 50 neurodevelopmental, neurodegenerative, and neuromuscular disorders. One of the main hallmarks of repeat expansion diseases is the formation of abnormal RNA or protein aggregates in the neuronal cells of affected individuals. Recent evidence indicates that alterations of the dynamic or material properties of biomolecular condensates assembled by liquid/liquid phase separation are critical for the formation of these aggregates. This is a thermodynamically-driven and reversible local phenomenon that condenses macromolecules into liquid-like compartments responsible for compartmentalizing molecules required for vital cellular processes. Disease-associated repeat expansions modulate the phase separation properties of RNAs and proteins, interfering with the composition and/or the material properties of biomolecular condensates and resulting in the formation of abnormal aggregates. Since several repeat expansions have arisen in genes encoding crucial players in transcription, this raises the hypothesis that wide gene expression dysregulation is common to multiple repeat expansion diseases. This review will cover the impact of these mutations in the formation of aberrant aggregates and how they modify gene transcription.}, }
@article {pmid36979898, year = {2023}, author = {Monroy, GR and Murguiondo Pérez, R and Weintraub Ben Zión, E and Vidal Alcántar-Garibay, O and Loza-López, EC and Tejerina Marion, E and Blancarte Hernández, E and Navarro-Torres, L and Ibarra, A}, title = {Immunization with Neural-Derived Peptides in Neurodegenerative Diseases: A Narrative Review.}, journal = {Biomedicines}, volume = {11}, number = {3}, pages = {}, pmid = {36979898}, issn = {2227-9059}, abstract = {Neurodegenerative diseases (NDDs) are a major health problem worldwide. Statistics suggest that in America in 2030 there will be more than 12 million people suffering from a neurodegenerative pathology. Furthermore, the increase in life expectancy enhances the importance of finding new and better therapies for these pathologies. NDDs could be classified into chronic or acute, depending on the time required for the development of clinical symptoms and brain degeneration. Nevertheless, both chronic and acute stages share a common immune and inflammatory pathway in their pathophysiology. Immunization with neural-derived peptides (INDP) is a novel therapy that has been studied during the last decade. By inoculating neural-derived peptides obtained from the central nervous system (CNS), this therapy aims to boost protective autoimmunity, an autoreactive response that leads to a protective phenotype that produces a healing environment and neuroregeneration instead of causing damage. INDP has shown promising findings in studies performed either in vitro, in vivo or even in some pre-clinical trials of different NDDs, standing as a potentially beneficial therapy. In this review, we will describe some of the studies in which the effect of INDP strategies have been explored in different (chronic and acute) neurodegenerative diseases.}, }
@article {pmid36979413, year = {2023}, author = {Roussos, A and Kitopoulou, K and Borbolis, F and Palikaras, K}, title = {Caenorhabditis elegans as a Model System to Study Human Neurodegenerative Disorders.}, journal = {Biomolecules}, volume = {13}, number = {3}, pages = {}, pmid = {36979413}, issn = {2218-273X}, mesh = {Animals ; Humans ; *Caenorhabditis elegans/metabolism ; Quality of Life ; Disease Models, Animal ; *Neurodegenerative Diseases/metabolism ; }, abstract = {In recent years, advances in science and technology have improved our quality of life, enabling us to tackle diseases and increase human life expectancy. However, longevity is accompanied by an accretion in the frequency of age-related neurodegenerative diseases, creating a growing burden, with pervasive social impact for human societies. The cost of managing such chronic disorders and the lack of effective treatments highlight the need to decipher their molecular and genetic underpinnings, in order to discover new therapeutic targets. In this effort, the nematode Caenorhabditis elegans serves as a powerful tool to recapitulate several disease-related phenotypes and provides a highly malleable genetic model that allows the implementation of multidisciplinary approaches, in addition to large-scale genetic and pharmacological screens. Its anatomical transparency allows the use of co-expressed fluorescent proteins to track the progress of neurodegeneration. Moreover, the functional conservation of neuronal processes, along with the high homology between nematode and human genomes, render C. elegans extremely suitable for the study of human neurodegenerative disorders. This review describes nematode models used to study neurodegeneration and underscores their contribution in the effort to dissect the molecular basis of human diseases and identify novel gene targets with therapeutic potential.}, }
@article {pmid36979267, year = {2023}, author = {Gandla, K and Babu, AK and Unnisa, A and Sharma, I and Singh, LP and Haque, MA and Dashputre, NL and Baig, S and Siddiqui, FA and Khandaker, MU and Almujally, A and Tamam, N and Sulieman, A and Khan, SL and Emran, TB}, title = {Carotenoids: Role in Neurodegenerative Diseases Remediation.}, journal = {Brain sciences}, volume = {13}, number = {3}, pages = {}, pmid = {36979267}, issn = {2076-3425}, abstract = {Numerous factors can contribute to the development of neurodegenerative disorders (NDs), such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and multiple sclerosis. Oxidative stress (OS), a fairly common ND symptom, can be caused by more reactive oxygen species being made. In addition, the pathological state of NDs, which includes a high number of protein aggregates, could make chronic inflammation worse by activating microglia. Carotenoids, often known as "CTs", are pigments that exist naturally and play a vital role in the prevention of several brain illnesses. CTs are organic pigments with major significance in ND prevention. More than 600 CTs have been discovered in nature, and they may be found in a wide variety of creatures. Different forms of CTs are responsible for the red, yellow, and orange pigments seen in many animals and plants. Because of their unique structure, CTs exhibit a wide range of bioactive effects, such as anti-inflammatory and antioxidant effects. The preventive effects of CTs have led researchers to find a strong correlation between CT levels in the body and the avoidance and treatment of several ailments, including NDs. To further understand the connection between OS, neuroinflammation, and NDs, a literature review has been compiled. In addition, we have focused on the anti-inflammatory and antioxidant properties of CTs for the treatment and management of NDs.}, }
@article {pmid36979000, year = {2023}, author = {Iova, OM and Marin, GE and Lazar, I and Stanescu, I and Dogaru, G and Nicula, CA and Bulboacă, AE}, title = {Nitric Oxide/Nitric Oxide Synthase System in the Pathogenesis of Neurodegenerative Disorders-An Overview.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {12}, number = {3}, pages = {}, pmid = {36979000}, issn = {2076-3921}, abstract = {Nitric oxide, a ubiquitous molecule found throughout the natural world, is a key molecule implicated in many central and benefic molecular pathways and has a well-established role in the function of the central nervous system, as numerous studies have previously shown. Dysregulation of its metabolism, mainly the upregulation of nitric oxide production, has been proposed as a trigger and/or aggravator for many neurological affections. Increasing evidence supports the implication of this molecule in prevalent neurodegenerative diseases, such as Parkinson's disease, Alzheimer's disease, or amyotrophic lateral sclerosis. The mechanisms proposed for its neurotoxicity mainly center around the increased quantities of nitric oxide that are produced in the brain, their cause, and, most importantly, the pathological metabolic cascades created. These cascades lead to the formation of neuronal toxic substances that impair the neurons' function and structure on multiple levels. The purpose of this review is to present the main causes of increased pathological production, as well as the most important pathophysiological mechanisms triggered by nitric oxide, mechanisms that could help explain a part of the complex picture of neurodegenerative diseases and help develop targeted therapies.}, }
@article {pmid36977124, year = {2023}, author = {Nugumanova, G and Ponomarev, ED and Askarova, S and Fasler-Kan, E and Barteneva, NS}, title = {Freshwater Cyanobacterial Toxins, Cyanopeptides and Neurodegenerative Diseases.}, journal = {Toxins}, volume = {15}, number = {3}, pages = {}, pmid = {36977124}, issn = {2072-6651}, mesh = {Animals ; Humans ; Cyanobacteria Toxins ; *Neurodegenerative Diseases ; Ecosystem ; *Amino Acids, Diamino/metabolism ; Fresh Water/microbiology ; Amino Acids/metabolism ; *Cyanobacteria/metabolism ; Mammals ; }, abstract = {Cyanobacteria produce a wide range of structurally diverse cyanotoxins and bioactive cyanopeptides in freshwater, marine, and terrestrial ecosystems. The health significance of these metabolites, which include genotoxic- and neurotoxic agents, is confirmed by continued associations between the occurrence of animal and human acute toxic events and, in the long term, by associations between cyanobacteria and neurodegenerative diseases. Major mechanisms related to the neurotoxicity of cyanobacteria compounds include (1) blocking of key proteins and channels; (2) inhibition of essential enzymes in mammalian cells such as protein phosphatases and phosphoprotein phosphatases as well as new molecular targets such as toll-like receptors 4 and 8. One of the widely discussed implicated mechanisms includes a misincorporation of cyanobacterial non-proteogenic amino acids. Recent research provides evidence that non-proteinogenic amino acid BMAA produced by cyanobacteria have multiple effects on translation process and bypasses the proof-reading ability of the aminoacyl-tRNA-synthetase. Aberrant proteins generated by non-canonical translation may be a factor in neuronal death and neurodegeneration. We hypothesize that the production of cyanopeptides and non-canonical amino acids is a more general mechanism, leading to mistranslation, affecting protein homeostasis, and targeting mitochondria in eukaryotic cells. It can be evolutionarily ancient and initially developed to control phytoplankton communities during algal blooms. Outcompeting gut symbiotic microorganisms may lead to dysbiosis, increased gut permeability, a shift in blood-brain-barrier functionality, and eventually, mitochondrial dysfunction in high-energy demanding neurons. A better understanding of the interaction between cyanopeptides metabolism and the nervous system will be crucial to target or to prevent neurodegenerative diseases.}, }
@article {pmid36975449, year = {2023}, author = {Tsalikidis, C and Mitsala, A and Mentonis, VI and Romanidis, K and Pappas-Gogos, G and Tsaroucha, AK and Pitiakoudis, M}, title = {Predictive Factors for Anastomotic Leakage Following Colorectal Cancer Surgery: Where Are We and Where Are We Going?.}, journal = {Current oncology (Toronto, Ont.)}, volume = {30}, number = {3}, pages = {3111-3137}, pmid = {36975449}, issn = {1718-7729}, mesh = {Humans ; *Anastomotic Leak/etiology/diagnosis/epidemiology ; Anastomosis, Surgical/adverse effects ; Risk Factors ; Biomarkers ; *Colorectal Neoplasms/surgery/complications ; }, abstract = {Anastomotic leakage (AL) remains one of the most severe complications following colorectal cancer (CRC) surgery. Indeed, leaks that may occur after any type of intestinal anastomosis are commonly associated with a higher reoperation rate and an increased risk of postoperative morbidity and mortality. At first, our review aims to identify specific preoperative, intraoperative and perioperative factors that eventually lead to the development of anastomotic dehiscence based on the current literature. We will also investigate the role of several biomarkers in predicting the presence of ALs following colorectal surgery. Despite significant improvements in perioperative care, advances in surgical techniques, and a high index of suspicion of this complication, the incidence of AL remained stable during the last decades. Thus, gaining a better knowledge of the risk factors that influence the AL rates may help identify high-risk surgical patients requiring more intensive perioperative surveillance. Furthermore, prompt diagnosis of this severe complication may help improve patient survival. To date, several studies have identified predictive biomarkers of ALs, which are most commonly associated with the inflammatory response to colorectal surgery. Interestingly, early diagnosis and evaluation of the severity of this complication may offer a significant opportunity to guide clinical judgement and decision-making.}, }
@article {pmid36973580, year = {2023}, author = {Marra, JM and de Castro Vieira, PV and de Senna Migueletto, AM and de Oliveira, LFA and de Souza, ECF and Marquini, GV}, title = {Neurogenic Disorders and the Lower Urinary Tract Dysfunction: Proposed Approach for the Gynecologist.}, journal = {Reproductive sciences (Thousand Oaks, Calif.)}, volume = {30}, number = {7}, pages = {2087-2091}, pmid = {36973580}, issn = {1933-7205}, mesh = {Humans ; *Urinary Bladder ; *Urinary Bladder, Neurogenic/diagnosis/therapy/etiology ; Quality of Life ; Activities of Daily Living ; Gynecologists ; }, abstract = {BACKGROUND: The scenario of the patient with neuropathies, which are related to urinary disorders, impacts the quality of life. Symptoms can lead to social isolation, impair activities of daily living, and shorten life expectancy. This study aims to make a practical and integrative review of current recommendations for the urogynecological approach of patients with neuropathy and urinary dysfunction.<br><br>METHODS: The authors searched for data on combinations of the terms "lower urinary tract symptoms" AND "neurogenic voiding dysfunction" from January 2012 to January 2022 in the following scientific databases: PUBMED, MEDLINE, EMBASE, and The Cochrane Library.<br><br>INCLUSION CRITERIA: randomized clinical trials, protocols from specialized societies and articles before that period, and according to clinical relevance.<br><br>EXCLUSION CRITERIA: case series or reports, expert opinions not endorsed by medical societies in the area.<br><br>RESULTS: From the 25 studies mentioned, 09 studies were selected according to pre-established criteria and qualitative analysis of relevance. The authors add 2 references for relevance in the area of &#x200b;&#x200b;urogynecology and neurological diseases. According to the selected scientific references, the main neuropathies that can cause urinary dysfunction are CNS injuries such as stroke, spinal cord injury, meningomyelocele, and amyotrophic lateral sclerosis. Ten steps below were compiled to facilitate the gynecological approach, according to the researched literature.<br><br>CONCLUSION: It is important for the medical assistant to pay close attention to careful anamnesis and post-emptying urinary residual volume. The treatment in general addresses greater fluid intake, maneuvers to favor bladder emptying, medications, and/or intermittent self-catheterization. The approach of a multidisciplinary team can make a difference in the patient's prognosis and quality of life.}, }
@article {pmid36970522, year = {2023}, author = {Saucier, D and Registe, PPW and Bélanger, M and O'Connell, C}, title = {Urbanization, air pollution, and water pollution: Identification of potential environmental risk factors associated with amyotrophic lateral sclerosis using systematic reviews.}, journal = {Frontiers in neurology}, volume = {14}, number = {}, pages = {1108383}, pmid = {36970522}, issn = {1664-2295}, abstract = {INTRODUCTION: Despite decades of research, causes of ALS remain unclear. To evaluate recent hypotheses of plausible environmental factors, the aim of this study was to synthesize and appraise literature on the potential associations between the surrounding environment, including urbanization, air pollution and water pollution, and ALS.<br><br>METHODS: We conducted a series (n = 3) of systematic reviews in PubMed and Scopus to identify epidemiological studies assessing relationships between urbanization, air pollution and water pollution with the development of ALS.<br><br>RESULTS: The combined search strategy led to the inclusion of 44 articles pertaining to at least one exposure of interest. Of the 25 included urbanization studies, four of nine studies on living in rural areas and three of seven studies on living in more highly urbanized/dense areas found positive associations to ALS. There were also three of five studies for exposure to electromagnetic fields and/or proximity to powerlines that found positive associations to ALS. Three case-control studies for each of diesel exhaust and nitrogen dioxide found positive associations with the development of ALS, with the latter showing a dose-response in one study. Three studies for each of high selenium content in drinking water and proximity to lakes prone to cyanobacterial blooms also found positive associations to ALS.<br><br>CONCLUSION: Whereas markers of air and water pollution appear as potential risk factors for ALS, results are mixed for the role of urbanization.}, }
@article {pmid36968195, year = {2023}, author = {Jagtap, YA and Kumar, P and Kinger, S and Dubey, AR and Choudhary, A and Gutti, RK and Singh, S and Jha, HC and Poluri, KM and Mishra, A}, title = {Disturb mitochondrial associated proteostasis: Neurodegeneration and imperfect ageing.}, journal = {Frontiers in cell and developmental biology}, volume = {11}, number = {}, pages = {1146564}, pmid = {36968195}, issn = {2296-634X}, abstract = {The disturbance in mitochondrial functions and homeostasis are the major features of neuron degenerative conditions, like Parkinson's disease, Amyotrophic Lateral Sclerosis, and Alzheimer's disease, along with protein misfolding. The aberrantly folded proteins are known to link with impaired mitochondrial pathways, further contributing to disease pathogenesis. Despite their central significance, the implications of mitochondrial homeostasis disruption on other organelles and cellular processes remain insufficiently explored. Here, we have reviewed the dysfunction in mitochondrial physiology, under neuron degenerating conditions. The disease misfolded proteins impact quality control mechanisms of mitochondria, such as fission, fusion, mitophagy, and proteasomal clearance, to the detriment of neuron. The adversely affected mitochondrial functional roles, like oxidative phosphorylation, calcium homeostasis, and biomolecule synthesis as well as its axes and contacts with endoplasmic reticulum and lysosomes are also discussed. Mitochondria sense and respond to multiple cytotoxic stress to make cell adapt and survive, though chronic dysfunction leads to cell death. Mitochondria and their proteins can be candidates for biomarkers and therapeutic targets. Investigation of internetworking between mitochondria and neurodegeneration proteins can enhance our holistic understanding of such conditions and help in designing more targeted therapies.}, }
@article {pmid36967829, year = {2023}, author = {Nilaver, BI and Urbanski, HF}, title = {Mechanisms underlying TDP-43 pathology and neurodegeneration: An updated Mini-Review.}, journal = {Frontiers in aging neuroscience}, volume = {15}, number = {}, pages = {1142617}, pmid = {36967829}, issn = {1663-4365}, support = {P30 AG066518/AG/NIA NIH HHS/United States ; P51 OD011092/OD/NIH HHS/United States ; RF1 AG062220/AG/NIA NIH HHS/United States ; }, abstract = {TAR DNA binding protein 43 kDa (TDP-43) plays an important role in several essential cell functions. However, TDP-43 dysfunction has been implicated in the development of various brain diseases including amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), and limbic predominant age-related TDP-43 encephalopathy (LATE). Recent investigations into the individual components of TDP-43 pathology show how broader TDP-43 dysfunction may precede these disease end states, and therefore could help to explain why TDP-43 dysfunction continues to be implicated in a rapidly expanding category of neurodegenerative diseases. The literature reviewed in this article suggests that dysregulation of TDP-43 initiated by some environmental and/or genetic insults can lead to a snowballing dysfunction across the cell, involving impaired gene expression, mRNA stability, as well as the function and coordination of those pathways directly regulated by TDP-43. Furthermore, the hallmarks of TDP-43 pathology, such as hyperphosphorylation and insoluble cytoplasmic accumulation of the protein may actually be artifacts of an upstream impairment in TDP-43's normal function. Overall, the present article summarizes current knowledge regarding TDP-43's normal and pathological cell functions and sheds light on possible mechanisms that underlie its causal role in neurodegeneration.}, }
@article {pmid36964253, year = {2023}, author = {Kim, J and Kim, HS and Chung, JH}, title = {Molecular mechanisms of mitochondrial DNA release and activation of the cGAS-STING pathway.}, journal = {Experimental &amp; molecular medicine}, volume = {55}, number = {3}, pages = {510-519}, pmid = {36964253}, issn = {2092-6413}, mesh = {Humans ; *DNA, Mitochondrial/genetics/metabolism ; Immunity, Innate ; *Inflammasomes/metabolism ; Inflammation/metabolism ; Mitochondria/metabolism ; Nucleotidyltransferases/genetics ; Signal Transduction ; Membrane Proteins/metabolism ; }, abstract = {In addition to constituting the genetic material of an organism, DNA is a tracer for the recognition of foreign pathogens and a trigger of the innate immune system. cGAS functions as a sensor of double-stranded DNA fragments and initiates an immune response via the adaptor protein STING. The cGAS-STING pathway not only defends cells against various DNA-containing pathogens but also modulates many pathological processes caused by the immune response to the ectopic localization of self-DNA, such as cytosolic mitochondrial DNA (mtDNA) and extranuclear chromatin. In addition, macrophages can cause inflammation by forming a class of protein complexes called inflammasomes, and the activation of the NLRP3 inflammasome requires the release of oxidized mtDNA. In innate immunity related to inflammasomes, mtDNA release is mediated by macropores that are formed on the outer membrane of mitochondria via VDAC oligomerization. These macropores are specifically formed in response to mitochondrial stress and tissue damage, and the inhibition of VDAC oligomerization mitigates this inflammatory response. The rapidly expanding area of research on the mechanisms by which mtDNA is released and triggers inflammation has revealed new treatment strategies not only for inflammation but also, surprisingly, for neurodegenerative diseases such as amyotrophic lateral sclerosis.}, }
@article {pmid36963821, year = {2023}, author = {Yang, T and Xiao, Y and Cheng, Y and Huang, J and Wei, Q and Li, C and Shang, H}, title = {Epigenetic clocks in neurodegenerative diseases: a systematic review.}, journal = {Journal of neurology, neurosurgery, and psychiatry}, volume = {94}, number = {12}, pages = {1064-1070}, doi = {10.1136/jnnp-2022-330931}, pmid = {36963821}, issn = {1468-330X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *Neurodegenerative Diseases/genetics/pathology ; *Alzheimer Disease/genetics ; *Parkinson Disease/genetics ; Epigenesis, Genetic/genetics ; }, abstract = {BACKGROUND: Biological ageing is one of the principal risk factors for neurodegenerative diseases. It is becoming increasingly clear that acceleration of DNA methylation age, as measured by the epigenetic clock, is closely associated with many age-related diseases.<br><br>METHODS: We searched the PubMed and Web of Science databases to identify eligible studies reporting epigenetic clocks in several neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD).<br><br>RESULTS: Twenty-three studies (12 for AD, 4 for PD, 5 for ALS, and 2 for HD) were included. We systematically summarised the clinical utility of 11 epigenetic clocks (based on blood and brain tissues) in assessing the risk factors, age of onset, diagnosis, progression, prognosis and pathology of AD, PD, ALS and HD. We also critically described our current understandings to these evidences, and further discussed key challenges, potential mechanisms and future perspectives of epigenetic ageing in neurodegenerative diseases.<br><br>CONCLUSIONS: Epigenetic clocks hold great potential in neurodegenerative diseases. Further research is encouraged to evaluate the clinical utility and promote the application.<br><br>PROSPERO REGISTRATION NUMBER: CRD42022365233.}, }
@article {pmid36963381, year = {2023}, author = {Piol, D and Robberechts, T and Da Cruz, S}, title = {Lost in local translation: TDP-43 and FUS in axonal/neuromuscular junction maintenance and dysregulation in amyotrophic lateral sclerosis.}, journal = {Neuron}, volume = {111}, number = {9}, pages = {1355-1380}, doi = {10.1016/j.neuron.2023.02.028}, pmid = {36963381}, issn = {1097-4199}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; DNA-Binding Proteins/genetics/metabolism ; Mutation ; Neuromuscular Junction/metabolism ; RNA, Messenger ; RNA-Binding Protein FUS/genetics/metabolism ; }, abstract = {Key early features of amyotrophic lateral sclerosis (ALS) are denervation of neuromuscular junctions and axonal degeneration. Motor neuron homeostasis relies on local translation through controlled regulation of axonal mRNA localization, transport, and stability. Yet the composition of the local transcriptome, translatome (mRNAs locally translated), and proteome during health and disease remains largely unexplored. This review covers recent discoveries on axonal translation as a critical mechanism for neuronal maintenance/survival. We focus on two RNA binding proteins, transactive response DNA binding protein-43 (TDP-43) and fused in sarcoma (FUS), whose mutations cause ALS and frontotemporal dementia (FTD). Emerging evidence points to their essential role in the maintenance of axons and synapses, including mRNA localization, transport, and local translation, and whose dysfunction may contribute to ALS. Finally, we describe recent advances in omics-based approaches mapping compartment-specific local RNA and protein compositions, which will be invaluable to elucidate fundamental local processes and identify key targets for therapy development.}, }
@article {pmid36963363, year = {2023}, author = {Mo, J and Hu, J and Cheng, X}, title = {The role of high mobility group box 1 in neuroinflammatory related diseases.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {161}, number = {}, pages = {114541}, doi = {10.1016/j.biopha.2023.114541}, pmid = {36963363}, issn = {1950-6007}, mesh = {Humans ; *HMGB1 Protein/metabolism ; *Brain Injuries, Traumatic ; *Amyotrophic Lateral Sclerosis ; *Parkinson Disease ; Inflammation ; Neuroinflammatory Diseases ; }, abstract = {High mobility group box 1 (HMGB1) is a ubiquitous and highly conserved non-histone DNA-binding protein with different biological functions according to its subcellular localization. It is widely believed that HMGB1, which is released into the extracellular space, plays a key role in the inflammatory response. In recent years, numerous studies have shown that the development of various neurological diseases such as epilepsy, Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), cerebrovascular disease and traumatic brain injury (TBI) are inextricably linked to inflammation. We will review the mechanisms of HMGB1 and its receptors in nervous system inflammation to provide a basis for further development of new HMGB1-based therapies.}, }
@article {pmid36959608, year = {2023}, author = {Yanful, B and Kirubarajan, A and Bhatia, D and Mishra, S and Allin, S and Di Ruggiero, E}, title = {Quality of care in the context of universal health coverage: a scoping review.}, journal = {Health research policy and systems}, volume = {21}, number = {1}, pages = {21}, pmid = {36959608}, issn = {1478-4505}, support = {407149/CAPMC/CIHR/Canada ; }, mesh = {Humans ; *Health Services ; Quality of Health Care ; *Universal Health Insurance ; }, abstract = {INTRODUCTION: Universal health coverage (UHC) is an emerging priority of health systems worldwide and central to Sustainable Development Goal 3 (target 3.8). Critical to the achievement of UHC, is quality of care. However, current evidence suggests that quality of care is suboptimal, particularly in low- and middle-income countries. The primary objective of this scoping review was to summarize the existing conceptual and empirical literature on quality of care within the context of UHC and identify knowledge gaps.<br><br>METHODS: We conducted a scoping review using the Arksey and O'Malley framework&#xa0;and further elaborated by Levac et al. and applied the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Extension for Scoping Reviews reporting guidelines. We systematically searched MEDLINE, EMBASE, CINAHL-Plus, PAIS Index, ProQuest and PsycINFO for reviews published between 1 January 1995 and 27 September 2021. Reviews were eligible for inclusion if the article had a central focus on UHC and discussed quality of care. We did not apply any country-based restrictions. All screening, data extraction and analyses were completed by two reviewers.<br><br>RESULTS: Of the 4128 database results, we included 45 studies that met the eligibility criteria, spanning multiple geographic regions. We synthesized and analysed our findings according to Kruk et&#xa0;al.'s conceptual framework for high-quality systems, including foundations, processes of care and quality impacts. Discussions of governance in relation to quality of care were discussed in a high number of studies. Studies that explored the efficiency of health systems and services were also highly represented in the included reviews. In contrast, we found that limited information was reported on health outcomes in relation to quality of care within the context of UHC. In addition, there was a global lack of evidence on measures of quality of care related to UHC, particularly country-specific measures and measures related to equity.<br><br>CONCLUSION: There is growing evidence on the relationship between quality of care and UHC, especially related to the governance and efficiency of healthcare services and systems. However, several knowledge gaps remain, particularly related to monitoring and evaluation, including of equity. Further research, evaluation and monitoring frameworks are required to strengthen the existing evidence base to improve UHC.}, }
@article {pmid36950516, year = {2023}, author = {Karvandi, MS and Sheikhzadeh Hesari, F and Aref, AR and Mahdavi, M}, title = {The neuroprotective effects of targeting key factors of neuronal cell death in neurodegenerative diseases: The role of ER stress, oxidative stress, and neuroinflammation.}, journal = {Frontiers in cellular neuroscience}, volume = {17}, number = {}, pages = {1105247}, pmid = {36950516}, issn = {1662-5102}, abstract = {Neuronal loss is one of the striking causes of various central nervous system (CNS) disorders, including major neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic lateral sclerosis (ALS). Although these diseases have different features and clinical manifestations, they share some common mechanisms of disease pathology. Progressive regional loss of neurons in patients is responsible for motor, memory, and cognitive dysfunctions, leading to disabilities and death. Neuronal cell death in neurodegenerative diseases is linked to various pathways and conditions. Protein misfolding and aggregation, mitochondrial dysfunction, generation of reactive oxygen species (ROS), and activation of the innate immune response are the most critical hallmarks of most common neurodegenerative diseases. Thus, endoplasmic reticulum (ER) stress, oxidative stress, and neuroinflammation are the major pathological factors of neuronal cell death. Even though the exact mechanisms are not fully discovered, the notable role of mentioned factors in neuronal loss is well known. On this basis, researchers have been prompted to investigate the neuroprotective effects of targeting underlying pathways to determine a promising therapeutic approach to disease treatment. This review provides an overview of the role of ER stress, oxidative stress, and neuroinflammation in neuronal cell death, mainly discussing the neuroprotective effects of targeting pathways or molecules involved in these pathological factors.}, }
@article {pmid36949305, year = {2023}, author = {Nainu, F and Mamada, SS and Harapan, H and Emran, TB}, title = {Inflammation-Mediated Responses in the Development of Neurodegenerative Diseases.}, journal = {Advances in experimental medicine and biology}, volume = {1411}, number = {}, pages = {39-70}, pmid = {36949305}, issn = {0065-2598}, mesh = {Animals ; Humans ; *Neurodegenerative Diseases/genetics ; Neuroinflammatory Diseases ; Genome-Wide Association Study ; Inflammation ; }, abstract = {Since its first description over a century ago, neurodegenerative diseases (NDDs) have impaired the lives of millions of people worldwide. As one of the major threats to human health, NDDs are characterized by progressive loss of neuronal structure and function, leading to the impaired function of the CNS. While the precise mechanisms underlying the emergence of NDDs remains elusive, association of neuroinflammation with the emergence of NDDs has been suggested. The immune system is tightly controlled to maintain homeostatic milieu and failure in doing so has been shown catastrophic. Here, we review current concepts on the cellular and molecular drivers responsible in the induction of neuroinflammation and how such event further promotes neuronal damage leading to neurodegeneration. Experimental data generated from cell culture and animal studies, gross and molecular pathologies of human CNS samples, and genome-wide association study are discussed to provide deeper insights into the mechanistic details of neuroinflammation and its roles in the emergence of NDDs.}, }
@article {pmid36935218, year = {2023}, author = {Copley, KE and Shorter, J}, title = {Repetitive elements in aging and neurodegeneration.}, journal = {Trends in genetics : TIG}, volume = {39}, number = {5}, pages = {381-400}, pmid = {36935218}, issn = {0168-9525}, support = {R21 NS090205/NS/NINDS NIH HHS/United States ; T32 GM132039/GM/NIGMS NIH HHS/United States ; F31 NS129101/NS/NINDS NIH HHS/United States ; R01 GM099836/GM/NIGMS NIH HHS/United States ; R21 AG061784/AG/NIA NIH HHS/United States ; R21 AG065854/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; *DNA Transposable Elements/genetics ; Mutagenesis, Insertional ; RNA, Small Interfering/genetics ; *Neurodegenerative Diseases/genetics ; Aging/genetics ; Mammals/genetics ; }, abstract = {Repetitive elements (REs), such as transposable elements (TEs) and satellites, comprise much of the genome. Here, we review how TEs and (peri)centromeric satellite DNA may contribute to aging and neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS). Alterations in RE expression, retrotransposition, and chromatin microenvironment may shorten lifespan, elicit neurodegeneration, and impair memory and movement. REs may cause these phenotypes via DNA damage, protein sequestration, insertional mutagenesis, and inflammation. We discuss several TE families, including gypsy, HERV-K, and HERV-W, and how TEs interact with various factors, including transactive response (TAR) DNA-binding protein 43 kDa (TDP-43) and the siRNA and piwi-interacting (pi)RNA systems. Studies of TEs in neurodegeneration have focused on Drosophila and, thus, further examination in mammals is needed. We suggest that therapeutic silencing of REs could help mitigate neurodegenerative disorders.}, }
@article {pmid36933816, year = {2023}, author = {Oliveira, NAS and Pinho, BR and Oliveira, JMA}, title = {Swimming against ALS: How to model disease in zebrafish for pathophysiological and behavioral studies.}, journal = {Neuroscience and biobehavioral reviews}, volume = {148}, number = {}, pages = {105138}, doi = {10.1016/j.neubiorev.2023.105138}, pmid = {36933816}, issn = {1873-7528}, mesh = {Animals ; Humans ; *Amyotrophic Lateral Sclerosis ; Zebrafish/genetics ; Swimming ; *Neurodegenerative Diseases ; Disease Models, Animal ; Superoxide Dismutase-1/genetics ; Mutation ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease that leads to progressive disability and motor impairment. Existing therapies provide modest improvements in patient survival, raising a need for new treatments for ALS. Zebrafish is a promising model animal for translational and fundamental research in ALS - it is an experimentally tractable vertebrate, with high homology to humans and an ample experimental toolbox. These advantages allow high-throughput study of behavioral and pathophysiological phenotypes. The last decade saw an increased interest in modelling ALS in zebrafish, leading to the current abundance and variety of available methods and models. Additionally, the rise of gene editing techniques and toxin combination studies has created novel opportunities for ALS studies in zebrafish. In this review, we address the relevance of zebrafish as a model animal for ALS studies, the strategies for model induction and key phenotypical evaluation. Furthermore, we discuss established and emerging zebrafish models of ALS, analyzing their validity, including their potential for drug testing, and highlighting research opportunities in this area.}, }
@article {pmid36931832, year = {2023}, author = {Fragaszy, DM}, title = {Adaptable navigation in bull ants (Myrmecia midas).}, journal = {Journal of comparative psychology (Washington, D.C. : 1983)}, volume = {137}, number = {1}, pages = {1-3}, doi = {10.1037/com0000343}, pmid = {36931832}, issn = {1939-2087}, mesh = {Animals ; *Ants/physiology ; Learning ; }, abstract = {In an early scientific description of navigation (finding one's way from a known location to a known destination) in an arthropod, Charles Turner, one of comparative psychology's staunchest early proponents of studying individual variation. The field of comparative psychology has caught up with Charles Turner. In this essay, the author presents an overview of the results of previous studies which suggest that several species of ants use vision effectively to navigate in three dimensions, in daylight, and in darkness. Bull ants, a species that navigates in dim light, have large compound eyes containing receptors that are sensitive to ultraviolet (UV), blue, and green regions of the electromagnetic spectrum. Islam et al.'s findings illustrate a very general point about behavior that comparative psychologists do (and should continue to) take seriously, theoretically, and empirically. When we take the time to look closely, the behavior of individuals varies in biologically and psychologically important ways, no matter the size of their bodies or nervous systems. The adaptability of individuals arises from variation within the individual over time, manifest in this study as the adoption of novel routes as circumstances required. The adaptability of populations arises from variation across individuals, evident in this study in ants that learned to travel directly to the edge of the barrier and ants that learned to travel directly to the barrier, then make a right-angle turn to travel along it to an edge. The sources and consequences of behavioral variability, within and across individuals, and its manifestations across species, must remain core concerns for comparative psychology, as they were for Charles Turner more than 100 years ago. (PsycInfo Database Record (c) 2023 APA, all rights reserved).}, }
@article {pmid36928224, year = {2023}, author = {Eshtiaghi, A and Margolin, E and Micieli, JA}, title = {Inaccuracy of idiopathic intracranial hypertension diagnosis in case reports.}, journal = {Eye (London, England)}, volume = {37}, number = {15}, pages = {3243-3248}, pmid = {36928224}, issn = {1476-5454}, mesh = {Humans ; *Pseudotumor Cerebri/complications ; *Papilledema/diagnosis/etiology ; Neuroimaging ; }, abstract = {BACKGROUND: We reviewed the medical case report literature to determine the proportion of cases of idiopathic intracranial hypertension (IIH) that were either inappropriately labelled as IIH or prematurely given this diagnosis.<br><br>METHODS: We searched OVID MEDLINE from 2012 to 2022 to identify case reports that diagnosed patients with IIH. Case reports were assessed for diagnostic accuracy using Friedman et al.'s revised diagnostic criteria for primary pseudotumor cerebri syndrome. Our primary outcome was the crude prevalence of inappropriate or premature IIH diagnoses. Our secondary outcome was determining if inaccurate IIH diagnoses were associated with variables such as journal subscription model and impact factor, author affiliation, country of origin, and year of publication.<br><br>RESULTS: A total of 33/185 case reports (17.8%) either incorrectly labelled a patient as having IIH or did not perform all of the investigations necessary to make a diagnosis of IIH. Some of these studies (4.8%) were believed to still represent 'probable' IIH given the clinical presentation, whereas 13.0% of studies were determined to have mislabelled their patients as having IIH. The most common reason that case reports did not meet diagnostic criteria included: a lack of MRV in atypical patient cases (42.4%, n&#x2009;=&#x2009;14), no papilledema in addition to a lack of characteristic neuroimaging features (33.3%, n&#x2009;=&#x2009;11), intracranial hypertension being secondary to another documented cause (12.1%, n&#x2009;=&#x2009;4), normal LP opening pressure in addition to other factors (12.1%,n&#x2009;=&#x2009;4), no description of neuroimaging (6.1%, n&#x2009;=&#x2009;2), and abnormal CSF composition (6.1%, n&#x2009;=&#x2009;2). Case reports that used the term 'IIH' incorrectly had a significantly lower journal impact factor (2.0 vs. 2.6, p&#x2009;=&#x2009;0.01).<br><br>CONCLUSIONS: There is a high prevalence of premature or inappropriate diagnoses of IIH in the peer-reviewed case report literature. Adherence to published diagnostic criteria is needed when publishing IIH case reports, and authors are expected to report all relevant data in their report to ensure that an accurate diagnosis is made.}, }
@article {pmid36927428, year = {2023}, author = {Rahman, MM and Tumpa, MAA and Rahaman, MS and Islam, F and Sutradhar, PR and Ahmed, M and Alghamdi, BS and Hafeez, A and Alexiou, A and Perveen, A and Ashraf, GM}, title = {Emerging Promise of Therapeutic Approaches Targeting Mitochondria in Neurodegenerative Disorders.}, journal = {Current neuropharmacology}, volume = {21}, number = {5}, pages = {1081-1099}, pmid = {36927428}, issn = {1875-6190}, mesh = {Humans ; Oxidative Stress/physiology ; *Mitochondrial Diseases/drug therapy/metabolism ; Mitochondria/metabolism ; *Neurodegenerative Diseases/drug therapy/genetics ; DNA, Mitochondrial/metabolism/therapeutic use ; }, abstract = {Mitochondria are critical for homeostasis and metabolism in all cellular eukaryotes. Brain mitochondria are the primary source of fuel that supports many brain functions, including intracellular energy supply, cellular calcium regulation, regulation of limited cellular oxidative capacity, and control of cell death. Much evidence suggests that mitochondria play a central role in neurodegenerative disorders (NDDs) such as Parkinson's disease, Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis. Ongoing studies of NDDs have revealed that mitochondrial pathology is mainly found in inherited or irregular NDDs and is thought to be associated with the pathophysiological cycle of these disorders. Typical mitochondrial disturbances in NDDs include increased free radical production, decreased ATP synthesis, alterations in mitochondrial permeability, and mitochondrial DNA damage. The main objective of this review is to highlight the basic mitochondrial problems that occur in NDDs and discuss the use mitochondrial drugs, especially mitochondrial antioxidants, mitochondrial permeability transition blockade, and mitochondrial gene therapy, for the treatment and control of NDDs.}, }
@article {pmid36925418, year = {2023}, author = {Prajjwal, P and Shashank, S and Al-Ezzi, SMS and Sharma, B and Aubourg, O and Kaushish, A and Marsool, MDM and Nagre, A and Asharaf, S}, title = {Frontotemporal dementia: Addressing the scattered harbingers of genetics and its relationship with glucose metabolism, bipolar disorder, and amyotrophic lateral sclerosis.}, journal = {Disease-a-month : DM}, volume = {69}, number = {5}, pages = {101545}, doi = {10.1016/j.disamonth.2023.101545}, pmid = {36925418}, issn = {1557-8194}, mesh = {Humans ; *Pick Disease of the Brain ; *Frontotemporal Dementia/diagnosis/genetics ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics ; *Bipolar Disorder/diagnosis/genetics ; Brain/diagnostic imaging ; Glucose ; }, abstract = {Frontotemporal Dementia, also known by the name Pick's disease, is a rare form of dementia that can run for several generations. The two key characteristics are argyrophilic, spherical intraneuronal inclusions, which most frequently impact the frontal and temporal poles, and localized cortical atrophy (Pick bodies). Although personality decline and memory loss are frequently more severe than the visuospatial and apraxia disorders that are common in Alzheimer's disease, clinical overlap with other non-Alzheimer degenerative disorders is being increasingly recognized. The limbic system, which includes the hippocampus, entorhinal cortex, and amygdala, typically experiences the greatest levels of neuronal loss and degeneration. In the hippocampus's dentate fascia, several Pick bodies are frequently seen. Leukoencephalopathy and inflated cortical neurons are less specific symptoms (Pick cells). In this paper, we review the factors leading to Picks disease along with its pathophysiology, clinical manifestations, diagnosis, imaging, treatment, prognosis, and a comprehensive discussion on the same. We have also discussed the relationship of frontotemporal dementia with glucose metabolism, bipolar disorder, and amyotrophic lateral sclerosis, all of which are emerging fields of interest and need more studies.}, }
@article {pmid36923490, year = {2023}, author = {Calderón-Garcidueñas, L and Torres-Jardón, R and Greenough, GP and Kulesza, R and González-Maciel, A and Reynoso-Robles, R and García-Alonso, G and Chávez-Franco, DA and García-Rojas, E and Brito-Aguilar, R and Silva-Pereyra, HG and Ayala, A and Stommel, EW and Mukherjee, PS}, title = {Sleep matters: Neurodegeneration spectrum heterogeneity, combustion and friction ultrafine particles, industrial nanoparticle pollution, and sleep disorders-Denial is not an option.}, journal = {Frontiers in neurology}, volume = {14}, number = {}, pages = {1117695}, pmid = {36923490}, issn = {1664-2295}, abstract = {Sustained exposures to ubiquitous outdoor/indoor fine particulate matter (PM2.5), including combustion and friction ultrafine PM (UFPM) and industrial nanoparticles (NPs) starting in utero, are linked to early pediatric and young adulthood aberrant neural protein accumulation, including hyperphosphorylated tau (p-tau), beta-amyloid (Aβ1 - 42), α-synuclein (α syn) and TAR DNA-binding protein 43 (TDP-43), hallmarks of Alzheimer's (AD), Parkinson's disease (PD), frontotemporal lobar degeneration (FTLD), and amyotrophic lateral sclerosis (ALS). UFPM from anthropogenic and natural sources and NPs enter the brain through the nasal/olfactory pathway, lung, gastrointestinal (GI) tract, skin, and placental barriers. On a global scale, the most important sources of outdoor UFPM are motor traffic emissions. This study focuses on the neuropathology heterogeneity and overlap of AD, PD, FTLD, and ALS in older adults, their similarities with the neuropathology of young, highly exposed urbanites, and their strong link with sleep disorders. Critical information includes how this UFPM and NPs cross all biological barriers, interact with brain soluble proteins and key organelles, and result in the oxidative, endoplasmic reticulum, and mitochondrial stress, neuroinflammation, DNA damage, protein aggregation and misfolding, and faulty complex protein quality control. The brain toxicity of UFPM and NPs makes them powerful candidates for early development and progression of fatal common neurodegenerative diseases, all having sleep disturbances. A detailed residential history, proximity to high-traffic roads, occupational histories, exposures to high-emission sources (i.e., factories, burning pits, forest fires, and airports), indoor PM sources (tobacco, wood burning in winter, cooking fumes, and microplastics in house dust), and consumption of industrial NPs, along with neurocognitive and neuropsychiatric histories, are critical. Environmental pollution is a ubiquitous, early, and cumulative risk factor for neurodegeneration and sleep disorders. Prevention of deadly neurological diseases associated with air pollution should be a public health priority.}, }
@article {pmid36922834, year = {2023}, author = {Mehta, PR and Brown, AL and Ward, ME and Fratta, P}, title = {The era of cryptic exons: implications for ALS-FTD.}, journal = {Molecular neurodegeneration}, volume = {18}, number = {1}, pages = {16}, pmid = {36922834}, issn = {1750-1326}, support = {102186/B/13/Z/WT_/Wellcome Trust/United Kingdom ; MR/M008606/1/MRC_/Medical Research Council/United Kingdom ; MR/S006508/1/MRC_/Medical Research Council/United Kingdom ; /DH_/Department of Health/United Kingdom ; U54 NS123743/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Frontotemporal Dementia/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism ; *TDP-43 Proteinopathies/metabolism ; Neurons/metabolism ; Exons/genetics ; *Neurodegenerative Diseases/metabolism ; }, abstract = {TDP-43 is an RNA-binding protein with a crucial nuclear role in splicing, and mislocalises from the nucleus to the cytoplasm in a range of neurodegenerative disorders. TDP-43 proteinopathy spans a spectrum of incurable, heterogeneous, and increasingly prevalent neurodegenerative diseases, including the amyotrophic lateral sclerosis and frontotemporal dementia disease spectrum and a significant fraction of Alzheimer's disease. There are currently no directed disease-modifying therapies for TDP-43 proteinopathies, and no way to distinguish who is affected before death. It is now clear that TDP-43 proteinopathy leads to a number of molecular changes, including the de-repression and inclusion of cryptic exons. Importantly, some of these cryptic exons lead to the loss of crucial neuronal proteins and have been shown to be key pathogenic players in disease pathogenesis (e.g., STMN2), as well as being able to modify disease progression (e.g., UNC13A). Thus, these aberrant splicing events make promising novel therapeutic targets to restore functional gene expression. Moreover, presence of these cryptic exons is highly specific to patients and areas of the brain affected by TDP-43 proteinopathy, offering the potential to develop biomarkers for early detection and stratification of patients. In summary, the discovery of cryptic exons gives hope for novel diagnostics and therapeutics on the horizon for TDP-43 proteinopathies.}, }
@article {pmid36922023, year = {2023}, author = {Hansen-Flaschen, J and Ackrivo, J}, title = {Practical Guide to Management of Long-Term Noninvasive Ventilation for Adults With Chronic Neuromuscular Disease.}, journal = {Respiratory care}, volume = {68}, number = {8}, pages = {1123-1157}, pmid = {36922023}, issn = {1943-3654}, support = {K23 HL151879/HL/NHLBI NIH HHS/United States ; }, mesh = {Adult ; Humans ; Respiration, Artificial ; *Noninvasive Ventilation ; Quality of Life ; *Respiratory Insufficiency/etiology/therapy ; Chronic Disease ; *Neuromuscular Diseases/complications/therapy ; }, abstract = {Recent technological advances in respiratory support and monitoring have dramatically enhanced the utility of long-term noninvasive ventilation (NIV). Improved quality of life and prolonged survival have been demonstrated for several common chronic neuromuscular diseases. Many adults with progressive neuromuscular respiratory disease can now comfortably maintain normal ventilation at home to near total respiratory muscle paralysis without needing a tracheostomy. However, current practice in many communities falls short of that potential. Mastery of the new technology calls for detailed awareness of the respiratory cycle; expert knowledge of mechanical devices, facial interfaces, and quantitative monitoring tools for home ventilation; and a willingness to stay current in a rapidly expanding body of clinical research. The depth and breadth of the expertise required to manage home assisted ventilation has given rise to a new focused medical subspecialty in chronic respiratory failure at the interface between pulmonology, critical care, and sleep medicine. For clinicians seeking pragmatic "how to" guidance, this primer presents a comprehensive, physician-directed management approach to long-term NIV of adults with chronic neuromuscular respiratory disease. Bi-level devices, portable ventilators, ventilation modalities, terminology, and monitoring strategies are reviewed in detail. Building on that knowledge base, we present a step-by-step guide to initiation, refinement, and maintenance of home NIV tailored to patient-centered goals of therapy. The quantitative approach recommended incorporates routine monitoring of home ventilation using technologies that have only recently become widely available including cloud-based device telemonitoring and noninvasive measurements of blood gases. Strategies for troubleshooting and problem solving are included.}, }
@article {pmid36921894, year = {2023}, author = {Khan, A and Frazer-Green, L and Amin, R and Wolfe, L and Faulkner, G and Casey, K and Sharma, G and Selim, B and Zielinski, D and Aboussouan, LS and McKim, D and Gay, P}, title = {Respiratory Management of Patients With Neuromuscular Weakness: An American College of Chest Physicians Clinical Practice Guideline and Expert Panel Report.}, journal = {Chest}, volume = {164}, number = {2}, pages = {394-413}, doi = {10.1016/j.chest.2023.03.011}, pmid = {36921894}, issn = {1931-3543}, mesh = {Humans ; Quality of Life ; Respiration, Artificial ; *Noninvasive Ventilation ; *Respiratory Insufficiency/etiology/therapy ; *Physicians ; }, abstract = {BACKGROUND: Respiratory failure is a significant concern in neuromuscular diseases (NMDs). This CHEST guideline examines the literature on the respiratory management of patients with NMD to provide evidence-based recommendations.<br><br>STUDY DESIGN AND METHODS: An expert panel conducted a systematic review addressing the respiratory management of NMD and applied the Grading of Recommendations, Assessment, Development, and Evaluations approach for assessing the certainty of the evidence and formulating and grading recommendations. A modified Delphi technique was used to reach a consensus on the recommendations.<br><br>RESULTS: Based on 128 studies, the panel generated 15 graded recommendations, one good practice statement, and one consensus-based statement.<br><br>INTERPRETATION: Evidence of best practices for respiratory management in NMD is limited and is based primarily on observational data in amyotrophic lateral sclerosis. The panel found that pulmonary function testing every 6&#xa0;months may be beneficial and may be used to initiate noninvasive ventilation (NIV) when clinically indicated. An individualized approach to NIV settings may benefit patients with chronic respiratory failure and sleep-disordered breathing related to NMD. When resources allow, polysomnography or overnight oximetry can help to guide the initiation of NIV. The panel provided guidelines for mouthpiece ventilation, transition to home mechanical ventilation, salivary secretion management, and airway clearance therapies. The guideline panel emphasizes that NMD pathologic characteristics represent a diverse group of disorders with differing rates of decline in lung function. The clinician's role is to add evaluation at the bedside to shared decision-making with patients and families, including respect for patient preferences and treatment goals, considerations of quality of life, and appropriate use of available resources in decision-making.}, }
@article {pmid36918362, year = {2023}, author = {Chapman, L and Cooper-Knock, J and Shaw, PJ}, title = {Physical activity as an exogenous risk factor for amyotrophic lateral sclerosis: a review of the evidence.}, journal = {Brain : a journal of neurology}, volume = {146}, number = {5}, pages = {1745-1757}, pmid = {36918362}, issn = {1460-2156}, support = {BRC-1215-20017/DH_/Department of Health/United Kingdom ; 216596/Z/19/Z/WT_/Wellcome Trust/United Kingdom ; NF-SI-0617-10077/DH_/Department of Health/United Kingdom ; }, mesh = {Humans ; Male ; Female ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Motor Neuron Disease/drug therapy ; Exercise ; Risk Factors ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and fatal neurodegenerative disorder. The only established epidemiological risk factors for ALS are male sex and increasing age. The role of physical activity has been debated as an environmental risk factor. Over the last decade multiple studies have attempted to delineate the architecture of ALS. These have not yet established definite risk factors, often due to low-powered studies, lack of focus on at-risk genotypes and sub-optimal methodology. We have conducted a review of all the studies published between 2009 and December 2021. The free text search terms were [(motor neuron disease) OR (MND) OR (Amyotrophic Lateral Sclerosis) OR (ALS)] AND [(Exercise) or (Physical Activity) or (PA) or (sport)]. We identified common themes, for example soccer, head injury and the physiological mechanisms that differ in ALS patients. We have analysed the relevant, available studies (n = 93), highlighting the underlying reasons for any reported discrepancies. Overall, we have found that the more highly powered studies using validated exposure methodologies, linked strenuous, anaerobic physical activity as a risk factor for ALS. Future large-scale studies focusing on specific at-risk genotypes and physical activity should be conducted to confirm this finding. This will strengthen the evidence already surrounding strenuous physical activity as an environmental risk factor for ALS and allow advice to be given to at-risk family members. Increasing our understanding of the genetic-environmental interactions in the pathophysiology of ALS will allow for the possibility of developing preventative therapeutic approaches.}, }
@article {pmid36913894, year = {2023}, author = {Jin, T and Zhang, Y and Botchway, BOA and Huang, M and Lu, Q and Liu, X}, title = {Quercetin activates the Sestrin2/AMPK/SIRT1 axis to improve amyotrophic lateral sclerosis.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {161}, number = {}, pages = {114515}, doi = {10.1016/j.biopha.2023.114515}, pmid = {36913894}, issn = {1950-6007}, mesh = {Humans ; AMP-Activated Protein Kinases/metabolism ; *Amyotrophic Lateral Sclerosis ; *Neurodegenerative Diseases ; Quercetin/pharmacology/therapeutic use ; Sirtuin 1/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a chronic neurodegenerative disease with poor prognosis. The intricacies surrounding its pathophysiology could partly account for the lack of effective treatment for ALS. Sestrin2 has been reported to improve metabolic, cardiovascular and neurodegenerative diseases, and is involved in the direct and indirect activation of the adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/silent information regulator 1 (SIRT1) axis. Quercetin, as a phytochemical, has considerable biological activities, such as anti-oxidation, anti-inflammation, anti-tumorigenicity, and neuroprotection. Interestingly, quercetin can activate the AMPK/SIRT1 signaling pathway to reduce endoplasmic reticulum stress, and alleviate apoptosis and inflammation. This report examines the molecular relationship between Sestrin2 and AMPK/SIRT1 axis, as well as the main biological functions and research progress of quercetin, together with the correlation between quercetin and Sestrin2/AMPK/SIRT1 axis in neurodegenerative diseases.}, }
@article {pmid36905838, year = {2023}, author = {Barone, M and Leo, AD and de van der Schueren, MAE}, title = {Malnutrition assessment by Global Leadership Initiative on Malnutrition criteria in patients with amyotrophic lateral sclerosis.}, journal = {Nutrition (Burbank, Los Angeles County, Calif.)}, volume = {109}, number = {}, pages = {111997}, doi = {10.1016/j.nut.2023.111997}, pmid = {36905838}, issn = {1873-1244}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/diagnosis ; Leadership ; Reproducibility of Results ; *Malnutrition/diagnosis/etiology ; Weight Loss ; Nutrition Assessment ; Nutritional Status ; }, abstract = {Malnutrition can play an important prognostic role in terms of survival in patients with amyotrophic lateral sclerosis (ALS). In this clinical context, applying criteria defining malnutrition requires particular attention, especially in the initial stage of the disease. This article discusses the application of the most recent criteria used for the definition of malnutrition when applied to patients with ALS. Currently, the Global Leadership Initiative on Malnutrition (GLIM) criteria, which have received a worldwide consensus, are based on parameters such as unintentional weight loss, low body mass index (BMI), and reduced muscle mass (phenotypic criteria) in combination with reduced food intake and assimilation or inflammation and disease (etiologic criteria). However, as discussed in this review, the initial unintentional weight loss and the consequent BMI reduction could be attributed, at least in part, to muscle atrophy, which also alters the reliability of muscle mass assessment. Moreover, the condition of hypermetabolism, which is observed in up to 50% of these patients, may complicate the calculation of total energy requirements. Finally, it remains to be established if the presence of neuroinflammation can be considered a type of inflammatory process able to induce malnutrition in these patients. In conclusion, the monitoring of BMI, associated with body composition evaluation by bioimpedance measurement or specific formulas, could be a practicable approach to the diagnosis of malnutrition in patients with ALS. In addition, attention should be given to dietary intake (e.g., in patients with dysphagia) and excessive involuntary weight loss. On the other hand, as suggested by GLIM criteria, a single assessment of BMI resulting in <20 kg/m[2] or <22 kg/m[2] in patients aged <70 y and ≥70 y, respectively, should always be considered a sign of malnutrition.}, }
@article {pmid36902233, year = {2023}, author = {Potes, Y and Cachán-Vega, C and Antuña, E and García-González, C and Menéndez-Coto, N and Boga, JA and Gutiérrez-Rodríguez, J and Bermúdez, M and Sierra, V and Vega-Naredo, I and Coto-Montes, A and Caballero, B}, title = {Benefits of the Neurogenic Potential of Melatonin for Treating Neurological and Neuropsychiatric Disorders.}, journal = {International journal of molecular sciences}, volume = {24}, number = {5}, pages = {}, pmid = {36902233}, issn = {1422-0067}, support = {PI21/01596//Instituto de Salud Carlos III/ ; IDI/2021/000033//Foundation for the Promotion of Applied Scientific Research and Technology in Asturias/ ; 2021-030-INTRAMURALES-POOCY//Instituto de Investigaci&#xf3;n Sanitaria del Principado de Asturias/ ; }, mesh = {*Melatonin/pharmacology ; *Neural Stem Cells ; Hippocampus ; Neurogenesis ; Neurons ; }, abstract = {There are several neurological diseases under which processes related to adult brain neurogenesis, such cell proliferation, neural differentiation and neuronal maturation, are affected. Melatonin can exert a relevant benefit for treating neurological disorders, given its well-known antioxidant and anti-inflammatory properties as well as its pro-survival effects. In addition, melatonin is able to modulate cell proliferation and neural differentiation processes in neural stem/progenitor cells while improving neuronal maturation of neural precursor cells and newly created postmitotic neurons. Thus, melatonin shows relevant pro-neurogenic properties that may have benefits for neurological conditions associated with impairments in adult brain neurogenesis. For instance, the anti-aging properties of melatonin seem to be linked to its neurogenic properties. Modulation of neurogenesis by melatonin is beneficial under conditions of stress, anxiety and depression as well as for the ischemic brain or after a brain stroke. Pro-neurogenic actions of melatonin may also be beneficial for treating dementias, after a traumatic brain injury, and under conditions of epilepsy, schizophrenia and amyotrophic lateral sclerosis. Melatonin may represent a pro-neurogenic treatment effective for retarding the progression of neuropathology associated with Down syndrome. Finally, more studies are necessary to elucidate the benefits of melatonin treatments under brain disorders related to impairments in glucose and insulin homeostasis.}, }
@article {pmid36902042, year = {2023}, author = {Gulino, R}, title = {Synaptic Dysfunction and Plasticity in Amyotrophic Lateral Sclerosis.}, journal = {International journal of molecular sciences}, volume = {24}, number = {5}, pages = {}, pmid = {36902042}, issn = {1422-0067}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Motor Neurons/pathology ; *Neurodegenerative Diseases/pathology ; Synapses/pathology ; Neuronal Plasticity/physiology ; }, abstract = {Recent evidence has supported the hypothesis that amyotrophic lateral sclerosis (ALS) is a multi-step disease, as the onset of symptoms occurs after sequential exposure to a defined number of risk factors. Despite the lack of precise identification of these disease determinants, it is known that genetic mutations may contribute to one or more of the steps leading to ALS onset, the remaining being linked to environmental factors and lifestyle. It also appears evident that compensatory plastic changes taking place at all levels of the nervous system during ALS etiopathogenesis may likely counteract the functional effects of neurodegeneration and affect the timing of disease onset and progression. Functional and structural events of synaptic plasticity probably represent the main mechanisms underlying this adaptive capability, causing a significant, although partial and transient, resiliency of the nervous system affected by a neurodegenerative disease. On the other hand, the failure of synaptic functions and plasticity may be part of the pathological process. The aim of this review was to summarize what it is known today about the controversial involvement of synapses in ALS etiopathogenesis, and an analysis of the literature, although not exhaustive, confirmed that synaptic dysfunction is an early pathogenetic process in ALS. Moreover, it appears that adequate modulation of structural and functional synaptic plasticity may likely support function sparing and delay disease progression.}, }
@article {pmid36899898, year = {2023}, author = {Kupershmidt, L and Youdim, MBH}, title = {The Neuroprotective Activities of the Novel Multi-Target Iron-Chelators in Models of Alzheimer's Disease, Amyotrophic Lateral Sclerosis and Aging.}, journal = {Cells}, volume = {12}, number = {5}, pages = {}, pmid = {36899898}, issn = {2073-4409}, mesh = {Mice ; Animals ; *Alzheimer Disease/metabolism ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Hydroxyquinolines/pharmacology/therapeutic use ; Mice, Inbred C57BL ; Iron Chelating Agents/therapeutic use ; Mice, Transgenic ; *Parkinson Disease/pathology ; Aging ; Iron/metabolism ; }, abstract = {The concept of chelation therapy as a valuable therapeutic approach in neurological disorders led us to develop multi-target, non-toxic, lipophilic, brain-permeable compounds with iron chelation and anti-apoptotic properties for neurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's disease (AD), age-related dementia and amyotrophic lateral sclerosis (ALS). Herein, we reviewed our two most effective such compounds, M30 and HLA20, based on a multimodal drug design paradigm. The compounds have been tested for their mechanisms of action using animal and cellular models such as APP/PS1 AD transgenic (Tg) mice, G93A-SOD1 mutant ALS Tg mice, C57BL/6 mice, Neuroblastoma × Spinal Cord-34 (NSC-34) hybrid cells, a battery of behavior tests, and various immunohistochemical and biochemical techniques. These novel iron chelators exhibit neuroprotective activities by attenuating relevant neurodegenerative pathology, promoting positive behavior changes, and up-regulating neuroprotective signaling pathways. Taken together, these results suggest that our multifunctional iron-chelating compounds can upregulate several neuroprotective-adaptive mechanisms and pro-survival signaling pathways in the brain and might function as ideal drugs for neurodegenerative disorders, such as PD, AD, ALS, and aging-related cognitive decline, in which oxidative stress and iron-mediated toxicity and dysregulation of iron homeostasis have been implicated.}, }
@article {pmid36899889, year = {2023}, author = {Abdelhamid, RF and Nagano, S}, title = {Crosstalk between Oxidative Stress and Aging in Neurodegeneration Disorders.}, journal = {Cells}, volume = {12}, number = {5}, pages = {}, pmid = {36899889}, issn = {2073-4409}, mesh = {Humans ; *Neurodegenerative Diseases ; Oxidative Stress ; Aging ; *Parkinson Disease ; *Alzheimer Disease ; }, abstract = {The world population is aging rapidly, and increasing lifespan exacerbates the burden of age-related health issues. On the other hand, premature aging has begun to be a problem, with increasing numbers of younger people suffering aging-related symptoms. Advanced aging is caused by a combination of factors: lifestyle, diet, external and internal factors, as well as oxidative stress (OS). Although OS is the most researched aging factor, it is also the least understood. OS is important not only in relation to aging but also due to its strong impact on neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alzheimer's disease (AD), and Parkinson's disease (PD). In this review, we will discuss the aging process in relation to OS, the function of OS in neurodegenerative disorders, and prospective therapeutics capable of relieving neurodegenerative symptoms associated with the pro-oxidative condition.}, }
@article {pmid36899872, year = {2023}, author = {Vidovic, M and Müschen, LH and Brakemeier, S and Machetanz, G and Naumann, M and Castro-Gomez, S}, title = {Current State and Future Directions in the Diagnosis of Amyotrophic Lateral Sclerosis.}, journal = {Cells}, volume = {12}, number = {5}, pages = {}, pmid = {36899872}, issn = {2073-4409}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology ; *Neurodegenerative Diseases ; Delayed Diagnosis ; Motor Neurons/pathology ; Biomarkers ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by loss of upper and lower motor neurons, resulting in progressive weakness of all voluntary muscles and eventual respiratory failure. Non-motor symptoms, such as cognitive and behavioral changes, frequently occur over the course of the disease. Considering its poor prognosis with a median survival time of 2 to 4 years and limited causal treatment options, an early diagnosis of ALS plays an essential role. In the past, diagnosis has primarily been determined by clinical findings supported by electrophysiological and laboratory measurements. To increase diagnostic accuracy, reduce diagnostic delay, optimize stratification in clinical trials and provide quantitative monitoring of disease progression and treatment responsivity, research on disease-specific and feasible fluid biomarkers, such as neurofilaments, has been intensely pursued. Advances in imaging techniques have additionally yielded diagnostic benefits. Growing perception and greater availability of genetic testing facilitate early identification of pathogenic ALS-related gene mutations, predictive testing and access to novel therapeutic agents in clinical trials addressing disease-modified therapies before the advent of the first clinical symptoms. Lately, personalized survival prediction models have been proposed to offer a more detailed disclosure of the prognosis for the patient. In this review, the established procedures and future directions in the diagnostics of ALS are summarized to serve as a practical guideline and to improve the diagnostic pathway of this burdensome disease.}, }
@article {pmid36897461, year = {2023}, author = {Zhang, G and E, M and Zhou, X}, title = {Environmental and Occupational solvents exposure and amyotrophic lateral sclerosis: a systematic review and meta-analysis.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {44}, number = {8}, pages = {2803-2809}, pmid = {36897461}, issn = {1590-3478}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/chemically induced/epidemiology ; Solvents/toxicity ; *Occupational Exposure/adverse effects ; Case-Control Studies ; Odds Ratio ; Risk Factors ; Environmental Exposure ; }, abstract = {Studies focusing on the association between environmental and occupational solvent exposure and amyotrophic lateral sclerosis (ALS) have yielded inconsistent results. Herein we present the results of a meta-analysis on the correlation between solvent exposure and ALS. We searched for eligible studies that reported ALS with exposure to solvents in PubMed, Embase, and Web of Science up to December 2022. The Newcastle-Ottawa scale was used to evaluate the quality of the article and a meta-analysis was performed using a random effect model. Thirteen articles, including two cohort studies and 13 case-control studies with 6365 cases and 173,321 controls were selected. The odds ratio (OR) for the association between solvent exposure and ALS was 1.31 (95% confidence interval [CI], 1.11-1.54) with moderate heterogeneity (I[2] = 59.7%; p = 0.002). Subgroup and sensitivity analyses confirmed the results, and publication bias was not detected. These results indicated that environmental and occupational solvent exposure was associated with the risk of ALS.}, }
@article {pmid36896705, year = {2023}, author = {Dilliott, AA and Al Nasser, A and Elnagheeb, M and Fifita, J and Henden, L and Keseler, IM and Lenz, S and Marriott, H and Mccann, E and Mesaros, M and Opie-Martin, S and Owens, E and Palus, B and Ross, J and Wang, Z and White, H and Al-Chalabi, A and Andersen, PM and Benatar, M and Blair, I and Cooper-Knock, J and Harrington, EA and Heckmann, J and Landers, J and Moreno, C and Nel, M and Rampersaud, E and Roggenbuck, J and Rouleau, G and Traynor, B and Van Blitterswijk, M and Van Rheenen, W and Veldink, J and Weishaupt, J and Drury, L and Harms, MB and Farhan, SMK and , }, title = {Clinical testing panels for ALS: global distribution, consistency, and challenges.}, journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration}, volume = {24}, number = {5-6}, pages = {420-435}, pmid = {36896705}, issn = {2167-9223}, support = {U24 HG009650/HG/NHGRI NIH HHS/United States ; Z01 AG000949/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics ; Mutation ; Genetic Testing/methods ; C9orf72 Protein/genetics ; }, abstract = {Objective: In 2021, the Clinical Genome Resource (ClinGen) amyotrophic lateral sclerosis (ALS) spectrum disorders Gene Curation Expert Panel (GCEP) was established to evaluate the strength of evidence for genes previously reported to be associated with ALS. Through this endeavor, we will provide standardized guidance to laboratories on which genes should be included in clinical genetic testing panels for ALS. In this manuscript, we aimed to assess the heterogeneity in the current global landscape of clinical genetic testing for ALS. Methods: We reviewed the National Institutes of Health (NIH) Genetic Testing Registry (GTR) and members of the ALS GCEP to source frequently used testing panels and compare the genes included on the tests. Results: 14 clinical panels specific to ALS from 14 laboratories covered 4 to 54 genes. All panels report on ANG, SOD1, TARDBP, and VAPB; 50% included or offered the option of including C9orf72 hexanucleotide repeat expansion (HRE) analysis. Of the 91 genes included in at least one of the panels, 40 (44.0%) were included on only a single panel. We could not find a direct link to ALS in the literature for 14 (15.4%) included genes. Conclusions: The variability across the surveyed clinical genetic panels is concerning due to the possibility of reduced diagnostic yields in clinical practice and risk of a missed diagnoses for patients. Our results highlight the necessity for consensus regarding the appropriateness of gene inclusions in clinical genetic ALS tests to improve its application for patients living with ALS and their families.}, }
@article {pmid36895420, year = {2023}, author = {Koike, Y and Onodera, O}, title = {Implications of miRNAs dysregulation in amyotrophic lateral sclerosis: Challenging for clinical applications.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1131758}, pmid = {36895420}, issn = {1662-4548}, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the selective degeneration of upper and lower motor neurons. Currently, there are no effective biomarkers and fundamental therapies for this disease. Dysregulation in RNA metabolism plays a critical role in the pathogenesis of ALS. With the contribution of Next Generation Sequencing, the functions of non-coding RNAs (ncRNAs) have gained increasing interests. Especially, micro RNAs (miRNAs), which are tissue-specific small ncRNAs of about 18-25 nucleotides, have emerged as key regulators of gene expression to target multiple molecules and pathways in the central nervous system (CNS). Despite intensive recent research in this field, the crucial links between ALS pathogenesis and miRNAs remain unclear. Many studies have revealed that ALS-related RNA binding proteins (RBPs), such as TAR DNA-binding protein 43 (TDP-43) and fused in sarcoma/translocated in liposarcoma (FUS), regulate miRNAs processing in both the nucleus and cytoplasm. Of interest, Cu[2+]/Zn[2+] superoxide dismutase (SOD1), a non-RBP associated with familial ALS, shows partially similar properties to these RBPs via the dysregulation of miRNAs in the cellular pathway related to ALS. The identification and validation of miRNAs are important to understand the physiological gene regulation in the CNS, and the pathological implications in ALS, leading to a new avenue for early diagnosis and gene therapies. Here, we offer a recent overview regarding the mechanism underlying the functions of multiple miRNAs across TDP-43, FUS, and SOD1 with the context of cell biology, and challenging for clinical applications in ALS.}, }
@article {pmid36894028, year = {2023}, author = {Costa, I and Barbosa, DJ and Benfeito, S and Silva, V and Chavarria, D and Borges, F and Remião, F and Silva, R}, title = {Molecular mechanisms of ferroptosis and their involvement in brain diseases.}, journal = {Pharmacology &amp; therapeutics}, volume = {244}, number = {}, pages = {108373}, doi = {10.1016/j.pharmthera.2023.108373}, pmid = {36894028}, issn = {1879-016X}, mesh = {Humans ; Cell Death/physiology ; *Ferroptosis ; Reactive Oxygen Species/metabolism ; Lipid Peroxidation ; *Brain Diseases/drug therapy ; }, abstract = {Ferroptosis is a type of regulated cell death characterized by intracellular accumulation of iron and reactive oxygen species, inhibition of system Xc-, glutathione depletion, nicotinamide adenine dinucleotide phosphate oxidation and lipid peroxidation. Since its discovery and characterization in 2012, many efforts have been made to reveal the underlying mechanisms, modulating compounds, and its involvement in disease pathways. Ferroptosis inducers include erastin, sorafenib, sulfasalazine and glutamate, which, by inhibiting system Xc-, prevent the import of cysteine into the cells. RSL3, statins, Ml162 and Ml210 induce ferroptosis by inhibiting glutathione peroxidase 4 (GPX4), which is responsible for preventing the formation of lipid peroxides, and FIN56 and withaferin trigger GPX4 degradation. On the other side, ferroptosis inhibitors include ferrostatin-1, liproxstatin-1, α-tocopherol, zileuton, FSP1, CoQ10 and BH4, which interrupt the lipid peroxidation cascade. Additionally, deferoxamine, deferiprone and N-acetylcysteine, by targeting other cellular pathways, have also been classified as ferroptosis inhibitors. Increased evidence has established the involvement of ferroptosis in distinct brain diseases, including Alzheimer's, Parkinson's and Huntington's diseases, amyotrophic lateral sclerosis, multiple sclerosis, and Friedreich's ataxia. Thus, a deep understanding of how ferroptosis contributes to these diseases, and how it can be modulated, can open a new window of opportunities for novel therapeutic strategies and targets. Other studies have shown a sensitivity of cancer cells with mutated RAS to ferroptosis induction and that chemotherapeutic agents and ferroptosis inducers synergize in tumor treatment. Thus, it is tempting to consider that ferroptosis may arise as a target mechanistic pathway for the treatment of brain tumors. Therefore, this work provides an up-to-date review on the molecular and cellular mechanisms of ferroptosis and their involvement in brain diseases. In addition, information on the main ferroptosis inducers and inhibitors and their molecular targets is also provided.}, }
@article {pmid36889133, year = {2023}, author = {Ma, L and Li, X and Petersen, RB and Peng, A and Huang, K}, title = {Probing the interactions between amyloidogenic proteins and bio-membranes.}, journal = {Biophysical chemistry}, volume = {296}, number = {}, pages = {106984}, doi = {10.1016/j.bpc.2023.106984}, pmid = {36889133}, issn = {1873-4200}, mesh = {Humans ; Amyloidogenic Proteins/metabolism ; *Diabetes Mellitus, Type 2/metabolism ; *Alzheimer Disease/metabolism ; *Parkinson Disease ; }, abstract = {Protein misfolding diseases (PMDs) in humans are characterized by the deposition of protein aggregates in tissues, including Alzheimer's disease, Parkinson's disease, type 2 diabetes, and amyotrophic lateral sclerosis. Misfolding and aggregation of amyloidogenic proteins play a central role in the onset and progression of PMDs, and these processes are regulated by multiple factors, especially the interaction between proteins and bio-membranes. Bio-membranes induce conformational changes in amyloidogenic proteins and affect their aggregation; on the other hand, the aggregates of amyloidogenic proteins may cause membrane damage or dysfunction leading to cytotoxicity. In this review, we summarize the factors that affect the binding of amyloidogenic proteins and membranes, the effects of bio-membranes on the aggregation of amyloidogenic proteins, mechanisms of membrane disruption by amyloidogenic aggregates, technical approaches for detecting these interactions, and finally therapeutic strategies targeting membrane damage caused by amyloidogenic proteins.}, }
@article {pmid36881218, year = {2023}, author = {Zahir, F and Hanman, A and Yazdani, N and La Rosa, S and Sleik, G and Sullivan, B and Mehdipour, A and Malouka, S and Kuspinar, A}, title = {Assessing the psychometric properties of quality of life measures in individuals with amyotrophic lateral sclerosis: a systematic review.}, journal = {Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation}, volume = {32}, number = {9}, pages = {2447-2462}, pmid = {36881218}, issn = {1573-2649}, mesh = {Adult ; Humans ; *Amyotrophic Lateral Sclerosis ; Patient Reported Outcome Measures ; Psychometrics/methods ; *Quality of Life/psychology ; Reproducibility of Results ; }, abstract = {PURPOSE: Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease in adults. There are many patient-reported outcome measures (PROMs) for measuring quality of life (QoL) and health-related QoL (HRQoL) within this population; however, there is limited consensus regarding which are most valid, reliable, responsive, and interpretable. This systematic review assesses the psychometric properties and interpretability of QoL and HRQoL PROMs for individuals with ALS.<br><br>METHODS: This review was conducted following the Consensus-based Standards for the selection of health Measurement Instruments&#xa0;(COSMIN) methodology for systematic reviews of PROMs. MEDLINE, EMBASE, and CINAHL databases were searched. Studies were included if their aim was to evaluate one or more psychometric properties or the interpretability of QoL or HRQoL PROMs in individuals with ALS.<br><br>RESULTS: We screened 2713 abstracts, reviewed 60 full-text articles, and included 37 articles. Fifteen PROMs were evaluated including generic HRQoL (e.g., SF-36), ALS-specific HRQoL (e.g., ALSAQ-40), and individualized QoL (e.g., SEIQoL) measures. Evidence for internal consistency and test-retest reliability were acceptable. For convergent validity, 84% of hypotheses were met. For known-groups validity, outcomes were able to distinguish between healthy cohorts and other conditions. Responsiveness results ranged from low to high correlations with other measures over 3-24&#xa0;months. Evidence for content validity, structural validity, measurement error, and divergent validity was limited.<br><br>CONCLUSION: This review identified evidence in support of the ALSAQ-40 or ALSAQ-5 for individuals with ALS. These findings can&#xa0;guide healthcare practitioners when selecting evidence-based QoL and HRQoL PROMs for patients and provide researchers with&#xa0;insight into gaps in the literature.}, }
@article {pmid36880940, year = {2023}, author = {Arslan, B and Zetterberg, H}, title = {Neurofilament light chain as neuronal injury marker - what is needed to facilitate implementation in clinical laboratory practice?.}, journal = {Clinical chemistry and laboratory medicine}, volume = {61}, number = {7}, pages = {1140-1149}, pmid = {36880940}, issn = {1437-4331}, mesh = {Humans ; Laboratories, Clinical ; Intermediate Filaments ; Neurofilament Proteins ; *Alzheimer Disease ; Biomarkers ; *Nervous System Diseases/diagnosis ; }, abstract = {Neurobiomarkers have attracted significant attention over the last ten years. One promising biomarker is the neurofilament light chain protein (NfL). Since the introduction of ultrasensitive assays, NfL has been developed into a widely used axonal damage marker of relevance to the diagnosis, prognostication, follow-up, and treatment monitoring of a range of neurological disorders, including multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer's disease. The marker is increasingly used clinically, as well as in clinical trials. Even if we have validated precise, sensitive, and specific assays for NfL quantification in both cerebrospinal fluid and blood, there are analytical, as well as pre- and post-analytical aspects of the total NfL testing process, including biomarker interpretation, to consider. Although the biomarker is already in use in specialised clinical laboratory settings, a more general use requires some further work. In this review, we provide brief basic information and opinions on NfL as a biomarker of axonal injury in neurological diseases and pinpoint additional work needed to facilitate biomarker implementation in clinical practice.}, }
@article {pmid36875937, year = {2023}, author = {Donohue, C and Carnaby, G and Reilly, MC and Colquhoun, RJ and Lacomis, D and Garand, KLF}, title = {A meta-analysis of post-exercise outcomes in people with amyotrophic lateral sclerosis.}, journal = {eNeurologicalSci}, volume = {31}, number = {}, pages = {100452}, pmid = {36875937}, issn = {2405-6502}, abstract = {OBJECTIVE: To systematically evaluate post-exercise outcomes related to function and quality of life in people with ALS.<br><br>METHODS: PRISMA guidelines were used for identifying and extracting articles. Levels of evidence and quality of articles were judged based on The Oxford Centre for Evidence-based Medicine Levels of Evidence and the QualSyst. Outcomes were analyzed with Comprehensive Meta-Analysis V2 software, random effects models, and Hedge's G. Effects were examined at 0-4&#xa0;months, up to 6&#xa0;months, and&#xa0;>&#xa0;6&#xa0;months. Pre-specified sensitivity analyses were performed for 1) controlled trials vs. all studies and 2) ALSFRS-R bulbar, respiratory, and motor subscales. Heterogeneity of pooled outcomes was computed with the I[2] statistic.<br><br>RESULTS: 16 studies and seven functional outcomes met inclusion for the meta-analysis. Of the outcomes explored, the ALSFRS-R demonstrated a favorable summary effect size and had acceptable heterogeneity and dispersion. While FIM scores demonstrated a favorable summary effect size, heterogeneity limited interpretations. Other outcomes did not demonstrate a favorable summary effect size and/or could not be reported due to few studies reporting outcomes.<br><br>CONCLUSIONS: This study provides inconclusive guidance regarding exercise regimens to maintain function and quality of life in people with ALS due to study limitations (e.g., small sample size, high attrition rate, heterogeneity in methods and participants, etc.). Future research is warranted to determine optimal treatment regimens and dosage parameters in this patient population.}, }
@article {pmid36875699, year = {2023}, author = {Jeon, YM and Kwon, Y and Lee, S and Kim, HJ}, title = {Potential roles of the endoplasmic reticulum stress pathway in amyotrophic lateral sclerosis.}, journal = {Frontiers in aging neuroscience}, volume = {15}, number = {}, pages = {1047897}, pmid = {36875699}, issn = {1663-4365}, abstract = {The endoplasmic reticulum (ER) is a major organelle involved in protein quality control and cellular homeostasis. ER stress results from structural and functional dysfunction of the organelle, along with the accumulation of misfolded proteins and changes in calcium homeostasis, it leads to ER stress response pathway such as unfolded protein response (UPR). Neurons are particularly sensitive to the accumulation of misfolded proteins. Thus, the ER stress is involved in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, prion disease and motor neuron disease (MND). Recently, the complex involvement of ER stress pathways has been demonstrated in experimental models of amyotrophic lateral sclerosis (ALS)/MND using pharmacological and genetic manipulation of the unfolded protein response (UPR), an adaptive response to ER stress. Here, we aim to provide recent evidence demonstrating that the ER stress pathway is an essential pathological mechanism of ALS. In addition, we also provide therapeutic strategies that can help treat diseases by targeting the ER stress pathway.}, }
@article {pmid36875645, year = {2023}, author = {Pan, X and Dutta, D and Lu, S and Bellen, HJ}, title = {Sphingolipids in neurodegenerative diseases.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1137893}, pmid = {36875645}, issn = {1662-4548}, support = {P50 HD103555/HD/NICHD NIH HHS/United States ; R24 OD022005/OD/NIH HHS/United States ; R24 OD031447/OD/NIH HHS/United States ; }, abstract = {Neurodegenerative Diseases (NDDs) are a group of disorders that cause progressive deficits of neuronal function. Recent evidence argues that sphingolipid metabolism is affected in a surprisingly broad set of NDDs. These include some lysosomal storage diseases (LSDs), hereditary sensory and autonomous neuropathy (HSAN), hereditary spastic paraplegia (HSP), infantile neuroaxonal dystrophy (INAD), Friedreich's ataxia (FRDA), as well as some forms of amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD). Many of these diseases have been modeled in Drosophila melanogaster and are associated with elevated levels of ceramides. Similar changes have also been reported in vertebrate cells and mouse models. Here, we summarize studies using fly models and/or patient samples which demonstrate the nature of the defects in sphingolipid metabolism, the organelles that are implicated, the cell types that are initially affected, and potential therapeutics for these diseases.}, }
@article {pmid36871963, year = {2023}, author = {Adams Nejatbakhsh, N and Dawson, D and Hutchison, M and Selby, P}, title = {Association between pediatric TBI and mental health and substance use disorders: A scoping review.}, journal = {Brain injury}, volume = {37}, number = {6}, pages = {525-533}, doi = {10.1080/02699052.2023.2184871}, pmid = {36871963}, issn = {1362-301X}, mesh = {Adolescent ; Child ; Humans ; Mental Health ; Cross-Sectional Studies ; Longitudinal Studies ; Prospective Studies ; *Brain Injuries, Traumatic/complications/epidemiology ; *Mental Disorders/epidemiology/etiology ; *Substance-Related Disorders/epidemiology ; }, abstract = {BACKGROUND: The relationship between pediatric Traumatic Brain Injury (TBI) and long-term mental health and substance use disorders is not well known, resulting in inadequate prevention and management strategies. The aim of this scoping review is to review the evidence on pediatric TBI and the development of mental health disorders and substance use later in life and to identify gaps in the literature to inform future research.<br><br>METHODS: We searched multiple databases for original articles published between September 2002 and September 2022 on TBI-related mental health and/or substance use disorders in children and youth. Two independent reviewers performed the screening using Arksey and O'Malley and Levac et al.'s scoping review framework.<br><br>RESULTS: A total of six papers are included in this scoping review. Studies included are comprised of cross-sectional and prospective longitudinal cohort studies.<br><br>DISCUSSION: A correlation between pediatric TBI and development of certain mental health disorders and substance use is suggested, although much of the current evidence is mixed and does not account for confounding variables. Future studies should aim to closely examine these links and identify modifiers that can influence these relationships.}, }
@article {pmid36860617, year = {2023}, author = {Spencer, PS and Palmer, VS and Kisby, GE and Lagrange, E and Horowitz, BZ and Valdes Angues, R and Reis, J and Vernoux, JP and Raoul, C and Camu, W}, title = {Early-onset, conjugal, twin-discordant, and clusters of sporadic ALS: Pathway to discovery of etiology via lifetime exposome research.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1005096}, pmid = {36860617}, issn = {1662-4548}, abstract = {The identity and role of environmental factors in the etiology of sporadic amyotrophic lateral sclerosis (sALS) is poorly understood outside of three former high-incidence foci of Western Pacific ALS and a hotspot of sALS in the French Alps. In both instances, there is a strong association with exposure to DNA-damaging (genotoxic) chemicals years or decades prior to clinical onset of motor neuron disease. In light of this recent understanding, we discuss published geographic clusters of ALS, conjugal cases, single-affected twins, and young-onset cases in relation to their demographic, geographic and environmental associations but also whether, in theory, there was the possibility of exposure to genotoxic chemicals of natural or synthetic origin. Special opportunities to test for such exposures in sALS exist in southeast France, northwest Italy, Finland, the U.S. East North Central States, and in the U.S. Air Force and Space Force. Given the degree and timing of exposure to an environmental trigger of ALS may be related to the age at which the disease is expressed, research should focus on the lifetime exposome (from conception to clinical onset) of young sALS cases. Multidisciplinary research of this type may lead to the identification of ALS causation, mechanism, and primary prevention, as well as to early detection of impending ALS and pre-clinical treatment to slow development of this fatal neurological disease.}, }
@article {pmid36857887, year = {2023}, author = {Zhang, N and Chen, KL and Huang, YY and Chen, SF and Dong, Q and Tan, L and Yu, JT}, title = {A new ERBB4 variant in amyotrophic lateral sclerosis type 19: Case report and review of the literature.}, journal = {Clinical neurology and neurosurgery}, volume = {227}, number = {}, pages = {107636}, doi = {10.1016/j.clineuro.2023.107636}, pmid = {36857887}, issn = {1872-6968}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Mutation/genetics ; Receptor, ErbB-4/genetics ; }, }
@article {pmid36855480, year = {2023}, author = {Ramsay, D and Miller, A and Baykeens, B and Hassan, H and Gentleman, S}, title = {Football (Soccer) as a Probable Cause of Long-Term Neurological Impairment and Neurodegeneration: A Narrative Review of the Debate.}, journal = {Cureus}, volume = {15}, number = {1}, pages = {e34279}, pmid = {36855480}, issn = {2168-8184}, abstract = {Football (soccer) is the most widely played sport across the globe. Due to some recent high-profile cases and epidemiological studies suggesting football can lead to neurodegeneration, scientific and public interest has been piqued. This has resulted in research into whether an association between football participation and neurodegeneration or neurological impairment is present. It has been theorised that a combination of repeated sub-concussive and concussive injuries, due to ball-heading and head collisions, may lead to neurodegeneration. However, evidence remains conflicting. Due to the popularity of the sport, and the serious conditions it has been linked to, it is important to determine whether repeated head impacts during football participation can play a causative role in neurodegenerative disease. To answer this question, a review of the current literature was carried out. Epidemiological evidence showed a higher incidence of amyotrophic lateral sclerosis amongst amateur and professional footballers and that footballers in positions that involve less contact and heading, e.g., goalkeepers lead significantly longer lives. Additionally, imaging studies reach a similar conclusion, reporting changes in brain structure, blood flow, and inflammatory markers in footballers when compared to controls. However, studies looking at an association between heading frequency and cognition show a lack of consensus on whether a higher heading exposure results in reduced cognition. Similarly, in neuropathological studies, signs of chronic traumatic encephalopathy (CTE) have been found in some former players, with contrasting studies suggesting low levels of CTE-type pathology are found in the general population, regardless of exposure to head trauma. The majority of studies suggest a link between football and neurodegenerative disease. However, the high prevalence of retrospective cohort and cross-sectional studies, often plagued by recall bias, undermine the conclusions drawn. Therefore, until larger prospective cohort studies are conducted, concrete conclusions cannot be made. However, caution can be exercised to limit head impacts.}, }
@article {pmid36855220, year = {2023}, author = {Albright, C and Limoges, J and Rempel, GR}, title = {Living with pulmonary sequelae of COVID-19 and the implications for clinical nursing practice: A qualitative systematised review.}, journal = {Journal of clinical nursing}, volume = {32}, number = {21-22}, pages = {7650-7660}, doi = {10.1111/jocn.16664}, pmid = {36855220}, issn = {1365-2702}, mesh = {Adult ; Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Qualitative Research ; *Nursing Care ; Clinical Competence ; }, abstract = {AIM: To synthesise qualitative research on pulmonary sequelae of COVID-19 and identify patient needs and experiences to develop nursing care strategies.<br><br>BACKGROUND: Qualitative research on long COVID by subtype has not yet occurred. As pulmonary sequelae constitute a serious long COVID subtype, exploring patient experience and needs can generate knowledge to guide nursing practice.<br><br>DESIGN: Systematised review methodology utilised on a purposive sample of published articles and reported using the PRISMA guidelines and checklists. Searched MEDLINE, Cumulative Index to Nursing and Allied Health, and Google Scholar, for English or French articles published from February 2020 to June 2022; qualitative research with adults recovering from COVID-19 with evidence of pulmonary sequelae.<br><br>METHODS: Established principles for data extraction followed related to data reduction, data presentation, data comparison, and conclusion formulation and verification. Analysis was informed by Thorne's Interpretive Description and extended with Meleis' transitions theory, Mishel's uncertainty in illness theory and Moore et al.'s holistic theory of unpleasant symptoms. The quality of included studies was assessed Joanna Briggs Institute critical appraisal tool for qualitative research.<br><br>RESULTS: Four articles with six pooled participants provided data to yield three main themes: (1) a novel health-illness transition, (2) lung injury and pulmonary fibrosis as antecedent to illness uncertainty, (3) and pulmonary symptoms that are compounded by fatigue and weakness.<br><br>CONCLUSION: Pulmonary sequelae of COVID-19 confers a unique health-illness transition, uncertainties and symptoms that can be addressed by theory informed nursing practice.<br><br>Advocacy, optimising the nurse-patient relationship, offering up-to-date information and addressing uncertainty may help patients cope with pulmonary sequelae, a complex subtype of long COVID with important considerations for clinical nursing care. Despite a lack of evidence-informed clinical pathways, nurses can support patients to understand novel treatments, support discharge planning and acknowledge the synergistic nature of pulmonary symptoms and fatigue to support health-illness transitions.<br><br>This article involved analysis of previously published works.}, }
@article {pmid36854331, year = {2023}, author = {Lim, SM and Nahm, M and Kim, SH}, title = {Proteostasis and Ribostasis Impairment as Common Cell Death Mechanisms in Neurodegenerative Diseases.}, journal = {Journal of clinical neurology (Seoul, Korea)}, volume = {19}, number = {2}, pages = {101-114}, pmid = {36854331}, issn = {1738-6586}, support = {NRF-2018M3C7A1056512//National Research Foundation of Korea/Korea ; }, abstract = {The cellular homeostasis of proteins (proteostasis) and RNA metabolism (ribostasis) are essential for maintaining both the structure and function of the brain. However, aging, cellular stress conditions, and genetic contributions cause disturbances in proteostasis and ribostasis that lead to protein misfolding, insoluble aggregate deposition, and abnormal ribonucleoprotein granule dynamics. In addition to neurons being primarily postmitotic, nondividing cells, they are more susceptible to the persistent accumulation of abnormal aggregates. Indeed, defects associated with the failure to maintain proteostasis and ribostasis are common pathogenic components of age-related neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Furthermore, the neuronal deposition of misfolded and aggregated proteins can cause both increased toxicity and impaired physiological function, which lead to neuronal dysfunction and cell death. There is recent evidence that irreversible liquid-liquid phase separation (LLPS) is responsible for the pathogenic aggregate formation of disease-related proteins, including tau, α-synuclein, and RNA-binding proteins, including transactive response DNA-binding protein 43, fused in sarcoma, and heterogeneous nuclear ribonucleoprotein A1. Investigations of LLPS and its control therefore suggest that chaperone/disaggregase, which reverse protein aggregation, are valuable therapeutic targets for effective treatments for neurological diseases. Here we review and discuss recent studies to highlight the importance of understanding the common cell death mechanisms of proteostasis and ribostasis in neurodegenerative diseases.}, }
@article {pmid36842953, year = {2023}, author = {Vautier, A and Lebreton, AL and Codron, P and Awada, Z and Gohier, P and Cassereau, J}, title = {Retinal vessels as a window on amyotrophic lateral sclerosis pathophysiology: A systematic review.}, journal = {Revue neurologique}, volume = {179}, number = {6}, pages = {548-562}, doi = {10.1016/j.neurol.2022.11.010}, pmid = {36842953}, issn = {0035-3787}, mesh = {*Amyotrophic Lateral Sclerosis/diagnostic imaging/physiopathology ; *Retinal Vessels/diagnostic imaging/physiopathology ; Humans ; *Microvessels/diagnostic imaging/physiopathology ; Angiography/methods ; *Tomography, Optical Coherence ; Saccades ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a rare fatal motor neuron disease. Although many potential mechanisms have been proposed, the pathophysiology of the disease remains unknown. Currently available treatments can only delay the progression of the disease and prolong life expectancy by a few months. There is still no definitive cure for ALS, and the development of new treatments is limited by a lack of understanding of the underlying biological processes that trigger and promote neurodegeneration. Several scientific results suggest a neurovascular impairment in ALS providing perspectives for the development of new biomarkers and treatments. In this article, we performed a systematic review using PRISMA guidelines including PubMed, EmBase, GoogleScholar, and Web of Science Core Collection to analyze the scientific literature published between 2000 and 2021 discussing the neurocardiovascular involvement and ophthalmologic abnormalities in ALS. In total, 122 articles were included to establish this systematic review. Indeed, microvascular pathology seems to be involved in ALS, affecting all the neurovascular unit components. Retinal changes have also been recently highlighted without significant alteration of the visual pathways. Despite the peripheral location of the retina, it is considered as an extension of the central nervous system (CNS) as it displays similarities to the brain, the inner blood-retinal barrier, and the blood-brain barrier. This suggests that the eye could be considered as a 'window' into the brain in many CNS disorders. Thus, studying ocular manifestations of brain pathologies seems very promising in understanding neurodegenerative disorders, mainly ALS. Optical coherence tomography angiography (OCT-A) could therefore be a powerful approach for exploration of retinal microvascularization allowing to obtain new diagnostic and prognostic biomarkers of ALS.}, }
@article {pmid36836867, year = {2023}, author = {Alessenko, AV and Gutner, UA and Shupik, MA}, title = {Involvement of Lipids in the Pathogenesis of Amyotrophic Lateral Sclerosis.}, journal = {Life (Basel, Switzerland)}, volume = {13}, number = {2}, pages = {}, pmid = {36836867}, issn = {2075-1729}, support = {&#x2116; 122041400080-0.//Ministry of Science and Higher Education of the Russian Federation/ ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive degeneration of upper and lower motor neurons. To study its underlying mechanisms, a variety of models are currently used at the cellular level and in animals with mutations in multiple ALS associated genes, including SOD1, C9ORF72, TDP-43, and FUS. Key mechanisms involved in the disease include excitotoxicity, oxidative stress, mitochondrial dysfunction, neuroinflammatory, and immune reactions. In addition, significant metabolism alterations of various lipids classes, including phospholipids, fatty acids, sphingolipids, and others have been increasingly recognized. Recently, the mechanisms of programmed cell death (apoptosis), which may be responsible for the degeneration of motor neurons observed in the disease, have been intensively studied. In this context, sphingolipids, which are the most important sources of secondary messengers transmitting signals for cell proliferation, differentiation, and apoptosis, are gaining increasing attention in the context of ALS pathogenesis given their role in the development of neuroinflammatory and immune responses. This review describes changes in lipids content and activity of enzymes involved in their metabolism in ALS, both summarizing current evidence from animal models and clinical studies and discussing the potential of new drugs among modulators of lipid metabolism enzymes.}, }
@article {pmid36835277, year = {2023}, author = {El Ouaamari, Y and Van den Bos, J and Willekens, B and Cools, N and Wens, I}, title = {Neurotrophic Factors as Regenerative Therapy for Neurodegenerative Diseases: Current Status, Challenges and Future Perspectives.}, journal = {International journal of molecular sciences}, volume = {24}, number = {4}, pages = {}, pmid = {36835277}, issn = {1422-0067}, support = {DOCPRO42551//Intern funding of the University of Antwerp: DOCPRO4 BOF PhD fellowship at the University of Antwerp/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/metabolism ; Nerve Growth Factors/metabolism ; *Parkinson Disease/metabolism ; Central Nervous System/metabolism ; *Alzheimer Disease ; }, abstract = {Neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), multiple sclerosis (MS), spinal cord injury (SCI), and amyotrophic lateral sclerosis (ALS), are characterized by acute or chronic progressive loss of one or several neuronal subtypes. However, despite their increasing prevalence, little progress has been made in successfully treating these diseases. Research has recently focused on neurotrophic factors (NTFs) as potential regenerative therapy for neurodegenerative diseases. Here, we discuss the current state of knowledge, challenges, and future perspectives of NTFs with a direct regenerative effect in chronic inflammatory and degenerative disorders. Various systems for delivery of NTFs, such as stem and immune cells, viral vectors, and biomaterials, have been applied to deliver exogenous NTFs to the central nervous system, with promising results. The challenges that currently need to be overcome include the amount of NTFs delivered, the invasiveness of the delivery route, the blood-brain barrier permeability, and the occurrence of side effects. Nevertheless, it is important to continue research and develop standards for clinical applications. In addition to the use of single NTFs, the complexity of chronic inflammatory and degenerative diseases may require combination therapies targeting multiple pathways or other possibilities using smaller molecules, such as NTF mimetics, for effective treatment.}, }
@article {pmid36834853, year = {2023}, author = {Weng, YT and Chang, YM and Chern, Y}, title = {The Impact of Dysregulated microRNA Biogenesis Machinery and microRNA Sorting on Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {24}, number = {4}, pages = {}, pmid = {36834853}, issn = {1422-0067}, support = {AS-IA-108-L06//Academia Sinica/ ; }, mesh = {Humans ; *MicroRNAs/genetics ; *Neurodegenerative Diseases/metabolism ; *Alzheimer Disease ; *Parkinson Disease ; *Huntington Disease ; RNA, Messenger ; }, abstract = {MicroRNAs (miRNAs) are 22-nucleotide noncoding RNAs involved in the differentiation, development, and function of cells in the body by targeting the 3'- untranslated regions (UTR) of mRNAs for degradation or translational inhibition. miRNAs not only affect gene expression inside the cells but also, when sorted into exosomes, systemically mediate the communication between different types of cells. Neurodegenerative diseases (NDs) are age-associated, chronic neurological diseases characterized by the aggregation of misfolded proteins, which results in the progressive degeneration of selected neuronal population(s). The dysregulation of biogenesis and/or sorting of miRNAs into exosomes was reported in several NDs, including Huntington's disease (HD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Alzheimer's disease (AD). Many studies support the possible roles of dysregulated miRNAs in NDs as biomarkers and therapeutic treatments. Understanding the molecular mechanisms underlying the dysregulated miRNAs in NDs is therefore timely and important for the development of diagnostic and therapeutic interventions. In this review, we focus on the dysregulated miRNA machinery and the role of RNA-binding proteins (RBPs) in NDs. The tools that are available to identify the target miRNA-mRNA axes in NDs in an unbiased manner are also discussed.}, }
@article {pmid36834792, year = {2023}, author = {Tsoi, PS and Quan, MD and Ferreon, JC and Ferreon, ACM}, title = {Aggregation of Disordered Proteins Associated with Neurodegeneration.}, journal = {International journal of molecular sciences}, volume = {24}, number = {4}, pages = {}, pmid = {36834792}, issn = {1422-0067}, support = {R01 GM122763/GM/NIGMS NIH HHS/United States ; R01 NS105874/NS/NINDS NIH HHS/United States ; R21 NS107792/NS/NINDS NIH HHS/United States ; R21 NS109678/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Alzheimer Disease/pathology ; Amyloid beta-Peptides/chemistry ; *Amyotrophic Lateral Sclerosis/metabolism ; *Neurodegenerative Diseases ; *Parkinson Disease/metabolism ; tau Proteins ; *Intrinsically Disordered Proteins ; }, abstract = {Cellular deposition of protein aggregates, one of the hallmarks of neurodegeneration, disrupts cellular functions and leads to neuronal death. Mutations, posttranslational modifications, and truncations are common molecular underpinnings in the formation of aberrant protein conformations that seed aggregation. The major proteins involved in neurodegeneration include amyloid beta (Aβ) and tau in Alzheimer's disease, α-synuclein in Parkinson's disease, and TAR DNA-binding protein (TDP-43) in amyotrophic lateral sclerosis (ALS). These proteins are described as intrinsically disordered and possess enhanced ability to partition into biomolecular condensates. In this review, we discuss the role of protein misfolding and aggregation in neurodegenerative diseases, specifically highlighting implications of changes to the primary/secondary (mutations, posttranslational modifications, and truncations) and the quaternary/supramolecular (oligomerization and condensation) structural landscapes for the four aforementioned proteins. Understanding these aggregation mechanisms provides insights into neurodegenerative diseases and their common underlying molecular pathology.}, }
@article {pmid36834611, year = {2023}, author = {Pizcueta, P and Vergara, C and Emanuele, M and Vilalta, A and Rodríguez-Pascau, L and Martinell, M}, title = {Development of PPARγ Agonists for the Treatment of Neuroinflammatory and Neurodegenerative Diseases: Leriglitazone as a Promising Candidate.}, journal = {International journal of molecular sciences}, volume = {24}, number = {4}, pages = {}, pmid = {36834611}, issn = {1422-0067}, support = {SPW-EER/DRDT/DPjR/DEMO/ML/D&#xe9;f-8296//Region Wallonne/ ; }, mesh = {Humans ; *Central Nervous System Diseases/metabolism ; *Neurodegenerative Diseases/metabolism ; Neuroinflammatory Diseases ; PPAR gamma/metabolism ; }, abstract = {Increasing evidence suggests that the peroxisome proliferator-activated receptor γ (PPARγ), a member of the nuclear receptor superfamily, plays an important role in physiological processes in the central nervous system (CNS) and is involved in cellular metabolism and repair. Cellular damage caused by acute brain injury and long-term neurodegenerative disorders is associated with alterations of these metabolic processes leading to mitochondrial dysfunction, oxidative stress, and neuroinflammation. PPARγ agonists have demonstrated the potential to be effective treatments for CNS diseases in preclinical models, but to date, most drugs have failed to show efficacy in clinical trials of neurodegenerative diseases including amyotrophic lateral sclerosis, Parkinson's disease, and Alzheimer's disease. The most likely explanation for this lack of efficacy is the insufficient brain exposure of these PPARγ agonists. Leriglitazone is a novel, blood-brain barrier (BBB)-penetrant PPARγ agonist that is being developed to treat CNS diseases. Here, we review the main roles of PPARγ in physiology and pathophysiology in the CNS, describe the mechanism of action of PPARγ agonists, and discuss the evidence supporting the use of leriglitazone to treat CNS diseases.}, }
@article {pmid36834005, year = {2023}, author = {Sanchez-Andrades, MJ and Vinolo-Gil, MJ and Casuso-Holgado, MJ and Barón-López, J and Rodríguez-Huguet, M and Martín-Valero, R}, title = {Measurement Properties of Self-Report Questionnaires for Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis of Commonly Used Instruments.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {4}, pages = {}, pmid = {36834005}, issn = {1660-4601}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; Quality of Life ; Self Report ; *Neurodegenerative Diseases ; Reproducibility of Results ; Surveys and Questionnaires ; }, abstract = {(1) Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease. There is no evidence on the analysis of the measurement instruments available to assess quality of life in these patients, following the consensus-based standards for the selection of health measurement instruments (COSMIN) checklist; (2) Methods: A systematic review was performed in PubMed, Embase, PEDro, Web of Science and Cochrane. The psychometric properties of the questionnaires were determined by using the COSMIN checklist. Two searches were carried out. This systematic review was registered in PROSPERO (CRD42021249005); (3) Results: There were four published articles that analysed the measurement properties in patients with ALS for the following scales: Amyotrophic Lateral Sclerosis Assessment Questionnaire 40, Amyotrophic Lateral Sclerosis-Specific Quality of Life Questionnaire, Short Form 36 Healthy Survey, Epworth Sleepiness Scale and Sickness Impact Profile. Another five scales also met the inclusion criteria: ALS-Depression-Inventory, State Trait Anxiety-Inventory, World Health Organization Quality of Life, Schedule for the Evaluation of Individual Quality of Life, Amyotrophic Lateral Sclerosis Assessment Questionnaire 5. Most Patient Reported Outcome Measures (PROMs) present a low-quality synthesis of evidence. It was observed an excellent pooled reliability of 0.92 (95% Confidence Interval: 0.83-0.96, I[2] = 87.3%) for four dimensions for questionnaires ALSAQ-40. (4) Conclusions: There is little evidence on generic instruments. Future studies are necessary to develop new tools.}, }
@article {pmid36833252, year = {2023}, author = {Barbo, M and Ravnik-Glavač, M}, title = {Extracellular Vesicles as Potential Biomarkers in Amyotrophic Lateral Sclerosis.}, journal = {Genes}, volume = {14}, number = {2}, pages = {}, pmid = {36833252}, issn = {2073-4425}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology ; Motor Neurons/pathology ; Biomarkers ; *Extracellular Vesicles/pathology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is described as a fatal and rapidly progressive neurodegenerative disorder caused by the degeneration of upper motor neurons in the primary motor cortex and lower motor neurons of the brainstem and spinal cord. Due to ALS's slowly progressive characteristic, which is often accompanied by other neurological comorbidities, its diagnosis remains challenging. Perturbations in vesicle-mediated transport and autophagy as well as cell-autonomous disease initiation in glutamatergic neurons have been revealed in ALS. The use of extracellular vesicles (EVs) may be key in accessing pathologically relevant tissues for ALS, as EVs can cross the blood-brain barrier and be isolated from the blood. The number and content of EVs may provide indications of the disease pathogenesis, its stage, and prognosis. In this review, we collected a recent study aiming at the identification of EVs as a biomarker of ALS with respect to the size, quantity, and content of EVs in the biological fluids of patients compared to controls.}, }
@article {pmid36831264, year = {2023}, author = {Cordts, I and Wachinger, A and Scialo, C and Lingor, P and Polymenidou, M and Buratti, E and Feneberg, E}, title = {TDP-43 Proteinopathy Specific Biomarker Development.}, journal = {Cells}, volume = {12}, number = {4}, pages = {}, pmid = {36831264}, issn = {2073-4409}, mesh = {Humans ; *TDP-43 Proteinopathies ; *Amyotrophic Lateral Sclerosis/metabolism ; *Frontotemporal Dementia/pathology ; Biomarkers ; DNA-Binding Proteins/metabolism ; }, abstract = {TDP-43 is the primary or secondary pathological hallmark of neurodegenerative diseases, such as amyotrophic lateral sclerosis, half of frontotemporal dementia cases, and limbic age-related TDP-43 encephalopathy, which clinically resembles Alzheimer's dementia. In such diseases, a biomarker that can detect TDP-43 proteinopathy in life would help to stratify patients according to their definite diagnosis of pathology, rather than in clinical subgroups of uncertain pathology. For therapies developed to target pathological proteins that cause the disease a biomarker to detect and track the underlying pathology would greatly enhance such undertakings. This article reviews the latest developments and outlooks of deriving TDP-43-specific biomarkers from the pathophysiological processes involved in the development of TDP-43 proteinopathy and studies using biosamples from clinical entities associated with TDP-43 pathology to investigate biomarker candidates.}, }
@article {pmid36831041, year = {2023}, author = {Marsili, L and Sharma, J and Outeiro, TF and Colosimo, C}, title = {Stem Cell Therapies in Movement Disorders: Lessons from Clinical Trials.}, journal = {Biomedicines}, volume = {11}, number = {2}, pages = {}, pmid = {36831041}, issn = {2227-9059}, abstract = {Stem cell-based therapies (SCT) to treat neurodegenerative disorders have promise but clinical trials have only recently begun, and results are not expected for several years. While most SCTs largely lead to a symptomatic therapeutic effect by replacing lost cell types, there may also be disease-modifying therapeutic effects. In fact, SCT may complement a multi-drug, subtype-specific therapeutic approach, consistent with the idea of precision medicine, which matches molecular therapies to biological subtypes of disease. In this narrative review, we examine published and ongoing trials in SCT in Parkinson's Disease, atypical parkinsonian disorders, Huntington's disease, amyotrophic lateral sclerosis, and spinocerebellar ataxia in humans. We discuss the benefits and pitfalls of using this treatment approach within the spectrum of disease-modification efforts in neurodegenerative diseases. SCT may hold greater promise in the treatment of neurodegenerative disorders, but much research is required to determine the feasibility, safety, and efficacy of these complementary aims of therapeutic efforts.}, }
@article {pmid36830535, year = {2023}, author = {Wolframm, IA and Douglas, J and Pearson, G}, title = {Changing Hearts and Minds in the Equestrian World One Behaviour at a Time.}, journal = {Animals : an open access journal from MDPI}, volume = {13}, number = {4}, pages = {}, pmid = {36830535}, issn = {2076-2615}, abstract = {Equestrianism is currently facing a range of pressing challenges. These challenges, which are largely based on evolving attitudes to ethics and equine wellbeing, have consequences for the sport's social licence to operate. The factors that may have contributed to the current situation include overarching societal trends, specific aspects of the equestrian sector, and factors rooted in human nature. If equestrianism is to flourish, it is evident that much needs to change, not the least, human behaviour. To this end, using established behaviour change frameworks that have been scientifically validated and are rooted in practice-most notably, Michie et al.'s COM-B model and Behaviour Change Wheel-could be of practical value for developing and implementing equine welfare strategies. This review summarises the theoretical underpinnings of some behaviour change frameworks and provides a practical, step-by-step approach to designing an effective behaviour change intervention. A real-world example is provided through the retrospective analysis of an intervention strategy that aimed to increase the use of learning theory in (educational) veterinary practice. We contend that the incorporation of effective behaviour change interventions into any equine welfare improvement strategy may help to safeguard the future of equestrianism.}, }
@article {pmid36830306, year = {2023}, author = {Castagneto-Gissey, L and Russo, MF and Casella-Mariolo, J and Serao, A and Marcellinaro, R and D'Andrea, V and Carlini, M and Casella, G}, title = {The Role of Antibiotic Prophylaxis in Anastomotic Leak Prevention during Elective Colorectal Surgery: Systematic Review and Meta-Analysis of Randomized Controlled Trials.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {12}, number = {2}, pages = {}, pmid = {36830306}, issn = {2079-6382}, abstract = {Introduction: Despite several perioperative care advancements and innovations in surgical procedures and technologies, the incidence rate of anastomotic leaks (ALs) after colorectal surgery has not substantially decreased. Gut microbiota can play a critical role in the healing process of anastomotic tissue and alterations in its composition may be largely to blame for anastomotic insufficiency. The use of specific antibiotics for preoperative large bowel decontamination could significantly influence the rate of ALs. The aim of this study was to systematically assess the various antibiotic prophylactic regimen strategies for primary prevention of ALs during colorectal surgery, in view of the available evidence. Methods: A systematic review of the literature was conducted, and randomized clinical trials (RCTs) analyzing prophylactic antibiotic bowel preparation in colorectal surgery were included. PubMed, Embase, the Web of Science Core Collection, and the Cochrane Central Register of Controlled Trials were searched from inception through to 30 November 2022. The methodological quality of the included trials was evaluated. The primary outcome was AL rate; secondary outcomes were superficial/deep surgical site infections (SSIs). The PRISMA guidelines were used to carry out the present systematic review. Results: Thirteen RCTs published between 1977 and 2022, with a total of 4334 patients were included in the meta-analysis. Antibiotic prophylaxis was administered orally in 11/13 studies and intravenously in 2 studies. Patients randomly assigned to antibiotic prophylaxis, regardless of the regimen, had a reduced risk of ALs (p = 0.003) compared to mechanical bowel preparation (MBP) alone. The use of antibiotic prophylaxis was also more effective in significantly reducing SSIs (p < 0.001). Conclusions: The evidence points to an advantage of oral antibiotic prophylaxis in terms of AL rate, a significant contributor to perioperative morbidity, mortality, and rising healthcare expenditures. In light of such results, the use of antibiotic prophylaxis should be strongly encouraged prior to colorectal surgery.}, }
@article {pmid36830075, year = {2023}, author = {Olufunmilayo, EO and Gerke-Duncan, MB and Holsinger, RMD}, title = {Oxidative Stress and Antioxidants in Neurodegenerative Disorders.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {12}, number = {2}, pages = {}, pmid = {36830075}, issn = {2076-3921}, abstract = {Neurodegenerative disorders constitute a substantial proportion of neurological diseases with significant public health importance. The pathophysiology of neurodegenerative diseases is characterized by a complex interplay of various general and disease-specific factors that lead to the end point of neuronal degeneration and loss, and the eventual clinical manifestations. Oxidative stress is the result of an imbalance between pro-oxidant species and antioxidant systems, characterized by an elevation in the levels of reactive oxygen and reactive nitrogen species, and a reduction in the levels of endogenous antioxidants. Recent studies have increasingly highlighted oxidative stress and associated mitochondrial dysfunction to be important players in the pathophysiologic processes involved in neurodegenerative conditions. In this article, we review the current knowledge of the general effects of oxidative stress on the central nervous system, the different specific routes by which oxidative stress influences the pathophysiologic processes involved in Alzheimer's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis and Huntington's disease, and how oxidative stress may be therapeutically reversed/mitigated in order to stall the pathological progression of these neurodegenerative disorders to bring about clinical benefits.}, }
@article {pmid36828272, year = {2023}, author = {Dave, BP and Shah, KC and Shah, MB and Chorawala, MR and Patel, VN and Shah, PA and Shah, GB and Dhameliya, TM}, title = {Unveiling the modulation of Nogo receptor in neuroregeneration and plasticity: Novel aspects and future horizon in a new frontier.}, journal = {Biochemical pharmacology}, volume = {210}, number = {}, pages = {115461}, doi = {10.1016/j.bcp.2023.115461}, pmid = {36828272}, issn = {1873-2968}, mesh = {Humans ; *Myelin Proteins/genetics/metabolism ; Nogo Proteins ; Nerve Regeneration/physiology ; Nerve Growth Factors ; *Neurodegenerative Diseases ; Nogo Receptors ; }, abstract = {Neurodegenerative diseases (NDs) such as Alzheimer's, Parkinson's, Multiple Sclerosis, Hereditary Spastic Paraplegia, and Amyotrophic Lateral Sclerosis have emerged as the most dreaded diseases due to a lack of precise diagnostic tools and efficient therapies. Despite the fact that the contributing factors of NDs are still unidentified, mounting evidence indicates the possibility that genetic and cellular changes may lead to the significant production of abnormally misfolded proteins. These misfolded proteins lead to damaging effects thereby causing neurodegeneration. The association between Neurite outgrowth factor (Nogo) with neurological diseases and other peripheral diseases is coming into play. Three isoforms of Nogo have been identified Nogo-A, Nogo-B and Nogo-C. Among these, Nogo-A is mainly responsible for neurological diseases as it is localized in the CNS (Central Nervous System), whereas Nogo-B and Nogo-C are responsible for other diseases such as colitis, lung, intestinal injury, etc. Nogo-A, a membrane protein, had first been described as a CNS-specific inhibitor of axonal regeneration. Several recent studies have revealed the role of Nogo-A proteins and their receptors in modulating neurite outgrowth, branching, and precursor migration during nervous system development. It may also modulate or affect the inhibition of growth during the developmental processes of the CNS. Information about the effects of other ligands of Nogo protein on the CNS are yet to be discovered however several pieces of evidence have suggested that it may also influence the neuronal maturation of CNS and targeting Nogo-A could prove to be beneficial in several neurodegenerative diseases.}, }
@article {pmid36825209, year = {2023}, author = {Joshi, T and Ahuja, N}, title = {The Prion Basis of Progressive Neurodegenerative Disorders.}, journal = {Interdisciplinary perspectives on infectious diseases}, volume = {2023}, number = {}, pages = {6687264}, pmid = {36825209}, issn = {1687-708X}, abstract = {The discovery of proteinaceous infectious agents by Prusiner in 1982 was sensational. All previously known pathogens contained nucleic acids, the code of life, that enabled them to reproduce. In contrast, the proteinaceous agents of disease, called prion proteins (PrP), lacked nucleic acids and propagated by binding to the functional, endogenous form of cellular prion protein (referred to as PrP[C]) and altering its conformation to produce the infectious disease-causing misfolded protein (referred to as PrP[Sc]). The accumulation and aggregation of these infectious prion proteins within the brain cause destruction of neural tissue and lead to fatal spongiform encephalopathies. In this review, we present the molecular pathology of prion-based diseases. These insights are of particular importance since the principles of prion pathogenesis apply to other neurodegenerative diseases such as Alzheimer's disease, Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Collectively, the global prevalence of these diseases is rapidly increasing while effective therapies against them are still lacking. Thus, the need to understand their etiology and pathogenesis is urgent, and it holds profound implications for societal health.}, }
@article {pmid36824265, year = {2023}, author = {Chen, X and He, E and Su, C and Zeng, Y and Xu, J}, title = {Huntingtin-associated protein 1-associated intracellular trafficking in neurodegenerative diseases.}, journal = {Frontiers in aging neuroscience}, volume = {15}, number = {}, pages = {1100395}, pmid = {36824265}, issn = {1663-4365}, abstract = {Huntingtin-associated protein 1 (HAP1), the first identified HTT-binding partner, is highly expressed in the central nervous system, and has been found to associated with neurological diseases. Mounting evidence suggests that HAP1 functions as a component of cargo-motor molecules to bind various proteins and participates in intracellular trafficking. It is known that the failure of intracellular transport is a key contributor to the progression of neurodegenerative disorders (NDs) including Alzheimer's disease (AD), Huntington's disease (HD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), spinal and bulbar muscular atrophy (SBMA) and spinocerebellar ataxia (SCA). The link between HAP1 and various NDs is supported by growing evidence. This review aims to provide a comprehensive overview of the intracellular trafficking function of HAP1 and its involvement in NDs.}, }
@article {pmid36822629, year = {2023}, author = {Zhang, B and Burke, R}, title = {Copper homeostasis and the ubiquitin proteasome system.}, journal = {Metallomics : integrated biometal science}, volume = {15}, number = {3}, pages = {}, pmid = {36822629}, issn = {1756-591X}, mesh = {Humans ; *Proteasome Endopeptidase Complex ; Ubiquitin/metabolism ; Copper/metabolism ; *Neurodegenerative Diseases/metabolism ; Homeostasis ; Copper Transport Proteins ; }, abstract = {Copper is involved in many physiological pathways and important biological processes as a cofactor of several copper-dependent enzymes. Given the requirement for copper and its potential toxicity, intracellular copper levels are tightly controlled. Disturbances of human copper homeostasis are characterized by disorders of copper overload (Wilson's disease) or copper deficiency (Menkes disease). The maintenance of cellular copper levels involves numerous copper transporters and copper chaperones. Recently, accumulating evidence has revealed that components of the ubiquitin proteasome system (UPS) participate in the posttranslational regulation of these proteins, suggesting that they might play a role in maintaining copper homeostasis. Cellular copper levels could also affect the activity of the UPS, indicating that copper homeostasis and the UPS are interdependent. Copper homeostasis and the UPS are essential to the integrity of normal brain function and while separate links between neurodegenerative diseases and UPS inhibition/copper dyshomeostasis have been extensively reported, there is growing evidence that these two networks might contribute synergistically to the occurrence of neurodegenerative diseases. Here, we review the role of copper and the UPS in the development of Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, and discuss the genetic interactions between copper transporters/chaperones and components of the UPS.}, }
@article {pmid36822211, year = {2023}, author = {Günther, R}, title = {[Gene Therapies in Motor Neuron Diseases ALS and SMA].}, journal = {Fortschritte der Neurologie-Psychiatrie}, volume = {91}, number = {4}, pages = {153-163}, doi = {10.1055/a-2002-5215}, pmid = {36822211}, issn = {1439-3522}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/therapy ; Genetic Therapy/methods ; *Motor Neuron Disease/genetics/therapy/diagnosis ; *Muscular Atrophy, Spinal/genetics/therapy ; }, abstract = {In the past, the diagnosis of motor neuron diseases such as amyotrophic lateral sclerosis (ALS) and 5q-associated spinal muscular atrophy (SMA) meant powerlessness in the face of seemingly untreatable diseases with severe motor-functional limitations and sometimes fatal courses. Recent advances in an understanding of the genetic causalities of these diseases, combined with success in the development of targeted gene therapy strategies, spell hope for effective, innovative therapeutic approaches, pioneering the ability to treat neurodegenerative diseases. While gene therapies have been approved for SMA since a few years, gene therapy research in ALS is still in clinical trials with encouraging results. This article provides an overview of the genetic background of ALS and SMA known to date and gene therapy approaches to them with a focus on therapy candidates that are in clinical trials or have already gained market approval.}, }
@article {pmid36821633, year = {2023}, author = {Mitchell, RE and Hartley, AE and Walker, VM and Gkatzionis, A and Yarmolinsky, J and Bell, JA and Chong, AHW and Paternoster, L and Tilling, K and Smith, GD}, title = {Strategies to investigate and mitigate collider bias in genetic and Mendelian randomisation studies of disease progression.}, journal = {PLoS genetics}, volume = {19}, number = {2}, pages = {e1010596}, pmid = {36821633}, issn = {1553-7404}, support = {MC_UU_00011/3/MRC_/Medical Research Council/United Kingdom ; MC_UU_00019/4/MRC_/Medical Research Council/United Kingdom ; MC_UU_00011/1/MRC_/Medical Research Council/United Kingdom ; MC_PC_20059/MRC_/Medical Research Council/United Kingdom ; MC_UU_00032/1/MRC_/Medical Research Council/United Kingdom ; MC_UU_00011/4/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *Genome-Wide Association Study ; Bias ; Risk Factors ; Phenotype ; *Mendelian Randomization Analysis/methods ; Disease Progression ; }, abstract = {Genetic studies of disease progression can be used to identify factors that may influence survival or prognosis, which may differ from factors that influence on disease susceptibility. Studies of disease progression feed directly into therapeutics for disease, whereas studies of incidence inform prevention strategies. However, studies of disease progression are known to be affected by collider (also known as "index event") bias since the disease progression phenotype can only be observed for individuals who have the disease. This applies equally to observational and genetic studies, including genome-wide association studies and Mendelian randomisation (MR) analyses. In this paper, our aim is to review several statistical methods that can be used to detect and adjust for index event bias in studies of disease progression, and how they apply to genetic and MR studies using both individual- and summary-level data. Methods to detect the presence of index event bias include the use of negative controls, a comparison of associations between risk factors for incidence in individuals with and without the disease, and an inspection of Miami plots. Methods to adjust for the bias include inverse probability weighting (with individual-level data), or Slope-Hunter and Dudbridge et al.'s index event bias adjustment (when only summary-level data are available). We also outline two approaches for sensitivity analysis. We then illustrate how three methods to minimise bias can be used in practice with two applied examples. Our first example investigates the effects of blood lipid traits on mortality from coronary heart disease, while our second example investigates genetic associations with breast cancer mortality.}, }
@article {pmid36821554, year = {2023}, author = {Saatchi, AG and Pallotti, F and Sullivan, P}, title = {Network approaches and interventions in healthcare settings: A systematic scoping review.}, journal = {PloS one}, volume = {18}, number = {2}, pages = {e0282050}, pmid = {36821554}, issn = {1932-6203}, mesh = {Humans ; *Health Personnel ; Hospitals ; Delivery of Health Care ; *Physicians ; Social Networking ; }, abstract = {INTRODUCTION: The growing interest in networks of interactions is sustained by the conviction that they can be leveraged to improve the quality and efficiency of healthcare delivery systems. Evidence in support of this conviction, however, is mostly based on descriptive studies. Systematic evaluation of the outcomes of network interventions in healthcare settings is still wanting. Despite the proliferation of studies based on Social Network Analysis (SNA) tools and techniques, we still know little about how intervention programs aimed at altering existing patterns of social interaction among healthcare providers affect the quality of service delivery. We update and extend prior reviews by providing a comprehensive assessment of available evidence.<br><br>METHODS AND FINDINGS: We searched eight databases to identify papers using SNA in healthcare settings published between 1st January 2010 and 1st May 2022. We followed Chambers et al.'s (2012) approach, using a Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist. We distinguished between studies relying on SNA as part of an intervention program, and studies using SNA for descriptive purposes only. We further distinguished studies recommending a possible SNA-based intervention. We restricted our focus on SNA performed on networks among healthcare professionals (e.g., doctors, nurses, etc.) in any healthcare setting (e.g., hospitals, primary care, etc.). Our final review included 102 papers. The majority of the papers used SNA for descriptive purposes only. Only four studies adopted SNA as an intervention tool, and measured outcome variables.<br><br>CONCLUSIONS: We found little evidence for SNA-based intervention programs in healthcare settings. We discuss the reasons and challenges, and identify the main component elements of a network intervention plan. Future research should seek to evaluate the long-term role of SNA in changing practices, policies and behaviors, and provide evidence of how these changes affect patients and the quality of service delivery.}, }
@article {pmid36816743, year = {2023}, author = {Zang, Y and Lai, X and Li, C and Ding, D and Wang, Y and Zhu, Y}, title = {The Role of Gut Microbiota in Various Neurological and Psychiatric Disorders-An Evidence Mapping Based on Quantified Evidence.}, journal = {Mediators of inflammation}, volume = {2023}, number = {}, pages = {5127157}, pmid = {36816743}, issn = {1466-1861}, mesh = {Humans ; *Autism Spectrum Disorder/microbiology ; Bacteria ; Bacteroidetes ; Clostridiales ; *Depressive Disorder, Major ; Firmicutes ; *Gastrointestinal Microbiome ; Systematic Reviews as Topic ; Meta-Analysis as Topic ; }, abstract = {METHODS: We searched PubMed, Cochrane Library, and Epistemonikos to identify systematic reviews and meta-analysis (SRs). We searched for neurological diseases and psychiatric disorders, including Alzheimer's disease (AD), attention deficit hyperactivity disorder (ADHD), amyotrophic lateral sclerosis (ALS), autism spectrum disorder (ASD), anorexia nervosa (AN), bipolar disorder (BD), eating disorder (ED), generalized anxiety disorder (GAD), major depressive disorder (MDD), multiple sclerosis (MS), obsessive compulsive disorder (OCD), Parkinson's disease (PD), posttraumatic stress disorder (PTSD), spinal cord injury (SCI), schizophrenia, and stroke. We used A Measurement Tool to Assess Systematic Reviews (AMSTAR-2) to evaluate the quality of included SRs. We also created an evidence map showing the role of gut microbiota in neurological diseases and the certainty of the evidence.<br><br>RESULTS: In total, 42 studies were included in this evidence mapping. Most findings were obtained from observational studies. According to the AMSTAR-2 assessment, 21 SRs scored "critically low" in terms of methodological quality, 16 SR scored "low," and 5 SR scored "moderate." A total of 15 diseases have been investigated for the potential association between gut microbiome alpha diversity and disease, with the Shannon index and Simpson index being the most widely studied. A total of 12 diseases were investigated for potential link between beta diversity and disease. At the phylum level, Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, and Verrucomicrobia were more researched. At the genus level, Prevotella, Coprococcus, Parabacteroides, Phascolarctobacterium, Escherichia Shigella, Alistipes, Sutteralla, Veillonella, Odoribacter, Faecalibacterium, Bacteroides, Bifidobacterium, Dialister, and Blautia were more researched. Some diseases have been found to have specific flora changes, and some diseases have been found to have common intestinal microbiological changes.<br><br>CONCLUSION: We found varied levels of evidence for the associations between gut microbiota and neurological diseases; some gut microbiota increased the risk of neurological diseases, whereas others showed evidence of benefit that gut microbiota might be promising therapeutic targets for such diseases.}, }
@article {pmid36812393, year = {2023}, author = {Bongioanni, P and Borasio, GD and Oliver, DJ and Romagnoli, A and Kapitza, KP and Sidle, K and Tramonti, F}, title = {Methods for informing people with amyotrophic lateral sclerosis/motor neuron disease of their diagnosis.}, journal = {The Cochrane database of systematic reviews}, volume = {2}, number = {2}, pages = {CD007593}, pmid = {36812393}, issn = {1469-493X}, mesh = {Adult ; Humans ; *Amyotrophic Lateral Sclerosis ; *Motor Neuron Disease/psychology/therapy ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND), causes increasing physical impairment and disability. People with ALS/MND face huge physical challenges, and the diagnosis can be a source of great psychological distress for both people with ALS/MND and their carers. In such a context, how news of the diagnosis is broken is important. At present, there are no systematic reviews of methods for informing people with ALS/MND of their diagnosis.<br><br>OBJECTIVES: To examine the effects and effectiveness of different methods for informing people of a diagnosis of amyotrophic lateral sclerosis/motor neuron disease (ALS/MND), including effects on the person's knowledge and understanding of their disease, its treatment, and care; and on coping and adjustment to the effects of ALS/MND, its treatment, and care.<br><br>SEARCH METHODS: We searched the Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, and two trials registers (February 2022). We contacted individuals or organisations to locate studies. We contacted study authors to obtain additional unpublished data.<br><br>SELECTION CRITERIA: We planned to include randomised controlled trials (RCTs) and quasi-RCTs of techniques for informing people with ALS/MND of their diagnosis. We planned to include adults (aged 17 years or over) with ALS/MND, according to the El Escorial criteria.<br><br>DATA COLLECTION AND ANALYSIS: Three review authors independently reviewed the results of the search to identify RCTs, and three review authors identified non-randomised studies to include in the discussion section. We planned that two review authors would independently extract data, and three would assess the risk of bias in any included trials.<br><br>MAIN RESULTS: We did not identify any RCTs that met our inclusion criteria.<br><br>AUTHORS' CONCLUSIONS: There are no RCTs that evaluate different communication strategies for breaking the bad news for people diagnosed with ALS/MND. Focused research studies are needed to assess the effectiveness and efficacy of different communication methods.}, }
@article {pmid36805318, year = {2023}, author = {Soto-Lara, M and Silva-Loredo, M and Monroy-Córdoba, JR and Flores-Ordoñez, P and Cervera-Delgadillo, NG and Carrillo-Mora, P}, title = {Alternative medicine therapies in neurological disorders: Prevalence, reasons and associated factors. A systematic review.}, journal = {Complementary therapies in medicine}, volume = {73}, number = {}, pages = {102932}, doi = {10.1016/j.ctim.2023.102932}, pmid = {36805318}, issn = {1873-6963}, mesh = {Adult ; Humans ; Female ; Middle Aged ; Male ; Prevalence ; Cross-Sectional Studies ; Retrospective Studies ; *Complementary Therapies/methods ; *Nervous System Diseases/epidemiology/therapy ; *Stroke ; }, abstract = {OBJECTIVE: This systematic review aimed to identify the prevalence of CAM use in patients with neurological disorders, and also to know most frequent types of CAM used.<br><br>METHODS: Five databases: PubMed, Science Direct, EBSCO, Latindex and Scielo (in English and Spanish) were searched from January 2010 to May 2021. Only original cross-sectional, retrospective and cohort studies were included, whose primary objective was to describe the frequency of CAM use in neurological disorders and/or the related factors to its use in adults. Based on the data, a descriptive analysis was performed, covering the characteristics of studies, measuring methods, prevalence, types and related factors. To control the risk of bias, a quality assessment of each study was performed using STROBE checklist.<br><br>RESULTS: For the final analysis, 40 studies were included. Most common pathologies observed in the studies were multiple sclerosis, headache, stroke, Parkinson and epilepsy. The STROBE score of studies ranged from 13 to 22 points, with an average of 18.2. Prevalence of CAM use was highly variable from one study to another (16% in stroke patients, to 100% in amyotrophic lateral sclerosis or spinal cord injury patients). Biological therapies (dietary supplements and herbal medicine) were the most commonly CAM types used. The associated factors identified were female sex, an age between 40 and 50 years, and higher socioeconomic level. Not all studies investigated about the results of CAMs but these ranged from 35% to more than 80% of reporting positive effects.<br><br>CONCLUSIONS: The prevalence of CAM use in neurological diseases is highly variable (16%-100%); the most used type of CAM was biological therapies and the associated factors were female sex, age between 40 and 50 years old and high socioeconomic level.}, }
@article {pmid36804755, year = {2023}, author = {Kooshki, L and Zarneshan, SN and Fakhri, S and Moradi, SZ and Echeverria, J}, title = {The pivotal role of JAK/STAT and IRS/PI3K signaling pathways in neurodegenerative diseases: Mechanistic approaches to polyphenols and alkaloids.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {112}, number = {}, pages = {154686}, doi = {10.1016/j.phymed.2023.154686}, pmid = {36804755}, issn = {1618-095X}, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Janus Kinases/metabolism ; Phosphatidylinositol 3-Kinase/metabolism ; Polyphenols/pharmacology ; Signal Transduction ; *Alkaloids/pharmacology ; *Biological Products ; }, abstract = {BACKGROUND: Neurodegenerative diseases (NDDs) are characterized by progressive neuronal dysfunctionality which results in disability and human life-threatening events. In recent decades, NDDs are on the rise. Besides, conventional drugs have not shown potential effectiveness to attenuate the complications of NDDs. So, exploring novel therapeutic agents is an urgent need to combat such disorders. Accordingly, growing evidence indicates that polyphenols and alkaloids are promising natural candidates, possessing several beneficial pharmacological effects against diseases. Considering the complex pathophysiological mechanisms behind NDDs, Janus kinase (JAK), insulin receptor substrate (IRS), phosphoinositide 3-kinase (PI3K), and signal transducer and activator of transcription (STAT) seem to play critical roles during neurodegeneration/neuroregeneration. In this line, modulation of the JAK/STAT and IRS/PI3K signaling pathways and their interconnected mediators by polyphenols/alkaloids could play pivotal roles in combating NDDs, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), stroke, aging, multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), depression and other neurological disorders.<br><br>PURPOSE: Thus, the present study aimed to investigate the neuroprotective roles of polyphenols/alkaloids as multi-target natural products against NDDs which are critically passing through the modulation of the JAK/STAT and IRS/PI3K signaling pathways.<br><br>STUDY DESIGN AND METHODS: A systematic and comprehensive review was performed to highlight the modulatory roles of polyphenols and alkaloids on the JAK/STAT and IRS/PI3K signaling pathways in NDDs, according to the PRISMA guideline, using scholarly electronic databases, including Scopus, PubMed, ScienceDirect, and associated reference lists.<br><br>RESULTS: In the present study 141 articles were included from a total of 1267 results. The results showed that phenolic compounds such as curcumin, epigallocatechin-3-gallate, and quercetin, and alkaloids such as berberine could be introduced as new strategies in combating NDDs through JAK/STAT and IRS/PI3K signaling pathways. This is the first systematic review that reveals the correlation between the JAK/STAT and IRS/PI3K axis which is targeted by phytochemicals in NDDs. Hence, this review highlighted promising insights into the neuroprotective potential of polyphenols and alkaloids through the JAK/STAT and IRS/PI3K signaling pathway and interconnected mediators toward neuroprotection.<br><br>CONCLUSION: Amongst natural products, phenolic compounds and alkaloids are multi-targeting agents with the most antioxidants and anti-inflammatory effects possessing the potential of combating NDDs with high efficacy and lower toxicity. However, additional reports are needed to prove the efficacy and possible side effects of natural products.}, }
@article {pmid36801857, year = {2023}, author = {Wang, P and Wei, Q and Li, H and Wu, ZY}, title = {Clinical feature difference between juvenile amyotrophic lateral sclerosis with SPTLC1 and FUS mutations.}, journal = {Chinese medical journal}, volume = {136}, number = {2}, pages = {176-183}, pmid = {36801857}, issn = {2542-5641}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; DNA Helicases/genetics ; Genetic Association Studies ; Multifunctional Enzymes/genetics ; Mutation/genetics ; RNA Helicases/genetics ; RNA-Binding Protein FUS/genetics ; Serine C-Palmitoyltransferase/genetics ; Child, Preschool ; Child ; Adolescent ; Young Adult ; }, abstract = {BACKGROUND: Juvenile amyotrophic lateral sclerosis (JALS) is an uncommon form of amyotrophic lateral sclerosis whose age at onset (AAO) is defined as prior to 25 years. FUS mutations are the most common cause of JALS. SPTLC1 was recently identified as a disease-causative gene for JALS, which has rarely been reported in Asian populations. Little is known regarding the difference in clinical features between JALS patients carrying FUS and SPTLC1 mutations. This study aimed to screen mutations in JALS patients and to compare the clinical features between JALS patients with FUS and SPTLC1 mutations.<br><br>METHODS: Sixteen JALS patients were enrolled, including three newly recruited patients between July 2015 and August 2018 from the Second Affiliated Hospital, Zhejiang University School of Medicine. Mutations were screened by whole-exome sequencing. In addition, clinical features such as AAO, onset site and disease duration were extracted and compared between JALS patients carrying FUS and SPTLC1 mutations through a literature review.<br><br>RESULTS: A novel and de novo SPTLC1 mutation (c.58G>A, p.A20T) was identified in a sporadic patient. Among 16 JALS patients, 7/16 carried FUS mutations and 5/16 carried respective SPTLC1 , SETX , NEFH , DCTN1 , and TARDBP mutations. Compared with FUS mutation patients, those with SPTLC1 mutations had an earlier AAO (7.9&#x200a;&#xb1;&#x200a;4.6 years vs. 18.1&#x200a;&#xb1;&#x200a;3.9 years, P &#x200a;<&#x200a;0.01), much longer disease duration (512.0 [416.7-607.3] months vs. 33.4 [21.6-45.1] months, P &#x200a;<&#x200a;0.01), and no onset of bulbar.<br><br>CONCLUSION: Our findings expand the genetic and phenotypic spectrum of JALS and help to better understand the genotype-phenotype correlation of JALS.}, }
@article {pmid36800114, year = {2023}, author = {de Oliveira, LMG and Carreira, RB and de Oliveira, JVR and do Nascimento, RP and Dos Santos Souza, C and Trias, E and da Silva, VDA and Costa, SL}, title = {Impact of Plant-Derived Compounds on Amyotrophic Lateral Sclerosis.}, journal = {Neurotoxicity research}, volume = {41}, number = {3}, pages = {288-309}, pmid = {36800114}, issn = {1476-3524}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/complications ; Riluzole ; Edaravone/therapeutic use ; Glutamic Acid ; Phytochemicals/therapeutic use ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal illness characterized by progressive motor neuron degeneration. Conventional therapies for ALS are based on treatment of symptoms, and the disease remains incurable. Molecular mechanisms are unclear, but studies have been pointing to involvement of glia, neuroinflammation, oxidative stress, and glutamate excitotoxicity as a key factor. Nowadays, we have few treatments for this disease that only delays death, but also does not stop the neurodegenerative process. These treatments are based on glutamate blockage (riluzole), tyrosine kinase inhibition (masitinib), and antioxidant activity (edaravone). In the past few years, plant-derived compounds have been studied for neurodegenerative disorder therapies based on neuroprotection and glial cell response. In this review, we describe mechanisms of action of natural compounds associated with neuroprotective effects, and the possibilities for new therapeutic strategies in ALS.}, }
@article {pmid36795184, year = {2023}, author = {Sharma, VK and Singh, TG and Mehta, V and Mannan, A}, title = {Biomarkers: Role and Scope in Neurological Disorders.}, journal = {Neurochemical research}, volume = {48}, number = {7}, pages = {2029-2058}, pmid = {36795184}, issn = {1573-6903}, mesh = {Humans ; *Nervous System Diseases/diagnosis ; Biomarkers ; Brain ; }, abstract = {Neurological disorders pose a great threat to social health and are a major cause for mortality and morbidity. Effective drug development complemented with the improved drug therapy has made considerable progress towards easing symptoms associated with neurological illnesses, yet poor diagnosis and imprecise understanding of these disorders has led to imperfect treatment options. The scenario is complicated by the inability to extrapolate results of cell culture studies and transgenic models to clinical applications which has stagnated the process of improving drug therapy. In this context, the development of biomarkers has been viewed as beneficial to easing various pathological complications. A biomarker is measured and evaluated in order to gauge the physiological process or a pathological progression of a disease and such a marker can also indicate the clinical or pharmacological response to a therapeutic intervention. The development and identification of biomarkers for neurological disorders involves several issues including the complexity of the brain, unresolved discrepant data from experimental and clinical studies, poor clinical diagnostics, lack of functional endpoints, and high cost and complexity of techniques yet research in the area of biomarkers is highly desired. The present work describes existing biomarkers for various neurological disorders, provides support for the idea that biomarker development may ease our understanding underlying pathophysiology of these disorders and help to design and explore therapeutic targets for effective intervention.}, }
@article {pmid36794866, year = {2024}, author = {Sibley, AK and McQuaid, W and Jain, TN and Mills, A and Travers, A}, title = {Paramedic Interventions and Adverse Patient Events during Prolonged Interfacility Ground Transport in a "Drip and Ship" Pharmacoinvasive Model of STEMI Care.}, journal = {Prehospital emergency care}, volume = {28}, number = {2}, pages = {375-380}, doi = {10.1080/10903127.2023.2179707}, pmid = {36794866}, issn = {1545-0066}, mesh = {Male ; Humans ; Middle Aged ; Female ; *ST Elevation Myocardial Infarction/therapy ; *Emergency Medical Services/methods ; *Myocardial Infarction/etiology ; *Percutaneous Coronary Intervention/adverse effects ; Paramedics ; Retrospective Studies ; }, abstract = {OBJECTIVE: Primary percutaneous coronary intervention (PCI) is the preferred reperfusion strategy for patients with ST-segment elevation myocardial infarction (STEMI). However, when primary PCI is not available in a timely fashion, fibrinolysis and early transfer for routine PCI is recommended. Prince Edward Island (PEI) is the only province in Canada without a PCI facility, and distances to the nearest PCI-capable facilities are between 290 and 374 kilometers. This results in prolonged out-of-hospital time for critically ill patients. We sought to characterize and quantify paramedic interventions and adverse patient events during prolonged ground transport to PCI facilities post-fibrinolysis.<br><br>METHODS: We performed a retrospective chart review of patients presenting to any of four emergency departments (ED) on PEI during the calendar years 2016 and 2017. We identified patients through administrative discharge data and cross referenced with emergent out-of-province ambulance transfers. All included patients were managed as STEMIs in the EDs and subsequently transferred (primary PCI, pharmacoinvasive) directly from the EDs to PCI facilities. We excluded patients having STEMIs on inpatient wards and those transported by other means. We reviewed electronic and paper ED charts plus paper EMS records. We performed summary statistics.<br><br>RESULTS: We identified 149 patients meeting inclusion criteria. Most patients were males (77.9%), mean age 62.1 (SD 13.8) years. The mean transport interval was 202 (SD 29.0) minutes. Thirty-two adverse events occurred during 24 transports (16.1%). There was one death, and four patients required diversion to non-PCI facilities. Hypotension was the most common adverse event (n&#x2009;=&#x2009;13, 8.7%), and fluid bolus (n&#x2009;=&#x2009;11, 7.4%) was the most common intervention. Three (2.0%) patients required electrical therapy. Nitrates (n&#x2009;=&#x2009;65, 43.6%) and opioid analgesics (n&#x2009;=&#x2009;51, 34.2%) were the most common drugs administered during transport.<br><br>CONCLUSION: In a setting where primary PCI is not feasible due to distance, a pharmacoinvasive model of STEMI care is associated with a 16.1% proportion of adverse events. Crew configuration including ALS clinicians is the key in managing these events.}, }
@article {pmid36794629, year = {2023}, author = {Çoban, M and Bilge, U and Balseven, H and Uysal, H and Artut, B}, title = {The economic evaluation of ALS care: quality and cost.}, journal = {Amyotrophic lateral sclerosis &amp; frontotemporal degeneration}, volume = {24}, number = {5-6}, pages = {502-513}, doi = {10.1080/21678421.2023.2176776}, pmid = {36794629}, issn = {2167-9223}, mesh = {Humans ; Cost-Benefit Analysis ; *Amyotrophic Lateral Sclerosis/diagnosis/therapy ; Social Support ; Research Design ; }, abstract = {Objective: The study aims to analyze the quality of studies that make economic evaluations for amyotrophic lateral sclerosis (ALS). Assessing the quality of studies can guide policy-making and planning. Methods: One of the most recognized checklists "The Consensus on Health Economic Criteria" (CHEC)-list designed by Evers et al. in 2005 aims to answer two important questions: is the methodology of the study appropriate